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Summary Recommendations The recommendations of the PROSPECT Working Group are graded A–D, based on the level of evidence from the studies, which is in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM website accessed Dec 2003, Sackett 2000). In the context of PROSPECT, recommendations based on procedure-specific evidence are grade A (randomised clinical trials), those based on transferable evidence are grade B (randomised clinical trials) or grade C (retrospective studies or case series) and those based on clinical practice are grade D. (Click here for further information on levels of evidence and grades of recommendation) PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted. The following pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following abdominal hysterectomy: Pre-operative Recommended:
  • Single-dose spinal local anaesthetic plus strong opioid, for anaesthetic (grade D) and postoperative analgesic purposes (grade A), but the benefits must be weighed against the risks of the invasive nature of the procedure
  • Cognitive intervention (grade A)
Not recommended:
  • Systemic analgesics (e.g. IV COX-2 inhibitors, conventional NSAIDs, strong opioids), except to secure sufficient analgesia when the patient wakes up (e.g. oral COX-2 inhibitors) (grade A)
  • Clonidine, NMDA-receptor antagonists and benzodiazepines (grade A)
  • Epidural single dose for postoperative analgesia (grade A)
  • Local anaesthetic skin infiltration at the proposed site of incision (grade A) (but intra-operative wound infiltration is recommended, see below)
  • Homeopathic arnica and self-relaxation techniques (grade A)
Intra-operative Recommended:  
  • General anaesthesia, or single dose spinal anaesthesia with or without light general anaesthesia in low-risk patients (grade D)
  • Epidural anaesthesia combined with light general anaesthesia or combined spinal-epidural anaesthesia, in high-risk patients (grade A)
  • Strong opioids administered in enough time to secure sufficient analgesia when the patient wakes (grade A)
  • Wound infiltration before closure (grade A)
  • LAVH or VH rather than abdominal hysterectomy, only if allowed by the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) (grade A)
  • Pfannenstiel incision, only if allowed by the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) (grade B)
  • Diathermy incision (grade B)
  • Active patient warming in high-risk patients (grade A)
  • Intra-operative music (grade A)
Not recommended:
  • Epidural single dose for postoperative analgesia (grade A)
  • Adenosine, NMDA-receptor antagonists, benzodiazepines or tryptophan (all grade A)
  • Intraperitoneal analgesia (grade A)
  • Unsutured peritoneum, wet film dressing (both grade A) or surgical drains (grade D)
  • Therapeutic suggestions or electroacupuncture (both grade A)
Postoperative Recommended:  
  • COX-2 selective inhibitors or conventional NSAIDs, in combination with strong opioids for high-intensity pain (VAS=50) or with weak opioids for moderate- (VAS<50>30) or low-intensity pain (VAS=30) (grade A)
  • Strong opioids by IV PCA or by fixed IV dosing titrated to pain intensity (grade A)
  • Paracetamol for moderate- (VAS>30<50) or low-intensity (VAS=30) pain, in combination with COX-2 inhibitors or conventional NSAIDs (grade A)
  • Epidural analgesia in high-risk patients (grade A and D)
Not recommended:
  • Epidural analgesia for routine use in low-risk patients (grade D)
  • Repeat spinal boluses of analgesic (grade D)
  • Concomitant administration of COX-2 selective inhibitors or conventional NSAIDs with epidural analgesia (grade B)
  • Continuous infusion of strong opioid during PCA bolus dosing (grade D)
  • IM administration of strong opioids (grade D)
  • Intra-nasal, slow-release oral and transdermal patch administration of strong opioids (grade D)
  • Paracetamol for high-intensity pain (VAS=50 mm) (grade B)
  • NMDA-receptor antagonists and benzodiazepines (both grade A)
  • Clonidine, pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone (all grade A)
  • Continuous wound infiltration of local anaesthetics after closure (grade A) (although pre-closure wound infiltration is recommended, see above)
  • Music in PACU, homeopathic arnica or self-relaxation techniques (all grade A)
See Overall PROSPECT Recommendations  for the overall strategy for managing pain after abdominal hysterectomy  
Overall PROSPECT Recommendations

Click here for Algorithm for the management of postoperative pain

This algorithm for managing postoperative pain is based on the PROSPECT recommendations and illustrates the different treatment pathways for low-  ¢ and high-  ¢ risk patients, as well as describing the steps of the peri-operative pathway/therapies that apply to all patients ¢. Therapies that are not recommend are also indicated. a Low-risk patients are otherwise healthy patients who are not considered to be at a higher risk than is typically associated with anaesthetic or analgesic agents b High-risk patients are those considered to be at a high risk of adverse effects from inhalation anaesthetics and high-dose opioids, e.g. those at risk of organ dysfunction or undergoing extensive surgery for malignancy.  

Description of studies 

Literature search

Explanation for the focus on abdominal over vaginal hysterectomy

  • The significant majority of studies found in the literature search were in abdominal hysterectomy, with the exception of: 
  • The studies showed that LAVH is associated with significantly lower postoperative pain scores than abdominal hysterectomy: meta-analyses showed a reduction of up to 29 mm at 48 h on a 100-mm VAS (p<0.00001) (see Operative Techniques section)
  • In light of the different pain profiles for LAVH and abdominal hysterectomy, and the absence of studies in LAVH, these procedures will be assessed separately, and an analysis of analgesia for controlling postoperative pain in LAVH conducted when more studies are available  

Transferable evidence
As for all of the procedures in PROSPECT, abdominal hysterectomy-specific evidence was supplemented with transferable evidence, the majority of which was from other major gynaecological and abdominal procedures.  

PROSPECT Recommendations

  • A recommendation of anaesthetic choice based on postoperative analgesic effect cannot be made for abdominal hysterectomy, because there is no evidence for the comparative benefits of different anaesthetic techniques in reducing postoperative pain. Moreover, anaesthetic choice should be based on factors other than the management of postoperative pain, including individual patient risk factors and local practice (Grade D)
  • General anaesthesia or single shot spinal anaesthesia with or without sedation is recommended for routine use in abdominal hysterectomy, but the continuous epidural catheter technique is not recommended for routine use, based on the relative risks and benefits of these techniques in this patient population (grade D)
  • Continuous epidural with or without a light general anaesthetic or combined epidural-spinal anaesthesia is recommended over general anaesthesia alone in high-risk patients, e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy. In these high-risk patients, the benefits of neuraxial anaesthesia (e.g. reduction in inhalation anaesthetics and opioid use as well as reduced paralytic ileus and improved pulmonary function) outweigh the risks. In these pa

Clinical Practice

  • The continuous epidural technique produces a less profound block than spinal anaesthesia and takes a longer time to perform as well as conveying a higher risk of rare complications such as epidural haematoma

Transferable Evidence from Other Procedures

  • Inhaled anaesthesia was similar to combined nitrous oxide/propofol anaesthesia for postoperative pain scores, supplementary analgesic consumption and time to recovery from anaesthetic in patients undergoing laparoscopic hysterectomy Nelskyla et al 1997 Click here for more information
  • Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, maternal satisfaction and the need for neonatal intervention as determined in a systematic review of caesarean section Ng et al 2004
  • Combined spinal-epidural anaesthesia has a higher postoperative analgesic efficacy than epidural anaesthesia alone Lew et al 2004 Click here for more information

Abdominal Hysterectomy-Specific Evidence - Study information

  • Combined general-epidural anaesthetic was superior to general anaesthetic alone for reducing postoperative pain scores in two studies, and one study showed greater postoperative benefits with an additional epidural bolus at closure Jorgensen et al 2001 Click here for more information
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthesia alone for reducing supplementary analgesic consumption Jorgensen et al 2001 Click here for more information
  • General plus epidural anaesthesia was superior to spinal plus epidural anaesthesia for reducing postoperative pain scores at rest (p=0.026) and on movement (p<0.001; n=40) within 0–72 h Callesen et al 1999
  • General plus epidural anaesthesia was superior to spinal plus epidural anaesthesia for reducing postoperative supplementary opioid consumption from PACU-72 h (p<0.05; n=40) Callesen et al 1999
  • Spinal plus epidural was associated with a significantly lower incidence of nausea (p<0.0001) and vomiting (p<0.002) than general plus epidural anaesthesia within 0–72 h (n=40) Callesen et al 1999

PROSPECT Recommendations

  • Intra-operative strong opioids are recommended for the treatment of postoperative pain in hysterectomy based on their analgesic efficacy in the early postoperative period (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Intra-operative adenosine is not recommended based on limited evidence of its analgesic efficacy (grade A) and a lack of clinical experience with this agent (grade D)
  • Intra-operative NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy and effect on reducing PONV (grade A), as well as a lack of clinical understanding of these agents
  • Intra-operative benzodiazepines are not recommended based on limited evidence for their analgesic efficacy (grade A)
  • Intra-operative tryptophan is not recommended based on a lack of analgesic efficacy (grade A)

Clinical Practice

  • Adenosine and tryptophan are not used routinely because of a lack of clinical experience with these agents
  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

PROSPECT Recommendations

  • Intra-operative administration of single dose epidural analgesia, in addition to anaesthesia, is not recommended for the treatment of postoperative pain based on evidence of a limited duration of effect in reducing postoperative pain and a lack of benefit in reducing supplementary analgesic consumption (grade A)
  • A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effects because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

  • Epidural and spinal anaesthesia were not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Intra-operative epidural morphine, with or without postoperative epidural boluses, provided a significant benefit over epidural saline placebo in reducing postoperative pain scores at 6 h, but the results at 12 and 24 h were not significant Jorgensen et al 1982 Click here for more information
  • Intra-operative epidural morphine extended the time to first analgesic request in one study (p<0.05; n=14) Jorgensen et al 1982
  • Intra-operative epidural clonidine provided a significant benefit over placebo in reducing postoperative pain scores on cough and mobilisation at 4–12 h (p<0.05 for all times; n=22) Mogensen et al 1992a
  • Intra-operative epidural ketamine conferred a significant benefit over placebo for reducing the supplementary analgesic consumption within 0–4 (p<0.05), 0–8, 0–12 and 0–24 h (p<0.001), but at 0–1 and 0–2 h the results were not significant (n=40) Abdel-Ghaffar et al 1998
  • Intra-operative ketamine conferred a significant benefit over placebo for extending the time to first analgesic request (p<0.01; n=40) Abdel-Ghaffar et al 1998
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthetic alone for reducing postoperative pain Jorgensen et al 2001 Click here for more information
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthetic alone for reducing supplementary analgesic consumption Jorgensen et al 2001 Click here for more information
  • Intra-operative epidural morphine plus postoperative IV morphine was associated with a similar incidence of PONV as placebo plus IV morphine in one study (n=14) Jorgensen et al 1982
  • Intra-operative epidural morphine provided no significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h Jorgensen et al 1982 Click here for more information
  • Intra-operative epidural bupivacaine plus fentanyl conferred no significant benefit over placebo for reducing postoperative pain scores within 0–48 h in one study (n=50) Richards et al 1998
  • Intra-operative epidural bupivacaine plus fentanyl conferred no significant benefit over placebo for reducing supplementary analgesic consumption within 0–48 h in one study (n=50) Richards et al 1998
  • Intra-operative epidural clonidine provided no significant benefit over placebo in reducing postoperative pain scores at rest (n=22; n=40) Mogensen et al 1992a
  • Intra-operative epidural clonidine was associated with a significant decrease in arterial blood pressure compared with placebo in two studies (p<0.05 for both; n=40; n=22) Mogensen et al 1992a
  • Intra-operative epidural ketamine conferred no significant benefit over placebo for reducing postoperative pain scores within 0–24 h (n=40) Abdel-Ghaffar et al 1998
  • Intra-operative epidural neostigmine conferred no significant benefit for reducing postoperative pain scores or supplementary analgesic consumption within 0–24 h (n=45) Nakayama et al 2001a

PROSPECT Recommendations

  • Intra-operative wound infiltration is recommended based on specific evidence that it reduces pain following hysterectomy at 8 h (grade A). Although this outcome did not reach clinical significance, this method of analgesia is convenient and has a favourable safety profile Gallagher et al 2001 Click here for more information

Clinical Practice

  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile

Transferable Evidence from Other Procedures

  • Intra-operative wound infiltration with local anaesthetic was superior to pre-incisional administration, which in turn was superior to placebo for reducing pain scores (mean VAS = 51, 59 and 76 mm, respectively) and the proportion of patients requiring postoperative analgesics (28, 50 and 76%, respectively), in patients undergoing laparoscopic cholecystectomy (n=70) Sarac et al 1996
  • Intra-operative wound infiltration plus intraperitoneal administration of bupivacaine reduced postoperative overall pain for 0–2 h and incisional pain for 0–3 h (p<0.01, for both comparisons), as well as 3-h morphine consumption (p<0.05) and nausea (p<0.05) in patients undergoing laparoscopic cholecystectomy (n=58) Bisgaard et al 1999

Abdominal Hysterectomy-Specific Evidence - Study information

  • There is mixed evidence for a benefit of intra-operative wound infiltration for reducing postoperative pain scores, and the benefits are of marginal clinical significance Cobby et al 1997 Click here for more information
  • Intra-operative wound infiltration provides no significant benefit over placebo for reducing supplementary analgesic consumption Cobby et al 1997 Click here for more information
  • Wound infiltration with ketorolac provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption in one study (n=20) Richman et al 1994
  • Wound infiltration with local anaesthetic provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996
  • Wound infiltration with local anaesthetic was not significantly different from placebo for the incidence of PONV in the three studies reporting this parameter (all groups received postoperative strong opioids) Klein et al 2000

PROSPECT Recommendations

  • Intraperitoneal analgesia is not recommended based on its lack of benefit in reducing pain scores and supplementary analgesic consumption following abdominal hysterectomy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Intraperitoneal analgesia is an effective method for controlling postoperative pain in gynaecological laparoscopy Narchi 1995
  • Intraperitoneal wound infiltration with local anaesthetic produced a clinically significant decrease in VAS score of 13 mm on a 100-mm scale at 1–4 h in patients undergoing laparoscopic cholecystectomy, from a meta-analysis of 13 studies (p<0.05) Møiniche et al 2000
  • Intraperitoneal plus wound infiltration with bupivacaine reduced postoperative overall pain for 0–2 h and incisional pain for 0–3 h (p<0.01, for both comparisons), as well as 3-h morphine consumption (p<0.05) and nausea (p<0.05) in patients undergoing laparoscopic cholecystectomy (n=58) Bisgaard et al 1999

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • The type of surgical technique for hysterectomy should be based on factors other than the management of postoperative pain, such as the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient (grade D)
  • If the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) allow, LAVH or VH is recommended over open hysterectomy because it is associated with significantly lower postoperative pain, reduced supplementary analgesic consumption and a shorter recovery time compared with abdominal hysterectomy (grade A)

Clinical Practice

  • Abdominal rather than transvaginal hysterectomy is indicated in patients who have never been pregnant, who suffer from cancer of the uterus or patients having a uterus size that precludes the transvaginal approach

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • LAVH provided a significant benefit over abdominal hysterectomy for reducing postoperative pain scores over the first week following surgery, providing a reduction in 100-mm VAS scores of 16 mm at 24 h, 24 mm at 48 h and 18 mm at 1 week Hwang et al 2002 Click here for more information
  • LAVH was superior to abdominal hysterectomy for reducing total supplementary analgesic consumption Falcone et al 1999 Click here for more information
  • There is some evidence that LAVH may be associated with a lower incidence of nausea at 34 h, in one study (p<0.05; n=40) Ellstrom et al 1998
  • LAVH was associated with a significantly shorter hospital stay/convalescence time than abdominal hysterectomy Howard et al 1993
  • LAVH and total vaginal hysterectomy were similar for postoperative pain scores (n=60) Hwang et al 2002
  • LAVH was associated with a lower total number of complications (e.g. febrile morbidity, infections and major organ or vessel injury) than total vaginal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • Vaginal hysterectomy was superior to abdominal hysterectomy for reducing postoperative pain scores at 24 h (p<0.001; n=60) Hwang et al 2002
  • Vaginal hysterectomy was associated with a lower total number of complications than abdominal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • Vaginal hysterectomy was associated with a shorter hospital stay and faster return to work than abdominal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • One study reported no significant difference between vaginal and laparoscopic hysterectomy for the complication rate (n=473) Garry et al 2004
  • Vaginal hysterectomy and laparoscopic hysterectomy produced no significant difference in postoperative pain scores over 24 h in one study (n=473) Garry et al 2004
  • LAVH was associated with significantly longer operating times than abdominal hysterectomy Ellstrom et al 1998
  • LAVH was associated with longer operative times and greater blood loss than total vaginal hysterectomy (p=0.01 for both comparisons; n=60) Hwang et al 2002
  • One study reported a significantly longer operative time for laparoscopic compared with vaginal hysterectomy (p<0.05; n=45) Richardson et al 1995

PROSPECT Recommendations

  • Active patient warming is recommended in high-risk patients because there is evidence that it reduces intra-operative bleeding (grade A) and improves outcome in high-risk patients (grade D); however, it has no analgesic benefit (grade A)
  • Leaving the peritoneum open is not recommended over the conventional technique of peritoneal closure because there is evidence that it has no significant analgesic benefit (grade A)
  • Routine use of drains is not recommended, despite some evidence for an analgesic benefit in laparoscopic hysterectomy, because there is a lack of specific evidence, and a risk of infection and patient dissatisfaction (grade D)
  • Wet dressings are not recommended over conventional dressings because there is not yet sufficient evidence to support their benefit in reducing postoperative pain (grade A)
  • It is recommended that the choice of surgical incision for hysterectomy is based on surgical requirements (dependent on the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient) rather than postoperative pain outcome. If allowed by the surgical requirements, a transverse incision is recommended over a vertical incision because it is associated with lower postoperative pain and less pulmonary dysfunction, while it is has a similar morbi
  • Diathermy is recommended over the scalpel for hysterectomy incisions based on lower postoperative pain and opioid use as well as greater speed of incision and less blood loss, as shown in patients undergoing elective midline laparotomy (grade B)

Clinical Practice

  • A transverse incision is the preferred method for hysterectomy for safety and cosmetic reasons. However, a vertical incision may be required where large fibroids need to be removed or where the upper abdomen must be explored. Pulmonary complications are also less likely with transverse incisions
  • Wound drains are invasive and can increase the risk of infection and, in addition, their extraction is associated with significant patient anxiety

Transferable Evidence from Other Procedures

  • Drains were superior to no drains for reducing postoperative shoulder-tip pain at 24 h (p=0.01) and 48 h (p=0.018) (non-significant at 3 h), and for reducing abdominal pain at 48 h (p=0.007) (non-significant at 3 and 24 h); but the results were not significant for back pain at any time, in LAVH Shen et al 2003 Click here for more information
  • Drains were superior to no drains for reducing postoperative paracetamol consumption, in LAVH (p<0.001; n=164) Shen et al 2003
  • The Pfannenstiel incision decreased the operating time and hospital stay without affecting morbidity and mortality compared with the vertical incision - as shown in two retrospective studies of surgery for uterine cancer, which did not assess postoperative pain (n=332; n=113) Horowitz et al 2003
  • Laparotomy incisions using diathermy were significantly faster (p<0.04) and were associated with significantly less blood loss (p=0.002), lower 48-h postoperative pain scores (p<0.05) and lower 5-day morphine consumption compared with scalpel incisions (p<0.04), in patients undergoing elective midline laparotomy (n=100) Kearns et al 2001
  • Active patient warming and prevention of intra-operative hypothermia decreases the risk of wound infection, hospitalisation time and the incidence of morbid cardiac events in high-risk patients, in a review Leslie et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • Operative time was significantly shorter for the unsutured compared with the conventional sutured peritoneum (n=66; n=144) Behtash et al 2001
  • Active intra-operative warming was associated with significantly less intra-operative bleeding than placebo (p<0.05; n=41) Persson et al 2001
  • Wet film dressing showed a marginally significant benefit over conventional dressing at day 3 for reducing postoperative pain scores (p=0.046; n=30), but this result was non-significant at all other times Briggs 1996
  • Unsutured and sutured peritoneum techniques were not significantly different for postoperative pain scores at rest or for supplementary analgesic consumption, for up to 5 days following the operation (n=66; n=144) Behtash et al 2001
  • There was no significant benefit of active intra-operative warming over placebo for reducing postoperative pain scores or supplementary analgesic consumption for the 48-h study period (n=41) Persson et al 2001
  • Wet film dressing was not significantly different from conventional dressing for supplementary analgesic consumption (n=30) Briggs 1996

PROSPECT Recommendations

  • Intra-operative music played to the patient during general anaesthesia is recommended based on its effects in reducing postoperative pain scores, supplementary analgesic consumption and rehabilitation time (grade A)
  • Therapeutic suggestions and electroacupuncture are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Intra-operative music was superior to placebo for reducing postoperative pain scores on the first postoperative day (p<0.001) (non-significant on the second and third day) (n=58) Nilsson et al 2001
  • Intra-operative music was superior to placebo for reducing supplementary analgesic consumption on the day of surgery (p=0.028), and there was a trend towards significance on the first postoperative day (p=0.057; n=89) Nilsson et al 2001
  • Intra-operative music was superior to placebo for time to sitting (p=0.008; n=89) Nilsson et al 2001
  • Of six studies, all showed no significant benefit of intra-operative therapeutic suggestions over placebo for reducing postoperative pain scores for up to 5 days Block et al 1991
  • Five out of six studies showed no significant benefit of intra-operative therapeutic suggestions over placebo for reducing supplementary analgesic consumption McLintock et al 1990 Click here for more information
  • Electroacupuncture provided no significant benefit over placebo for reducing postoperative pain scores at rest and on coughing, or for reducing supplementary analgesic consumption (n=50) Christensen et al 1993

PROSPECT Recommendations

  •  Pre-operative local anaesthetic infiltration at the proposed site of incision is not recommended for abdominal hysterectomy because of its lower benefit compared with post-incisional infiltration for reducing postoperative pain in hysterectomy (grade A). Post-incisional wound infiltration is recommended (see Intra-operative Wound Infiltration)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Pre-incisional wound infiltration of local anaesthetic had a lower analgesic efficacy than post-incisional infiltration: mean 100-mm VAS score was 59 mm and 51 mm, respectively; and the proportion of patients requiring postoperative analgesics was 50 and 28%, respectively, in patients undergoing laparoscopic cholecystectomy (n=45) Sarac et al 1996

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-incisional wound infiltration provided a significant benefit over placebo for reducing supplementary analgesic consumption, in two of three studies Eriksson-Mjoberg et al 1997a Click here for more information
  • Pre-incisional wound infiltration and placebo were associated with a similar incidence of PONV in five of the studies reporting this parameter Hannibal et al 1996
  • Pre-incisional wound infiltration provided no significant benefit over placebo for reducing postoperative pain scores in three studies (n=19, n=41, n=40) Eriksson-Mjoberg et al 1997a
  • Pre-incisional wound infiltration provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996
  • Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing postoperative pain scores within 0–96 h in two studies Click here for more information
  • Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing supplementary analgesic consumption within 0–96 h in two studies Click here for more information

PROSPECT Recommendations

  • Pre-operative cognitive intervention for patients undergoing hysterectomy is recommended based on its effect on reducing postoperative pain, analgesic consumption and anxiety as well as increasing patient satisfaction (grade A)
  • Homeopathic arnica and self-relaxation techniques are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Cognitive intervention reduced postoperative pain scores and the duration of pain compared with no cognitive intervention Cheung et al 2003 Click here for more information
  • Cognitive intervention was superior to placebo for reducing supplementary analgesics Ridgeway et al 1982 Click here for more information
  • One study reported that state and trait anxiety scores were significantly lower for patients receiving pre-operative cognitive therapy than those not receiving cognitive intervention (p<0.05; n=96) Cheung et al 2003
  • One study reported that patient satisfaction was significantly higher in patients receiving pre-operative cognitive therapy than those not receiving cognitive intervention (p<0.05; n=96) Cheung et al 2003
  • Homeopathic arnica had no significant benefit compared with placebo for VAS pain scores or supplementary analgesia (n=73) Hart et al 1997
  • Self-relaxation provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=28) Mogan et al 1985

Pre-operative analgesia

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively. However, a previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). Nevertheless, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period. 

PROSPECT Recommendations

  • Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea
  • Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)
  • Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • One systematic review Ho et al 2006
  • One systematic review Ho et al 2006

Abdominal Hysterectomy-Specific Evidence – Study information

  • Three out of five studies demonstrated that pre- and postoperative oral gabapentin was superior compared with placebo for reducing pain scores Gilron et al 2005 Click here for more information
  • Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005 Click here for more information
  • Four out of five studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004 Click here for more information
  • Two out of two studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo Gilron et al 2005 Click here for more information
  • Qualitative analysis demonstrated that in three out of four studies there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004
  • Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information
  • The incidence of side effects following pre- and postoperative oral gabapentin + rofecoxib was significantly lower in two studies out of two when compared with placebo Gilron et al 2005 Click here for more information
  • Patient satisfaction with postoperative pain management was significantly higher at 24 h following pre- and postoperative oral gabapentin compared with placebo (p<0.001) Turan et al 2006
  • Patient satisfaction with postoperative pain management was significantly higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with placebo at 24 (p<0.01), 48 (p<0.01) and 72 h (p value not stated) postoperatively Turan et al 2006
  • There was a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0–4 h postoperatively (R2=0.30, p=0.003, and R2=0.24, p=0.008, respectively), compared with placebo Dierking et al 2004
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin group compared with the placebo group throughout postoperative days 1 and 2 (p=0.002-0.0032) Gilron et al 2005
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with the placebo group throughout postoperative days 1 and 2 (p<0.001) Gilron et al 2005

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors for hysterectomy are recommended because they have an analgesic effect postoperatively (grade A). However, there is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • A pre-operative single bolus of IV parecoxib was superior to placebo for postoperative pain scores on sitting up over 24 h (p=0.02), providing a mean drop of 14 mm in VAS scores on a 100-mm scale (n=36) Ng et al 2003
  • A pre-operative single bolus of IV parecoxib or oral rofecoxib reduced morphine consumption over 24 h compared with placebo Ng et al 2003 Click here for more information
  • Pre-operative oral rofecoxib was associated with a lower incidence of PONV compared with placebo in one study (p<0.05; n=40) Celik et al 2003
  • Pre-operative oral COX-2-selective inhibitors were as effective as oral conventional NSAIDs for reducing postoperative pain scores in two studies (n=25; n=40) Celik et al 2003
  • COX-2-selective inhibitors are similarly effective compared with conventional NSAIDs for reducing postoperative opioid consumption Celik et al 2003 Click here for more information
  • Compared with the conventional NSAID diclofenac, pre-operative rofecoxib was associated with significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) in a group of patients undergoing abdominal or vaginal hysterectomy (n=25) Hegi et al 2004
  • A pre-operative single bolus of rofecoxib or parecoxib did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies (n=40; n=36) Celik et al 2003

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended because there is evidence that pre-operative administration of conventional NSAIDs is no more effective than postoperative administration (grade A). Moreover, pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative conventional NSAIDs significantly reduced postoperative pain scores compared with placebo, but a significant clinical benefit was only evident for up to 4 h Scott et al 1994 Click here for more information
  • The combination of paracetamol with a conventional NSAID was superior to a higher dose of paracetamol alone, administered as a single pre-operative rectal dose for VAS pain scores at rest at 4 h (p<0.05), but there was no significant difference at 2 h and 6–24 h (n=46) Beck et al 2000b
  • Conventional NSAIDs were equally as effective as COX-2-selective inhibitors for reducing postoperative pain scores in two studies Celik et al 2003
  • Pre-operative conventional NSAIDs showed no significant or clinically meaningful benefit over placebo in reducing supplementary analgesic consumption Beck et al 2000b Click here for more information
  • Pre-operative conventional NSAIDs provided no significant benefit over placebo for extending the time to first analgesic request in two out of the three studies that reported this parameter Scott et al 1994 Click here for more information
  • Pre-operative conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all studies used postoperative PCA strong opioids) Beck et al 2000a Click here for more information
  • Conventional NSAIDs and COX-2-selective inhibitors similarly reduce the use of supplementary analgesics Celik et al 2003 Click here for more information
  • Compared with diclofenac, pre-operative rofecoxib caused significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) following abdominal hysterectomy (n=25) Hegi et al 2004
  • There was no significant benefit of pre-incisional conventional NSAIDs over post-incisional conventional NSAIDs in two of three studies for reducing postoperative pain scores Nakayama et al 2001b Click here for more information
  • Of three studies, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=77; n=30) Gabbott et al 1997
  • Pre-incisional administration of flurbiprofen was associated with a shorter time to first analgesic request compared with post-incisional administration of a conventional NSAID, in one study (p<0.05; n=30) Nakayama et al 2001b
  • Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for the incidence of PONV in two studies (n=65, n=30) Gabbott et al 1997

PROSPECT Recommendations

  • Pre-incisional administration of strong opioids is not recommended because of the lack of effect in reducing postoperative pain and supplementary analgesic consumption compared with placebo, and the lack of benefit over post-incisional administration of strong opioids (grade A). Moreover, post-incisional strong opioids are significantly more effective for reducing postoperative pain compared with a similar dose of pre-incisional strong opioids (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Pre-operative clonidine is not recommended based on its limited analgesic efficacy (grade A) and risk of side effects (grade D)
  • NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side effects (grade D)
  • Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • Clonidine is not used routinely for postoperative analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia
  •  NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

  • Pre-operative clonidine provided no consistent significant benefit over placebo for reducing postoperative pain scores; and other postoperative pain outcomes were mixed Dimou et al 2003 Click here for more information
  • Pre-operative benzodiazepines provided no significant benefit in reducing postoperative pain scores, and there is evidence that they have a limited effect on reducing supplementary analgesic consumption Caumo et al 2002 Click here for more information
  • NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

PROSPECT Recommendations

  • Pre-operative administration of single dose epidural analgesia, in addition to that required for anaesthetic purposes, is not recommended for the treatment of postoperative pain following hysterectomy, based on specific evidence that pre-operative epidural analgesia is not as effective as postoperative epidural analgesia (grade A)
  • A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effect because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)
  • Despite the analgesic benefits of pre-operative epidural clonidine, it is not recommended for treating postoperative pain following abdominal hysterectomy because of the incidence of hypotension, sedation and bradycardia (grade D)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

  • Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative pain scores at rest and on movement at 1 and 6 h (p<0.05 for all comparisons; n=36) Goyagi et al 1999
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative supplementary analgesic consumption at 6 and 12 h (p<0.05 for both times; n=36) Goyagi et al 1999
  • Pre-operative epidural morphine was superior to placebo for extending the time to first analgesic request (p<0.05; n=36) Goyagi et al 1999
  • Pre-operative plus postoperative treatment with epidural bupivacaine plus fentanyl was superior to postoperative treatment alone for reducing postoperative pain scores at rest and on coughing within 0–72 h (no p-values; n=41) Beilin et al 2003
  • Pre-operative epidural clonidine was superior to placebo for reducing postoperative pain scores in the PACU (p<0.003; n=40) Murga et al 1994
  • Pre-operative epidural clonidine was superior to placebo for reducing intra-operative anaesthetic requirement (p<0.0001; n=40) Murga et al 1994
  • There was no difference between epidural morphine and placebo (with rescue PCA morphine) for the incidence of postoperative nausea (n=36) Goyagi et al 1999
  • Pre-operative epidural ketamine conferred no significant benefit over placebo for reducing postoperative pain scores within 0–24 h (n=40) Murga et al 1994
  • Pre-operative epidural ketamine conferred no significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h (n=41) Abdel-Ghaffar et al 1998
  • Pre-incisional epidural analgesia provided no significant benefit over post-incisional administration for reducing postoperative pain scores in four out of four studies Garcia et al 2002 Click here for more information
  • Three of four studies showed no significant benefit of pre-incisional epidural analgesia compared with post-incisional administration for reducing supplementary analgesic consumption Espinet et al 1996 Click here for more information

PROSPECT Recommendations

  • Pre-operative single-shot spinal analgesia with local anaesthetic and strong opioid reduces postoperative pain scores and opioid consumption for up to 24 h (grade A). However, these benefits should be weighed against the risks associated with the invasive nature of this technique
  • Pre-operative single-shot spinal local anaesthetic plus strong opioid can be used, with or without sedation, as an alternative to general anaesthesia (Grade A). However, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (Grade D) (see Anaesthetic techniques section)
  • Spinal neostigmine is not recommended based on limited evidence for its analgesic efficacy, evidence of an associated increase in PONV (grade A) and a lack of clinical experience with this agent (grade D)

Clinical Practice

  • There is limited clinical experience of spinal neostigmine

Transferable Evidence from Other Procedures

  • Spinal and epidural anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative spinal analgesia (local anaesthetic, strong opioid or both) was superior to placebo for reducing postoperative pain scores within 0–24 h Vaida et al 2000 Click here for more information
  • Pre-operative spinal local anaesthetic or strong opioid provided a significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h (p<0.05; n=20) Lauretti et al 1998b
  • There was no significant difference between spinal strong opioid and placebo for the incidence of PONV in two studies (all groups received postoperative diclofenac) (n=20, n=30) Lauretti et al 1998b
  • Pre-operative spinal neostigmine (25, 50 or 75 µg) was superior to placebo for reducing postoperative pain scores at the following times: 30 and 60 min (p<0.05; n=92) Lauretti et al 1998a
  • Pre-operative spinal neostigmine (25, 50 or 75 µg) was superior to placebo for reducing supplementary analgesic consumption within 0–24 h (p<0.05; n=92, n=20) Lauretti et al 1998a
  • There is evidence from one of two studies showing a significant benefit of pre-operative spinal neostigmine over placebo for extending the time to first analgesic request (p<0.05; n=92) Lauretti et al 1998a
  • Spinal morphine was superior to IV analgesia for reducing postoperative pain scores Yokota et al 2000 Click here for more information
  • Pre-operative bolus dose of spinal morphine was superior to IV buprenorphine for extending the time to first analgesic request (p<0.01) in one study (n=29) Beltrutti et al 2002
  • Pre-operative spinal neostigmine was associated with a higher incidence of postoperative nausea than placebo Lauretti et al 1998a Click here for more information
  • Pre-operative spinal adenosine provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption within 0–24 h (n=40) Rane et al 2000
  • Pre-induction spinal local anaesthetic was not significantly different to local anaesthetic given at extubation for postoperative pain scores within 0–12 h (n=38) Dakin et al 1996
  • Pre-induction spinal local anaesthetic was not significantly different to local anaesthetic given at extubation for postoperative pain scores within 0–12 h (n=38) Dakin et al 1996

PROSPECT Recommendations

  • The choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure, rather than on the management of postoperative pain (grade D)
  • Combined spinal-epidural anaesthesia is a recommended alternative to epidural plus light general anaesthesia for hysterectomy in high-risk patients (grade D), and may have a greater analgesic efficacy compared with epidural alone as shown in caesarean section (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

Abdominal Hysterectomy-Specific Evidence

  • [No data found within the parameters of this review]

PROSPECT Recommendations

  • Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea
  • Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)
  • Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • One systematic review Ho et al 2006
  • One systematic review Ho et al 2006

Abdominal Hysterectomy-Specific Evidence - Study information

  • Three out of five studies demonstrated that pre- and postoperative oral gabapentin was superior compared with placebo for reducing pain scores Gilron et al 2005 Click here for more information
  • Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005 Click here for more information
  • Four out of five studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004 Click here for more information
  • Two out of two studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo Gilron et al 2005 Click here for more information
  • Qualitative analysis of three out of four studies demonstrated that there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004
  • Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information
  • The incidence of side effects following pre- and postoperative oral gabapentin + rofecoxib was significantly lower in two studies out of two when compared with placebo Gilron et al 2005 Click here for more information
  • Patient satisfaction with postoperative pain management was significantly higher at 24 h following pre- and postoperative oral gabapentin compared with placebo (p<0.001) Turan et al 2006
  • Patient satisfaction with postoperative pain management was significantly higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with placebo at 24 (p<0.01), 48 (p<0.01) and 72 h (p value not stated) postoperatively Turan et al 2006
  • There was a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0–4 h postoperatively (R2 =0.30, p=0.003, and R2 =0.24, p=0.008, respectively), compared with placebo Dierking et al 2004
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin group compared with the placebo group throughout postoperative days 1 and 2 (p=0.002-0.0032) Gilron et al 2005
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with the placebo group throughout postoperative days 1 and 2 (p<0.001) Gilron et al 2005

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended for their effect in reducing supplementary analgesic use (grade B). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)
  • In patients receiving postoperative epidural analgesia, it is recommended that COX-2-selective inhibitors are used only if analgesia is inadequate (grade B) (see Postoperative, Conventional NSAIDs section)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Parecoxib 20 or 40 mg IV every 12 h reduced supplementary analgesic consumption compared with placebo in patients undergoing major gynaecological surgery (n=60) (p<0.05) Tang et al 2002
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Parecoxib 20 or 40 mg IV every 12 h did not significantly reduce postoperative pain scores compared with placebo in patients undergoing major gynaecological surgery (n=60) (p<0.05) Tang et al 2002
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Abdominal Hysterectomy-Specific Evidence

  • [No data found within the parameters of this review]

PROSPECT Recommendations

  • Conventional NSAIDs are recommended for their analgesic and opioid-sparing effects (grade A). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)
  • In patients receiving epidural analgesia, it is recommended that conventional NSAIDs are used only if analgesia is inadequate (grade B)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications including epidural haematoma, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Piroxicam plus thoracic epidural analgesia using bupivacaine and morphine provided no significant benefit over epidural analgesia alone for reducing postoperative pain scores and supplementary analgesic consumption, in major upper abdominal surgery (n=44) Mogensen et al 1992b
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for postoperative pain scores Ng et al 2002a Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more Blackburn et al 1995 Click here for more information
  • One study showed a marginal but significant benefit of rectal diclofenac over rectal paracetamol for reducing mean pain scores over 24 h (p=0.008; n=44): mean reduction in VAS of 0 mm at 8 h, 8 mm at 16 h and 21 mm for 0–24 h on a 100-mm scale Cobby et al 1999
  • Ketorolac combined with morphine was not significantly different from a higher dose of morphine alone for reducing postoperative pain scores in one study (n=22) Kim et al 2001
  • Ketorolac combined with morphine was superior to a higher dose of morphine alone for significantly reducing postoperative morphine consumption at 4 h (p=0.037) and 24 h (p=0.015) in one study (n=22) Kim et al 2001
  • There was no significant difference between postoperative ketorolac and morphine each given by IM PCA for reducing postoperative pain scores at the doses studied (both study groups were allowed rescue morphine) (n=29) Black et al 1990
  • Four studies and two arms of a fifth study showed no significant difference between conventional NSAIDs and weak opioids for VAS pain scores at rest over 24 h Rodriguez et al 1993 Click here for more information
  • There was no significant difference between conventional NSAIDs and weak opioids for time to first analgesic request in one study reporting this parameter (n=58) Ilias et al 1996
  • There is evidence that diclofenac is superior to paracetamol for reducing mean 24-h postoperative pain scores Cobby et al 1999 Click here for more information
  • Results were mixed for conventional NSAIDs compared with placebo for the time to first analgesic request Ilias et al 1996 Click here for more information
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) Blackburn et al 1995 Click here for more information
  • There is evidence that weak opioids are superior to conventional NSAIDs for reducing supplementary analgesic consumption Rodriguez et al 1993 Click here for more information
  • There was no significant difference between conventional NSAIDs and paracetamol for the requirement of postoperative supplementary analgesics Cobby et al 1999 Click here for more information
  • Conventional NSAIDs and paracetamol were not significantly different for the incidence of vomiting Cobby et al 1999 Click here for more information
  • There is limited evidence of a reduction in the incidence of PONV with a conventional NSAID compared with a weak opioid Torres et al 2001 Click here for more information

PROSPECT Recommendations

  • Strong opioids are recommended based on their analgesic efficacy in reducing high-intensity pain (VAS=50) in the early postoperative period (grade A)
  • At clinical doses, different strong opioids are equally effective (grade A)
  • IV PCA administration of strong opioids is recommended based on its greater analgesic efficacy, lower opioid load and greater patient satisfaction compared with regular (fixed-interval) or on-request dosing in hysterectomy and other procedures (grade A); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (grade D)
  • Continuous infusion of strong opioid during PCA bolus dosing is not recommended, despite its analgesic efficacy over PCA bolus doses alone (grade A), because of potential opioid accumulation (grade D)
  • IM administration of strong opioids is not recommended based on the pain associated with these injections (grade D)
  • To minimise the dose of strong opioids, and associated side-effects, it is recommended that strong opioids are combined with COX-2-selective inhibitors or conventional NSAIDs, plus paracetamol (grade B) (see respective sections)
  • There are not currently enough data to make a recommendation for other modes of administration of strong opioids, such as intra-nasal or slow-release tablets
  • Transdermal patches are not recommended: they are not approved for routine use due to the risk of opioid accumulation (grade D)

Clinical Practice

  • Strong opioids are considered to be an effective analgesic for postoperative pain following abdominal hysterectomy, but, because of their adverse effects, they are generally used in combination with non-opioid analgesics to minimise the opioid
  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • IM administration of strong opioids is considered to be more painful than IV administration. However, the dose and rapidity of IV administration should be assessed to minimise the risk of respiratory depression
  • Transdermal patches are not approved for routine use because of the risk of opioid accumulation
  • Continuous infusions of strong opioids by PCA, on top of PCA bolus doses, are being used less frequently as a precaution against opioid accumulation

Transferable Evidence from Other Procedures

  • Opioids administered by PCA decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or subcutaneous opioid treatment, although there was no significant difference for pain scores, as determined in a quantitative systematic review of randomised trials in various surgical procedures Walder et al 2001

Abdominal Hysterectomy-Specific Evidence - Study information

  • Strong opioids administered pre-, intra- and postoperatively were superior to placebo for reducing postoperative pain scores Broome et al 1995 Click here for more information
  • Three studies showed that strong opioids administered pre-, intra- and postoperatively were superior to placebo for reducing supplementary analgesic consumption Broome et al 1995 Click here for more information
  • Strong opioid administered as a single postoperative bolus provided a significant benefit over placebo for reducing postoperative pain scores at 24 h Collis et al 1995 Click here for more information
  • The incidence of PONV was not significantly different between strong opioid and placebo plus rescue strong opioid in four out of five studies reporting this parameter Broome et al 1995 Click here for more information
  • Sufentanil provided a significant benefit over morphine for reducing postoperative pain scores at rest and on movement for the first 2 h following initiation of PCA, but there was no significant difference for the remaining 24 h Ginsberg et al 2000 Click here for more information
  • Sufentanil provided a significant benefit over morphine for reducing the supplementary analgesic consumption from 0–24 h (p<0.05), in one study reporting this parameter (n=40) Ginsberg et al 2000
  • Three out of five studies showed a significant benefit of IV PCA over IM regular/on-request administration of strong opioids for reducing postoperative pain scores D'Haese et al 1998 Click here for more information
  • There is mixed evidence for the benefit of PCA compared with regular/on-request IM administration of strong opioids for reducing overall opioid consumption, although one study suggests that they produced different patterns of dosing Thomas et al 1995 Click here for more information
  • The incidence of PONV was not significantly different between PCA and IM morphine, in two studies reporting this parameter (n=126, n=22) Choiniere et al 1998
  • Bolus plus infusion IV PCA morphine conferred a significant benefit over bolus IV PCA morphine alone for reducing postoperative pain scores with no significant difference in overall analgesic consumption El-Falaki et al 2000 Click here for more information
  • IV pethidine was superior to intranasal pethidine for reducing postoperative pain scores at 5–80 min (p<0.05) and for reducing the total amount of pethidine consumed (p<0.05), in one study (n=60) Striebel et al 1993
  • Oral slow-release and IM morphine were similar for postoperative pain scores, supplementary analgesic consumption and the incidence of PONV in two studies (n=38; n=30) Fell et al 1982
  • Strong opioids gave numerically lower postoperative pain scores than weak opioids in three studies Coetzee et al 1998
  • Morphine gave a numerically longer time to first analgesic request than tramadol in one study reporting this parameter, although the result did not reach statistical significance Coetzee et al 1998
  • Different strong opioids were not significantly different from each other, for reducing postoperative pain scores, supplementary analgesia and PONV, in the majority of studies assessing different strong opioid regimens Chui et al 1992 Click here for more information
  • Bolus IV PCA plus background infusion of morphine was associated with a consistently greater consumption of morphine than IV PCA alone but the results did not reach statistical significance, in two studies (n=20, n=20) El-Falaki et al 2000
  • Three studies showed no significant benefit of a postoperative bolus of strong opioid over placebo for reducing supplementary analgesic consumption Collis et al 1995
  • Strong opioids provided no significant benefit over NMDA-receptor antagonists for postoperative pain scores or supplementary analgesic consumption in two studies Knoche et al 1983 Click here for more information

PROSPECT Recommendations

  • Weak opioids are recommended based on evidence for their analgesic efficacy in gynaecological and abdominal surgery, as well as in other procedures (grade B). Weak opioids should be combined with COX-2-selective inhibitors or conventional NSAIDs and paracetamol, for controlling moderate- (VAS<50>30) or low-intensity (VAS £30) pain later in the postoperative period (grade D)

Clinical Practice

  • It is considered that maximum doses of weak opioids have a plateau of effect on controlling high-intensity pain (VAS³ 50) following abdominal hysterectomy and that strong opioids should be used instead; weak opioids are considered to be effective for lower intensity pain later in the postoperative period

Transferable Evidence from Other Procedures

  • Tramadol 20 mg was superior to placebo for reducing postoperative pain scores measured after an initial bolus dose (p=0.002) in patients undergoing gynaecological or abdominal surgery (n=120) Stamer et al 1997
  • Tramadol plus paracetamol is superior to either drug administered alone for reducing postoperative pain in a meta-analysis of gynaecological, dental and orthopaedic patients McQuay H et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • Four studies and two arms of a fifth study showed that weak opioids and conventional NSAIDs had a similar effect of reducing VAS pain scores at rest over 24 h Rodriguez et al 1993 Click here for more information
  • Weak opioids and conventional NSAIDs had a similar effect of reducing supplementary analgesic consumption in one study reporting this parameter (n=130) Torres et al 2001
  • Conventional NSAIDs and weak opioids have a similar effect for prolonging the time to first analgesic request in one study reporting this parameter (n=58) Ilias et al 1996
  • Tramadol 50 mg IV administered postoperatively on request gave numerically lower postoperative pain scores than placebo, but this was not statistically significant, in one study (n=40) Ilias et al 1996
  • Tramadol 50 mg IV administered postoperatively on request gave a numerically longer time to first analgesic request than placebo but this was not statistically significant in one study (n=80) Ilias et al 1996
  • Strong opioids gave numerically lower postoperative pain scores than weak opioids in three studies Coetzee et al 1998
  • Morphine gave a numerically longer time to first analgesic request than tramadol in one study reporting this parameter, although the result did not reach statistical significance Coetzee et al 1998

PROSPECT Recommendations

  • Paracetamol is recommended for moderate- (VAS<50>30 mm) or low-intensity (VAS £30 mm) pain, in combination with COX-2-inhibitors or conventional NSAIDs, based on its mild analgesic and opioid-sparing effect following hysterectomy (grade A)
  • However, paracetamol is not recommended for high-intensity pain (VAS³ 50 mm) because it has no additional analgesic benefit over that conferred by NSAIDs following abdominal gynaecological procedures (grade B)

Clinical Practice

  • Paracetamol is a well-established analgesic for mild-to-moderate pain (VAS <50 mm) and has a favourable safety profile

Transferable Evidence from Other Procedures

  • Paracetamol 1 g plus diclofenac 100 mg was superior to diclofenac 100 mg alone given once postoperatively, for reducing postoperative pain in dental surgery (p<0.05; n=46) Breivik et al 1999
  • There was no benefit of paracetamol with NSAID compared with NSAID alone for reducing pain scores in a meta-analysis of results from a variety of surgical procedures including dental, orthopaedic and gynaecological operations Rømsing et al 2002
  • Paracetamol 1.5 g plus diclofenac 100 mg was not significantly different from diclofenac 100 mg alone given once pre-operatively, for reducing postoperative pain in abdominal gynaecological surgery (n=39) Montgomery et al 1996

Abdominal Hysterectomy-Specific Evidence - Study information

  • Paracetamol was superior to placebo for reducing postoperative pain scores, producing reductions in VAS scores of £13 mm Cobby et al 1999 Click here for more information
  • Paracetamol was superior to placebo for reducing supplementary analgesic consumption within 0–24 h Cobby et al 1999 Click here for more information
  • One study showed that IV paracetamol was as effective as IV ketorolac for reducing postoperative pain scores (n=176) Varrassi et al 1999
  • One study showed a marginal but significant benefit of rectal diclofenac compared with rectal paracetamol for reducing mean pain scores over 24 h, giving a mean difference in VAS of 0 mm at 8 h, 8 mm at 16 h and 21 mm for 0–24 h, on a 100-mm scale (p=0.008; n=44) Cobby et al 1999

PROSPECT Recommendations

  • NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side-effects (grade D)
  • Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)
  • Other agents, such as pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone cannot be recommended for postoperative analgesia based on limited evidence for their analgesic efficacy (grade A) and a lack of clinical experience with these agents (grade D)

Clinical Practice

  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship. In addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria
  • There is limited clinical experience of using pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone for analgesic purposes

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

  • A regimen of ketamine plus midazolam was superior to pethidine for reducing postoperative pain scores, and was associated with a lower incidence of PONV compared with pethidine Jahangir et al 1993 Click here for more information
  • Piritramide was superior to pentazocine, which was superior to ketamine for reducing postoperative pain scores Knoche et al 1983 Click here for more information
  • Buprenorphine 0.4 mg SL on request was superior to papaveretum 20 IM on request for reducing postoperative pain scores (p<0.01) and supplementary analgesic consumption (p<0.001; n=60) Fry 1979
  • NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the timing of administration Burstal et al 2001 Click here for more information
  • Postoperative midazolam provided no significant benefit in reducing postoperative pain scores or supplementary analgesic consumption for 0–24 h in one study Egan et al 1992 Click here for more information
  • Clomipramine 50 mg IM and pentazocine 30 mg IM, each administered 30 min postoperatively, were similar for postoperative pain scores within 0–7 h (n=40) Tiengo et al 1987
  • Delta-9-tetrahydrocannabinol 5 mg, administered as a single dose orally 24 h after surgery, did not provide a significant benefit over placebo for reducing postoperative pain scores at 0–6 h after administration (n=40) Buggy et al 2003
  • Naloxone 0.25 µg/kg/h or 1 µg/kg/h conferred no benefit over placebo for reducing postoperative pain scores within 0–24 h and high-dose naloxone increased analgesic consumption over 0–24 h (p<0.05) (although low-dose naloxone decreased analgesic consumption, p<0.05) (n=60) Gan et al 1997

PROSPECT Recommendations

  • Continuous postoperative epidural infusion is not recommended for routine use in hysterectomy patients because its analgesic benefits compared with systemic analgesia are short-lasting and are of marginal clinical significance (up to 4 h) (grade A). Therefore, the risks of the epidural technique outweigh the analgesic benefits in low-risk patients (grade D)
  • Continuous postoperative epidural analgesia with local anaesthetic plus strong opioid is recommended in high-risk patients (e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy) – and in these patients it is recommended that the epidural is also used for anaesthesia – because the benefits of the epidural technique, e.g. reduction in inhaled anaesthetics and systemic opioids as well as reduced paralytic ileus and improved pulmonary function (grade
  • Despite the analgesic benefits of epidural clonidine, it is not recommended to control postoperative pain following abdominal hysterectomy because of the incidence of hypotension (grade A), sedation and bradycardia (grade D)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Transferable Evidence from Other Procedures

  • Epidural analgesia using local anaesthetic was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using a combination of local anaesthetic and strong opioid was superior to local anaesthetic alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using local anaesthetics was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery Jorgensen et al 2000b

Abdominal Hysterectomy-Specific Evidence - Study information

  • Postoperative epidural ropivacaine was superior to placebo for reducing postoperative pain scores at rest and on coughing within 0–2, 0–4 and 4–12 h, but results at 2–22 h were non-significant (n=104) Chinachoti et al 2002
  • Combined epidural strong opioid and local anaesthetic was superior to epidural strong opioid alone for reducing postoperative pain scores within 12–24 h (p<0.05; n=40) Madej et al 1992
  • Combined epidural strong opioid and local anaesthetic was associated with a lower incidence of PONV than epidural strong opioid alone (p<0.05; n=40) Madej et al 1992
  • Addition of sufentanil to morphine, as an epidural bolus dose, gave lower postoperative pain scores than morphine alone for 0–6 h (n=30; n=120) Sinatra et al 1991
  • Epidural bolus morphine alone was superior to sufentanil alone and to morphine plus sufentanil, at 240 min after administration (n=45) Sinatra et al 1991
  • Bupivacaine was superior to morphine for reducing pain scores and for reducing times to recovery of bowel motility Thoren et al 1989 Click here for more information
  • Postoperative epidural high-dose naloxone (0.167 µg/kg/hr) was superior to placebo for reducing postoperative pain scores at 8, 16 and 32 h (p<0.05), but results at 2, 4 and 48 h were non-significant Choi et al 2000 Click here for more information
  • Clonidine or clonidine plus sumatriptan conferred a significant benefit over sumatriptan alone for reducing postoperative pain scores within 0–4 h (p<0.01) in one study Liu at al 1997b Click here for more information
  • Epidural bupivacaine was superior to ropivacaine for reducing supplementary ketorolac consumption and gave a larger spread of sensory block than ropivacaine, while recovery outcomes were not significantly different Jorgensen et al 2000a Click here for more information
  • Diamorphine was superior to ketamine for reducing postoperative pain scores and for extending the time to first analgesic request Peat et al 1989 Click here for more information
  • Epidural analgesia had a statistically significant, and marginally clinically significant, benefit over systemic analgesia for reducing postoperative pain scores at 4 h Hindsholm et al 1993 Click here for more information
  • Epidural analgesia provided a significant benefit over IV administration for reducing analgesic consumption over 24 h Eriksson-Mjoberg et al 1997b Click here for more information
  • Epidural analgesia was associated with a significantly lower incidence of PONV compared with systemic analgesia Camu et al 1991 Click here for more information
  • There is evidence for a limited benefit of epidural clonidine over epidural morphine for reducing postoperative pain scores, but two of two studies showed that clonidine causes hypotension Lund et al 1989 Click here for more information

PROSPECT Recommendations

  • Repeated peri-operative doses by the spinal route are not recommended because they are not considered to be safe or practical (grade D)
  • Spinal local anaesthetic plus strong opioid should be administered only as a single pre-operative bolus dose for postoperative analgesia (grade A) or anaesthetic (grade D) purposes (see Pre-operative Spinal analgesia and Intra-operative Anaesthetic techniques sections)

Clinical Practice

  • Spinal anaesthetics are generally administered as a single pre-operative bolus, and repeated peri-operative doses are not considered to be safe or practical

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Postoperative wound infiltration administered by PCA may have a benefit in controlling postoperative pain, but there is not currently enough evidence to recommend it. However, intra-operative wound infiltration is recommended (grade A) (see Intra-operative Wound Infiltration)

Clinical Practice

  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infiltration are not well established

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Postoperative wound infiltration administered by PCA with a 1-h lockout showed a significant benefit of reducing postoperative pain scores on coughing and when raising leg at 4 h (p=0.006 and p=0.009 respectively); however, these comparisons at 1–3 and 5–24 h were non-significant, and results at rest showed no significant benefit at all times (n=36) Zohar et al 2001
  • Postoperative wound infiltration administered by PCA with a 1-h lockout showed a significant benefit in reducing supplementary analgesic consumption within 0–24 h (p<0.001; n=36) Zohar et al 2001
  • Postoperative wound infiltration administered as regular 4-hourly doses provided no significant benefit over placebo for reducing postoperative pain scores at any time (n=41) Kristensen et al 1999
  • Postoperative wound infiltration administered as regular 4-hourly doses provided no significant benefit over placebo for reducing supplementary analgesic consumption (n=41) Kristensen et al 1999

PROSPECT Recommendations

  • Postoperative music is not recommended based on its lack of analgesic efficacy (grade A). However intra-operative music is recommended (See Intra-operative section)
  • Homeopathic arnica and self-relaxation techniques are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Homeopathic arnica had no significant benefit compared with placebo for VAS pain scores or supplementary analgesic consumption (n=73) Hart et al 1997
  • Postoperative music conferred no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=40) Taylor et al 1998
  • Self-relaxation provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=28) Mogan et al 1985
A systematic search of the literature between January 2004 and June 2006 identified additional studies of interventions in abdominal hysterectomy, as listed in this folder, together with brief summaries of the study outcomes and a comment from the PROSPECT Working Group regarding the impact of the recent evidence on the recommendations. Additional details of the studies will be included in the main review text at the next full update of the evidence and recommendations.
  • Four out of four studies found that conventional NSAID was superior to placebo or no treatment. In two studies pre-operative conventional NSAID significantly reduced postoperative VAS pain scores at 2 h (at rest and on coughing; Akarsu 2004) and 2, 4, 6 and 12 h (Karaman 2006), compared with placebo. In one study, pre- and intra-operative conventional NSAID significantly reduced postoperative VAS pain scores at 6 h compared with control (no treatment) (Yan 2004). In one study postoperative conventional NSAID significantly increased pain intensity difference (VAS) scores compared with placebo (at 30 min–24 h) and compared with morphine (at 30 min and 1–12 h) groups (Bikhazi 2004)
  • In one study, time to first request for rescue analgesia was significantly longer, and total analgesic consumed was less, following pre-operative conventional NSAID administration, compared with placebo (Akarsu 2004); in another study, PCA morphine consumption was significantly reduced in the group receiving pre-operative conventional NSAID at 2, 4, 6, 12 and 24 h compared with the saline control group (Karaman 2006)
  • In one study there was a significantly higher incidence of nausea and vomiting in the placebo group compared with the pre-operative conventional NSAID group (Akarsu 2004). In two studies there were no significant differences between the incidence of adverse events in the conventional NSAID and placebo groups (Bikhazi 2004; Karaman 2006)

No change to recommendations

  • Three studies out of three showed COX-2-selective inhibitor superior to control for reducing pain scores:
    • In one study, the pre-operative COX-2-selective inhibitor significantly reduced postoperative VAS pain scores at 1, 2, 4, 6, 8 and 12 h compared with placebo (Karamanlioglu 2004)
    • In one study peri-operative COX-2-selective inhibitor, alone and in combination with gabapentin, significantly reduced postoperative VAS pain scores at rest at 20, 24, 28, 32, 44, 48, 52 and 56 h compared with placebo; VAS pain scores at sitting were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20h, and following the COX-2-selective inhibitor both alone and in combination with gabapentin at 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores at peak expiration were significantly reduced following administration of the COX-2-selective inhibitor alone and in combination with gabapentin at 20, 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores during coughing were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20, 24, 28, 32 h, and following administration of the COX-2-selective inhibitor both alone and in combination with gabapentin at 44, 48, 52 and 56 h, compared with placebo (Gilron 2005)
    • In one study, peri-operative COX-2-selective inhibitor, alone and in combination with gabapentin, significantly reduced VRS postoperative pain scores at rest at 4, 8, 16 and 20 h, compared with placebo; COX-2-selective inhibitor in combination with gabapentin significantly reduced VRS pain scores at rest at 12 and 24 h compared with placebo; COX-2-selective inhibitor alone, and in combination with gabapentin, significantly reduced VRS postoperative pain scores during movement at 8 h, and the COX-2 inhibitor alone also showed a significant reduction at 20 h, compared with placebo (Turan 2006)
  • Three out of three studies showed COX-2-selective inhibitor superior to placebo for reducing supplementary analgesic consumption
    • Total and incremental supplementary analgesic consumptions were significantly less in the pre-operative COX-2-selective inhibitor group compared with placebo at 1, 2, 4, 6, 8, and 12 h postoperatively (Karamanlioglu 2004)
    • Cumulative morphine consumption was significantly less in the COX-2-selective inhibitor plus gabapentin group compared with placebo at 2, 3, 4, 8, 20, 24, 28 and 32 h postoperatively, and interval morphine consumption was significantly less in the COX-2-selective inhibitor group at 4–8, 8–20, 20–32, 32–44 and 44–56 h and in the COX-2-selective inhibitor plus gabapentin group at all time points recorded after surgery, compared with placebo (Gilron 2005)
    • PCA morphine requirement was significantly less following administration of the COX-2-selective inhibitor, alone and in combination with gabapentin at 1, 8, 12, 16, 24, and 30 h postoperatively, and at 20 h following the COX-2-selective inhibitor plus gabapentin, compared with placebo (Turan 2006)
  • Three out of three studies showed that COX-2-selective inhibitors are not superior to placebo for reducing the incidence of adverse effects
    • In two studies there was no significant difference in the incidence of adverse events between the COX-2-selective inhibitor group and control (Gilron 2005; Karamanlioglu 2004)
    • In one study there was no significant difference between COX-2 inhibitor alone or gabapentin alone compared with placebo, but there was a significantly lower incidence of nausea in the combination of COX-2-selective inhibitor and gabapentin group compared with the placebo group (Turan 2006)

No change to recommendations

  • One study showed that pre-operative oral clonidine did not significantly reduce pain scores both at rest and during movement compared with placebo at all time points assessed (Oofuvong 2005); one study showed that pre- and postoperative oral clonidine significantly reduced pain scores compared with placebo at all time points assessed (Hidalgo 2005
  • One study showed that intra-operative dexmedetomidine had no effect on pain scores at rest and during movement compared with placebo, both in the PACU and 0–48 h after surgery (Gurbet 2006)
  • Morphine consumption was not significantly different between clonidine and placebo groups at all time points assessed (Hidalgo 2005; Oofuvong 2005)
  • Patients in the intra-operative dexmedetomidine group consumed significantly less postoperative morphine compared with the placebo group, both in the PACU and 0–48 h after surgery (Gurbet 2006)

Systemic clonidine: no change to recommendation
Dexmedetomidine: limited data, so not recommended at the current time

  • One study showed that pre-operative morphine did not significantly reduce subjective pain scores (0–10) compared with saline control (Goldstein 2005)
  • One study showed that postoperative IV morphine significantly reduced VRS pain scores compared with placebo 2 min after administration, but not at any other time point assessed (5, 10 and 15 min) (Larijani 2004)
  • One study showed that intraoperative pethidine significantly reduced VAS pain scores at rest at 0–120 min after surgery compared with postoperative pethidine (Mavioglu 2005)
  • One study showed a significant reduction in supplemental analgesic demands between 15 and 30 min postoperatively, cumulative PCA demands, cumulative pethidine consumption after the first 24 h, and additional pethidine consumption during the first 2 h, in the intraoperative pethidine group compared with the postoperative pethidine group (Mavioglu 2005)

No change to recommendations

  • One study showed that postoperative tramadol significantly reduced VAS pain scores compared with saline control at all time points assessed (0–24 h) (Kocabas 2005)
  • One study demonstrated a significant reduction in PCA morphine requirements at 1, 2, 3, 4, 8, 12, 16, 20 and 24 h after surgery in the postoperative tramadol group compared with the saline control group (Kocabas 2005)

No change to recommendation

  • One study showed that pre-operative spinal morphine significantly reduced VAS pain scores at rest and during coughing at all time points assessed (up to 20 h post-surgery) compared with control (no treatment) (Karaman 2006)
  • One study showed that intra-operative spinal morphine significantly reduced VAS pain scores at 0, 1, 2, 4, and 8 h after surgery compared with IV morphine (Togal 2004)
  • One study showed that pre-operative spinal morphine significantly reduced postoperative morphine consumption in 20 h compared with control (no treatment) (Karaman 2006)
  • One study showed that postoperative total morphine consumption and PCA demands were significantly lower in the group receiving intra-operative spinal morphine compared with the IV morphine group during postoperative 24 h (Togal 2004)

No change to recommendations

  • One study showed that postoperative IV PCA droperidol (50 µg droperidol premixed with 1 mg/ml morphine compared with morphine alone) significantly reduced VRS pain scores at rest (at 72 h) and on coughing/movement (at 48 and 72 h) compared with control (no droperidol). Morphine consumption was significantly lower in the postoperative IV droperidol group at all time points assessed, when compared with control (no droperidol) (Lo 2005)

Not recommended for pain relief due to limited procedure-specific evidence (although droperidol has proven effects on nausea and vomiting)

  • One study showed that pre-operative antihistamine, combined with either a 1.2:1 or a 4.8:1 ratio of antihistamine-morphine mixture for postoperative PCA, did not significantly reduce VAS pain scores at rest or supplemental analgesic requirements at any time point assessed (0–24 h) compared with saline control (Lin 2005)
  • One study showed that neither pre-operative antihistamine alone nor postoperative antihistamine alone significantly reduced VAS pain scores at rest or during movement compared with saline control (Chia 2004)
  • One study showed that patients in the pre-operative antihistamine alone group consumed significantly less morphine at 3, 6, 12, and 24 h postoperatively compared with patients in the postoperative antihistamine alone and saline control groups (Chia 2004)

Not recommended due to limited evidence of analgesic efficacy

  • One study showed that pre- and intra-operative beta-blockers had no effect on VAS pain scores at rest and during movement at all time points assessed compared with saline control (Chia 2004)
  • Patients receiving beta-blockers consumed significantly less PCA morphine at all time points assessed, and the mean total morphine consumption was significantly less, compared with saline control (Chia 2004)

Not recommended because of limited evidence of analgesic efficacy

Single bolus wound instillation

  • One study showed that intra-operative single bolus wound instillation (topically on to peritoneum for 10 min) significantly reduced NRS pain scores at 60 min after surgery compared with placebo (pain assessed every 15 min from 0–120 min after surgery; all other time points not significantly different) (Heid 2005)
  • There were no differences in cumulative morphine consumption or adverse effects observed between the wound instillation and placebo groups (Heid 2005)

Not recommended currently due to limited procedure-specific evidence

 

Continuous wound infusion

  • One study showed that postoperative continuous wound infusion significantly reduced VAS pain scores compared with no wound infusion at rest at 4, 5, 6, and 12h, on coughing at 0–24 h, and on leg raising at 3, 4, 5, 6, and 12 h after surgery (Gupta 2005)
  • Significantly less rescue analgesia was consumed in the continuous wound infusion group compared with the no wound infusion group (pentazocine administered 0–6 h, diclofenac administered 6–24 h) (Gupta 2005)

Not recommended currently due to limited procedure-specific evidence

 

PCA wound infusion

  • One study (published January 2004–June 2006) showed that there were no significant differences in analgesic outcomes between two doses of ropivacaine delivered via PCA wound infusion (Zohar 2004)

Not recommended currently due to limited procedure-specific evidence  

  • One study showed that IP LA + IP conventional NSAID + IP weak opioid significantly reduced VAS pain scores compared with IP LA + IP conventional NSAID (at 1 and 2 h) and IP LA + IP weak opioid (at 2 h) (Pirbudak 2004)
  • Time to first analgesic request was significantly longer, and total supplementary analgesic consumption was significantly lower, in the IP LA + IP conventional NSAID + IP weak opioid group compared with the IP LA + IP conventional NSAID group and the IP LA + IP weak opioid group (Pirbudak 2004)

No change to recommendations

  • One study showed that there were no significant differences in analgesic efficacy between pre-operative and postoperative epidural analgesia (LA + ketamine) (DeCastro 2005)
  • One study showed that there were no significant differences in VAS pain scores at rest and during coughing (at 4, 8, and 21 h), or total morphine consumption, between the postoperative epidural 0.1% ropivacaine + fentanyl group and the postoperative epidural 0.2% ropivacaine group (Thienthong 2004)

No change to recommendations

Two studies showed that abdominal laparoscopic hysterectomy significantly reduced pain scores compared with abdominal hysterectomy (Garry 2004; Garry 2004). One study showed that laparoscopic hysterectomy significantly reduced pain scores compared with abdominal hysterectomy (Learman 2004). One study showed that vaginal hysterectomy significantly reduced pain compared with abdominal hysterectomy (Silva 2006)

 Vaginal hysterectomy studies:

  • Two studies showed that there were no significant differences in pain scores between vaginal hysterectomy and vaginal laparoscopic hysterectomy (Garry 2004; Garry 2004)
  • One study showed that electrosurgical bipolar vessel sealing significantly reduced pain compared with traditional suturing in vaginal hysterectomy (Cronjé 2005)

Further data are required before any changes can be made to the recommendations

Notes on PROSPECT recommendations

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.Grades of recommendation (GoR) are assigned according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence.

Grades of recommendation (GoR) based on source and level of evidence (LoE): Summary table



An explanation of how study quality assessments are performed to determine the LoE and GoR can be found at the following link: C-Section: levels of evidence and grades of recommendation.

The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT C-Section review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:
  • Systematic methods were used to search for evidence.
  • The criteria for selecting the evidence are clearly described.
  • The strengths and limitations of the body of evidence are clearly described.
  • The methods for formulating the recommendations are clearly described.
  • The health benefits, side effects, and risks have been considered in formulating the recommendations.
  • There is an explicit link between the recommendations and the supporting evidence.
  • The guideline has been externally reviewed by experts prior to its publication. [The evidence and recommendations will be submitted for peer-review after publication on the PROSPECT website]
  • A procedure for updating the guideline is provided. [Methodology is provided so that the systematic review can be updated as required]

Summary recommendations

Pre-operative interventions that are recommended for C-Section

Note: Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Oral gabapentin

·        A single dose of pre-operative oral gabapentin is recommended (GoR A) for improving postoperative pain relief (LoE 1)

Anaesthetic techniques and co-administered analgesics

Anaesthetic techniques: Combined spinal-epidural anaesthesia or spinal anaesthesia

·        Combined spinal-epidural anaesthesia or spinal anaesthesia are recommended (GoR A) based on procedure-specific evidence (LoE 1)

·        There is no evidence of analgesic benefit to recommend general anaesthesia over neuraxial anaesthesia (i.e., epidural anaesthesia, spinal anaesthesia, and combined spinal epidural anaesthesia), due to lack of direct comparative studies focusing on postoperative analgesia (GoR D).

·        However, neuraxial anaesthesia techniques are recommended for safety reasons (e.g., neuraxial anaesthesia obviates the need for airway manipulation and avoids the postoperative sedative effects of general anaesthetics) (GoR D)

Intrathecal opioid analgesia

·        Intrathecal morphine below 200 µg is recommended if the patient has received spinal anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

·        However, due to opioid-related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Epidural opioid analgesia

·        Epidural opioids are recommended if the patient has received epidural anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

·        However, due to opioid related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Surgical techniques that are recommended for C-Section

Surgical techniques: Transverse abdominal incision and non-closure of the peritoneum

·        Transverse abdominal incision is recommended over vertical incision (GoR A, LoE 1). Amongst transverse incisions the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain (GoR A, LoE 1)

·        Non-closure of the peritoneum is recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Intraoperative interventions that are recommended for C-Section

Note: Unless otherwise stated, ‘intra-operative’ refers to interventions applied after incision and before wound closure. In C-Section, ‘post-delivery’ refers to administration after the umbilical cord is clamped and the baby is delivered.

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Post-delivery
IV NSAIDs

·        Post-delivery NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)

Post-delivery
IV paracetamol

·        Post-delivery paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Post-delivery iliohypogastric and ilioinguinal blocks

·        Bilateral iliohypogastric and ilioinguinal blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Post-delivery bilateral TAP blocks

·        Bilateral TAP blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Post-delivery wound infiltration with local anaesthetics

·        Wound infiltration with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Postoperative interventions that are recommended for C-Section

Note: ‘Postoperative’ refers to interventions applied at or after wound closure

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Oral NSAIDs

·        Postoperative NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)

Oral paracetamol

·        Postoperative paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Systemic opioids as rescue analgesia

·        Systemic opioids provide effective analgesia (GoR A, LoE 1), but are only recommended as rescue analgesics due to side effects (GoR D)

Continuous wound infusion with local anaesthetics

·        Continuous wound infusion with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)


Overall Recommendations: Pain Management for Elective Caesarean Section Surgery

Pre-operative 

Oral gabapentin

Pre-/intra-operative anaesthetic technique

CSEA or SpA*

Intra-operative, post-delivery

IV paracetamol + IV NSAID #

Wound infiltration with LA or TAP blocks or iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative analgesic techniques such as wound infiltration with LA, TAP block, iliohypogastric and ilioinguinal blocks should be considered to avoid the potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAID may not be necessary if neuraxial opioids are used

† Amongst transverse incisions, the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain


Not recommended for C-Section

Dexamethasone

Pre-operative dexamethasone cannot be recommended at this time (GoR D) based on limited procedure-specific evidence

Neuraxial clonidine

Neuraxial clonidine is not recommended (GoR D), although procedure-specific evidence suggests it provides superior analgesia, because of side effects (e.g. hypotension)

Ketamine

Ketamine cannot be recommended at this time (GoR D) based on inconsistent procedure-specific evidence

TENS

TENS is not recommended (GoR D) based on limited procedure-specific evidence

Wound infiltration with NSAIDs

Wound infiltration with NSAIDs is not recommended at this time (GoR D) due to limited comparative data with systemic administration

Continuous wound infusion with NSAIDs

Continuous wound infusion with NSAIDs is not recommended (GoR D) based on limited procedure-specific evidence

Overall Recommendations: Pain Management for Elective Caesarean Section Surgery

Pre-operative 

Oral gabapentin

Pre-/intra-operative anaesthetic technique

CSEA or SpA*

Intra-operative, post-delivery

IV paracetamol + IV NSAID #

Wound infiltration with LA or TAP blocks or iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative analgesic techniques such as wound infiltration with LA, TAP block, iliohypogastric and ilioinguinal blocks should be considered to avoid the potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAID may not be necessary if neuraxial opioids are used

† Amongst transverse incisions, the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain


PROSPECT C-Section Subgroup and Working Group process

For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. For the C-Section review, the Subgroup members were:
  • Professor Marc Van De Velde (PROSPECT Working Group member)
  • Professor Girish Joshi (PROSPECT Working Group member)
  • Professor Narinder Rawal (PROSPECT Working Group member)
Dr Thomas Jaschinski (IFOM - Institut für Forschung in der Operativen Medizin, Universität Witten/Herdecke, Köln, Germany) provided support in conducting the literature search, preparing the evidence summary and coordinating the Subgroup and Working Group reviews of the evidence to prepare the final recommendations. The recommendations for postoperative pain management in C-Section were voted on by nine Working Group members to show the strength of consensus. The results of each vote are indicated within the PROSPECT recommendations sub-folders.

Literature search

  • Systematic review of the literature from 1966–April 2014 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration
  • Inclusion of randomised/controlled studies assessing analgesic, anaesthetic or operative techniques in C-Section and reporting pain assessment, required analgesia or adverse events (C-Section: Inclusion criteria, C-Section: Search strategy)
  • 137 studies included (C-Section: Included studies)
  • 139 studies excluded after full-text screening (C-Section: Excluded studies)
  • The most common reason for exclusion was that the study did not investigate an intervention affecting postoperative pain (63 studies)
C-Section: Sources and levels of evidence (LoE) determine the grades of recommendation (GoR)

GoR are assigned according to the overall LoE, which is determined by the quality of studies cited, the consistency of evidence and the source of evidence:
C-Section: levels of evidence and grades of recommendation

Sources of evidence in PROSPECT

The evidence for prospect is derived from three separate sources, and this evidence is taken into consideration by the prospect Working Group to determine the prospect recommendations:
  • Procedure-specific evidence derived from the systematic reviews of the literature
  • Transferable evidence from comparable procedures, or from other relevant sources, identified by the members of the prospect Working Group
  • Current practice – A commentary on the interventions from the members of the prospect Working Group
  • Practical prospect recommendations are based on all the information
Study quality assessment
For the C-Section review, the quality of procedure-specific evidence has been assessed according to NICE methodology, to determine the possibility of selection bias, performance bias, attrition bias and detection bias (http://www.nice.org.uk/article/pmg6b).

Quality indicators used to determine the LoE of individual studies:
  • Allocation concealment: indicates whether there was adequate prevention of foreknowledge of treatment assignment by those involved in recruitment (in the table below, A=adequate, B=unclear, C=inadequate, D=not used). Empirical research has shown that trials with inadequate or unclear allocation concealment report significantly greater estimates of treatment effect than those trials in which concealment was adequate (Chalmers 1983, Schulz 1995, Moher 1998). Allocation concealment was found to be more important for preventing bias than other aspects of study quality, such as generation of the allocation sequence and double-blinding (Chalmers 1983, Schulz 1995, Moher 1998, HigginsandGreen 2005, http://handbook.cochrane.org/)
  • Statistical analyses and patient follow-up: indicates whether statistical analyses were reported, and whether patient follow-up was greater or less than 80%.
  • Numerical scores (total 1–5) for study quality: assigned using the method proposed by Jadad 1996, to indicate whether a study reports appropriate randomisation, double-blinding and statements of possible withdrawals. Empirical research found that low-quality trials were associated with an increased estimate of treatment benefit compared with high-quality trials (Moher 1998)
Study quality assessments for the C-Section review are summarised:
For systematic reviews, a critical appraisal was performed to determine the LoE:


Quantitative analyses

No meta-analyses were performed due to a limited number of studies of homogeneous design that reported similar outcome measures. Therefore, the procedure-specific evidence was only assessed qualitatively.

Transferable evidence

Transferable evidence has not been included in the C-Section review as there was sufficient procedure-specific evidence on which to base the recommendations for the most common analgesic interventions.
Topics for future research
  • Transcutaneous (Electrical) Nerve Stimulation (TNS or TENS)
  • Transversus abdominis plane blocks (TAP block)
  • Other abdominal wall local anaesthetic nerve blocks
  • Postoperative non-steroidal anti-inflammatory drug (NSAID) wound infiltration
  • Preoperative dexamethasone
List of abbreviations

CG

control group

CS

caesarean section

CSEA

combined spinal-epidural anaesthesia

EA

epidural anaesthesia

EVE

epidural volume extension

GA

general anaesthesia

h

hours

IG

intervention group

IHII

iliohypogastric-ilioinguinal

IM

intramuscular

iPCA

intravenous patient controlled analgesia

IQR

interquartile range

IT

intrathecal

IV

intravenous

LoE

level of evidence

MD

mean difference

n. r.

not reported

PACU

post-anaesthesia care unit

PO

peroral

rg.

range

SEM

standard error of mean

SpA

spinal anaesthesia

TENS

transcutaneous electrical nerve stimulation

mEq

milliequivalent

PCA

patient controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

POW

postoperative week

SMD

standardised mean difference

VAS

visual analogue scale

wk.

weeks

yr.

years


PROSPECT Recommendations

  • A single dose of pre-operative oral gabapentin is recommended (GoR A) for improving postoperative pain relief (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The administration of oral gabapentin 300 mg 2 h before surgery during spinal anaesthesia (without fentanyl) was superior to placebo capsule combined with fentanyl 10 µg during spinal anaesthesia for pain relief and time to first analgesic request Najafi Anaraki and Mirzaei 2014
  • A single pre-operative dose of oral gabapentin 600 mg compared to placebo reduced post-caesarean pain and increased maternal satisfaction Moore et al 2011
  • A single pre-operative dose of either 300 mg or 600 mg oral gabapentin did not improve post-caesarean pain management and maternal satisfaction (Study was underpowered) Short et al 2012
  • Gabapentin study details Click here for more information

PROSPECT Recommendations

  • Pre-operative dexamethasone cannot be recommended at this time (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Dexamethasone 10 mg given intravenously before surgery decreased postoperative pain with movement at 1 h, 6 h, 12 h and 24 h, but not at 2 h and 3 h, compared with placebo. Although the cumulative incidence of PONV was significantly lower in women receiving dexamethasone, there were no significant differences in PONV at specific assessment time points Cardoso et al 2013
  • Intravenous dexamethasone 8 mg administered before skin incision was superior to placebo in pain scores at rest and on movement between 6 and 24 h, but not before. However, there was no significant difference in the consumption of supplemental analgesia Wu et al 2007
  • Dexamethasone study details Click here for more information

PROSPECT Recommendations

  • Combined spinal-epidural anaesthesia or spinal anaesthesia are recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • There is no evidence of analgesic benefit to recommend general anaesthesia over neuraxial anaesthesia (i.e., epidural anaesthesia, spinal anaesthesia, and combined spinal epidural anaesthesia), due to lack of direct comparative studies focusing on postoperative analgesia (GoR D). However, neuraxial anaesthesia techniques are recommended for safety reasons (e.g., neuraxial anaesthesia obviates the need for airway manipulation and avoids the postoperative sedative effects of general anaesthetics)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Three studies comparing CSEA with EA showed a significant reduction in pain scores with CSEA during or after surgery but the results related to the time to first analgesic request were inconsistent Davies et al 1997 Click here for more information
  • A systematic review comparing the efficacy and side effects of SpA and EA showed no differences in unplanned interventions for pain relief postoperatively. However, there was an increased need for treatment for hypotension in women undergoing SpA Ng et al 2004
  • A systematic review comparing the effects of regional anaesthesia with those of GA showed (based upon one RCT) that the time to first request for analgesia was longer with EA compared with GA. There were no significant differences in the Apgar scores at 1, 5 and 10 min Afolabi and Lesi 2012
  • CSEA with epidural volume extension (EVE) was not superior to SpA in reducing intraoperative pain scores and the time to first analgesic request Lew et al 2004
  • One study showed a significant reduction in the time to first analgesic request for the SpA group compared with the CSEA group. However, there was no significant difference in supplemental analgesic use Thorén et al 1994
  • Two studies comparing EA with SpA showed inconsistent results related to pain scores and the need for supplemental analgesic use Paraskeva et al 2012 Click here for more information
  • Combined spinal-epidural anaesthesia (CSEA) vs epidural anaesthesia (EA) or spinal anaesthesia (SpA) study details Click here for more information
  • EA vs SpA study details Click here for more information
  • EA or SpA versus general anaesthesia (GA) study details Click here for more information
  • CSEA vs EA or SpA
  • EA vs SpA
  • EA or SpA vs GA

PROSPECT Recommendations

  • Intrathecal morphine below 200 µg is recommended if the patient has received spinal anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)
  • However, due to opioid-related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered
  • Consensus agreement 100% (9/9)
  • Epidural opioids are recommended if the patient has received epidural anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)
  • However, due to opioid related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence: Epidural or IT Analgesia With Anaesthesia

  • Fewer patients receiving IT morphine 100 µg during surgery requested supplemental analgesia compared with patients receiving postoperative oral oxycodone, but there was no significant difference in pain scores or consumption of supplemental analgesia and IT morphine was associated with a higher incidence of pruritus McDonnell et al 2010 Click here for more information
  • The combination of IT morphine 0.2 mg with spinal bupivacaine compared with spinal bupivacaine alone prolonged the time to first analgesic request. However, women receiving IT morphine reported nausea and pruritus significantly more often Abouleish et al 1988
  • The time to first PCA demand was longer in each of four groups receiving IT morphine (0.1, 0.2, 0.3, 0.4 mg) in combination with SpA bupivacaine than in the control group (0 mg morphine). The IT morphine groups showed a significantly lower total PCA morphine demand in the first 24 hours than the control group. There were no significant differences between mean VAS scores Girgin et al 2008
  • IT morphine 50 µg or 100 µg reduced pain scores, rescue analgesia requirements and increased the time to first request for rescue analgesics compared with no IT morphine Mikuni et al 2010 Click here for more information
  • Postoperative pain was significantly lower in a group receiving IT morphine added to SpA with bupivacaine than in a group receiving saline plus SpA. Morphine consumption was significantly lower in the IT morphine group Swart et al 1997
  • The addition of IT morphine 0.2 mg to hyperbaric bupivacaine 0.5% for SpA compared with hyperbaric bupivacaine alone reduced postoperative pain scores, the need for additional analgesia and prolonged the time to first analgesic request Terajima et al 2003
  • The administration of IT morphine 0.25 mg or 0.1 mg during SpA was superior to saline for postoperative pain relief. However, the higher dose of IT morphine was associated with significantly increased occurrence of pruritus Abboud et al 1988
  • The coadministration of IT sufentanil 5 µg and IT morphine 100 µg was superior to IT sufentanil 5 µg plus a single injection of s.c. morphine 10 mg for postoperative pain relief and consumption of supplemental analgesia Draisci et al 2009
  • Women undergoing caesarean delivery with CSEA benefited from the additional administration of IT morphine (0.1 and 0.2 mg) to 15 mg of spinal levobupivacaine. It prolonged the time to the first analgesic request compared with saline; however, there were no significant differences in postoperative pain scores Unlugenc et al 2012
  • Time to first analgesic request was significantly shorter following epidural diamorphine 3 mg (2 boluses) administration compared with IT morphine 0.2 mg. However, IT morphine was associated with higher incidence of PONV Caranza et al 1999
  • Similar pain relief was achieved with the administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine. Patients receiving epidural pethidine had a trend for higher pain scores but also lower nausea and pruritus scores Paech et al 2000
  • CSEA with hyperbaric bupivacaine plus sufentanil 5 µg and epidural lidocaine combined with either epidural morphine or IT morphine produced similar postoperative pain relief and similar time to first analgesic demand. However, women receiving epidural morphine had a decreased 24 h morphine consumption Dualé et al 2003
  • A randomised controlled study comparing IT morphine 100 µg, IT morphine 200 µg and epidural morphine 3 mg showed no significant differences in postoperative pain scores and the time to first request for rescue analgesia Sarvela et al 2002
  • The combination of neostigmine 12.5 µg and morphine 50 µg administered with SpA with 0.5% hyperbaric bupivacaine 12 mg had a prolonged analgesic effect compared with either neostigmine or morphine alone Chung et al 1998 Click here for more information
  • In combination with SpA with 0.5% hyperbaric bupivacaine 10 mg, morphine 0.2 mg was associated with longer duration of analgesia and less requirement for supplementary analgesia compared with nalbuphine 0.2 mg, 0.8 mg or 1.6 mg Culebras et al 2000 Click here for more information
  • IT morphine 0.1 mg was superior in postoperative pain relief, supplemental need for analgesia and time to first analgesic request compared with IT fentanyl 25 µg, when combined with IT hyperbaric bupivacaine Siti Salmah and Choy 2009
  • For patients receiving IT morphine, the addition of diclofenac IM every 8 h compared to diclofenac IM only on request significantly reduced pain scores at 24 h, independent of the doses of IT morphine (0.1 mg, 0.05 mg, 0.025 mg) Cardoso et al 1998
  • IT ketamine 0.1 mg/kg added to spinal bupivacaine compared with bupivacaine alone prolonged intraoperative anaesthesia, increased the time to the first analgesic request and decreased the total analgesic consumption in the first 24 postoperative hours Khezri et al 2013
  • The addition of IT fentanyl 0, 5, 10 or 25 µg to SpA with IT morphine showed no difference in postoperative morphine consumption via PCA. However, pain scores were higher in women receiving fentanyl 5, 10 and 25 µg compared with 0 µg Carvalho et al 2012
  • The addition of dextromethorphan to different doses of IT morphine was not superior to placebo combined with the same doses of IT morphine for pain relief. Higher doses of morphine were associated with a significantly increased incidence of PONV and pruritus Choi et al 2003
  • Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996
  • The administration of IT fentanyl 25 µg was superior to IT ketamine 0.05 mg/kg, both added to plain bupivacaine for spinal analgesia, for providing postoperative pain relief and prolonging the time to first analgesic request Unlugenc et al 2006
  • IT or epidural opioids study details
  • IT ketamine study details Click here for more information
  • IT opioid vs placebo/control or systemic opioid
  • IT opioid vs epidural opioid
  • Comparisons of different IT opioid regimens
  • Other regimens
  • IT ketamine with spinal LA
  • The comparison of either IT morphine 0.1 mg or diamorphine 0.25 mg in combination with SpA using hyperbaric bupivacaine and fentanyl 12.5 µg showed no differences in postoperative pain relief, time of first PCA use or cumulative morphine requirement postoperatively Barkshire et al 2001
  • There were no significant differences between groups receiving either morphine 0.1 mg or 0.2 mg combined with IT 0.5% bupivacaine 2.5 mL in VAS pain scores and time to first analgesic request Milner et al 1996

C-Section-Specific Evidence: Epidural Analgesia Continued After Anaesthesia

  • Epidural morphine was superior to placebo for pain relief, duration of pain relief and reduction of additional analgesics. However, patients in the morphine group reported pruritus significantly more frequently Binsted 1983
  • A systematic review of RCTs comparing epidural morphine with parenteral opioids showed that a single bolus of epidural morphine provides better pain relief than parenteral opioids but with an effect limited to the POD 1 and with an increase in morphine side effects Bonnet et al 2010
  • There were no significant differences in pain scores, morphine consumption and time to first analgesic request between butorphanol 2 mg IV (with epidural saline) and epidural butorphanol 2 mg (plus saline IV), but both regimens provided superior analgesia to saline placebo in the first 2 h postoperatively Camann et al 1992
  • Epidural morphine 5 mg compared with IV morphine 5 mg was superior for reducing the need for supplemental analgesics and prolonging the time to first analgesic request. However, significantly more patients receiving epidural morphine experienced pruritus Cohen and Woods 1983
  • Epidural fentanyl was associated with lower postoperative pain scores and a lower incidence of PONV than IV fentanyl Cohen et al 2002
  • Fentanyl (20 µg, 10 min lockout) administered via PCEA compared with the same dose via IV PCA resulted in lower pain scores at rest at 8, 12, 24 h, but not at 0.5 and 4 h and in lower pain scores on coughing at 8 and 12 h, but not at remaining points in time. There was no significant difference in PONV between the two groups, but patients receiving fentanyl via PCEA experienced pruritus significantly more frequently Cooper et al 1995
  • The administration of epidural fentanyl via PCA was superior to IV morphine via PCA in pain scores at rest 4 and 8 h, but not at recovery, 12 and 21 h as well as in lower pain scores on coughing at 4, 8 and 21 h, but not at remaining assessment times. The incidence of PONV and drowsiness was significantly lower in patients receiving epidural fentanyl via PCA Cooper et al 1999
  • Epidural morphine was superior to IM morphine in pain relief and the need for morphine consumption. The two groups were similar in the occurrence of PONV and pruritus Daley et al 1990
  • The administration of sufentanil PCEA was superior to morphine iPCA in reducing pain at rest at 30 min and 2 h, but not between 6 h and POD 2 and in reducing pain on movement at POD 2, but not on POD 1. The incidence of PONV was similar between the two groups, but patients receiving epidural sufentanil experienced pruritus significantly more frequently Grass et al 1994
  • PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997
  • The administration of epidural meperidine via PCA was superior to IV meperidine via PCA for pain, sedation and satisfaction scores Paech et al 1994
  • There was no significant difference between the incidence of PONV, sedation and dizziness in the epidural pethidine group and IM pethidine group. However, patients receiving epidural pethidine had lower pain scores during the first 2 h Perriss et al 1990
  • The duration of analgesia was significantly longer in patients receiving epidural diamorphine 3 mg compared with IM morphine 10 mg. However, only the pain score at 5 hours was lower in the diamorphine group Stevens et al 1991
  • The administration of epidural diamorphine was superior to IV diamorphine via PCA for pain scores at 1 and 2 h, but not between 4 and 48 h. The incidence of pruritus and PONV was similar between the two groups Stoddart et al 1993
  • The combination of epidural morphine 2 mg plus diclofenac sodium 75 mg IM was superior to epidural morphine 2 mg plus saline solution IM and to epidural saline plus diclofenac 75 mg IM for pain relief. However, patients receiving epidural morphine experienced PONV and pruritus significantly more often Sun et al 1992
  • PCEA meperidine was significantly superior to IM meperidine for pain relief. The incidence of nausea and pruritus was similar between the two groups Yarnell et al 1992
  • The duration of analgesia was significantly longer in patients receiving epidural buprenorphine plus bupivacaine in comparison to patients receiving epidural bupivacaine plus clonidine and it was the lowest in patients receiving epidural bupivacaine alone Agarwal et al 2010
  • Ropivacaine plus fentanyl administered by PCEA was superior to ropivacaine alone for pain scores and supplemental analgesics. But patients receiving ropivacaine plus fentanyl reported pruritus significantly more frequently Buggy et al 2000
  • Epidural fentanyl plus bupivacaine was associated with reduced fentanyl consumption in 48 h compared with epidural fentanyl alone Cohen et al 2002
  • The administration of fentanyl or bupivacaine plus fentanyl administered via PCEA was superior to bupivacaine alone via PCEA in pain scores at rest at 12 h, but not at 0.5, 4, 8 and 24 h. There were no significant differences between the three groups in pain scores on coughing at any assessment time. However, the incidence of pruritus was significantly lower in patients receiving only bupivacaine compared with the two other groups Cooper et al 1996
  • Epidural morphine 2 mg twice per day for 3 days was not superior to 0.1% ropivacaine administered by PCEA (5 mg bolus, 15 min lockout, with 3 mg/h background infusion, <60 mg/4 h) for 3 days in pain relief and supplemental analgesic request. Moreover, epidural morphine was associated with significantly higher incidence of nausea, vomiting and pruritus Chen et al 2011
  • The duration of analgesia was significantly longer in patients receiving epidural buprenorphine plus bupivacaine in comparison to patients receiving epidural bupivacaine plus clonidine and it was the lowest in patients receiving epidural bupivacaine alone Agarwal et al 2010
  • No significant additive or synergistic interactions were observed between the administration of epidural fentanyl, epidural clonidine and combined epidural fentanyl plus clonidine with regards to morphine given via iPCA Eisenach et al 1994
  • Epidural opioids vs systemic opioids/placebo study details
    Click here for more information
  • Epidural opioid vs IT opioid study details Click here for more information
  • Epidural opioid +/- LA vs epidural opioid or LA study details Click here for more information
  • Comparative studies of different epidural opioids study details Click here for more information
  • Epidural clonidine study details Click here for more information
  • Epidural opioids vs systemic opioids/placebo
  • Epidural opioid vs IT opioid
  • Epidural opioid +/- LA vs epidural opioid or LA
  • Comparative studies of different opioids
  • Epidural clonidine
  • The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000
  • Epidural butorphanol (1 mg, or 2 mg, or 4 mg) provided significantly faster pain relief compared with 5 mg epidural morphine, but the duration of pain relief and the time before remedication was significantly longer in patients receiving morphine instead of butorphanol Abboud et al 1987
  • The duration of analgesia was significantly longer in patients receiving epidural morphine compared with epidural fentanyl, buprenorphine or butorphanol. However, the incidence of pruritus was significantly higher in the morphine and fentanyl groups Ackerman et al 1989
  • Epidural butorphanol produced a longer duration of analgesia with less pruritus than epidural sufentanil, but pain scores of patients receiving sufentanil were significantly lower Bansal et al 2009
  • Epidural morphine was superior to epidural fentanyl for duration of analgesia. However patients that received fentanyl had significantly lower pain scores during the first two hours, but not afterwards Blanco et al 1987
  • The epidural administration of morphine 4 mg and combination of morphine 2 mg plus sufentanil 25 µg was superior compared to sufentanil 50 µg in pain relief between 2 and 12 h, but not before. Patients receiving sufentanil 50 µg required more frequent supplementary analgesia. The incidence of pruritus and PONV did not differ between the three groups; however, dizziness was only observed in patients receiving sufentanil alone or in combination with morphine Dottrens et al 1992
  • PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997
  • Epidural meperidine 30 mg (10 mg/mL) followed by epidural meperidine via PCA for 24 h (group 1) produced higher pain scores between 8 and 16 h compared with epidural morphine 3 mg (1 mg/mL) followed by saline via PCA for 24 h (group 2) or epidural morphine 3 mg (1 mg/mL) without saline PCEA (group 3). However, women receiving epidural morphine (groups 2 and 3) experienced nausea and pruritus more frequently Rosaeg et al 1994
  • The epidural administration of morphine bolus (5 mg) and subsequent saline infusion for 24 h compared with morphine bolus (2.6 mg) and subsequent morphine infusion (0.1 mL/h, 5 mg/24 h) produced similar pain scores and occurrence of side effects Sharar et al 1991
  • Epidural sufentanil delivered by PCA with a concomitant infusion of either sufentanil or saline produced similar pain scores overall, with significantly less pain at 6 h in the sufentanil infusion group, but not at 0,12, 18 and 24h. The incidence of PONV did not differ between the groups Vercauteren et al 1995
  • The comparison of patients receiving epidural fentanyl intraoperatively and epidural fentanyl via PCEA after surgery with patients receiving epidural morphine during surgery and saline via PCEA afterwards showed no significant difference for pain relief Yu and Gambling 1993

C-Section-Specific Evidence: IT Analgesia Continued After Anaesthesia

  • IT morphine was superior to wound infiltration with ropivacaine or placebo for reducing the consumption of supplemental analgesics Kainu et al 2012 Click here for more information
  • IT opioid versus LA wound infiltration or placebo study details Click here for more information
  • IT opioid vs epidural opioid study details Click here for more information
  • IT opioid vs LA wound infiltration or placebo
  • IT opioid vs epidural opioid
  • The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000

PROSPECT Recommendations

  • Neuraxial clonidine is not recommended (GoR D), although procedure-specific evidence suggests it provides superior analgesia, because of side effects (e.g. hypotension)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The comparison of three doses of IT clonidine (150 µg, 300 µg and 450 µg) demonstrated a dose-dependent effect. A higher dose was significantly associated with lower pain scores and a delayed request for supplemental analgesics Filos et al 1994
  • Epidural infusion of clonidine (400 µg bolus plus 10 µg/h) and (800 µg bolus plus 20 µg/h) compared with placebo prolonged the time to first analgesic request. Only the high-dose clonidine group needed less morphine via iPCA compared with the placebo group Mendez et al 1990
  • Analgesia with bupivacaine (0.06 mg/cm body height) plus clonidine (75 µg) or plus clonidine and fentanyl (12.5 µg) was superior to bupivacaine alone. Time to first analgesic request was significantly prolonged following anaesthesia with bupivacaine, clonidine and fentanyl compared with the other groups. Intraoperative nausea-vomiting was more frequent in the group given bupivacaine alone Benhamou et al 1998
  • The administration of IT clonidine 150 µg was superior to placebo in terms of postoperative pain relief and time to first analgesic request. However, the side effects sedation, hypotension and dryness of mouth were more frequent in the clonidine group Filos et al 1992
  • Spinal bupivacaine combined with sufentanil 2 µg and 75 µg clonidine was superior to sufentanil 2 µg alone and 150 µg clonidine alone in the time to first analgesic request. However, there was no significant difference among the three groups in postoperative pain scores and in the need for supplemental analgesia Lavand'homme et al 2008
  • Spinal anaesthesia with a combination of subarachnoid morphine100 µg and clonidine at different doses compared with subarachnoid morphine100 µg alone or clonidine 150 µg alone significantly improves postoperative pain relief, but increases intraoperative sedation Paech et al 2004
  • Spinal bupivacaine plus clonidine 75 µg was superior in terms of duration of postoperative analgesia compared with spinal bupivacaine plus fentanyl 25 µg without any increase in maternal side effects Singh et al 2013
  • Spinal anaesthesia with bupivacaine 0.5% (2.2 mL) plus clonidine 75 µg was superior to bupivacaine 0.5% (2.2 mL) alone in time to first analgesic request and pain score at 1h, but not on 24h, without significant maternal and neonatal side-effects van Tuijl et al 2006
  • Neuraxial clonidine study details Click here for more information

PROSPECT Recommendations

  • Transverse abdominal incision is recommended over vertical incision (GoR A, LoE 1). Amongst transverse incisions the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain (GoR A, LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Joel-Cohen-based compared with Pfannenstiel caesarean section techniques were associated with lower duration of postoperative pain and with less use of analgesia Hofmeyr et al 2008
  • The Joel-Cohen incision was significantly superior to the Pfannenstiel incision for operative time, postoperative pain, postoperative need for supplemental analgesia, time to get out from bed and time to walk straight without support Abuelghar et al 2013
  • A systematic review of RCTs comparing different abdominal incisions showed that the Joel-Cohen incision was superior to the Pfannenstiel approach in reducing postoperative analgesic requirements, total dose of analgesia in the first 24 h and in increasing the time to first analgesic request Mathai et al 2013
  • A systematic review showed that there is little information available to inform the choice of the most appropriate surgical technique for uterine incision and uterine closure to adopt Dodd et al 2008
  • Surgical techniques study details Click here for more information

PROSPECT Recommendations

  • Non-closure of the peritoneum is recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • A systematic review evaluating the effects of non-closure as an alternative to closure of the peritoneum showed that the number of postoperative analgesic doses was reduced in the peritoneal non-closure group Bamigboye and Hofmeyr 2003
  • Non-closure of both the visceral and the parietal peritoneum produced a significant reduction in pain scores and need for supplemental analgesia compared with closure Tabasi et al 2013
  • Non-closure and closure of the parietal peritoneum showed no differences in duration of surgery and postoperative pain scores. However, the non-closure group had a significantly reduced requirement for supplemental analgesia as well as shorter time to mobilisation and oral intake Altinbas et al 2013
  • Parietal peritoneal non-closure was associated with significantly lower pain scores and morphine consumption compared with closure Shahin et al 2009
  • Non-closure versus closure study details Click here for more information

PROSPECT Recommendations

  • No recommendation can be made with respect to skin closure techniques, as there is no effect on postoperative analgesia (GoR A, LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • A systematic review assessing different effects of skin closure techniques and materials showed no conclusive evidence about how the skin should be closed after caesarean section Mackeen et al 2012
  • Techniques and materials for skin closure study details Click here for more information

PROSPECT Recommendations

  • Post-delivery NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Rectal naproxen followed by oral naproxen compared with placebo reduced postoperative pain scores, especially on the first day after surgery, reduced the need for additional analgesics and prolonged the time to first analgesic request Angle et al 2002
  • For patients receiving IT morphine, the addition of diclofenac IM every 8 h compared to diclofenac IM only on request significantly reduced pain scores at 24 h, independent of the doses of IT morphine (0.1 mg, 0.05 mg, 0.025 mg) Cardoso et al 1998
  • Rectal diclofenac 100 mg every 12 h led to less morphine consumption compared with placebo. However, pain scores were similar between the two groups Dahl et al 2002
  • The use of diclofenac suppository 100 mg compared to no suppository reduced the need for ropivacaine and fentanyl given via PCEA from 6 to 18 h, but not from 0 to 6 h and not from 18 to 24 h. There was no significant difference between the two group in pain scores on movement Lim et al 2001
  • The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008
  • Administration of rectal diclofenac (3x 50 mg) was superior to placebo for reducing the need for supplemental analgesia. Postoperative pain was lower in patients receiving diclofenac during the first 3 h, but not afterwards Olofsson et al 2000
  • Rectal indomethacin significantly reduced pain scores and prolonged the time to first analgesic request compared with placebo Pavy et al 1995
  • The administration of intravenous ketorolac (</=120 mg/day) compared with placebo reduced the consumption of meperidine for 24 h, but not afterwards. The pain relief was similar between the two groups Pavy et al 2001
  • Diclofenac rectally plus propacetamol IV or diclofenac rectally provided more effective analgesia compared with placebo or propacetamol IV alone Siddik et al 2001 Click here for more information
  • Diclofenac suppository 100 mg after surgery followed by 3 additional doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by three additional doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine reported dizziness significantly more frequently Soroori et al 2006
  • The combination of epidural morphine 2 mg plus diclofenac sodium 75 mg IM was superior to epidural morphine 2 mg plus saline solution IM and to epidural saline plus diclofenac 75 mg IM for pain relief. However, patients receiving epidural morphine experienced PONV and pruritus significantly more often Sun et al 1992
  • The administration of diclofenac 75 mg IM every 12 h for 2 doses compared to no intervention reduced the need for rescue analgesia and produced significantly lower pain scores Surakarn and Tannirandorn 2009
  • Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993
  • There were no significant differences in postoperative pain scores and supplemental analgesic use between the intravenous paracetamol group versus oral ibuprofen group Alhashemi et al 2006
  • The administration of oral valdecoxib 20 mg every 12 h for 72 h compared with placebo was not superior in pain relief, need for supplemental analgesics and time to first analgesic request Carvalho et al 2006
  • Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996
  • The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily in terms of the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009
  • NSAIDs study details Click here for more information

PROSPECT Recommendations

  • Ketamine cannot be recommended at this time (GoR D) based on inconsistent procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The administration of IV low-dose ketamine as an adjuvant to bupivacaine for spinal anaesthesia was associated with longer postoperative analgesia and a reduced need for analgesia consumption than bupivacaine alone Menkiti et al 2012
  • IV low-dose ketamine combined with IT bupivacaine provided better pain relief and lower postoperative analgesic consumption than bupivacaine alone Sen et al 2005
  • The administration of IV ketamine 0.2 mg/kg before the induction of anaesthesia decreased postoperative pain scores, the need for supplemental analgesia and prolonged the time to first analgesic request Ghazi-Saidi and Hajipour 2002
  • Women receiving IM S-ketamine 0.5 mg/kg followed by a 2 µg/kg/min IV continuous infusion over 12 h had a prolonged time to first analgesic request and a reduced cumulative morphine consumption compared with placebo. However, ketamine was associated with a significantly increased incidence of drowsiness, diplopia, nystagmus, dizziness, light-headness, positive dysphoria and vomiting Suppa et al 2012
  • The addition of IV ketamine compared to placebo for postoperative analgesia showed no benefit in time to first analgesic request, incidence of breakthrough pain and supplemental analgesics Bauchat et al 2011
  • The IV use of different doses of ketamine (0.25 mg/kg, 0.5 mg/kg, 1 mg/kg) compared with placebo produced similar postoperative pain scores and need for supplemental analgesia Bilgen et al 2012
  • Intraoperative IV ketamine (0.5 mg/kg) compared with placebo had no effect on pain relief and morphine consumption between 2 and 24 h Reza et al 2010
  • The administration of IV ketamine 0.5 mg/kg before the skin incision and infused continually at 0.25 mg/kg/h until the end of surgery was not superior to placebo in postoperative pain relief and supplemental fentanyl consumption Han et al 2013
  • Ketamine study details Click here for more information

PROSPECT Recommendations

  • Systemic opioids provide effective analgesia (GoR A, LoE 1), but are only recommended as rescue analgesics due to side effects (GoR D)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Oral opioid vs IT opioid Click here for more information
  • The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily for the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009
  • Oral oxycodone and IT morphine were similar for postoperative pain scores, but fewer patients receiving IT morphine requested supplemental analgesia McDonnell et al 2010 Click here for more information
  • Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993
  • Diclofenac suppository 100 mg after surgery followed by another three doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by another three doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine experienced dizziness significantly more frequently Soroori et al 2006
  • Oral opioid versus IT opioid study details Click here for more information
  • Systemic opioid versus conventional NSAID study details Click here for more information
  • Systemic opioid: route of administration study details Click here for more information
  • Systemic opioid vs NSAID
  • Systemic opioid: route of administration
  • Transnasal butorphanol was superior to butorphanol IV in terms of quality and duration of analgesia Abboud et al 1991 Click here for more information
  • Pain relief was significantly greater in the group receiving oral oxycodone-paracetamol compared with the group receiving morphine via iPCA for 12 h and oral oxycodone-paracetamol after 12 h Davis et al 2006
  • The administration of piritramide via iPCA versus oral oxycodone was similar in terms of pain scores, need for supplemental anagesics and in the incidence of PONV Dieterich et al 2012
  • Subcutaneous and IM morphine produced a similar incidence of side effects and pain scores at rest, but pain scores on movement were reduced in the subcutaneous morphine group at 12, 16 and 20 h Safavi and Honarmand 2007

PROSPECT Recommendations

  • Post-delivery paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • There were no significant differences in postoperative pain scores and supplemental analgesic use between the IV paracetamol group and the oral ibuprofen group
  • The administration of IV paracetamol at the end of surgery and every 6 h for 24 h was superior to placebo for pain scores at 6, 12 and 24 h and for consumption of rescue analgesia Omar and Issa 2011
  • The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008
  • Paracetamol study details Click here for more information

PROSPECT Recommendations

  • Bilateral iliohypogastric and ilioinguinal blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • In a systematic review, abdominal nerve blocks were found to reduce pain scores and postoperative opioid requirements vs placebo/no block Bamigboye and Hofmeyr 2009
  • An iliohypogastric-ilioinguinal peripheral nerve block using 0.5% bupivacaine 24 mL compared to saline decreased pain scores and delayed the first request for analgesia Wolfson et al 2012
  • Ilioinguinal and iliohypogastric nerve block with 0.5% ropivacaine was superior to nerve block with saline for pain scores at rest at 6, 8, 12, and 24 h and with movement at 6 and 8 h and led to a decreased supplemental analgesia need without increasing side effects Sakalli et al 2010
  • Ilioinguinal nerve block with 0.5% bupivacaine was superior to no nerve block for pain scores at 0, 4, 8 and 24 h while consumption of supplemental analgesia was decreased Bunting and McConachie 1988
  • Ilioinguinal and iliohypogastric nerve block under ultrasound guidance compared with placebo did not improve postoperative analgesia or decrease postoperative analgesic requirements Vallejo et al 2012
  • Iliohypogastric and ilioinguinal blocks study details Click here for more information

PROSPECT Recommendations

  • Bilateral TAP blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • US-guided TAP block compared with no block significantly reduced postoperative morphine consumption. There were no differences between the groups in pain scores at rest and on moving, sedation level and PONV Tan et al 2012
  • TAP block compared with no block significantly reduced postoperative tramadol consumption, postoperative pain scores at rest and on coughing Eslamian et al 2012
  • A systematic review comparing TAP block with placebo showed inconsistent results concerning time to first analgesic request, postoperative opioid consumption and postoperative pain scores Fusco et al 2014
  • Spinal morphine 100 µg, but not TAP block, improved postoperative pain relief. The additional use of bilateral TAP block with bupivacaine 2 mg/kg combined with spinal morphine did not further improve postoperative pain relief McMorrow et al 2011
  • TAP block study details Click here for more information

PROSPECT Recommendations

  • TENS is not recommended (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 78% (7/9)

C-Section-Specific Evidence

  • IV morphine-PCA combined with Hi-TENS significantly reduced the consumption of morphine compared with IV morphine-PCA alone. However, there were no significant differences in pain scores between the two groups Binder et al 2011
  • TENS versus placebo-TENS was superior for pain relief at rest and on movement. There was no difference in the request for additional analgesics Smith et al 1986
  • TENS was superior to placebo-TENS for pain relief at 8 h after delivery and associated with a reduced need for supplemental analgesia Kayman-Kose et al 2014
  • TENS study details Click here for more information

PROSPECT Recommendations

  • Wound infiltration with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • Wound infiltration with NSAIDs is not recommended at this time (GoR D) due to limited comparative data with systemic administration
  • Consensus agreement 89% (8/9)
  • Continuous wound infusion with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • Continuous wound infusion with NSAIDs is not recommended (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • In a systematic review, wound infiltration with LA reduced opioid use compared with control Bamigboye and Hofmeyr 2009
  • Combined pre- plus post-incisional local wound infiltration with lidocaine was superior to either pre-incisional or post-incisional local wound infiltration alone in postoperative pain scores Fouladi et al 2013
  • The addition of ketorolac to subcutaneous wound instillation of bupivacaine compared with bupivacaine resulted in lower pain scores on movement, but not at rest. However, the addition of hydromorphone to LA wound instillation did not significantly decrease postoperative pain scores at all. The use of supplemental analgesics was significantly lower in the group with additional ketorolac compared to the only bupivacaine group Carvalho et al 2013
  • Ropivacaine wound instillation via an elastometric pump was superior to sterile water in the reduction of postoperative morphine consumption. Pain scores at rest did not differ between the groups during the first 6 h. However, patients receiving ropivacaine had lower pain scores during coughing and leg raising between 3 and 6 h, but not before Fredman et al 2000
  • Continuous wound infusion with ropivacaine for 48 h was superior to epidural morphine for postoperative pain at rest and on movement. Patients receiving epidural morphine experienced significantly more PONV, pruritus and urinary retention O'Neill et al 2012
  • Wound infiltration with tramadol or levobupivacaine was superior to saline for the consumption of supplemental analgesia and for pain relief at 15 min, but not between 2 and 24 h Demiraran et al 2013
  • Continuous wound infusion for 48 h with 0.5% ropivacaine and ketoprofen through a multiholed wound catheter inserted below the fascia resulted in a reduced need for supplemental morphine compared with administration above the fascia. The groups did not differ in pain scores at movement. However, patients receiving administration below the fascia reported lower pain scores at 3, 6, 12, 24 and 36 h, but not at 48 h Rackelboom et al 2010
  • Subcutaneous surgical wound infiltration with bupivacaine 5 mg/mL compared with saline at 2 mL/h for 24 h resulted in similar postoperative pain scores and need for supplemental and rescue analgesia Carvalho et al 2010
  • IT morphine was superior to wound infiltration with ropivacaine or placebo for reducing the consumption of supplemental analgesics Kainu et al 2012 Click here for more information
  • Epidural levobupivacaine was superior to levobupivacaine administered via subfascial catheter in reducing pain scores at rest during the first 4 hours, but not afterwards. However, pain scores at walking and consumption for opioids were similar between the groups Ranta et al 2006
  • The IV system with morphine 10 mg and ketorolac 120 mg was more effective than continuous infusion of 0.2% levobupivacaine in reducing the need for supplemental analgesic and in reducing pain scores Magnani et al 2006
  • Wound infiltration or infusion study details Click here for more information

PROSPECT Colonic Resection Subgroup

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.

For the colonic resection surgery review (update 2009), the Subgroup members were:

  • Professor Francis Bonnet (PROSPECT Working Group member)
  • Professor Frederic Camu (PROSPECT Working Group member)

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following colonic resection. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following pre-, intra- and postoperative interventions have been evaluated, for the management of postoperative pain following open colonic resection:

Pre-operative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural analgesia)
  • Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period (Grade B), when epidural analgesia is not feasible or contra-indicated

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)
  • A combination of strong opioid and local anaesthetic is recommended (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone

Not recommended:

Systemic analgesia 

  • IV clonidine (Grade D) because it is associated with an increased risk of hypotension and bradycardia
  • Conventional NSAIDs (Grade B) because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding
  • Corticosteroids for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing pain scores and concerns that they could affect anastomotic and wound integrity (but they may be used for reduction of PONV)
  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specifc evidence
  • Strong opioids (Grade B) as they are significantly less effective than postoperative strong opioids for reducing postoperative pain
  • Weak opioids (Grade B) based on procedure-specific evidence that they provide limited postoperative analgesic benefit compared with postoperative administration
  • Calcium channel antagonists (Grade B) based on limited procedure-specific evidence showing a lack of postoperative analgesic effect

Spinal anaesthesia

  • Spinal morphine (Grade D) because of the risk of side effects
  • Spinal clonidine (Grade B) based on procedure-specific evidence showing limited analgesic effect and the risk of side effects

Non-pharmacological therapy

  • Pre-operative use of guided imagery (Grade D) because of limited procedure-specific evidence
  • Laxatives for analgesia (Grade B) because limited procedure-specific evidence shows no analgesic benefit (but they may be used for reasons other than pain relief
  • Pentoxifylline (Grade D) due to limited procedure-specific evidence of its analgesic effect

LA for analgesia

  • Bilateral TAP block (Grade D) because of limited procedure-specific evidence

Intra-operative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural anaesthesia)
  • Strong opioids (Grade B) (only for patients who do not receive epidural anaesthesia) 
  • Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B)

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)
  • Combination of strong opioid and local anaesthetic is recommended (Grade A) based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and opioid use, compared with LA alone

Operative techniques

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease operative risk factors of the patient, risk of wound infection, and availability of surgical expertise (Grade D)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain, if the conditions outlined above allow (Grade A)
  • Horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits if the operative conditions allow (Grade B). In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D)
  • Diathermy is recommended over the scalpel (Grade C)
  • Maintenance of normothermia is recommended for improved clinical outcomes, but it is not helpful for reducing postoperative pain (Grade A)

Not recommended:

Systemic analgesia

  • IV clonidine (Grade D) because it associated with an increased risk of hypotension, sedation and bradycardia
  • Calcium channel antagonists (Grade B), based on limited procedure-specific evidence showing a lack of postoperative analgesic effect
  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specific evidence of analgesic efficacy
  • Strong opioids (Grade D), in patients receiving epidural analgesia
  • Weak opioids (Grade D), as placebo-controlled evidence for their benefit in reducing postoperative pain is limited. In patients not receiving epidural analgesia, strong opioids, not weak opioids, are recommended

Epidural analgesia

  • Addition of clonidine to the combination of epidural LA + opioid (Grade D) because of side effects

Spinal analgesia

  • Spinal analgesia in combination with epidural anaesthesia (Grade B) based on a lack of benefit in reducing postoperative pain in colonic resection

Postoperative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural analgesia or with the cessation of epidural analgesia)
  • Conventional NSAIDs (Grade A) (only for patients who do not receive epidural analgesia or with cessation of epidural analgesia)
  • IV lidocaine (Grade B) (when epidural is not feasible or contra-indicated)
  • Strong opioids (Grade B) (for high-intensity pain)
  • Weak opioids (Grade B) in association with other non-opioid analgesics (for moderate- or low-intensity pain), or if non-opioid analgesia is insufficient or contra-indicated
  • Paracetamol (Grade B) for moderate- or low-intensity pain (only for patients that do not receive epidural analgesia, or after cessation of epidural analgesia)

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia at a level appropriate to the site of incision (Grade A)
  • A combination of strong opioid and local anaesthetic is recommended for epidural analgesia (Grade A)

Wound infiltration or infusion

  • Continuous pre-peritoneal infusion of LA, as an alternative when epidural analgesia is not feasible or contra-indicated (Grade B)

Multi-modal rehabilitation protocols

  • Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) (Grade A)

Not recommended:

Systemic analgesia

  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specific evidence of analgesic efficacy
  • IM strong opioids (Grade D)
  • Weak opioids (for controlling high-intensity pain) (Grade B)

Wound infiltration or infusion

  • Continuous postoperative wound infusion with LA (Grade D) as procedure-specific evidence is limited and inconsistent
  • Pre-closure wound infiltration with local anaesthetic (Grade D) due to lack of procedure-specific evidence and inconclusive transferable evidence from other large abdominal surgeries

Multi-modal rehabilitation protocols

  • Mechanical massage with aspiration of abdominal wall (Grade D) as further supportive data are needed
  • Nasogastric tubes (Grade A) because they are associated with discomfort and inconvenience and do not decrease the duration of postoperative ileus

Laparoscopic colonic resection:

Recommended:

Systemic analgesia

  • Conventional NSAIDs (Grade B) based on limited procedure-specific evidence

Epidural analgesia

  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D)

Wound infiltration/infusion

  • Pre-closure wound infiltration with LA (Grade B)

Operative techniques

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain, if the conditions outlined above allow (Grade A)

Not recommended:

Systemic analgesia

  • Continuous intra-/postoperative IV lidocaine (Grade D) because of limited procedure-specific data, despite some postive transferable evidence

Spinal analgesia

  • Combination of spinal analgesia and general anaesthesia (Grade D) as the risk: benefit balance is not positive, and because of limited procedure-specific evidence

Epidural analgesia

  • Epidural LA + strong opioid (Grade D) due to poor risk:benefit ratio

Gasless laparoscopic colectomy

  • Gasless laparoscopy (Grade B) based on procedure-specific evidence showing lack of analgesic effect

Laxatives

  • Laxatives for analgesia (Grade B) because limited procedure-specific evidence shows no analgesic benefit (but they may be used for reasons other than pain relief)

Multi-modal rehabilitation protocols

  • Postoperative restriction of IV fluids (Grade B) due to procedure-specific evidence showing limited analgesic efficacy

See Overall PROSPECT Recommendations for the overall strategy for managing pain after colonic resection

Overall PROSPECT Recommendations for open and laparoscopic colonic resection

Algorithm for the management of postoperative pain

Not recommended for open and laparoscopic colonic resection

This algorithm for treating postoperative pain is based on the PROSPECT Recommendations and illustrates the different treatment pathways for patients with no contra-indications to epidurals, patients with contra-indications to epidurals, patients undergoing laparoscopic colonic resection, as well as describing the steps of the peri-operative pathway and therapies that apply to all patients. Therapies that are not recommended are also indicated.

 

Literature search

 • Systematic review of the literature from 1966–March 2009 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration

 • Inclusion of randomised studies assessing analgesic interventions in colonic resection and reporting pain on a linear analogue scale (Colonic Resection Search terms March 2009)

 • Identification of studies of peri-operative interventions for postoperative pain following colonic resection

80 studies included (Click here for further information)

73 studies excluded (Click here for further information)

• The most common reasons for exclusion were the lack of VAS postoperative pain scores (32 studies), and the lack of a defined subgroup of patients undergoing colonic resection (16 studies)

This website provides recommendations for open and laparoscopic colonic resection. Results from the open and laparoscopic colonic resection studies are dealt with separately, because of the different pain profiles associated with these approaches.

• A majority of the studies assessed the effect of analgesic interventions in open colonic resection with the exception of:

• In five of seven studies, laparoscopic colonic resection was superior to open colonic resection for reducing postoperative pain scores: at rest, during coughing and mobilisation at 6 h (all p<0.05; n=29) (Stage 1997; LoE 2); at rest at 48 h (p<0.01) and during coughing 24–72 h, (p<0.01; n=44) (Danelli 2002; LoE 2); at rest and on coughing within the first week (p<0.02; n=60) (Schwenk 1998; LoE 2) and on Day 1 in two studies (p=0.003; n=403; p<0.05, n=39) (Leung 2004; LoE 1, Liang 2002; LoE 2). One study reported that open colonic resection was superior to laparoscopic colonic resection for the reduction of VAS pain scores at rest and activity at day 1 (p<0.05; n=60), but not from days 2–30 (Basse 2005; LoE 1). Another study showed no significant difference between laparoscopic-assisted colectomy and open colectomy for pain distress scores from baseline to 2 days, 2 weeks and 2 months postoperatively (Weeks 2002; LoE 1)

• In two of three studies, hand-assisted laparoscopic colonic surgery was superior to open colonic surgery for reduction of postoperative pain scores: during the first postoperative week (p<0.001; n=81) (Chung 2007; LoE 1), and on Day 1 (p=0.03), Day 3 and Day 14 (p<0.001; n=60) (Kang 2004; LoE 2); the third study reported no significant difference in postoperative VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55) (Maartense 2004; LoE 1)

• In addition, a meta-analysis of randomized clinical trials (comprising of 2512 procedures from 12 trials) comparing the short-term outcomes of laparoscopic with those of open resection for colorectal cancer demonstrated that laparoscopic colonic resection is associated with lower morbidity, reduced pain and/or analgesic consumption, a faster recovery and a shorter hospital stay than open resection, without compromising oncological clearance (Abraham 2004; LoE 1)

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendations in PROSPECT reviews (from 2006).

Click here for quality scores and levels of evidence for included procedure-specific studies: Colonic Resection September 2009 Quality Scoring + Levels of Evidence. 

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures, or evidence of other outcomes such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Most of the transferable evidence for colonic resection was supplemented from major abdominal surgery and gynaecological procedures.

Quantitative analyses

Overall, few meta-analyses could be performed that used data from more than two studies. This is because there are a limited number of studies of homogeneous design that report similar outcome measures. Therefore, the majority of the procedure-specific evidence was assessed only qualitatively.

Topics for future research

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are as follows:

  • TAP blocks
  • Alpha-2-delta ligands
  • NMDA receptor antagonists
  • Postoperative continuous LA wound infusion
Abbreviations

AUC

area under curve

GA

general anaesthetic

IM

intramuscular

Intra-op

intra-operatively

IV

intravenous

LA

local anaesthetic

NRS  

numerical rating scale

PACU

post-anaesthesia care unit

PCA   

patient-controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

Postop

postoperatively

Pre-op

pre-operatively

VAS   

visual analogue scale

VRS   

verbal rating scale

VNS

verbal numerical scale

In this section, data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively.

A previous systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). More recently, a meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures, found that pre-operative epidural analgesia was effective in reducing postoperative pain scores, but that pre-operative NSAIDs, local anaesthetic wound infiltration, NMDA antagonists and opioids did not improve postoperative analgesia (Ong 2005b).

 Despite these findings, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

PROSPECT Recommendations

  • Clonidine is not recommended (Grade D), despite limited procedure-specific evidence for analgesic efficacy, because it is associated with an increased risk of hypotension and bradycardia (LoE 4)

Clinical Practice

  • The risk:benefit ratio for clonidine is unclear. Recognised side-effects include hypotension, sedation, dizziness and bradycardia
  • There is no consensus among clinicians on the optimum dose of clonidine that should be used

Transferable Evidence from Other Procedures

Open Colonic Resection-Specific Evidence - Study information

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B): cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3), or actual or recent gastroduodenal ulcer history (LoE 4). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of N

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • There is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • A pre-operative single bolus of parecoxib was superior to placebo for postoperative pain scores on sitting-up over 24 h (p=0.02), providing a mean decrease of 14 mm in VAS scores on a 100 mm scale in patients undergoing abdominal hysterectomy (n=36)
  • Pre-operative oral etoricoxib was superior to placebo for reducing pain scores at rest and on coughing at a minority of timepoints Chau-in et al 2008 Click here for more information
  • A pre-operative single bolus of IV parecoxib or oral rofecoxib reduced morphine consumption over 24 h compared with placebo in patients undergoing abdominal hysterectomy Ng et al 2003 Click here for more information
  • One study found that pre-operative oral etoricoxib was superior to placebo for reducing mean postoperative morphine consumption after 24 h (120 and 180 mg etoricoxib versus placebo, p=0.012) (n=49)
  • Pre-operative oral rofecoxib was associated with a lower incidence of PONV compared with placebo in one study (p<0.05; n=40)
  • Pre-operative oral COX-2-selective inhibitors were as effective as oral conventional NSAIDs for reducing postoperative pain scores in two studies of patients undergoing abdominal hysterectomy (n=25; n=40)
  • COX-2-selective inhibitors are similarly effective compared with conventional NSAIDs for reducing postoperative opioid consumption in patients undergoing abdominal hysterectomy Celik et al 2003 Click here for more information
  • Pre-operative oral rofecoxib compared with placebo had significantly lower pain scores at rest and after spirometry at 12 h postoperatively in patients undergoing abdominal surgery (rofecoxib 25 mg and 50 mg versus placebo p<0.05; n=48)
  • Pre-operative oral rofecoxib reduced morphine consumption at 24 h postoperatively compared with placebo in patients undergoing abdominal surgery (rofecoxib 25 mg versus placebo p<0.01; n=48)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting (
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence – Study information

  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative pain scores Sim et al 2007 Click here for more information
  • Pre-operative parecoxib was superior to placebo for reducing postoperative morphine consumption at a minority of timepoints Lee et al 2008 Click here for more information
  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative morphine consumption Sim et al 2007 Click here for more information
  • The time until first flatus and first bowel movement was significantly shorter with pre-operative + postoperative oral valdecoxib, compared with placebo (p=0.003 and p=0.041, respectively; n=79)
  • The time taken to tolerate a solid diet was significantly shorter with pre-operative + postoperative oral valdecoxib versus placebo (p=0.029; n=79)
  • The length of hospital stay was significantly shorter for patients in the pre-operative + postoperative oral valdecoxib group, compared with the placebo group (p=0.009; n=79)
  • Pre-operative + postoperative administration of oral valdecoxib was associated with superior patient-assessed global evaluation scores (p=0.001; n=79), compared with placebo, but not with surgeon-assessed global evaluation scores
  • Pre-operative IV parecoxib did not confer any significant benefit over intra-operative IV parecoxib or placebo for the reduction of postoperative pain scores Lee et al 2008 Click here for more information
  • There was no significant difference in postoperative morphine consumption between the pre-operative IV parecoxib and intra-operative IV parecoxib groups from 0–48 h postoperatively (n=40)
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar between the pre-operative IV parecoxib, intra-operative IV parecoxib and placebo groups (n=60)
  • The incidence of postoperative sedation and nausea was similar with pre-operative + postoperative oral valdecoxib, and placebo (n=79)
  • Pre-operative + postoperative oral valdecoxib had no significant effect on the time taken to tolerate intake of liquids compared with placebo (n=79)
  • The hospital re-admission rate was similar in both the pre-operative + postoperative oral valdecoxib, and placebo groups (n=79)
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar in the pre-operative IV parecoxib and intra-operative IV parecoxib groups

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended (Grade B) despite their analgesic efficacy, because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (transferable evidence, LoE 1)
  • In addition, pre-operative conventional NSAIDs are not recommended, because there is evidence from other procedures that pre-operative administration of conventional NSAIDs is no more effective than postincisional administration for reducing pain scores (Grade B) (transferable evidence, LoE 1). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures - Study information

  • Pre-operative naproxen was equally as effective as the COX-2-selective inhibitor rofecoxib for reducing postoperative pain scores at rest over 24 h, in patients undergoing abdominal hysterectomy (n=40)
  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A meta-analysis of randomised controlled trials performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs, demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Pre-operative rofecoxib was superior to naproxen for reducing the use of postoperative supplementary analgesics within 12–18 h (p<0.05), but there was no significant difference within 0–24 h in patients undergoing abdominal hysterectomy
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • Two of three studies showed no significant difference between single bolus conventional NSAIDs administered before or after incision for postoperative pain scores in patients undergoing abdominal hysterectomy Nakayama et al 2001a Click here for more information
  • Of three studies in abdominal hysterectomy, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=30; n=77)
  • Post-incisional NSAID was superior to pre-incisional NSAID for extending the time to first analgesic request in one study (n=30)
  • Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for reducing the incidence of PONV in two studies of patients undergoing abdominal hysterectomy (n=65, n=30)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • A restrospective, case-control study showed that postoperative analgesia with the conventional NSAID diclofenac (150 mg daily) was associated with a significantly higher number of anastomotic leakages than postoperative opioid analgesia in patients undergoing laparoscopic colorectal surgery

Open Colonic Resection-Specific Evidence

  • Pre-operative + postoperative IV flurbiprofen was superior to placebo for reducing postoperative pain scores Xu et al 2008 Click here for more information
  • Pre-operative + postoperative IV flurbiprofen axetil was superior to placebo for reducing the time to first pass of flatus and first bowel movement (both p=0.01; n=40)
  • The incidence of postoperative nausea and vomiting was similar in the pre-operative + postoperative flurbiprofen axetil and placebo groups (n=40)

PROSPECT Recommendations

  • Pre-operative corticosteroids are not recommended for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing VAS pain scores (LoE 1) and concerns that they could affect anastomotic and wound integrity (LoE 4). However, they may be used for reduction of PONV (transferable evidence, LoE 1)

Clinical Practice

  • Nausea and vomiting are frequent in abdominal surgeries, and corticosteroids may be used for their anti-emetic effects in patients at risk
  • A single pre-operative high-dose bolus of corticosteroid may be considered in high-risk pulmonary patients
  • Corticosteroids are not used in routine clinical practice because of the concerns that they could affect anastomotic and wound integrity

Transferable Evidence from Other Procedures - Study information

  • A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects
  • A review of major abdominal surgery, a randomised study of patients at high-risk of nausea and vomiting undergoing surgery, and a systematic review of drugs that prevent PONV, all showed that corticosteroids decrease PONV
  • IV methylprednisolone significantly improved postoperative recovery outcomes compared with placebo in abdominal surgery Krantz et al 1990 Click here for more information
  • A meta-analysis showed that a single pre-operative dose of IV methylprednisolone (15–30 mg/kg) was associated with significantly fewer pulmonary complications compared with placebo or no treatment, but data on postoperative pain could not be meta-analysed Sauerland et al 2000 Click here for more information
  • IV methylprednisolone (30 mg/kg) significantly decreased pulmonary complications compared with placebo in one study identified in a review of major abdominal surgery
  • Corticosteroids did not significantly decrease pain compared with placebo in two studies identified in a review of major abdominal surgery

Open Colonic Resection-Specific Evidence - Study information

  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia significantly improved mobilisation and recovery compared with IV placebo (p<0.05) Schulze et al 1997 Click here for more information
  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia significantly improved pulmonary function (as measured by peak flow, forced vital capacity, and forced expiratory volume) compared with IV placebo 6 hours postoperatively (p<0.05; n=24)
  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia and epidural analgesia did not confer a significant benefit over IV placebo for cumulative VAS pain scores Schulze et al 1997 Click here for more information
  • Pre-operative IV dexamethasone did not confer a significant benefit over placebo for reduction of VAS pain scores at rest at any time point assessed (4 and 8 h, Days 1, 2 and 3) (n=27)
  • Pre-operative IV dexamethasone had no signficant effect on postoperative IM morphine (10 mg) requirements, compared with placebo (n=27)
  • Incidence of postoperative nausea and vomiting was similar in the pre-operative IV dexamethasone and placebo groups (n=27)
  • There were no significant differences in the time to first flatus, first bowel sound or first bowel movement with pre-operative IV dexamethasone versus placebo (n=27)
  • The length of hospital stay was similar for patients in the pre-operative IV dexamethasone and placebo groups (n=27)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period is not recommended (Grade D, LoE 4) because of inconsistent and insufficient procedure-specific evidence (LoE 1)
  • Continuous administration of pre/intra-operative IV lidocaine is recommended if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits, compared with control (see Intra-operative and Postoperative IV lidocaine sections)

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures

  • [None cited]

Open Colonic Resection-Specific Evidence - Study information

  • Pre-/intra-operative IV lidocaine reduced postoperative pain scores at rest and on coughing at a minority of time points compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced postoperative morphine requirement compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced intra-operative fentanyl requirement compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine was associated with a lower incidence of morphine-related nausea or vomiting compared with control (p<0.01; n=40)
  • Pre-/intra-operative IV lidocaine significantly reduced the time to first flatus, compared with the control group (p<0.01; n=40)
  • Peri-operative IV lidocaine significantly reduced the time to first flatus, compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine, compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay compared with the control (p=0.004; n=60)
  • Pre-/intra-operative IV lidocaine conferred no significant benefit over control for reducing the length of hospital stay (n=40)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 minutes) (n= 60)

PROSPECT Recommendations

  • Pre-operative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Open Colonic Resection-Specific Evidence - Study information

  • IM dextromethorphan was superior to control for reducing postoperative pain scores during coughing at 1, 2, 4, 8 and 24 h (p<0.001; n=60), although there were no significant differences in resting pain scores between the groups at any time point assessed
  • IM dextromethorphan was more effective than control for reducing postoperative opioid requirements Yeh et al 2005 Click here for more information
  • IM dextromethorphan significantly reduced the time to passage of first flatus, compared with the control (p<0.0001; n=60)
  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)
  • The incidence of morphine-related side-effects (drowsiness, dizziness, nausea, vomiting and pruritus) was similar in both the IM dextromethorphan and control groups (n=60)
  • Dextromethorphan conferred no significant benefit over control for reducing the length of hospital stay (n=60)

PROSPECT Recommendations

  • Pre-operative administration of strong opioids is not recommended (Grade B) for colonic resection as they are significantly less effective than postoperative strong opioids for reducing postoperative pain (transferable evidence, LoE 1)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures - Study information

  • Pre-incisional strong opioids showed no significant benefit over post-incisional strong opioids for reducing postoperative pain scores (LoE 1) Fassoulaki et al 1995 Click here for more information
  • Pre-incisional strong opioids did not confer a significant benefit over post-incisional strong opioids for reducing supplementary analgesic consumption in patients undergoing abdominal hysterectomy (LoE 1) Kilickan et al 2001 Click here for more information
  • Pre-incisional strong opioids provided no significant benefit over post-incisional strong opioids for increasing the time to first analgesic request in three studies of patients undergoing abdominal hysterectomy reporting this parameter (n=34, n=85, n=39)
  • A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids
  • Pre-incisional strong opioids were associated with a similar incidence of PONV to post-incisional strong opioids in patients undergoing abdominal hysterectomy (n=34, n=40, n=60)

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Pre-operative administration of weak opioids is not recommended (Grade B) based on procedure-specific evidence that it has limited postoperative analgesic benefit compared with postoperative administration (LoE 2)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is probably too low to provide sufficient pain relief

Transferable Evidence from Other Procedures

  • A systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration
  • A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)
  • Pre-, or intra-operative IV tramadol 100 mg did not confer any benefit for reducing postoperative pain scores compared with postoperative IV tramadol 100 mg Wordliczek et al 2002 Click here for more information
  • Pre-operative administration of IV tramadol resulted in a significantly shorter time to first analgesic request compared with administration immediately after peritoneal closure, or immediately following surgery (p<0.01; n=90)
  • Tramadol 100 mg administered pre- or intra-operatively, did not confer any benefit for reducing the incidence of PONV compared with postoperative IV tramadol 100 mg (n=90)

PROSPECT Recommendations

  • Continuous thoracic epidural anaesthesia and analgesia at a level appropriate to the site of incision are recommended for routine use (Grade A), based on superior postoperative analgesic and safety benefits compared with systemic techniques (procedure-specific evidence, LoE 1, also see Intra-operative and Postoperative Epidural Analgesia sections), except in a minority of patients with a contra-indication to epidural administration
  • Pre-operative administration of a single-shot epidural analgesia produces a similar postoperative analgesic efficacy to postoperative administration
  • Where epidural techniques are used, it is recommended that a combination of strong opioid and local anaesthetic is used (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone and to reduce the dose of strong opioid and its associated side-effects (procedure-specific evidence, LoE 1, see Intra-operative and Postoperative Epidural Analgesia sections)
  • Where epidural techniques are used, it is recommended that the epidural catheter is inserted pre-operatively because this is the most practical timing for insertion (Grade D, LoE 4)

Clinical Practice

  • In colonic surgery, the analgesic and recovery benefits of an epidural outweigh the risks of rare major complications and warrant the use of this more labour-intensive treatment
  • Where epidural techniques are used, the most practical timing for insertion of the epidural catheter is pre-operatively
  • 1 mg epidural morphine is considered inadequate to block visceral pain; however, larger doses are likely to cause bladder dysfunction. Therefore, pre-operative epidural administration of local anaesthetic with opioids is preferred to opioids alone

Transferable Evidence from Other Procedures - Study information

  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative pain scores at rest and on movement at 1 and 6 h (p<0.05 for all comparisons; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative supplementary analgesic consumption at 6 and 12 h (p<0.05 for both times; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for extending the time to first analgesic request (p<0.05; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine and placebo were not different for the incidence of postoperative nausea in patients undergoing abdominal hysterectomy (n=36)
  • Pre- plus intra-operative epidural ropivacaine was superior to placebo for reducing intra-operative sufentanil in major abdominal tumour surgery (p<0.001; n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing postoperative pain scores for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing supplementary analgesic consumption for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing side-effects for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre-incisional epidural analgesia provided no significant benefit for reducing postoperative pain scores compared with post-incisional administration in a variety of abdominal procedures (LoE 1) Abdel-Ghaffar et al 1998 Click here for more information
  • Evidence for the benefit of pre-incisional compared with post-incisional epidural analgesia for reducing supplementary analgesic consumption in abdominal procedures is inconsistent (LoE 4) Espinet et al 1996 Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative bolus epidural morphine 1 mg plus postoperative parenteral analgesia was superior to postoperative parenteral analgesia alone on the day of surgery for VAS scores Simpson et al 1993 Click here for more information
  • Adding pre-operative bolus epidural morphine reduced parenteral opioid consumption on the first and second postoperative day compared with parenteral analgesia alone (p=0.002 and p=0.07, respectively; n=13)
  • Adding pre-operative bolus epidural morphine increased the time to first request of analgesia compared with parenteral analgesia alone (p=0.03; n=13)
  • Pre-operative + postoperative epidural clonidine was superior to control for the reduction of postoperative pain scores Wu et al 2004 Click here for more information
  • Pre-operative + postoperative epidural clonidine was superior to control for reducing postoperative analgesic requirement Wu et al 2004 Click here for more information
  • Pre-operative + postoperative epidural clonidine significantly reduced the time to return of normal bowel function, compared with control (p<0.001; n=40)
  • The incidence of morphine-associated nausea, vomiting, and itching was significantly lower with pre-operative + postoperative epidural clonidine, compared with control (p<0.001; n=40)
  • Epidural LA plus morphine 40 min before surgical incision conferred no significant benefit over administration at wound closure for reducing postoperative VAS pain scores Dahl et al 1992 Click here for more information
  • Epidural LA plus morphine given 40 min before surgical incision was similar to that given at closure for level of sensory block to pinprick for 0–72 h (n=32)
  • The length of hospital stay was similar for patients in the pre-operative + postoperative epidural clonidine and control groups (n=40)

PROSPECT Recommendations

  • Spinal morphine is not recommended (Grade D) because of the risk of side-effects (LoE 4)
  • Spinal clonidine is not recommended (Grade B) because of limited analgesic effect (procedure-specific evidence LoE 2) and the risk of side-effects (LoE 4)

Clinical Practice

  • Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus, and limited duration of analgesic effect

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • The incidence of postoperative nausea or vomiting was similar with pre-operative spinal morphine + IV PCA morphine, compared with PCA morphine alone (n=52)
  • Pre-operative spinal morphine + IV PCA morphine was superior to IV PCA morphine alone for reducing postoperative pain scores Click here for more information
  • Spinal clonidine was superior to placebo for reducing postoperative pain at a minority of time points Click here for more information
  • Spinal clonidine was superior to placebo for reducing postoperative morphine requirements Click here for more information
  • Pre-operative spinal bupivacaine significantly reduced the incidence of postoperative residual pain, compared with placebo, at 2 weeks, and after 1 month (p<0.05; n=40)
  • Spinal bupivacaine significantly reduced the area of hyperalgesia around the incision site, compared with placebo, at 24, 48, and 72 h postoperatively (p<0.05; n=40)
  • Spinal bupivacaine was superior to placebo for reducing postoperative PCA morphine consumption Click here for more information
  • There were no significant differences between the spinal morphine and spinal morphine + sufentanil groups for VAS pain scores at rest and coughing during the first 48 h postoperatively (n=77)
  • There was no significant difference in postoperative PCA morphine consumption with spinal morphine versus spinal morphine + sufentanil in the PACU, or at 24 or 48 h postoperatively (n=77)
  • Intra-operative IV sufentanil requirements were similar in the spinal morphine and spinal morphine + sufentanil groups (n=77)
  • There was no significant difference in patient satisfaction (VAS scale 1–100) with pre-operative spinal morphine versus spinal morphine + sufentanil (n=77)
  • Incidence of postoperative nausea and vomiting was similar between the pre-operative spinal morphine group and the pre-operative spinal morphine + sufentanil group (n=77)
  • Spinal bupivacaine conferred no significant benefit over placebo for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)
  • Spinal clonidine conferred no significant benefit over spinal bupivacaine for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)
  • The incidence of intra-operative adverse haemodynamic events was significantly greater with pre-operative spinal clonidine compared with pre-operative spinal bupivacaine or placebo (p<0.05) (n=20/group)
  • Pre-operative spinal morphine + IV PCA morphine versus IV PCA morphine alone
  • Spinal morphine versus spinal morphine + sufentanil
  • Spinal clonidine versus placebo
  • Spinal bupivacaine versus placebo
  • Spinal clonidine versus spinal bupivacaine

PROSPECT Recommendations

  • Bilateral TAP block is not recommended at the current time (Grade D, LoE 4) because of limited procedure-specific evidence, despite some positive transferable evidence (LoE 1)

Clinical Practice

  • The single-shot TAP block technique may provide effective postoperative analgesia but the duration is limited. Despite this, further study evidence is expected which may support the use of this technique

Transferable Evidence from Other Procedures

  • Unilateral TAP block significantly reduced postoperative VAS pain scores and postoperative morphine consumption compared with control, in patients undergoing open appendicectomy (n=52)
  • Bilateral TAP block with ropivacaine significantly reduced postoperative VAS pain scores, postoperative morphine consumption and the incidence of postoperative sedation, compared with placebo, in patients undergoing abdominal hysterectomy (n=50)

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative bilateral TAP block was superior to control for reducing postoperative pain scores Click here for more information
  • Pre-operative bilateral TAP block was superior to control for reducing postoperative morphine requirements Click here for more information
  • Pre-operative bilateral TAP block significantly reduced postoperative sedation scores, compared with control, at 4 and 6 h postoperatively (p=0.01), although there was no significant difference between the groups at 2 and 24 h, or in the PACU
  • Pre-operative bilateral TAP block was associated with a significantly higher incidence of PONV, compared with control (p<0.05)

PROSPECT Recommendations

  • Pre-operative use of guided imagery is not recommended (Grade D, LoE 4) because of limited procedure-specific evidence, despite some evidence of analgesic effect (LoE 1)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • Pre-operative use of guided imagery was significantly more effective for reducing postoperative pain intensity (p<0.05), distress from pain (p<0.01) and the ability to cope with pain (p<0.01) compared with routine postoperative care, in patients undergoing abdominal surgery (n=51)
  • Pre-operative use of guided imagery resulted in significantly lower supplementary analgesic consumption over 0–48 h compared with routine postoperative care (p<0.05; n=51)

Open Colonic Resection-Specific Evidence - Study information

  • One of two studies showed that care by guided imagery was more effective than standard care for reducing postoperative pain scores Click here for more information
  • One of two studies found that care by guided imagery was more effective than routine postoperative care for reducing postoperative analgesic requirements Click here for more information
  • One of two studies showed that care by guided imagery was more effective than routine postoperative care for reducing time to first bowel movement Click here for more information
  • Guided imagery tapes provided no significant benefit over relaxation tapes for reducing VAS pain scores at rest or coughing during postoperative Days 1–4 (n=38)
  • Relaxation tapes provided no significant benefit over routine postoperative care for the reduction of VAS pain scores at rest or coughing during postoperative Days 1–4 (n=40)
  • There was no significant difference in the total analgesic consumption or the number of analgesic requests between patients in the relaxation and guided imagery groups (n=42)
  • Time to first flatus and first bowel movement was similar for patients in the guided imagery and relaxation groups (n=42)
  • Time to first flatus and first bowel movement was similar for patients in the relaxation and routine care groups (n=42)
  • One study found that care by guided imagery provided no benefit over routine postoperative care for reducing the median length of hospital stay, postoperative ileus or the incidence of nausea or vomiting (n=130)

PROSPECT Recommendations

  • Laxatives are not recommended for analgesia (Grade B) because limited procedure-specifc evidence shows no analgesic benefit (LoE 2), but they may be used for reasons other than pain relief (LoE 4)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • Time until first defecation and GI recovery were significantly shorter with biscodyl versus placebo (p=0.001 and p=0.007, respectively; n=169)
  • Pre-operative + postoperative administration of biscodyl provided no significant benefit over placebo for the reduction of VAS pain scores (n=169)
  • There was no significant difference in the level of opioid consumption between patients who received bisacodyl or placebo during the first 8 postoperative days (n=169)
  • The incidence of postoperative cramping and nausea was similar in the biscodyl and placebo groups (n=169)
  • Biscodyl conferred no significant benefit over placebo for reducing the length of hospital stay (n=169)

Open Colonic Resection-Specific Evidence - Study information

  • [None Cited]

PROSPECT Recommendations

  • Pre-operative pentoxifylline is not recommended (Grade D, LoE 4) due to limited procedure-specific evidence of its analgesic effect

Clinical Practice

  • Further studies are needed to recommend the use of pentoxifylline in clinical practice

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative IV pentoxifylline was superior to placebo for the reduction of VAS pain scores during coughing after 1, 2, and 4 h, and on Days 1 and 2 (p<0.05; n=40), however, there was no siginificant difference between the groups for resting pain scores at each of the time points assessed (1, 2, 4 h and Days 1, 2 and 3)
  • Pre-operative IV pentoxifylline was superior to placebo for reducing morphine consumption during Days 1–3 (p<0.0001; n=40)
  • Pre-operative IV pentoxifylline was superior to placebo for extending the time until first PCA morphine trigger (p<0.0001; n=40)
  • Pre-operative IV pentoxifylline was superior to placebo for reducing the time until first flatus
  • Pre-operative IV pentoxifylline was superior to placebo for reducing inflammatory cytokines related to postoperative pain
  • The incidence of morphine-related adverse effects (drowsiness, dizziness, nausea, and vomiting) was similar in both the pre-operative IV pentoxifylline and placebo groups

PROSPECT Recommendations

  • Intra-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity [transferable evidence, LoE 1], renal function and hepatic function [transferable evidence, LoE 3], or actual or recent gastroduodenal ulcer history [LoE 4]). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of NSAIDs and

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • There is no procedure-specific evidence that intra-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence - Study information

  • Intra-operative parecoxib was superior to placebo for the reduction of postoperative morphine consumption Click here for more information
  • Intra-operative IV parecoxib (40 mg) conferred some benefit over placebo for the reduction of postoperative resting pain scores Click here for more information
  • There were no significant differences between the intra-operative IV parecoxib and pre-operative IV parecoxib groups for NRS pain scores at rest, or during coughing, during the first 48 h postoperatively
  • Intra-operative IV parecoxib conferred no significant benefit over placebo for reducing PCA morphine consumption in the recovery room
  • There was no significant difference in postoperative morphine consumption between the intra-operative IV parecoxib group and the pre-operative IV parecoxib group within 0–48 h after surgery
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar between the intra-operative IV parecoxib, pre-operative IV parecoxib, and placebo groups

PROSPECT Recommendations

  • Clonidine is not recommended (Grade D), despite limited procedure-specific evidence for analgesic efficacy, because it is associated with an increased risk of hypotension, sedation and bradycardia (LoE 4)

Clinical Practice

  • The risk/benefit ratio for clonidine is unclear. Recognised side effects include hypotension, sedation, dizziness and bradycardia
  • There is no consensus among clinicians on the optimum dose of clonidine that should be used

Transferable Evidence from Other Procedures

Open Colonic Resection-Specific Evidence - Study information

  • IV clonidine given before skin incision, or before peritoneal incision, was superior to fentanyl given before skin incision for postoperative analgesic outcomes Click here for more information

PROSPECT Recommendations

  • Pre- or intra-operative calcium channel antagonists are not recommended (Grade B), based on limited procedure-specific evidence showing a lack of postoperative analgesic effect (LoE 2)

Clinical Practice

  • Clinical experience with calcium channel antagonists is lacking

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • IV nimodipine conferred no significant benefit over placebo for postoperative pain scores at rest or movement 0–120 h postoperatively, except at 72 h when a reduction in movement pain reached significance (n=47)
  • Oral nifedipine was significantly inferior to placebo for postoperative pain scores at rest at 16 and 24 h (p<0.05; n=46)
  • Nimodipine or nifedipine provided no significant benefit over placebo for reducing the following postoperative outcomes: morphine requirements for 0–24 h; sedation scores for 0–48 h; the incidence of nausea and vomiting; time to first bowel movement and time to first flatus (n=69)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous administration of IV lidocaine limited to the pre/intra-operative period is not recommended (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • Continuous administration of pre/intra-operative IV lidocaine continuous administration is recommended if continued during the immediate postoperative period when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures - Study information

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

Open Colonic Resection-Specific Evidence - Study information

  • Pre-/intra-operative IV lidocaine reduced postoperative pain scores compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced postoperative morphine requirement compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced intra-operative fentanyl requirement compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine was associated with a lower incidence of morphine-related nausea or vomiting compared with control (p<0.01; n=40)
  • Pre-/intra-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.01; n=40)
  • Peri-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake, compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay, compared with the control (p=0.004; n=60)
  • Pre-/intra-operative IV lidocaine conferred no significant benefit over control for reducing the length of hospital stay (n=40)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 minutes) (n= 60)

PROSPECT Recommendations

  • Intra-operative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use (

Open Colonic Resection-Specific Evidence - Study information

  • Intra-operative ketamine was superior to placebo for reducing postoperative pain scores in the first 15 min (p<0.05), decreasing morphine use for 0–24 h compared with placebo (p<0.01), and extending the time to first analgesic request (p<0.001) compared with placebo (n=50)
  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

PROSPECT Recommendations

  • In patients undergoing colonic resection and receiving epidural anaesthesia, intra-operative administration of systemic, long-acting strong opioids to provide postoperative analgesia is not recommended (Grade D, LoE 4)
  • However, in patients not indicated for epidural anaesthesia, systemic intra-operative strong opioids are recommended to provide early postoperative pain relief (Grade B), based on transferable evidence (LoE 1) of analgesic efficacy

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures - Study information

  • Intra-operative strong opioid provided a benefit over placebo up to 4 h for reducing postoperative pain scores at rest (one of three studies) and reducing the supplementary analgesic consumption (three studies), but showed no significant difference for the time to first analgesic request (one study), in patients undergoing hysterectomy Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Low-dose remifentanil infusion plus titrated desflurane conferred a benefit for reducing postoperative pain scores at 3 and 4 h compared with a high-dose remifentanil infusion plus fixed-dose desflurane (both times p<0.05; n=49)
  • Low-dose remifentanil infusion plus titrated desflurane was superior for reducing cumulative supplementary analgesic consumption compared with a high-dose remifentanil infusion plus fixed-dose desflurane (p<0.01; n=49)
  • Low-dose remifentanil infusion plus titrated desflurane increased the number of patients classified as 'calm' compared with a high-dose remifentanil infusion plus fixed-dose desflurane Click here for more information
  • Low-dose remifentanil infusion plus titrated desflurane had a similar time to first request of supplementary analgesia and a similar incidence of PONV compared with a high-dose remifentanil infusion plus fixed-dose desflurane (n=49)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for reducing postoperative pain scores at 2 h, but the scores were similar from 2–12 h (p<0.01; n=30)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for the reduction of supplementary analgesic consumption in the PACU and at 4, 12 and 24 h (p<0.05; n=30)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for extending the time to first analgesic request (p<0.05; n=30)
  • Sufentanil anaesthesia was similar to remifentanil anaesthesia plus intra-operative bolus IV morphine for the incidence of PONV and sedation scores (n=30)
  • Remifentanil infusion at a low-dose compared with remifentanil infusion at a high-dose was associated with a similar percentage of sedated patients Click here for more information

PROSPECT Recommendations

  • Intra-operative systemic weak opioids are not recommended (Grade D, LoE 4), as placebo-controlled evidence for their benefit in reducing postoperative pain is limited. Moreover, epidural LA + strong opioid is the regimen recommended for routine use in patients undergoing colonic resection
  • In patients not receiving epidural anaesthesia, intra-operative strong opioids, not weak opioids, are recommended to provide early postoperative pain relief (Grade B, see Intra-operative Strong Opioid section)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is likely to be too low to provide sufficient pain relief

Transferable Evidence from Other Procedures - Study information

  • Intra-operative IV tramadol was superior to placebo for reducing tramadol use and postoperative pain scores in the PACU following abdominal surgery (p<0.05 for all comparisons; n=60)
  • Intra-operative IV tramadol was superior to placebo for reducing the incidence (p<0.05) and severity (p<0.05) of PONV following abdominal surgery (n=60)
  • For patients undergoing laparoscopic cholecystectomy, intra-operative tramadol IV at wound closure was superior to control for reducing VAS scores, reducing the use of supplementary analgesics and increasing the time to first analgesic request
  • Intra-operative IV tramadol was similar to placebo for the number of postoperative PCA boluses delivered and total tramadol consumption (n=60)

Open Colonic Resection-Specific Evidence - Study information

  • Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)
  • Pre-, or intra-operative IV tramadol 100 mg did not confer any benefit for reducing postoperative pain scores compared with postoperative IV tramadol 100 mg Click here for more information
  • Tramadol 100 mg administered pre- or intra-operatively, did not confer any benefit for reducing the incidence of PONV compared with postoperative IV tramadol 100 mg (n=90)
  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)

PROSPECT Recommendations

  • Continuous thoracic epidural anaesthesia and analgesia is recommended (Grade A) for routine use in colonic resection based on its benefit in reducing postoperative pain, systemic opioid use and bowel recovery time (procedure-specific evidence, LoE 1)
  • A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)
  • Addition of clonidine to the combination of epidural LA + opioid is not recommended (Grade D) because of side effects, despite favourable effects on pain scores

Clinical Practice

  • Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in colonic resection
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • A minority of patients may need to receive general anaesthesia plus systemic analgesia due to a contra-indication to the epidural technique

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Epidural LA and opioid showed a significant benefit for reducing postoperative pain scores compared with GA plus systemic analgesia in six studies Click here for more information
  • Epidural LA and strong opioid produced a significant reduction in the use of supplementary analgesia compared with GA plus systemic analgesia in two studies (p<0.05, n=64; p<0.001, n=20)
  • Epidural LA and strong opioid was superior to GA plus systemic analgesia for increasing the time to first request of supplementary analgesia in one study (p<0.005; n=20)
  • Epidural LA plus opioid was associated with a similar length of hospital stay compared with GA plus systemic analgesia in two studies (n=42, n=20)
  • Epidural LA plus opioid produced a significantly quicker time for first flatus and time for first bowel movement compared with GA plus systemic analgesia in two studies (all p<0.05; n=64, n=42)
  • Epidural bupivacaine plus morphine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV plus postoperative PCA morphine (p<0.005; n=26)
  • Epidural bupivacaine plus morphine had a similar incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=26)
  • Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly fewer patients requiring supplementary analgesia compared with GA plus systemic analgesia for 1–48 h postoperatively (p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly more patients having a bowel movement by Day 4 compared with GA plus systemic analgesia (p<0.05; n=116)
  • Epidural bupivacaine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV bolus plus postoperative PCA morphine (p<0.005; n=26)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, reported that epidural analgesia significantly reduced postoperative VAS pain scores at 24 h (11 studies analysed, n=630) and 48 h postoperatively (6 studies analysed, n=281) (p<0.001 for both comparisons)
  • A meta-analysis of 11 randomised studies showed that the duration of gastrointestinal dysfunction was significantly shorter with epidural analgesia, compared with parenteral opioid analgesia (n=510, p<0.001)
  • GA + intra-operative epidural lidocaine + postop PCEA was superior to GA alone + postop PCEA for reducing VAS pain scores on coughing at a minority of time points Click here for more information
  • GA + intra-operative epidural lidocaine + postoperative PCEA was more effective than GA alone + postoperative PCEA for reducing postoperative opioid requirements Click here for more information
  • GA + intra-operative epidural lidocaine + postoperative PCEA significantly reduced the time to first flatus compared with GA alone + postoperative PCEA (p<0.0001; n=60)
  • Epidural lidocaine was more effective than the control for the reduction of postoperative pain scores Click here for more information
  • Epidural lidocaine was superior to the control for reducing postoperative opioid requirement Click here for more information
  • The proportion of patients receiving intra-operative epidural lidocaine that required an intra-operative fentanyl supplement, was significantly lower compared with the control group (n=40)
  • Epidural lidocaine was superior to control for reducing the time until first flatus (p<0.01; n=40)
  • Epidural lidocaine was associated with a lower incidence of morphine-related nausea or vomiting, compared with control (p<0.01; n=40)
  • The addition of opioid to epidural LA conferred a benefit over epidural LA alone in reducing postoperative pain scores in two studies Click here for more information
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine was superior to intra-operative IV lidocaine-sufentanil-clonidine + postoperative IV lidocaine-morphine-clonidine for reducing postoperative pain Click here for more information
  • Cumulative number of satisfied analgesic requests was significantly lower with intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine, from 24–72 h after surgery (p<0.05; n=40), but not at 12 h
  • Epidural infusion of opioid was similar to GA and IV plus postoperative PCA morphine for postoperative pain scores
  • Epidural morphine was associated with a similar incidence of nausea and orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=24)
  • Epidural bupivacaine was associated with an increased incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (p<0.05) (n=26)
  • Epidural bupivacaine had a similar incidence of nausea compared with GA and IV plus postoperative PCA morphine (n=26)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)
  • Epidural lidocaine + GA conferred no significant benefit over GA alone for reducing the length of hospital stay (n=60)
  • There was no significant difference in the incidence of morphine-related side-effects (drowsiness, dizziness, nausea, vomiting and pruritus) with epidural lidocaine + GA versus GA alone (n=60)
  • Epidural lidocaine conferred no significant benefit over the control for reducing the length of hospital stay (n=40)
  • Epidural LA plus strong opioid showed no difference in the incidence of nausea and vomiting compared with GA plus systemic analgesia in four studies Click here for more information
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was associated with a higher incidence of orthostatic hypotension at first mobilisation, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine (p=0.05; n=40)

PROSPECT Recommendations

  • Spinal analgesia is not recommended in combination with epidural anaesthesia (Grade B), based on a lack of benefit in reducing postoperative pain in colonic resection (LoE 2). Moreover, it introduces a greater level of complexity (LoE 4)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Combined spinal/thoracic epidural anaesthesia conferred no additional benefit over peri-operative thoracic epidural infusion alone for postoperative pain scores at rest and on coughing from 4–24 h (n=20)
  • Combined spinal/thoracic epidural anaesthesia compared with continuous epidural infusion alone were similar for supplementary analgesic consumption (n=20)

PROSPECT Recommendations

  • No recommendation can be made about general anaesthetic techniques for open colonic resection because of limited procedure-specific evidence

Clinical Practice

  • For laparoscopic procedures, the use of nitrous oxide may result in increased bowel distension

Transferable Evidence from Other Procedures

  • One randomised study investigating the efficacy of prophylactic antimetic interventions in patients undergoing surgery with general anaesthesia concluded that the risk of PONV was 12% greater with N2O compared with nitrogen
  • One randomised study comparing nitrous oxide-based anaesthesia with nitrous oxide-free anaesthesia in patients undergoing major surgery, found that the avoidance of nitrous oxide decreased the incidence of postoperative complications, but did significantly reduce the length of hospital stay (Myles 2007)

Open Colonic Resection-Specific Evidence - Study information

  • Two studies reported that postoperative VAS pain scores were significantly lower with nitrogen compared with nitrous oxide after 2 h (p=0.02; n=344 and p=0.014; n=408)
  • Two studies reported that VAS nausea scores were significantly lower with nitrogen compared with nitrous oxide (p=0.04; n=344 and p=0.007; n=408)
  • One study reported that moderate-to-severe bowel distension was significantly less common in patients following GA with nitrogen, compared with nitrous oxide (p<0.001; n=344)
  • Nitrous oxide was superior to intra-operative IV remifentanil for the reduction of VAS pain scores on arrival in the PACU (p<0.05; n=60), but not after 5, 10 or 15 min
  • Two studies reported no significant difference in the level of PCA opioid consumption (piritramide) between patients receiving GA with nitrogen or nitrous oxide (n=344; n=408)
  • Two studies showed that the incidence of postoperative nausea and vomiting was similar with nitrous oxide and nitrogen (n=344; n=408)
  • There was no significant difference in the time to first flatus, first bowel movement, or first intake of solid food between patients in the groups receiving GA with nitrogen or nitrous oxide (n=408)
  • The length of hospital stay was similar for patients in the groups that received general anaesthesia with nitrogen and general anaesthesia with nitrous oxide (n=408)
  • There were no significant differences between the nitrous oxide and intra-operative IV remifentanil groups in VAS pain scores at rest or movement from 0–24 h postoperatively (n=60)
  • There was no significant difference between the nitrous oxide and intra-operative IV remifentanil groups for postoperative morphine consumption in the PACU, or during the first postoperative day (n=60)
  • There was a similar incidence of postoperative nausea and vomiting between patients receiving nitrous oxide and IV remifentanil (n=60)

PROSPECT Recommendations

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D, LoE 4)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain (Grade A), if the conditions outlined above allow, based on procedure-specific evidence (LoE 1).
  • See laparoscopic section for recommendations on pain management for laparoscopic colonic resection
  • A horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits, if the operative conditions allow (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence. In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D, LoE 4)
  • Diathermy is recommended over the scalpel (Grade B), based on analgesic benefits as well as greater speed of incision and less blood loss (transferable evidence, LoE 2)

Clinical Practice

  • The decision to employ a laparoscopic versus open approach for colonic surgery is based on multiple factors such as the indication for surgery (e.g. benign or malignant disease) and surgical expertise, as well as the desired outcomes
  • If the surgical indication allows, a transverse incision is preferred for abdominal procedures such as colonic resection

Transferable Evidence from Other Procedures

  • The transverse incision was similar to the vertical incision for access to intra-abdominal structures and resulted in significantly less postoperative pain and a lower incidence of pulmonary complications; however, vertical laparotomy is associated with a shorter operating time and better possibilities for extension of the incision, as found in a systematic review in abdominal surgery
  • Laparotomy incisions using diathermy had significantly lower VAS scores at 48 h (p<0.05), morphine consumption over the first 5 days (p<0.04), less blood loss (p=0.002), and were associated with a faster speed of incision (p<0.04) compared with scalpel incisions in patients undergoing elective midline laparotomy (n=100)
  • Laparoscopic surgery resulted in an increased operating time, but reduced postoperative pain, hospital stay and return to normal activity compared with open surgery, as demonstrated in a number of reviews of the literature of patients undergoing resection for colonic cancer, cholecystectomy, appendectomy (systematic) and groin hernia (systematic)

Open Colonic Resection-Specific Evidence - Study information

  • A transverse incision conferred significant benefit over a midline vertical incision for reducing postoperative pain on movement on Days 1 and 3, and reducing supplementary analgesic consumption (all p<0.05); however, both incision techniques were similar for postoperative pain scores at rest (n=40)
  • A transverse incision was similar to a midline vertical incision for the time to resume normal diet, time to first bowel movement and duration of hospital stay (n=40)
  • Laparoscopic resection was superior to open colonic resection for reducing postoperative pain scores Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing supplementary analgesic consumption Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing time to first flatus and bowel movement in three studies Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing length of hospital stay in four of five studies Click here for more information
  • One study reported that there was no significant difference in the incidence of PONV between the laparoscopic colonic resection and open colonic resection techniques (n=60)
  • A meta-analysis of seven studies reporting analgesic outcomes showed a significant benefit of laparoscopic resection over open colonic resection for reduced pain at rest and on coughing, and reduced analgesic requirement for up to 3 days (not all studies recorded pain scores)
  • Meta-analysis of twelve studies showed that laparoscopic resection reduced morbidity, wound infection, time to recovery and hospital stay compared with open resection
  • A systematic review of laparoscopic resection of colon cancer, combined with expert opinion, concluded that pain is less severe and that less analgesia is required after laparoscopic resection than open resection
  • A systematic review comparing laparoscopic with open surgery for colorectal cancer, concluded that laparoscopic surgery was associated with less blood loss, less postoperative pain, less postoperative analgesic consumption, faster return to normal bowel function, and a shorter hospital stay
  • A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that one of two randomised controlled studies showed laparoscopic surgery was superior for reducing postoperative pain scores
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for the reduction of postoperative pain scores Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing supplementary analgesic consumption Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time to first flatus and first bowel movement Click here for more information
  • Two studies showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the length of hospital stay (p=0.004, n=81; p<0.001, n=60)
  • One study showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time until first oral food intake (p<0.05, n=60)
  • A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that two of three randomised studies found no significant difference between laparoscopic and open techniques for reducing postoperative analgesic consumption. However, there was a trend for less analgesia in the laparoscopic group
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctocolectomy for reducing VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55)
  • There was no significant difference in the postoperative morphine requirement between patients who received hand-assisted laparoscopic proctocolectomy versus open proctolectomy at 24, 48 or 72 h (n=55)
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctolectomy for reducing the time taken for patients to return to normal fluid or food consumption (n=55)

PROSPECT Recommendations

  • Maintenance of normothermia is recommended (Grade A) for improved clinical outcomes (procedure-specific evidence, LoE 1) but it is not helpful for reducing postoperative pain (LoE 1)

Clinical Practice

  • Although there are no benefits for pain reduction, keeping patients normothermic has benefits for reducing oxygen consumption and decreasing myocardial work, which is important for elderly patients and those at risk of cardiac events

Transferable Evidence from Other Procedures - Study information

  • One study showed that aggressive warming was superior to conventional warming in total hip arthroplasty for reducing intra-operative and total blood loss (p=0.002), but no difference in postoperative blood loss was observed (n=150)
  • A randomized controlled trial in high-risk patients showed that maintenance of normothermia reduced the incidence of morbid cardiac events in the peri-operative period compared with routine thermal care (p=0.02, n=300)
  • Maintenance of normothermia decreased the post-anaesthetic recovery time compared with routine thermal management (p<0.001, n=150) in patients undergoing abdominal surgery
  • Maintenance of normothermia may prevent adverse effects of mild hypothermia, which reduces resistance to wound infection, is associated with increased protein wasting and decreased collagen synthesis, reduces platelet function and impairs coagulation, increases the incidence of morbid cardiac events, decreases drug metabolism, increases anaesthetic recovery time, and induces shivering
  • Patients kept normothermic showed no significant difference in postoperative pain scores compared with patients kept hypothermic during elective major abdominal surgery (n=150)

Open Colonic Resection-Specific Evidence - Study information

  • Patients kept normothermic required significantly less bupivacaine to maintain adequate epidural blockade than patients kept hypothermic in one study (p=0.006; n=30)
  • Maintenance of normothermia was associated with higher comfort scores and a similar heart rate and blood pressure than maintenance of hypothermia in one study (n=74)
  • Maintenance of normothermia was associated with lower incidence of wound infections, fewer transfusions and quicker suture removal and hospital discharge compared with maintenance of hypothermia (p=0.01 for all outcomes) (n=200)
  • Patients kept normothermic were similar to patients kept hypothermic for postoperative pain scores in three studies (n=74, n=200, n=30)

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence (LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE1) or who have NSAID-induced asthma (transferable, LoE 1)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B), cardiovascular morbidity (transferable evidence, LoE 1), actual or recent gastroduodenal ulcer history (LoE 4), renal function and hepatic function (transferable evidence, LoE 3). In addition, the potential risk of anastomotic leakage should be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of NSAIDs and COX-2-selective inhibitors o

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • Parecoxib 20 or 40 mg IV every 12 h reduced supplementary analgesic consumption compared with placebo in patients undergoing major gynaecological surgery (p<0.05; n=60)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • A meta-analysis that included data from 17 parecoxib and 15 parecoxib placebo-controlled trials in non-cardiac surgery, showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • Parecoxib 20 or 40 mg IV every 12 h did not significantly reduce postoperative pain scores compared with placebo in patients undergoing major gynaecological surgery (p<0.05; n=60)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence

  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative pain scores Click here for more information
  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative morphine requirement Click here for more information
  • Pre-/postoperative oral valdecoxib was associated with superior patient-assessed global evaluation scores (p=0.001; n=79), compared with placebo, but not with surgeon-assessed global evaluation scores
  • The time until first flatus and first bowel movement was significantly shorter with pre-/postoperative oral valdecoxib, compared with placebo (p=0.003 and p=0.041, respectively)
  • The time taken to tolerate solids was significantly shorter with pre-operative + postoperative oral valdecoxib versus placebo (p=0.029)
  • The length of hospital stay was significantly shorter for patients in the pre-/ postoperative oral valdecoxib group, compared with the placebo group (p=0.009)
  • The incidence of postoperative sedation or nausea was similar with pre-/ postoperative oral valdecoxib, and placebo (n=79)
  • Pre-operative + postoperative oral valdecoxib had no significant effect on the time taken to tolerate intake of liquids compared with placebo
  • The hospital re-admission rate was similar for patients in the pre-/ postoperative oral valdecoxib and placebo groups

PROSPECT Recommendations

  • Conventional NSAIDs are recommended (Grade A), for their analgesic and opioid-sparing effect (procedure-specific evidence, LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE 1)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures - Study information

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information
  • Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information
  • Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information
  • Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease. Aspirin-induced asthma occurs in approximately 4–10% of the adult asthmatic population
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • A restrospective, case-control study showed that postoperative analgesia with the conventional NSAID diclofenac (150 mg daily) was associated with a significantly higher number of anastomotic leakages than postoperative opioid analgesia in patients undergoing laparoscopic colorectal surgery

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative + postoperative IV flurbiprofen was superior to placebo for reducing postoperative pain scores Click here for more information
  • Pre-operative + postoperative IV flurbiprofen axetil was superior to placebo for reducing the time to first pass of flatus and first bowel movement (both p=0.01; n=40)
  • Regular IM ketorolac was superior to regular IV morphine for reducing supplementary PCA morphine use 0–24 h and total morphine consumption 0–72 h (p=0.001; n=30)
  • IM ketorolac (PRN) was superior to IM morphine (PCA or PRN) alone for reducing postoperative pain scores at 3–6 h and 18–110 h (dosing regimens not clear) (all p<0.05; n=90)
  • IM ketorolac (PRN) was superior to IM morphine (PCA or PRN) for reducing the time to first flatus (p<0.05) and length of hospital stay (dosing regimens not clear) (p<0.01; n=90)
  • IM ketorolac was superior to IM ketorolac plus IM or IV morphine on demand for reducing the length of time taken to recover from postoperative ileus (2.3 ± 0.5 days versus 4.2 ± 0.6 days; p<0.05; n=14)
  • IV PCA morphine + ketorolac was superior to IV PCA morphine alone for reducing total morphine consumption (p<0.05; n=74); however there was no significant difference between the groups for the duration of IV PCA morphine use
  • IV PCA morphine + ketorolac significantly reduced the time to first mobilisation, compared with IV PCA morphine alone (p<0.05; n=74)
  • IV PCA morphine + ketorolac significantly reduced the time to first bowel movement, compared with IV PCA morphine alone (P<0.05; n=74)
  • The incidence of postoperative nausea and vomiting was similar in the pre-operative + postoperative flurbiprofen axetil and placebo groups (n=40)
  • IM ketorolac plus PCA morphine conferred no significant benefit over PCA morphine alone for reducing postoperative pain scores, time to first flatus, time to first bowel movement and tolerance to liquids and regular diet (n=30)
  • There were no significant differences between the groups receiving IV PCA morphine or IV PCA morphine + ketorolac for VAS pain scores at rest or movement during postoperative Days 1–3 (n=74)
  • IV PCA morphine + ketorolac conferred no significant benefit over IV PCA morphine alone for reducing the time to first flatus (n=74)
  • The incidence of morphine-related side-effects (pruritus, nausea and vomiting and dizziness) was similar in the groups receiving IV PCA morphine + ketorolac or IV PCA morphine alone (n=74)
  • IV PCA morphine + ketorolac and IV PCA morphine alone were associated with a similar length of hospital stay (n=74)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Postoperative IV lidocaine is recommended (Grade D, LoE 4) for open colonic resection when epidural analgesia is not feasible or contra-indicated (Grade B) based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • If IV lidocaine is used it is recommended that safety data be taken into account
  • IV lidocaine may induce hypotension
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

Open Colonic Resection-Specific Evidence - Study information

  • Peri-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay compared with control (p=0.004; n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 min) (n= 60)

PROSPECT Recommendations

  • Postoperative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • The maximum dose of ketamine that should be given to avoid side effects is 0.5 mg/kg
  • Clinical experience with NMDA receptor antagonists is lacking. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Open Colonic Resection-Specific Evidence - Study information

  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

PROSPECT Recommendations

  • Systemic strong opioids are recommended (Grade B) following colonic resection, based on transferable evidence for their efficacy in reducing high-intensity postoperative pain (VAS =50 mm) (LoE 1), with the following considerations:
  • In patients receiving epidural anaesthesia, epidural strong opioids are recommended 2–3 days postoperatively; after the catheter has been removed, systemic strong opioids can be administered for analgesia (Grade D, LoE 4)
  • Systemic strong opioids should only be used in combination with conventional NSAIDs or COX-2-selective inhibitors and paracetamol to reduce opioid use and its associated side-effects (Grade D, LoE 4)
  • Even though IV PCA strong opioids showed no analgesic benefit over IM PRN opioids in procedure-specific evidence (LoE 1), they are recommended (Grade B) based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (transferable evidence, LoE 1); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (LoE 4)
  • IM strong opioids are not recommended because of the pain associated with these injections (Grade D, LoE 4)

Clinical Practice

  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery
  • The opioid antagonist alvimopan has been demonstrated to reduce the incidence of postoperative ileus and accelerate GI function without compromising opioid analgesia in patients undergoing bowel resection (Ludwig 2008)
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Transferable Evidence from Other Procedures - Study information

  • Three out of five studies showed a significant benefit of IV PCA over IM regular/PRN administration of strong opioids for reducing postoperative pain scores in patients undergoing abdominal hysterectomy Click here for more information
  • Evidence for a benefit of PCA compared with regular/PRN IM administration of strong opioids for reducing overall opioid consumption is inconsistent, although one study suggests that they produced different patterns of dosing in patients undergoing abdominal hysterectomy Click here for more information
  • The incidence of PONV was not significantly different between PCA and IM morphine Click here for more information
  • Opioids administered by PCA improved analgesia, decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or SC opioid treatment, as determined in a quantitative systematic review of randomised trials in various surgical procedures
  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention

Open Colonic Resection-Specific Evidence - Study information

  • IM regular or PRN morphine was superior to IV PCA morphine for reducing daily opioid use (both p<0.05) and the total amount of opioid used in two studies (no statistics provided, n=41; p<0.05, n=62)
  • IM morphine was similar to PCA morphine for the frequency of PONV in one study reporting this parameter (n=41)
  • IM morphine was similar to PCA morphine for the level of postoperative pain and activity (measured by patient questionnaire), frequency of PONV, level of sedation and the duration of ileus and of hospital stay. However, this study did not record pain on a linear scale (n=62)
  • PCA morphine had a similar effect to PRN or regular IM morphine for reducing postoperative pain scores in two studies Click here for more information
  • PCA morphine and IM morphine use were associated with similar length of hospital stay in two studies (n=41, n=62)
  • IM or IV morphine plus IM ketorolac prolonged the length of time taken to recover from postoperative ileus compared with IM ketorolac alone (2.3 ± 0.5 days versus 4.2 ± 0.6 days; p<0.05; n=14)

PROSPECT Recommendations

  • Weak opioids are not recommended for controlling high-intensity pain (Grade D, LoE 4)
  • Weak opioids are recommended to be used for moderate- or low-intensity pain if non-opioid analgesia is insufficient or is contra-indicated (Grade B, transferable evidence, LoE 1)
  • Weak opioids are recommended to be used in combination with non-opioid analgesics (Grade B, transferable evidence, LoE 1)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is probably too low to provide sufficient pain relief

Transferable Evidence from Other Procedures

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone
  • Two studies found that codeine 30mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo

Open Colonic Resection-Specific Evidence - Study information

  • Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)
  • Pre-, intra- or postoperative IV tramadol 100 mg were similar for postoperative pain scores Click here for more information
  • Pre-, intra- or postoperative administration of tramadol 100 mg were similar for the incidence of PONV (n=90)
  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)

PROSPECT Recommendations

  • Paracetamol is recommended for pain of moderate- (>30 VAS <50) or low- (VAS =30) intensity, in combination with COX-2-selective inhibitors or conventional NSAIDs (Grade B), based on its mild analgesic and opioid-sparing effect in transferable evidence (LoE 1), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • However, paracetamol is not recommended for high-intensity pain (VAS =50 mm) (Grade B) because it has no additional analgesic benefit over that conferred by conventional NSAIDs in transferable evidence (LoE 1)

Clinical Practice

  • Paracetamol is a well-established analgesic for low- (VAS=30) or moderate- (VAS>30<50) intensity pain and has a favourable safety profile
  • If paracetamol is used as part of a multi-modal regimen, the anti-pyretic effect can mask complications such as anastomotic leakage

Transferable Evidence from Other Procedures - Study information

  • Paracetamol was superior to placebo for reducing postoperative pain scores, but produced reductions in VAS scores of <13 mm Click here for more information
  • Paracetamol was superior to placebo for reducing supplementary analgesic consumption within 0–24 h in patients undergoing abdominal hysterectomy Click here for more information
  • One study showed that IV paracetamol was equally as effective as IV ketorolac for reducing postoperative pain scores in patients undergoing abdominal hysterectomy (n=176)
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery
  • A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone
  • One study showed a marginal but significant benefit of rectal diclofenac over rectal paracetamol for reducing average pain scores over 24 h, (p=0.008; n=44) in patients undergoing abdominal hysterectomy
  • In a systematic review of a variety of surgical procedures, paracetamol plus NSAID conferred no significant benefit over NSAID alone for reducing pain scores in orthopaedic and gynaecological operations. However, a significant benefit was seen in the lower-intensity pain associated with dental operations
  • Paracetamol 1.5 g plus diclofenac 100 mg was not significantly different from diclofenac 100 mg alone given once pre-operatively, for reducing postoperative pain in abdominal gynaecological surgery

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous epidural anaesthesia and postoperative analgesia is recommended for routine use in colonic resection (Grade A), based on its benefits for reducing postoperative pain, systemic opioid use and improving bowel recovery time (procedure-specific evidence, LoE 1)
  • A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)

Clinical Practice

  • Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in open colon surgery
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures - Study information

  • Epidural analgesia using LA was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery
  • Epidural analgesia using a combination of LA and strong opioid was superior to epidural LA alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery
  • Epidural analgesia using LA was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery
  • Epidural LA was superior to epidural LA plus opioid for reducing the time to first passage of stool Click here for more information
  • Epidural LA was suggested to be the most effective method of reducing ileus and improving postoperative catabolism in patients undergoing abdominal surgery Click here for more information
  • Results for the incidence of postoperative nausea were inconsistent for comparison of epidural LA with epidural LA plus opioid, and no significant difference for the incidence of vomiting was seen Click here for more information
  • Epidural clonidine is associated with an increased risk of hypotension, sedation and bradycardia Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Epidural LA and opioid showed a significant benefit for reducing postoperative pain scores compared Click here for more information
  • Epidural LA plus opioid produced a significant reduction in the use of supplementary analgesia compared with GA plus systemic analgesia in two studies (p<0.05, n=64; p<0.001, n=20)
  • Epidural LA plus opioid was superior to GA plus systemic analgesia for increasing the time to first request of supplementary analgesia in one study (p<0.005; n=20)
  • Epidural LA plus opioid was associated with a similar length of hospital stay compared with GA plus systemic analgesia in two studies (n=42, n=20)
  • Epidural LA plus opioid produced a significantly quicker time for first flatus and time for first bowel movement compared with GA plus systemic analgesia in two studies (all p<0.05; n=64, n=42)
  • Epidural bupivacaine plus morphine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV plus postoperative PCA morphine (p<0.005; n=26)
  • Epidural bupivacaine plus morphine had a similar incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=26)
  • Postoperative thoracic epidural analgesia was superior to postoperative PCA for reduction of VAS pain scores at Day 2 (p=0.01; n=59), but there was no significant difference between the groups at discharge, or on Days 1, 10 and 30
  • Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly fewer patients requiring supplementary analgesia compared with GA plus systemic analgesia for 1–48 h postoperatively (p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly more patients having a bowel movement by Day 4 compared with GA plus systemic analgesia (p<0.05; n=116)
  • Epidural bupivacaine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV bolus plus postoperative PCA morphine (p<0.005; n=26)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, reported that epidural analgesia significantly reduced postoperative VAS pain scores at 24 h (11 studies analysed, n=630) and 48 h postoperatively (6 studies analysed, n=281) (p<0.001 for both comparisons)
  • Continuous epidural infusion of opioids was superior to systemic regimens for reducing postoperative pain scores in two out of three studies Click here for more information
  • Continuous epidural morphine was superior to control for reducing supplementary analgesic consumption in one study (p<0.01; n=30)
  • Daily bolus epidural morphine was superior to IM oxycodone for reducing postoperative pain scores at 3 h (n=30) Click here for more information
  • Daily bolus epidural morphine was superior to IM oxycodone for reducing supplementary analgesic consumption (p<0.01; n=30)
  • The addition of opioid to epidural LA conferred a benefit over epidural LA alone in reducing postoperative pain scores in two studies Click here for more information
  • Continuous epidural bupivacaine was similar to continuous epidural morphine for reducing postoperative pain scores (n=45) Click here for more information
  • Continuous epidural bupivacaine was associated with similar supplementary analgesic consumption compared with epidural morphine (bolus or continuous) (n=45)
  • Continuous epidural bupivacaine was superior to epidural morphine (bolus or continuous) in reducing the time to first bowel movement (p<0.05; n=45)
  • Epidural clonidine was superior to control for reducing the amount of fentanyl administered postoperatively for 12–24 and 24–36 h (all p<0.05; n=25)
  • Pre-/postoperative epidural clonidine was superior to control for the reduction of postoperative pain scores Click here for more information
  • Pre-/postoperative epidural clonidine was superior to the control for reducing postoperative analgesic requirement Click here for more information
  • Pre-/postoperative epidural clonidine significantly reduced the time to return of normal bowel function compared with control (p<0.001; n=40)
  • The incidence of morphine-associated nausea, vomiting, and itching was significantly lower with pre-/postoperative epidural clonidine, compared with control (p<0.001; n=40)
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was superior to intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine for reducing postoperative pain Click here for more information
  • Cumulative number of satisfied analgesic requests was significantly lower with intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine, from 24–72 h after surgery
  • Mean summary area under the curve (AUC) of VRS pain scores at rest for 0–72 h postoperatively was significantly lower with PCEA, compared with continuous epidural analgesia (p<0.001; n=205), and median summary VRS pain scores on movement for 24–72 h postoperatively were significantly lower in the PCEA group compared with the continuous epidural group (p<0.001; n=205)
  • PCEA was superior to continuous epidural infusion for reducing postoperative analgesic consumption Click here for more information
  • A significantly higher proportion of patients in the PCEA group were 'very satisfied' with the treatment compared with the continuous epidural infusion group at 72 h postoperatively and at discharge (both p<0.0001; n=205)
  • Epidural LA plus strong opioid showed no difference in the incidence of nausea and vomiting compared with GA plus systemic analgesia in four studies Click here for more information
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)
  • Postoperative thoracic epidural analgesia conferred no significant benefit over postoperative PCA for reducing the time to first bowel movement (n=34 analysed)
  • There was no significant difference in patient quality of life or satisfaction with hospital stay scores between the groups receiving postoperative thoracic epidural analgesia and postoperative PCA (n=59)
  • There was no significant difference between the postoperative thoracic epidural analgesia group and postoperative PCA group for a return to normal levels of activities at discharge, 10 days and 30 days postoperatively ((n=59)
  • Postoperative thoracic epidural analgesia conferred no significant benefit over postoperative PCA for reducing the length of hospital stay (n=59)
  • Epidural morphine (bolus or continuous) was similar to IM baralgine or IM oxycodone for the time to first bowel movement in two studies (n=21, n=30)
  • Epidural morphine was associated with a similar incidence of nausea and orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=24)
  • Epidural bupivacaine was associated with an increased incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (p<0.05) (n=26)
  • Epidural bupivacaine had a similar incidence of nausea compared with GA and IV plus postoperative PCA morphine (n=26)
  • Continuous epidural morphine was similar to systemic analgesia for the length of postoperative hospital stay in two studies (n=21, n=24)
  • High dose continuous epidural infusion of bupivacaine plus fentanyl provided no significant benefit over a lower dose regimen for improving various postoperative outcomes (n=100) Click here for more information
  • Epidural clonidine provided no significant benefit for postoperative pain scores 0–72 h (n=25)
  • Epidural clonidine provided no significant benefit for sedation scores compared with control at 12–24 h and 24–36 h postoperatively (p<0.05; n=25)
  • Pre-/postoperative epidural clonidine provided no significant benefit for reducing the length of hospital stay compared with control (n=40)
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was associated with a higher incidence of orthostatic hypotension at first mobilisation, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine (p=0.05; n=40)

PROSPECT Recommendations

  • Continuous postoperative wound infusion with LA is not recommended (Grade D, LoE 4) as procedure-specific evidence is limited and inconsistent
  • Pre-closure wound infiltration with local anaesthetic is not recommended for open colonic resection (Grade D, LoE 4), due to lack of procedure-specific evidence and inconclusive transferable evidence from other large abdominal surgeries

Clinical Practice

  • Continuous pre-peritoneal infusion of LA may be considered as an alternative when epidural analgesia is not feasible or contraindicated based on limited procedure-specific evidence for analgesic benefit (LoE 2)
  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infusion are not well established

Transferable Evidence from Other Procedures - Study information

  • A qualitative and quantitative systematic review compared continuous postoperative wound infusion with LA versus control in multiple surgical procedures (cardiothoracic, general, gynaecology-urology, orthopaedics). Meta-analysis of 44 randomised studies showed that continuous wound infusion with LA was superior to control for reduction of postoperative pain scores and postoperative morphine consumption (n=1814)
  • Five of eight studies showed no significant benefit of intra-operative wound infiltration over placebo for reducing postoperative pain scores following abdominal hysterectomy Click here for more information
  • Postoperative PCA wound infiltration with LA following hysterectomy provided limited benefit over placebo for reducing postoperative pain scores, but significantly reduced postoperative analgesic consumption Click here for more information
  • A systematic review of incisional local anaesthesia showed that evidence of analgesic efficacy in hysterectomy (4 studies), open cholecystectomy (8 studies) and a variety of other surgical procedures (9 studies) was inconclusive Click here for more information
  • Three randomised trials in patients undergoing abdominal hysterectomy showed that single-shot postoperative LA wound infiltration conferred no significant benefit over placebo/no treatment for reducing postoperative pain scores

Open Colonic Resection-Specific Evidence - Study information

  • Continuous wound infusion with Lidocaine and bupivacaine was similar to an intermittent IV morphine infusion for postoperative pain scores Click here for more information
  • Continuous wound infusion with Lidocaine and bupivacaine was superior to IV morphine infusion for the total amount of morphine used (p<0.001; n=70)
  • Continous wound infusion with ropivacaine was superior to placebo for reducing postoperative pain scores during movement at a minority of timepoints Click here for more information
  • Continuous pre-peritoneal infusion with ropivacaine was superior to placebo for reducing postoperative pain scores Click here for more information
  • Continuous pre-peritoneal infusion with 0.2% ropivacaine significantly reduced postoperative consumption of PCA morphine compared with placebo during the first 3 postoperative days (p=0.0004) (n=42)
  • Continuous pre-peritoneal infusion with ropivacaine was superior to placebo for reducing the time to hospital discharge (p=0.02) (n=42)
  • Continuous wound infusion with lidocaine and bupivacaine conferred no benefit over intermittent IV morphine infusion for reducing time to first bowel movement, time to first flatus and timing of postoperative mobilisation (n=70)
  • Continuous wound infusion with lidocaine and bupivacaine was associated with a similar incidence of vomiting compared with intermittent IV PCA morphine infusion (n=70)
  • Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for reducing PCA morphine use on postoperative Days 1, 2 and 3 (n=310 analysed)
  • Continuous wound infusion with ropivacaine conferred no significant benefit over placebo for reducing the length of hospital stay (n=310)
  • Continuous wound infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=42)
  • Pre-peritoneal continuous infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=310)
  • Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for the reduction of VAS mobility scores on postoperative Days 1,2, and 3 (n=310)

PROSPECT Recommendations

  • Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) following colonic resection are recommended (Grade A) based on factors other than the management of postoperative pain (e.g. postoperative ileus (procedure specific LoE 1) and length of hospital stay (procedure specifc LoE 1)), as postoperative pain benefits are inconsistent (LoE 4). Controlled studies are necessary to define the influence of the various components
  • The 'anti-inflammatory regimen' (GA combined with spinal, epidural, IV corticosteroid and NSAID) is not recommended over GA + IV opioid analgesia (Grade D, LoE 4) because of limited evidence in colonic resection. Moreover, it introduces an increased level of complexity

Clinical Practice

  • Epidural anaesthesia combined with general anaesthesia is used routinely for colonic resection, except in patients with contra-indications to epidurals, where general anaesthesia alone is used.
  • Nasogastric tubes should be removed as early as possible to avoid gastroparesis.

Transferable Evidence from Other Procedures - Study information

  • Multimodal rehabilitation protocols (the fast-track methodology, enhanced recovery programmes, etc.) have been assessed in large prospective cohort studies, randomised trials and systematic reviews. These concluded that integration of optimised pain relief together with early oral nutrition, anti-ileus treatment, mobilisation, appropriate fluid therapy and revision of perioperative care principles hasten recovery, thereby decreasing duration of postoperative hospitalisation as well as reducing m
  • Studies integrating continuous epidural LA with enforced early nutrition and mobilisation uniformly suggest an improved recovery, and decreased hospital stay and convalescence Click here for more information
  • A meta-analysis showed that omitting nasogastric tubes conferred a significant benefit over their use for reducing the time to first oral intake, pulmonary complications, fever, atelectasis and pneumonia
  • A meta-analysis showed that patients managed without nasogastric tubes had significantly greater abdominal distension and vomiting

Open Colonic Resection-Specific Evidence - Study information

  • Care by CREAD numerically, but not statistically, lowered morphine consumption compared with patients undergoing TRAD care (137 ± 109 versus 187 ± 125 mg; p=0.08; n=64)
  • Care by CREAD was superior to TRAD care for reducing the time to discharge and length of hospital stay (5.4 versus 7.1 days, p=0.02; n=64)
  • Care by CREAD numerically but not statistically reduced the number of patients with postoperative ileus or small-bowel obstruction compared with patients undergoing TRAD care (3 versus 4 patients; n=64)
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for reducing postoperative pain scores Click here for more information
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for reducing postoperative fatigue scores on Day 7 (p=0.008; n=25)
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for tolerating a regular hospital diet earlier (48 versus 76 h; p<0.001), and reduced the median length of hospital stay (3 versus 7 days; p<0.002; n=25)
  • Gastrostomy tubes were superior to nasogastric tubes for reducing patient discomfort levels (p<0.01; n=107)
  • Patients receiving gastrostomy tubes reported significantly less tube-related inconvenience than patients receiving nasogastric tubes on postoperative Day 2, at discharge and at 4 weeks postoperatively (all p<0.02; n=107)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing mean postoperative pain scores from Days 2–5 (p<0.001; n=50)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing supplementary analgesic consumption Days 1–3 (p<0.05; n=50)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing the time to first flatus (p<0.01; n=50)
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) reduced VAS pain scores at rest and during coughing for 0–8 days postoperatively compared with GA and IV opioid analgesia (p<0.001; n=20)
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) significantly reduced fatigue compared with GA and IV opioid analgesia (p<0.05; n=20) Schulze et al 1992
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) significantly enhanced ambulatory function (i.e. washing and mobility) compared with GA and IV opioid analgesia (p<0.05; n=20) Schulze et al 1992
  • Care by CREAD did not confer a benefit over TRAD care for reducing postoperative pain scores on Days 2, 10 or 30 (n=64)
  • Care by CREAD showed that pain scores evaluated by the McGill pain questionnaire were higher at discharge but were equal on postoperative Day 10 compared with care by TRAD (p<0.02; n=64)
  • Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups both demonstrated similar Hamilton anxiety scores at the end of the study (n=50)
  • Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups had a similar time to discharge from hospital (n=50)
  • Gastrostomy and nasogastric tubes were associated with similar postoperative pain scores (n=107)
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing VAS pain scores at rest or during movement during the hospital stay (n=80)
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the consumption of postoperative supplementary analgesics (n=80) Click here for more information
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the incidence of postoperative nausea and vomiting (n=80)
  • Time to passage of first flatus was similar for patients allocated to the restricted postoperative IV fluid and standard postoperative IV fluid regimens (n=80)
  • Postoperative restriction of IV fluids conferred no significant benefit over the standard postoperative fluid regimen for reducing the time to medical discharge or hospital discharge (n=80)
  • Peri-operative IV glucose + amino acids conferred no signficant benefit over peri-operative IV glucose alone, for the reduction of VAS pain scores at rest or during movement at 12, 24, 36 or 48 h postoperatively (n=16)

PROSPECT Recommendations

  • Conventional NSAIDs are recommended (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence (LoE1) showing analgesic benefit

Clinical Practice

  • Conventional NSAIDs are used in preference to strong opioids in laparoscopic procedures

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information
  • Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information
  • Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information
  • Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • A case-control study in patients undergoing laparoscopic colonic resection with primary anastomosis found that patients given postoperative oral diclofenac (150 mg daily) were at higher risk of anastomotic leakage, compared with patients receiving postoperative opioid analgesics

Laparoscopic Colonic Resection-Specific Evidence

  • Postoperative IV ketorolac was superior to placebo for reduction of VAS pain scores during walking on Days 1 (p<0.001), 2 (p<0.05) and 3 (p<0.001), but not on Day 4
  • Postoperative IV ketorolac significantly reduced postoperative PCA morphine requirement, compared with placebo (p=0.011; n=44)
  • Postoperative IV ketorolac was superior to placebo for reducing the time to first flatus (p=0.005; n=44)
  • Postoperative IV ketorolac significantly reduced the time to return to full diet, compared with placebo (p=0.033; n=44)
  • VAS pain scores on coughing were significantly greater with IV ketorolac, compared with placebo at Day 4 (p<0.001), but there was no significant difference between the groups on Days 1, 2, and 3 (n=44)
  • There was no significant difference between the IV ketorolac and placebo groups for VAS pain scores at rest on Days 1–4
  • There was no significant difference in the length of hospital stay between the postoperative IV ketorolac and placebo groups (n=44)
  • There was no significant difference in the incidence of anastomotic leaks in the IV ketorolac and placebo groups (n=44)

PROSPECT Recommendations

  • Continuous intra-/postoperative IV lidocaine is not recommended currently (Grade D, LoE 4) because of limited procedure-specific data, despite some positive transferable evidence

Clinical Practice

  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used, it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery, reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV and length of hospital stay, compared with the controls

Laparoscopic Colonic Resection-Specific Evidence

  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing postoperative pain scores during mobilization and on coughing Click here for more information
  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing postoperative opioid consumption Click here for more information
  • Continuous intra-/postoperative IV lidocaine significantly reduced the dose of IV sufentanil administered during surgery, compared with placebo (p< 0.001; n=40)
  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing the time to first flatus and first bowel movement (both p=0.001; n=40)
  • Continuous intra-/postoperative IV lidocaine significantly reduced the length of hospital stay compared with placebo (p=0.001; n=40)
  • Incidence of postoperative nausea or vomiting was similar in both the continuous intra-/postoperative lidocaine and placebo groups (n=40)

PROSPECT Recommendations

  • Epidural LA + strong opioid reduces postoperative pain (procedure-specific evidence, LoE 1), but is not recommended (Grade D), due to poor risk:benefit ratio (LoE 4)
  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D; LoE 4)

Clinical Practice

  • The risk of side-effects associated with epidural analgesia may outweigh the benefits of analgesia in laparoscopic colonic resection

Transferable Evidence from Other Procedures

  • None cited

Laparoscopic Colonic Resection-Specific Evidence

  • Two of two studies showed that epidural LA plus opioid was superior to IV PCA morphine for reducing postoperative pain scores Click here for more information
  • One study showed that thoracic epidural LA + opioid was associated with significantly lower VAS fatigue scores on postoperative Day 3 (p=0.025), compared with IV PCA morphine, although there was no significant difference between the groups on Days 1, 2 and 4
  • One study found that thoracic epidural LA + opioid was superior to IV PCA opioid for reducing postoperative vomiting on Days 1 and 2 (p=0.033 and p=0.005; n=50), but not on Days 3 or 4
  • One study showed that time to first flatus and first bowel movement was significantly shorter with thoracic epidural LA + opioid, compared with IV PCA morphine (p=0.0061 and p=0.0027, respectively; n=50)
  • One study reported that time taken to return to fluid diet and full diet was significantly shorter for patients in the thoracic epidural LA + opioid group, compared with the IV PCA group (p=0.0442 and p=0.0436, respectively; n=50)
  • Thoracic epidural ropivacaine + IV PCA morphine was superior to IV PCA opioid alone, for reducing the amount of supplementary IV PCA morphine administered between surgery to Day 2 (p=0.04). However, there was no significant difference between the groups from Day 2–4, or from surgery to Day 4 overall (n=20)
  • VAS pain scores during Days 1–8 were significantly lower in the group receiving GA + thoracic epidural analgesia, compared with the group receiving GA alone (p=0.004; n=75 overall)
  • GA + thoracic epidural analgesia was superior to GA alone for reducing postoperative analgesic consumption Click here for more information
  • GA + thoracic epidural analgesia was associated with a significantly shorter time to recovery of GI function (GI-3) and time to first bowel movement (p=0.025 and p=0.038, respectively; n=75), compared with GA alone, but there was no significant difference for time to first flatus or time to solid food tolerance
  • One study reported that thoracic epidural LA + opioid conferred no significant benefit over IV PCA morphine for reducing postoperative analgesic requirements (n=50)
  • One study reported that the incidence of postoperative nausea was similar in patients receiving thoracic epidural LA + opioid and IV PCA opioid (n=50)
  • One study reported that the incidence of nausea requiring antiemetics, urinary retention, hypotension, and respiratory depression was similar in the groups receiving thoracic epidural LA + opioid and IV PCA morphine (n=38)
  • Two studies of two reported no significant difference in the length of hospital stay between the groups receiving thoracic epidural LA + opioid or PCA IV morphine (n=38)
  • Thoracic epidural ropivacaine + IV PCA morphine did not confer any significant benefit for reducing VAS pain scores at rest, or during coughing, from surgery to Day 4, or the time to first bowel movement, compared with IV PCA morphine alone (n=20)
  • The incidence of postoperative nausea and vomiting, frequency of naso-gastric tube reinsertion and length of hospital stay was similar between the groups receiving GA + thoracic epidural analgesia or GA alone (n=75 overall)
  • Continuous epidural LA + IV PCA opioid versus control (IV PCA opioid alone) Click here for more information
  • GA plus thoracic epidural analgesia (TEA) versus GA alone Click here for more information

PROSPECT Recommendations

  • The combination of spinal analgesia and general anaesthesia is not recommended (Grade D) as the risk:benefit balance is not positive (LoE 4), and because of limited procedure-specific evidence

Clinical Practice

  • Spinal analgesia (LA + opioid) has a limited duration of action
  • Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus, and limited duration of analgesic ef