Literature Reviews

Procedure-specific systematic review summary

Bibliography

Laparoscopic Cholecystectomy Update

Sung et al 2000

Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy.

Sung CS, Lin SH, Chan KH, Chang WK, Chow LH, Lee TY.

Acta Anaesthesiol Sin 2000;38:23-29.

BACKGROUND: To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS: One hundred and ten patients, scheduled for elective laparoscopic cholecystectomy, were recruited for the prospective, randomized, single-blind, comparative study. They were randomly allotted to either of the placebo or clonidine group. Patients of the placebo group (n = 65) were premedicated with oral antacid (alugel hydroxide 300 mg), while those in the clonidine group (n = 45) were premedicated with oral clonidine 150 µg prior to anesthesia. The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia. Normocapnia was maintained throughout the perioperative period. Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane, the anesthetic used for maintenance of anesthesia. Postoperative pain intensity, sedation scores, adverse events, time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded. Data were expressed as mean +/- SD. RESULTS: Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced (30% less). The postoperative analgesic requirement was less (1.5 +/- 1.3 vs. 2.2 +/- 1.3 dose, P < 0.05) and the time for the first dose of analgesic was prolonged (411 +/- 565 vs. 264 +/- 441 min) in comparison with the placebo group but no statistic difference was found. CONCLUSIONS: Oral clonidine premedication helped to provide perioperative hemodynamic stability, spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC.


De Kock et al 1994

Intraoperative and postoperative analgesia using intravenous opioid, clonidine and lignocaine.

De Kock M, Lavandhomme P, Scholtes JL.

Anaesth Intensive Care 1994;22(1):15–21.

The postoperative analgesia afforded after colonic surgery by IV opioid, clonidine and lignocaine given intra- and postoperatively was evaluated. In a double-blind randomised trial, 80 male patients scheduled for colonic resection under general anaesthesia received fentanyl 5 micrograms.kg-1 at induction and another 4 micrograms.kg-1 before skin incision (group A) or fentanyl (same dose) plus clonidine 4 micrograms.kg-1 in 20 min + 2 micrograms.kg-1.h-1 (group B, C) or fentanyl plus clonidine (same dosage) plus lignocaine 2 mg.kg-1 before skin incision, repeated before peritoneal incision and retractor placement (group D). In the four groups, intraoperative boluses of fentanyl 2 micrograms.kg-1 were given in response to the painful stimulation of the procedure. Postoperative pain was managed with PCA delivering 2 mg morphine per request in group A, 1.5 mg morphine in group B, 1.5 mg morphine + 15 micrograms clonidine in group C and 1.2 mg morphine + 15 micrograms clonidine + 23 mg lignocaine in group D. Postoperative analgesia was assessed by recording the analgesic demands (met and unmet) and the dose of morphine delivered at 6, 12, 18, 24, 36 hours. Side-effects, pain and sedation analogue scores were also recorded. Analgesic demands and delivered morphine dose were reduced, at any time interval considered, in groups B, C, D, compared with A (P < 0.001). No differences were noted between the group B, C, D. Pain analogue scores were better in groups B, C, D compared with group A (P < 0.001). Sedation and side-effects were not increased in groups B, C, D.(ABSTRACT TRUNCATED AT 250 WORDS)


Dimou et al 2003

Transdermal clonidine: does it affect pain after abdominal hysterectomy?

Dimou P, Paraskeva A, Papilas K, Fassoulaki A.

Acta Anaesthesiol Belg 2003;54(3):227–232.

Clonidine has analgesic properties. We evaluated the analgesic effect of clonidine perioperatively. Forty patients undergoing abdominal hysterectomy received randomly the evening before surgery transdermal clonidine covered with overlay (CLO group) or the overlay alone (CTL group). Ten min before induction they received i.v. clonidine 1 microgram.kg-1 (CLO) or normal saline (CTL). Induction was accomplished with fentanyl 5 micrograms.kg-1, thiopentone 5 mg.kg-1, cis-atracurium 0.15 mg.kg-1 and maintenance with sevoflurane 2% in 70% N2O. Hemodynamic parameters were recorded intraoperatively. Pain was assessed by VAS at rest and movement 2, 4, 6, 8, 24, 48, 72 h and 30 days, postoperatively. During the first 8 h postoperatively all patients received controlled analgesia with fentanyl followed by morphine i.m. 0.15 mg.kg-1 and paracetamol. From 24-72 h postoperatively, patients received 75 mg propoxyphene and 600 mg paracetamol i.m., on demand. Arterial blood pressure was lower in the CLO group 0, 3, 10 min after intubation. There was no difference in pain or fentanyl consumption 8 h postoperatively. The CLO group required less analgesics 24 h postoperatively (p = 0.023). The two groups did not differ in pain or analgesic requirements 72 h and 30 days postoperatively. Clonidine had a weak opioid sparing effect 24 h post-operatively, but did not affect pain in long term.


Pandey et al 2004

Preemptive gabapentin decreases postoperative pain after lumbar discoidectomy.

Pandey CK, Sahay S, Gupta D, Ambesh SP, Singh RB, Raza M, Singh U, Singh PK.

Can J Anaesth 2004;51(10):986–9.

PURPOSE: We investigated whether the preemptive use of gabapentin, a structural analogue of gamma amino butyric acid could reduce postoperative pain and fentanyl consumption in patients after single-level lumbar discoidectomy. METHODS: Fifty-six ASA I and II patients were randomly allocated into two equal groups to receive either gabapentin 300 mg or placebo two hours before surgery. After surgery, the pain was assessed on a visual analogue scale (VAS) at intervals of 0-6, 6-12, 12-18, and 18-24 hr at rest. Total fentanyl consumption in the first 24 hr after surgery was also recorded. Fentanyl 2 mug.kg(-1) intravenously was used to treat postoperative pain on patients' demand. RESULTS: Patients in the gabapentin group had significantly lower VAS scores at all time intervals of 0-6, 6-12, 12-18, and 18-24 hr than those in the placebo group (3.5 +/- 2.3, 3.2 +/- 2.1, 1.8 +/- 1.7, 1.2 +/- 1.3 vs 6.1 +/- 1.7, 4.4 +/- 1.2, 3.3 +/- 1.1, 2.1 +/- 1.2; P < 0.05). The total fentanyl consumed after surgery in the first 24 hr in the gabapentin group (233.5 +/- 141.9, mean + SD) was significantly less than in the placebo group (359.6 +/- 104.1; P < 0.05). CONCLUSION: Preemptive gabapentin 300 mg po significantly decreases the severity of pain postoperatively in patients who undergo single-level lumbar discoidectomy.


Dahl et al 2004

'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain.

Dahl JB, Mathiesen O, Moiniche S.

Acta Anaesthesiol Scand 2004;48:1130–1136.

Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a 'physiological' to a 'pathological' mode of processing afferent information. Gabapentin, which binds to the alpha(2)delta subunit of the voltage-dependent calcium channel, is active in animal models of 'pathological' but not in models of 'physiological' pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post-operative pain. This article presents a brief summary of the potential mechanisms of post-operative pain, and a systematic review of the available data of gabapentin and pregabalin for post-operative analgesia. It is concluded that the results with gabapentin and pregabalin in post-operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of 'protective premedication' with combinations of various antihyperanalgesic and analgesic drugs for post-operative analgesia.


Ho et al 2006

Gabapentin and postoperative pain--a systematic review of randomized controlled trials

Ho KY, Gan TJ, Habib AS

Pain. 2006 Dec 15;126(1-3):91-101. Epub 2006 Jul 18

The objective of this systematic review was to evaluate the efficacy and tolerability of perioperative gabapentin administration for the control of acute postoperative pain. We searched Medline (1966-2006), the Cochrane Library (2006), Scopus, CINAHL and bibliographies from clinical trials and review articles. We included randomized controlled trials (RCTs) comparing gabapentin with inactive controls in surgical patients. Sixteen valid RCTs were included. Weighted mean difference (WMD) for postoperative pain intensity (0-100 mm visual analogue scale) was -16.55 mm at 6 h and -10.87 mm at 24 h for treatment with a single preoperative dose of gabapentin 1200 mg. Cumulative opioid consumption at 24 h was also significantly decreased with gabapentin (WMD, -27.90 mg). When gabapentin was administered at doses less than 1200 mg, pain intensity was also lower at 6 h (WMD, -22.43 mm) and 24 h (WMD, -13.18 mm). Cumulative 24 h opioid consumption was also lower (WMD, -7.25 mg). Gabapentin was associated with an increased risk of sedation (Peto OR 3.86; 95% CI 2.50-5.94) but less opioid-related side effects such as vomiting (Peto OR 0.58; 95% CI 0.39-0.86) and pruritus (Peto OR 0.27; 95% CI 0.10-0.74). In conclusion, gabapentin has an analgesic and opioid-sparing effect in acute postoperative pain management when used in conjunction with opioids.


Boccara et al 2005

The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen.

Boccara G, Chaumeron A, Pouzeratte Y, Mann C

Br J Anaesth 2005;94(3):347–51

BACKGROUND: Non-opioid analgesics, paracetamol and non-steroid anti-inflammatory drugs (NSAIDs) are proposed for pain relief after laparoscopy. We compared perioperative propacetamol (P) and ketoprofen (K) to provide analgesia after laparoscopic cholecystectomy. METHODS: After ethical committee approval, we included 104 ASA I-II patients, without preoperative analgesic drugs, who were scheduled to undergo laparoscopic cholecystectomy. Anaesthesia was standardized using propofol, fentanyl, atracurium, isoflurane and N(2)O 50%. Ketoprofen 100 mg or propacetamol 2 g or a saline drip (a 100-ml unit of saline in 10 min) was infused blindly and randomly. Patients received either ketoprofen (group K1) or propacetamol (group P1) before induction of anaesthesia and saline after surgery, or saline before surgery and ketoprofen (group K2) or propacetamol (group P2) after surgery. Postoperative visual analogue pain scores (VAS 0-100 mm) were recorded during 24 h. If VAS was >30, a second dose (placebo, ketoprofen or propacetamol) was infused. Nalbuphine 0.2 mg kg(-1) i.v. was given as rescue analgesic if VAS was > or =50. RESULTS: Ninety-eight patients were studied The number of patients not requiring the second analgesic was greater in K1 (33.5%) than the others (K2 0%, P1 0%, P2 7.5%). VAS scores were significantly lower in K1 (P=0.001), with less nalbuphine consumption compared with P1. VAS and opioid request were similar in K2 and P2. CONCLUSION: Preoperative administration of ketoprofen improves postoperative analgesia after laparoscopic cholecystectomy compared with its postoperative administration and pre- and postoperative propacetamol.


Elhakim et al 1995

Effects of odansetron and balanced analgesia on postoperative nausea and vomiting in laparoscopic surgery.

Elhakim M, Ghalaab M, Soliman M

Acta Anaesthesiologica Italica 1995;46(SUPPL. 1):23–28

We have compared the anti-emetic effects of ondansetron with that of ondansetron with tenoxicam, and saline in the prevention of postoperative nausea and vomiting, in 75 patients undergoing laparoscopic cholecystectomy. Before anaesthesia, patients were randomly allocated to receive iv: saline (group 1), ondansetron 4 mg (group 2), or ondansetron 4 mg with tenoxicam 20 mg as a component of balanced analgesia. All patients received standard general anaesthesia with nalbuphine 0.25 mg kg-1. Laparoscopy entery sites were infiltrated by bupivacaine 0.5% in a volume of 0.25 ml kg-1. Verbal scores and visual analogue scores for nausea, vomiting and pain were assessed for 24 h. Patients receiving ondansetron with tenoxicam experienced significantly less nausea and vomiting compared with ondansetron group (P < 0.05). The incidence and severity of nausea were 24% grade 1-3 for saline and ondansetron groups compared to 4% grade 1 for ondansetron tenoxicam group (P < 0.05). Vomiting occurred in 40% of saline treated patients compared with 12% of ondansetron-treated patients (P < 0.05) and 8% of ondansetron tenoxicam treated patients (P < 0.01). The use of balanced analgesia during operation produced effective early postoperative pain relief, opioid sparing effect and early passage of bowel gas. Our results suggest that ondansetron with balanced analgesia may be better than ondansetron with conventional opioid regimen in reducing postoperative nausea and vomiting.


Munro et al 1998

Intravenous tenoxicam for analgesia following laparoscopic cholecystectomy.

Munro FJ, Young SJ, Broome IJ, Robb HM, Wardall GJ.

Anaesth Intens Care 1998;26:56–60.

In a double-blind, placebo-controlled clinical trial (power of 80% to detect a 30% reduction in morphine consumption, p < 0.05) we have determined that intraoperative intravenous administration of tenoxicam 40 mg during laparoscopic cholecystectomy, when compared with placebo, was associated with a significant reduction in consumption of morphine at 6 hours and 12 hours (p < 0.05) but not at 24 hours, when assessed by patient-controlled analgesia. Furthermore there was a significantly greater requirement for "rescue" analgesia with intramuscular morphine in the placebo group during the period of the study. There was no difference between the groups in pain scores, either at rest or on movement, nor in the incidence of nausea and vomiting. No patient in either group suffered a respiratory rate less than 8/min or oversedation at any time, and there were no other adverse effects.


Forse et al 1996

Indomethacin and ketorolac given preoperatively are equally effective in reducing early postoperative pain after laparoscopic cholecystectomy.

Forse A, El Beheiry H, Butler PO, Pace RF.

JCC 1996;39(1):26–30.

OBJECTIVE: To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain after laparoscopic cholecystectomy. DESIGN: A prospective, randomized, placebo-controlled, double-blind study. SETTING: A university hospital. PATIENTS: Fifty-two patients with cholelithiasis but without known allergy to one of the study drugs, history of bleeding, peptic ulcer disease, known cardiac, lung or renal disease, abnormal liver function or use of opiates or NSAIDs within 2 weeks before operation. Patients were assigned to one of three groups and treatment was randomized by placing the drugs in sealed, numbered envelopes. INTERVENTION: Administration of the NSAIDs ketorolac, intramuscularly, or indomethacin, rectally, before laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Postoperative pain scored on a a visual analogue scale and by nurse assessment, total dose of fentanyl citrate given, and nausea or emesis. RESULTS: Patients in the placebo group reported significantly more pain than either NSAID group (p < 0.05) and were reported as having significantly more pain by the nurses (p < 0.05). These patients were subsequently treated with a higher mean postoperative dose of fentanyl citrate than either NSAID group (p < 0.05). Furthermore, the placebo group reported more nausea and emesis (p < 0.05). There was no significant difference in any of the parameters measured between the ketorolac or indomethacin group. CONCLUSIONS: The data demonstrate that the NSAIDs ketorolac and indomethacin, administered preoperatively, decrease early postoperative pain and nausea after laparoscopic cholecystectomy and are equally efficacious in producing these results.


Lane et al 1996

Effect of intramuscular intraoperative pain medication on narcotic usage after laparoscopic cholecystectomy.

Lane GE, Lathrop JC, Boysen DA, Lane RC.

Am Surg 1996;62:907–910.

The purpose of this randomized, double-blind, clinical trial was to determine whether intraoperative, intramuscular (i.m.) injections of meperidine or ketorolac would improve postoperative pain relief in patients undergoing elective laparoscopic cholecystectomy. A total of 125 patients were entered into five study groups: 1) (n = 23) control placebo; 2) (n= 31) meperidine 100 mg i.m. intraoperative preprocedure; 3) (n= 20) meperidine 100 mg i.m. intraraoperative postprocedure; 4) (n= 25) ketorolac tromethamine 60 mg i.m.intraoperative preprocedure; 5) (n= 26) ketorolac tromethamine 60 mg i.m. postprocedure. All groups were analyzed by comparing the amount of pain medication received in the recovery room, the time until first oral pain medication was requested, the overall amount of pain medication used in the first 24 hours, the percent requiring IM medication, and the pain score ratings from each group. There was decreased pain medication usage in the recovery room in all groups compared to control (p < 0.05). Group 4 had a longer painfree interval than meperidine groups or control. Both Groups 4 and 5 had decreased postoperative narcotic usage. Finally, the analogue pain scores showed that both ketorolac groups had significantly less postoperative pain compared to control, whereas the meperidine groups showed no improvement in postoperative pain relief. Intraoperative ketorolac given preprocedure or postprocedure significantly improved postoperative pain management and facilitated the transition to oral pain medication.


Liu et al 1993

Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy.

Liu J, Ding Y, White PF, Feinstein R, Shear JM.

Anesth Analg 1993;76:1061–1066.

Ketorolac, a nonsteroidal anti-inflammatory drug, is alleged to produce postoperative analgesia without opioid-related side effects. Patients undergoing laparoscopic cholecystectomy were assigned randomly to receive either ketorolac or a placebo (saline) according to a double-blind protocol. Preoperative (baseline) pulmonary function was evaluated using a Respiradyne II monitor. Patients received midazolam, 2 mg, and 2 ml of either ketorolac, 60 mg (n = 31), or saline (n = 29), 20–40 min before surgery. Anesthesia consisted of thiopental, 4–5 mg/kg, and vecuronium, 0.1 mg/kg, for induction, and isoflurane, 0.5%–2.0%, with 67% nitrous oxide in oxygen for maintenance. A second 2-mL dose of the same study medication (ketorolac, 60 mg, or saline) was administered 4 h after the initial dose. Postoperatively, 66% of patients in the saline group complained of pain requiring treatment with fentanyl compared to 32% in the ketorolac group (p < 0.05). There were no significant differences between the two groups with respect to postoperative sedation, anxiety, pain, or nausea visual analog scores. Compared to the preoperative values, significant decreases in pulmonary function tests were noted in both groups at 4 h after the operation and the following morning (p < 0.01). In the ketorolac group, only values of forced expiratory volume at 1 s and forced expiratory flow at 25%–75% of the forced vital capacity at 4 h after the operation were significantly higher than those in the saline group (p < 0.05). Incidences of nausea (45% vs 52%) and vomiting (10% vs 10%) were similar in both groups. In conclusion, ketorolac decreased the postoperative requirement for opioid analgesic medication.(ABSTRACT TRUNCATED AT 250 WORDS)


Yeh et al 2004

Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy

Yeh CC, Wu CT, Lee MS, Yu JC, Yang CP, Lu CH, Wong CS

Acta Anaesthesiol Scand. 2004 Sep;48(8):1049-53

BACKGROUND: Pre-incisional treatment with either N-methyl-D-aspartate (NMDA) receptor antagonists or non-steroidal anti-inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA-receptor antagonist, and tenoxicam, a NSAID, given preoperatively. METHODS: Eighty-eight ASA I or II patients scheduled for LC were entered into a randomized, double-blind study and randomly allocated to one of four groups. Controls received 20 mg (4 ml) of chlorpheniramine maleate (CPM) IM and 4 ml of normal saline (N/S) IV. Group DM received 40 mg of DM (containing 20 mg of CPM) IM and 4 ml of N/S IV. Group T were given CPM 20 mg IM, and tenoxicam 40 mg (4 ml) IV. Group DM + T were given DM 40 mg (containing 20 mg of CPM) IM, and tenoxicam 40 mg IV. All treatments were given 30 min before skin incision. Analgesic effects were evaluated by Visual Analog Scale (VAS) pain scores at rest and during coughing, at 1, 2, 4, 12, 24 and 48 h after surgery. The time to the first request for meperidine for pain relief, and total meperidine consumption, were recorded for 48 h after surgery. RESULTS: Compared to controls, patients given DM and DM + T first requested meperidine significantly later, had lower meperidine consumption, made fewer requests for meperidine, and had lower pain scores. There were significant differences between the DM + T and T groups at 2 and 4 h in both resting and incident VAS pain scores, the incidence of meperidine requests and the time to first meperidine injection. There were significant differences between groups DM and T at 1 h for resting pain and at 2 and 4 h for incident pain. Except for a significant difference in the incident pain score 1 h after surgery, there were no other differences in pain scores between the DM and DM + T groups. Neither synergistic nor antagonistic interaction was observed between DM and tenoxicam. CONCLUSIONS: The results suggest that pretreatment with DM, but not tenoxicam, provides significant pre-emptive analgesia for postoperative pain management in patients after LC surgery. Combining DM and tenoxicam also gives good pain relief.


Michaloliakou et al 1996

Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy.

Michaloliakou C, Chung F, Sharma S

Anesth Analg 1996;82(1):44–51

Laparoscopy approach to cholecystectomy has shortened the recovery period, reducing discharge times from 1 to 3 days to same-day discharge. We hypothesize that the use of more than one modality to prevent postoperative pain may be more efficacious than single modality. Patients were randomized to a treatment (n = 24) or control (n = 25) group and studied using a prospective, double-blind design. Preoperatively, at 45 min before induction of anesthesia, the treatment group received an intramuscular (IM) bolus injection of meperidine 0.6 mg/kg and ketorolac 0.5 mg/kg. The control group received two bolus IM injections of placebo (normal saline). Ten minutes before incision, local anesthesia (treatment group) or saline (control group) was infiltrated into the skin of each patient. Anesthetic management, postoperative pain, and nausea treatment were standardized. Pain and nausea assessment were done 1 h preoperatively, 0, 0.5, 1, 2, 3, and 4 h postoperatively, at discharge, and 10, 24, and 48 h postoperatively. Patients were discharged by scoring criteria. Postoperatively, significantly more patients in the treatment group were without pain on arrival in the postanesthesia care unit (PACU), 12/21 (57.1%) vs 1/24 (4.2%) in the control group (P < 0.001). Similarly, the severity of pain was sixfold less in the treatment group than in the control group. The incidence of nausea in the PACU was significantly less in the treatment group; 4.7% vs 29.5% in the control group (P < 0.05). Patients from the treatment group satisfied Postanesthesia Discharge Score significantly earlier than those in the control group (281 +/- 12 min vs 375 +/- 19 min; P < 005). The concomitant use of local anesthetic and nonsteroidal antiinflammatory and opioid drugs proved to be highly effective in our patients, resulting in faster recovery and discharge.


Yeh et al 2005

Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improves postoperative pain and bowel function in patients undergoing colonic surgery

Yeh CC, Jao SW, Huh BK, Wong CS, Yang CP, White WD, Wu CT

Anesth Analg 2005;100(5):1384–9

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.


Wilson et al 1994

Intramuscular diclofenac sodium for postoperative analgesia after laparoscopic cholecystectomy: a randomised, controlled trial.

Wilson YG, Rhodes M, Ahmed R, Daugherty M, Cawthorn SJ, Armstrong CP.

Surg Laparosc Endosc 1994;4(5):340–4.

Laparoscopic cholecystectomy is the surgical treatment of choice for symptomatic gallstones. Nonsteroidal antiinflammatory drugs offer effective analgesia, avoiding the central side effects of opiate drugs. To assess intramuscular diclofenac sodium (Voltarol; Ciba-Geigy) after laparoscopic cholecystectomy, 55 consecutive patients (41 female; 14 male; mean age: 50 years) were randomised to receive either diclofenac or placebo in double-blind fashion. Six patients were withdrawn from study (three conversions to open cholecystectomy; three incomplete documentation). Pain scores were assessed at 4, 24, and 48 h using a linear analogue scale; opiate consumption and time to first oral fluid and food were recorded. In 26 patients receiving diclofenac, median scores at 4 h were 1.6 (range 0-7.6) as compared with 4.1 (range 0-7.6) in 23 control patients (p = 0.05, 95% confidence limits 3.2, 0; Mann-Whitney U test). Nausea scores, return to diet, and time to discharge did not differ significantly between the groups. Intramuscular diclofenac significantly reduces early postoperative pain after laparoscopic cholecystectomy and is worthy of consideration if the procedure were ever undertaken as day case surgery.


Barden et al 2004

Single dose oral diclofenac for postoperative pain.

Barden J, Edwards J, Moore RA, McQuay HJ.

Cochrane Database Syst Rev 2004(2):CD004768.

BACKGROUND: Diclofenac is a benzene-acetic acid derivative that acts, like other NSAIDs, by inhibiting cyclo-oxygenase isoforms that mediate the body's production of the prostaglandins implicated in pain and inflammation. Diclofenac is widely available as a sodium or potassium salt. Diclofenac potassium tablets are known as 'immediate-release' diclofenac as absorption takes place in the gastrointestinal tract whereas 'delayed-release' (enteric-coated) diclofenac tablets resist dissolution until reaching the duodenum. An existing review showed that diclofenac was an effective treatment for acute postoperative pain but did not address the distinction between potassium and sodium salts due to lack of data. The aim of this update is to gather and add appropriate information published subsequently and, data permitting, examine any potential differences between the two different diclofenac formulations. OBJECTIVES: To assess single dose oral diclofenac for the treatment of acute postoperative pain and determine whether there are differences between the different formulations. SEARCH STRATEGY: We searched the Cochrane Library (Issue 2, 2003), MEDLINE (1966 to May 1996), EMBASE (1980 to 1996), Biological Abstracts (1985 to 2003), the Oxford Pain Relief Database (1950 to 1994), PubMed (1996 to 2003) and reference lists of articles. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac sodium or diclofenac potassium for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion in the review, quality and extracted data. The area under the pain relief versus time curve was used to derive the proportion of patients prescribed diclofenac or placebo with at least 50% pain relief over four to six hours using validated equations. The number needed to treat (NNT) was calculated. Information on adverse effects was also collected. MAIN RESULTS: One additional trial was included and added to the six trials included in the original review. All seven trials provided data for quantitative analysis: 581 patients were treated with diclofenac and 364 were treated with placebo. The NNT for at least 50% relief over four to six hours with diclofenac 25 mg, 50 mg and 100 mg compared with placebo was 2.8 (95% CI 2.1 to 4.3), 2.3 (2.0 to 2.7) and 1.9 (1.6 to 2.2) respectively. Though higher doses produced lower (better) NNTs, statistical significance was not achieved. There was no significant difference between diclofenac 50 mg and placebo in the proportion of patients experiencing dizziness, headache, nausea or vomiting. The weighted median duration of analgesia was 2 hours for placebo, 6.7 hours for diclofenac 50 mg and 7.2 hours for diclofenac 100 mg. Sensitivity analyses for drug formulation, pain model, trial size and quality did not reveal any statistically significant differences. REVIEWERS' CONCLUSIONS: Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. There was no significant difference between diclofenac and placebo in the incidence of adverse effects, or between diclofenac sodium and potassium, different pain models, smaller and larger trials and trials of higher and lower quality.


Marret et al 2005

Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials.

Marret E, Kurdi O, Zufferey P, Bonnet F.

Anesthesiology 2005;102(6):1249–1260.

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly combined with intravenous morphine patient-controlled analgesia to relieve postoperative pain. NSAIDs have a documented 30-50% sparing effect on morphine consumption. However, most of the studies have not demonstrated a decrease in morphine adverse effects. A meta-analysis of randomized controlled trials was performed to evaluate the risk of morphine adverse effects in patients treated with NSAIDs. Twenty-two prospective, randomized, double-blind studies including 2,307 patients were selected. NSAIDs decreased significantly postoperative nausea and vomiting by 30%, nausea alone by 12%, vomiting alone by 32% and sedation by 29%. A regression analysis yielded findings indicating that morphine consumption was positively correlated with the incidence of nausea and vomiting. Pruritus, urinary retention, and respiratory depression were not significantly decreased by NSAIDs.


Bricker et al 1987

Peri-operative blood loss and non-steroidal anti-inflammatory drugs: an investigation using diclofenac in patients undergoing transurethral resection of the prostate

Bricker S, Savage M, Hanning C.

Eur J Anaesthesiol 1987;4(6):429–434.

Peri-operative blood loss was compared in a prospective, randomized double-blind study between two groups of patients undergoing transurethral prostatectomy (TURP) under spinal (subarachnoid) analgesia: the first received the non-steroidal anti-inflammatory drug diclofenac sodium, the second group received placebo. The total blood loss and the blood loss per gram of prostate resected did not differ significantly. Some 80% of patients were completely pain free at 8 and 24 h post-operation, and low pain scores recorded by the remaining 20% of patients supported the conclusion that TURP performed under spinal analgesia is not commonly associated with severe post-operative pain.


Møiniche et al 2002

A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia.

Møiniche S, Kehlet H, Dahl JB.

Anesthesiology 2002;96(3):725–741.


Harris et al 2001

Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo.

Harris SI, Kuss M, Hubbard RC, Goldstein JL

Clin Ther 2001;23(9):1422–1428.

BACKGROUND: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of ulcers and upper gastrointestinal (GI) ulcer complications, which has been attributed to the inhibition of cyclooxygenase-1. These risks are usually increased in elderly populations. Parecoxib sodium is an injectable prodrug of the cyclooxygenase-2-specific inhibitor valdecoxib that has exhibited analgesic activity in previous trials. OBJECTIVE: The purpose of this study was to compare the GI safety and tolerability profile of parecoxib sodium with that of ketorolac, naproxen, and placebo in a 7-day endoscopic trial in elderly subjects. METHODS: This was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. After a normal baseline endoscopy, healthy elderly subjects aged 66 to 75 years were randomized to receive i.v. parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days, or placebo for 2 days followed by i.v. ketorolac (15 mg QID) for 5 days. Endoscopy was performed again after 7 days. RESULTS: Among the first 17 subjects enrolled, ulcers were observed in all treatment groups except the parecoxib sodium group (ketorolac, 4/4 subjects; naproxen, 2/4 subjects; and placebo, 2/5 subjects). Four subjects in the ketorolac group and 1 subject in the naproxen group had multiple gastric ulcers or combined gastric and duodenal ulcers. Because of the unexpectedly high incidence of gastroduodenal ulcers observed, the study was terminated early and the randomization blind broken. CONCLUSION: These findings suggest that elderly patients may be at risk for GI ulceration even after short-term use of the conventional NSAIDs ketorolac and naproxen.


Greer et al 1999

Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.

Greer I, Gibson J, Young A, Johnstone J, Walker I.

Blood Coagul Fibrinolysis 1999;10(6):367–373.

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.


Marret et al 2003

Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy: meta-analysis of randomized, controlled trials.

Marret E, Flahault A, Samama CM, Bonnet F.

Anesthesiology 2003;98(6):1497–1502.


Niemi et al 1997

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.

Niemi T, Taxell C, Rosenberg P.

Acta Anaesthesiol Scand 1997;41(10):1353–1358.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo-oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. METHODS: Ten healthy male volunteers were given ketoprofen 1.4 mg/kg, ketorolac 0.4 mg/kg and diclofenac 1.1 mg/kg in saline i.v. on three different occasions, at more than one-week intervals, in a randomized double-blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. RESULTS: Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 µg/ml) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (p < 0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 µg/ml) induced platelet aggregation was still seen (26.7%) (p < 0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 µM and 6 µM ) induced platelet aggregation and ketoprofen in ADP (6 µM ) induced platelet aggregation in sample 2. Bleeding time was prolonged (p < 0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. CONCLUSION: Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.


Forrest et al 2002

Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery.

Forrest J, Camu F, Greer I, Kehlet H, Abdalla M, Bonnet F, Ebrahim S, Escolar G, Jage J, Pocock S, Velo G, Langman M, Bianchi P, Samama M, Heitlinger E.

Br J Anaesth 2002;88(2):227–233.

BACKGROUND: Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death. Two regulatory reviews in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs. The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery. METHODS: This prospective, randomized multicentre trial evaluated the risks of death, increased surgical site bleeding, gastrointestinal bleeding, acute renal failure, and allergic reactions, with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment. Patients were followed for 30 days after surgery. RESULTS: A total of 11,245 patients completed the trial at 49 European hospitals. Of these, 5634 patients received ketorolac and 5611 patients received one of the comparators. 155 patients (1.38%) had a serious adverse outcome, with 19 deaths (0. 17%), 117 patients with surgical site bleeding (1.04%), 12 patients with allergic reactions (0.12%), 10 patients with acute renal failure (0.09%), and four patients with gastrointestinal bleeding (0.04%). There were no differences between ketorolac and ketoprofen or diclofenac. Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac (odds ratio=2.65, 95% CI=1.51-4.67) and the comparators (odds ratio=3.58, 95% CI=1.93-6.70). Other risk factors for serious adverse outcomes were age, ASA score, and some types of surgery (plastic/ear, nose and throat, gynaecology, and urology). CONCLUSION: We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery.


Hegi et al 2004

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac.

Hegi TR, Bombeli T, Seifert B, Baumann PC, Haller U, Zalunardo MP, Pasch T, Spahn DR.

Br J Anaesth 2004;92(4):523–531.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti- inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side-effects. COX-2-selective inhibitors may have a more favourable side-effect profile. This study tested the hypothesis that the COX-2-selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side-effects of the two drugs were compared. METHODS: In this single-centre, prospective, double-blind, active controlled study, women undergoing vaginal hysterectomy (n = 25) or breast surgery (n = 25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid-stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side-effects were also recorded. RESULTS: In the rofecoxib group, stimulated platelet aggregation was disturbed less (p = 0.02), and estimated intraoperative blood loss (p = 0.01) and the decrease in haemoglobin were lower (p = 0.01). At similar pain ratings, the use of anti-emetic drugs was less in the rofecoxib group (p = 0.03). CONCLUSION: Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti-emetics and less surgical blood loss in gynaecological surgery compared with diclofenac.


Stevenson 2004

Aspirin and NSAID sensitivity.

Stevenson DD.

Immunol Allergy Clin North Am 2004;24(3):491–505, vii.

Aspirin and the older nonsteroidal anti-inflammatory drugs (NSAIDs) that block cyclo-oxygenase-1 (COX-1) induce asthma attacks in patients with aspirin-exacerbated respiratory disease and urticaria in patients with chronic idiopathic urticaria. Weak inhibitors of COX-1, such as acetaminophen and salsalate, crossreact also but only with high doses of the drugs. Partial inhibitors of both COX-1 and COX-2, such as nimesulide and meloxicam, also cross-react but only at high drug doses. COX-2 inhibitors do not cross-react; however, all NSAIDs, including the selective COX-2 inhibitors, can sensitize patients and induce urticaria or anaphylaxis on next exposure to the drug.


O'Connor et al 2003

Hepatocellular damage from non-steroidal anti-inflammatory drugs.

O'Connor N, Dargan PI, Jones AL.

QJM 2003;96(11):787–791.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the management of rheumatological disorders, and as analgesics and antipyretics. Hepatotoxicity is an uncommon, but potentially lethal complication, which usually occurs within 12 weeks of starting therapy. It can occur with all NSAIDs, but appears to be more common with diclofenac and particularly sulindac. Female patients aged >50 years, with autoimmune disease, and those on other potentially hepatotoxic drugs, appear to be particularly susceptible. Liver function test abnormalities generally settle within 4-6 weeks of stopping the causative drug. However, some patients may develop acute liver failure and successful orthotopic liver transplantation may be undertaken in such patients. Recent in vitro animal studies have shown that the mechanism of diclofenac toxicity relates both to impairment of ATP synthesis by mitochondria, and to production of active metabolites, particularly n,5-dihydroxydiclofenac, which causes direct cytotoxicity. Mitochondrial permeability transition (MPT) has also been shown to be important in diclofenac-induced liver injury, resulting in generation of reactive oxygen species, mitochondrial swelling and oxidation of NADP and protein thiols. Physicians and hepatologists must be vigilant to the hepatotoxic potential of any NSAID, as increased awareness, surveillance and reporting of these events will lead to a better understanding of the risk factors and the pathophysiology of NSAID-related hepatotoxicity.


Cheng et al 2004

Cyclooxygenases, the kidney, and hypertension.

Cheng HF, Harris RC.

Hypertension 2004;43(3):525–530.

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.


Bisgaard et al 2003

Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial.

Bisgaard T, Klarskov B, Kehlet H, Rosenberg J.

Ann Surg 2003;238(5):651–660.

SUMMARY: OBJECTIVE To determine the effects of preoperative dexamethasone on surgical outcome after laparoscopic cholecystectomy (LC).SUMMARY BACKGROUND DATA Pain and fatigue are dominating symptoms after LC and may prolong convalescence.METHODS In a double-blind, placebo-controlled study, 88 patients were randomized to intravenous dexamethasone (8 mg) or placebo 90 minutes before LC. Patients received a similar standardized anesthetic, surgical, and multimodal analgesic treatment. All patients were recommended 2 days postoperative duration of convalescence. The primary endpoints were fatigue and pain. Preoperatively and at several times during the first 24 postoperative hours, we measured C-reactive protein (CRP) and pulmonary function, pain scores, nausea, and number of vomiting episodes were registered. Analgesic and antiemetic requirements were recorded. Also, on a daily basis, patients reported scores of fatigue and pain before and during the first postoperative week and the dates for resumption of work and recreational activities.RESULTS Eight patients were excluded from the study, leaving 40 patients in each study group for analysis. There were no apparent side effects of the study drug. Dexamethasone significantly reduced postoperative levels of CRP (P = 0.01), fatigue (P = 0.01), overall pain, and incisional pain during the first 24 postoperative hours (P < 0.05) and total requirements of opioids (P < 0.05). In addition, cumulated overall and visceral pain scores during the first postoperative week were significantly reduced (P < 0.05). Dexamethasone also reduced nausea and vomiting on the day of operation (P < 0.05). Resumption of recreational activities was significantly faster in the dexamethasone group versus placebo group (median 1 day versus 2 days) (P < 0.05).CONCLUSION Preoperative dexamethasone (8 mg) reduced pain, fatigue, nausea and vomiting, and duration of convalescence in patients undergoing noncomplicated LC, when compared with placebo, and is recommended for routine use.


Elhakim et al 2002

Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy.

Elhakim M, Nafie M, Mahmoud K, Atef A

Can J Anaesth 2002;49(9):922–6

PURPOSE: The combination of antiemetic drugs could be a solution to prevent severe postoperative nausea and vomiting (PONV). The aim of this randomized double blind, dose-ranging study was to determine the minimum single effective dose of dexamethasone combined with ondansetron for the prevention of PONV in patients undergoing laparoscopic cholecystectomy. METHODS: One hundred eighty patients were allocated randomly to one of six groups to receive saline (P group), ondansetron 4 mg (O group), or ondansetron 4 mg and dexamethasone at doses of 2 mg (OD2 group), 4 mg (OD4 group), 8 mg (OD8 group), and 16 mg (OD16 group). A standardized general anesthetic was used. All episodes of PONV during the intervals of zero to six hours, 6-12 hr and 12-24 hr after surgery were evaluated using a numeric scoring system. Mean visual analogue scale pain scores at rest and on movement, the time to first demand of analgesia, total analgesic consumption in 12 hr epochs, duration of hospital stay, and side effects were recorded. RESULTS: The incidence of PONV in the OD8 (16%) and OD16 (16%) groups was lower than in the 83% (P < 0.001) and O groups (50%) at the 12-24 hr epoch (P < 0.05). There were no differences in antiemetic effect between the O, OD2 and OD4 groups and between the OD8 and OD16 groups. Pain scores, total analgesic consumption, duration of hospital stay and side effects were similar among groups. CONCLUSION: Our results suggest that 8 mg is the minimum dose of dexamethasone that, combined with ondansetron 4 mg will effectively prevent PONV in patients undergoing laparoscopic cholecystectomy.


Henzi et al 2000

Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review.

Henzi I, Walder B, Tramér MR.

Anesth Analg 2000;90:186–194.

The role of dexamethasone in the prevention of postoperative nausea and vomiting (PONV) is unclear. We reviewed efficacy and safety data of dexamethasone for prevention of PONV. A systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, bibliographies, all languages, up to April 1999) was done for full reports of randomized comparisons of dexamethasone with other antiemetics or placebo in surgical patients. Relevant end points were prevention of early PONV (0 to 6 h postoperatively), late PONV (0 to 24 h), and adverse effects. Data from 1,946 patients from 17 trials were analyzed: 598 received dexamethasone; 582 received ondansetron, granisetron, droperidol, metoclopramide, or perphenazine; 423 received a placebo; and 343 received a combination of dexamethasone with ondansetron or granisetron. With placebo, the incidence of early and late PONV was 35% and 50%, respectively. Sixteen different regimens of dexamethasone were tested, most frequently, 8 or 10 mg IV in adults, and 1 or 1.5 mg/kg IV in children. With these doses, the number needed to treat to prevent early and late vomiting compared with placebo in adults and children was 7.1 (95% CI 4.5 to 18), and 3.8 (2.9 to 5), respectively. In adults, the number needed to treat to prevent late nausea was 4.3 (2.3 to 26). The combination of dexamethasone with ondansetron or granisetron further decreased the risk of PONV; the number needed to treat to prevent late nausea and vomiting with the combined regimen compared with the 5-HT3 receptor antagonists alone was 7.7 (4.8 to 19) and 7.8 (4.1 to 66), respectively. There was a lack of data from comparisons with other antiemetics for sensible conclusions. There were no reports on dexamethasone-related adverse effects. IMPLICATIONS: When there is a high risk of postoperative nausea and vomiting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo, without evidence of any clinically relevant toxicity in otherwise healthy patients. Late efficacy seems to be most pronounced. It is very likely that the best prophylaxis of postoperative nausea and vomiting currently available is achieved by combining dexamethasone with a 5-HT3 receptor antagonist. Optimal doses of this combination need to be identified.


Joshi et al 2004

Effective Treatment of Laparoscopic Cholecystectomy Pain with Intravenous Followed by Oral COX-2 Specific Inhibitor.

Joshi GP, Viscusi ER, Gan TJ, Minkowitz H, Cippolle M, Shuller R, Cheung RY, Fort JG

Anesthesia & Analgesia 2004;98(2):336–342

In his multicenter, double-blinded, randomized, placebo, controlled study we evaluated the analgesic and opioid-sparing efficacy of a preoperative dose of IV parecoxib followed by oral valdecoxib in treating pain associated with elective laparoscopic cholecystectomy. Patients were randomized to receive a single IV dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30-45 min before induction of anesthesia. Six to 12 h after the IV dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg qd on postoperative days 1-4, then 40 mg qd prn days 5-7. The placebo IV group received oral placebo on an identical schedule. All patients were allowed supplemental IV fentanyl as needed during the first 4 h postoperatively (T0-240 min) followed by hydrocodone 5 mg/acetaminophen 500 mg (Vicodin(R); 1-2 tablets orally every 4-6 h as needed). Patients taking parecoxib used 21% less fentanyl than those receiving placebo (P = 0.011). The mean area under the curve of pain intensity (PI) scores over time from T0-240 min was 55.2 for parecoxib and 61.2 for placebo (P = 0.083). At T180 and T240 min, mean PI score was 7.0 and 7.6 points lower in the parecoxib group, respectively (P < 0.02). Fewer patients on valdecoxib required supplemental analgesics (P < 0.05) after discharge. At T240 min and at day 7, Patient's and Physician's/Nurse's Global Evaluations were significantly better in the parecoxib/valdecoxib group (P < 0.05). Incidences of adverse events, adverse events causing withdrawal, and serious adverse events were less for parecoxib/valdecoxib than for placebo. The authors conclude that preoperative parecoxib is a valuable opioid-sparing adjunct to the standard of care for treating pain after laparoscopic cholecystectomy, and subsequent treatment with oral valdecoxib extends this clinical benefit.


Gan et al 2004

Preoperative parenteral parecoxib, and follow-up oral valdecoxib reduce length of stay and improve quality of patient recovery after laparoscopic cholecystectomy surgery.

Gan TJ, Joshi GP, Viscusi E, Cheung RY, Dodge W, Fort JG, Chen C

Anesthesia & Analgesia 2004;98(6):1665–1673

In this randomized, double-blinded, placebo-controlled study, we evaluated the effects of preoperative IV parecoxib sodium (parecoxib) followed by postoperative oral valdecoxib on length of stay, resource utilization, opioid-related side effects, and patient recovery after elective laparoscopic cholecystectomy. Patients were randomized to receive a single IV dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30-45 min before the induction of anesthesia. Six to 12 h after the IV dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg once daily on postoperative Days 1-4 and then 40 mg once daily as needed on Days 5-7. Patients in the parecoxib/valdecoxib group had a shorter length of stay in the postanesthesia care unit (78 +/- 47 min) compared with those taking placebo (90 +/- 49 min; P < 0.05). Patients in the parecoxib/valdecoxib group also had reduced pain intensity and, after discharge, experienced a significant reduction in vomiting in the first 24 h, slept better, returned to normal activity earlier, and expressed greater satisfaction than placebo patients (P < 0.05). Preoperative parecoxib followed by postoperative valdecoxib is a valuable adjunct for treating pain and improving patient outcome after laparoscopic cholecystectomy.


Rømsing et al 2004

A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain.

Rømsing J, Moiniche S.

Acta Anaesthesiol Scand 2004;48(5):525–546.

BACKGROUND: We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia 0-24 h after surgery. RESULTS: Thirty-three studies were included in which four COX-2 inhibitors, rofecoxib 50 mg, celecoxib 200 and 400 mg, parecoxib 20, 40 and 80 mg, and valdecoxib 10, 20, 40, 80 mg were evaluated. Ten of these studies included 18 comparisons of rofecoxib, celecoxib, or parecoxib with NSAIDs. Rofecoxib 50 mg and parecoxib 40 mg provided analgesic efficacy comparable to that of the NSAIDs in the comparisons, and with a longer duration of action after dental surgery but possibly not after major procedures. Celecoxib 200 mg and parecoxib 20 mg provided less effective pain relief. Four studies included five comparisons of rofecoxib 50 mg with celecoxib 200 and 400 mg. Rofecoxib 50 mg provided superior analgesic effect compared with celecoxib 200 mg. Data on celecoxib 400 mg were too sparse for firm conclusions. Thirty-three studies included 62 comparisons of the four COX-2 inhibitors with placebo and the COX-2 inhibitors significantly decreased post-operative pain. CONCLUSION: Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures, and after dental surgery these COX-2 inhibitors have a longer duration of action. Besides, rofecoxib 50 mg provides superior analgesic effect compared with celecoxib 200 mg.


Greenberg et al 2000

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

Greenberg HE, Gottesdiener K, Huntington M, Wong P, Larson P, Wildonger L, Gillen L, Dorval E, Waldm

J Clin Pharmacol 2000;40(12 Pt 2):1509–1515.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n=12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37oC. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 µg/ml collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.


Bavbek et al 2004

Safety of selective COX-2 inhibitors in aspirin/nonsteroidal anti-inflammatory drug-intolerant patients: comparison of nimesulide, meloxicam, and rofecoxib.

Bavbek S, Celik G, Ozer F, Mungan D, Misirligil Z.

J Asthma 2004;41(1):67–75.

BACKGROUND: Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. OBJECTIVE: To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX-2 inhibitors, in a group of ASA/NSAIDs-intolerant patients. METHOD: Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single-blind placebo-controlled oral challenges. One hundred twenty-seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one-fourth and three-fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60-minute intervals. There was at least a 3-day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV1) and hypotension were considered as positive reactions. RESULTS: Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. CONCLUSION: This is the first placebo-controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs-intolerant patients, rofecoxib seems to have the most favorable tolerability.


Nussmeier et al 2006

Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery.

Nussmeier NA, Whelton AA, Brown MT, Joshi GP, Langford RM, Singla NK, Boye ME, Verburg KM.

Anesthesiology 2006;104(3):518–526.

Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures. Methods: The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up. Patients (n = 1,062) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout. The frequency of predefined adjudicated postrandomization adverse events, including cardiovascular thromboembolism, renal dysfunction, gastroduodenal ulceration, and wound-healing complications, was assessed in each group. Secondary efficacy endpoints included patients' pain ratings, opioid analgesic consumption (recorded as morphine equivalents), and reports of opioid-related adverse effects. Results: Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib (2.7%) and placebo patients (3.2%) (P = 0.58), including cardiovascular thromboembolic events (1.0% in each group; P = 1.0). Placebo patients consumed more morphine equivalents (66.2 +/- 92.4 mg) than did patients receiving parecoxib and valdecoxib (43.2 +/- 65.7 mg) (P < 0.001). Placebo patients had higher mean pain ratings on each of study days 2-10 (P < 0.01) and reported more opioid-related symptom distress on days 2-6 (P < 0.01). Conclusions: Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients. Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery.


Nussmeier et al 2005

Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.

Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM.

N Engl J Med 2005;352(11):1081–1091.

Background Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. Methods In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. Results As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4% in each of these two groups vs. 4.0% in the placebo group; risk ratio for each comparison, 1.9; 95% confidence interval, 1.1 to 3.2; p = 0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0% vs. 0.5%; risk ratio, 3.7; 95% confidence interval, 1.0 to 13.5; p = 0.03). Conclusions The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.


EMEA 2004a

Committee for Medicinal Products for Human Use, European Public Assessment Report (EPAR): Bextra.

EMEA.

Available at http://www.emea.eu.int/humandocs/Humans/EPAR/bextra/bextra.htm


Blomme et al 2003

Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.

Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS

Br J Dermatol 2003;148(2):211–223.

BACKGROUND: The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair. OBJECTIVE: Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing. METHODS: Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength. RESULTS: COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period. CONCLUSIONS: These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.


Wu CT et al 2005

The interaction effect of perioperative cotreatment with dextromethorphan and intravenous lidocaine on pain relief and recovery of bowel function after laparoscopic cholecystectomy

Wu CT, Borel CO, Lee MS, Yu JC, Liou HS, Yi HD, Yang CP

Anesth Analg 2005;100(2):448–53

Both dextromethorphan (DM) and IV lidocaine improve postoperative pain relief. In the present study, we evaluated the interaction of DM and IV lidocaine on pain management after laparoscopic cholecystectomy (LC). One-hundred ASA physical status I or II patients scheduled for LC were randomized into four equal groups to receive either: (a) chlorpheniramine maleate (CPM) intramuscular injection (IM) 20 mg and IV normal saline (N/S) (group C); (b) DM 40 mg IM and IV N/S (group DM); (c) CPM 20 mg IM and IV lidocaine 3 mg . kg(-1) . h(-1) (group L); or (d) DM 40 mg IM and IV lidocaine (group DM+L). All treatments were administered 30 min before skin incision. Analgesic effects were evaluated using visual analog scale pain scores at rest and during coughing, time to meperidine request, total meperidine consumption, and the time to first passage of flatus after surgery. Patients of the DM+L group exhibited the best pain relief and fastest recovery of bowel function among groups. Patients in the DM and L groups had significantly better pain relief than those in the C group. The results showed an additional effect on pain relief and a synergistic effect on recovery of bowel function when DM was combined with IV lidocaine after LC.


Wu et al 1999

Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy.

Wu CT, Yu JC, Yeh CC, Liu ST, Li CY, Ho ST, Wong CS.

Anesth Analg 1999;88:1331–1334.

In the present study, we examined whether preincisional treatment with dextromethorphan (DM) provides preemptive analgesia. Ninety patients scheduled for laparoscopic cholecystectomy were included. Patients receiving chlorpheniramine maleate (CPM) 20 mg via an IM injection 30 min before skin incision were designated as the control group. Patients in Group A received DM 40 mg (containing CPM 20 mg) IM after removal of the gallbladder, whereas in Group B, DM 40 mg (containing CPM 20 mg) was administered IM 30 min before skin incision. Meperidine (1 mg/kg IM) was given for postoperative pain relief as required. Times to first meperidine injection, total meperidine consumption, worst pain score, bed rest time, and side effects were recorded for 48 h after surgery. Times to first meperidine injection were 9.3+/-15.9, 17.4+/-3.4, and 28.6+/-3.9 h for the control group and Groups A and B, respectively. The total meperidine consumption was 90.7+/-11.9, 77.5+/-12.7, and 20.0+/-4.4 mg for the control group and Groups A and B, respectively. The worst visual analog pain scores were 6.0+/-0.2, 6.0+/-0.2, and 4.0+/-0.4 for the control group and Groups A and B, respectively. The bed rest times were 21.0+/-0.5, 20.0+/-0.5, and 19.0+/-0.4 h for the control group and Groups A and B, respectively. The number of patients who required meperidine injection was 26, 22, and 12 for the control group and Groups A and B, respectively. We conclude that DM is more effective in producing postoperative analgesia when it is administered preincision rather than after the gallbladder removal treatment, which suggests a preemptive analgesic effect. IMPLICATIONS: Preincisional dextromethorphan (40 mg IM) treatment offers a preemptive analgesic effect, thus improving the postoperative pain management.


Ayoglu et al 2005

The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy.

Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O

The Pain Clinic 2005;17(1):45–53

In this randomized, double blind study, we investigated the analgesic effect of ketamine and magnesium sulfate in patients scheduled for laparoscopic cholecystectomy. Sixty patients were randomly assigned into three groups. Before the induction of anesthesia, Group 1 received a bolus of magnesium sulfate 50 mg/kg, and an infusion of 8 mg/kg/h for the next 4 h; Group 2 received a bolus of ketamine 0.5 mg/kg and an infusion of 0.15 mg/kg/h for the next 4 h; Group 3 received the same volume of saline solution. Intraoperative pain was treated with bolus alfentanil. Patient controlled analgesia (PCA) was used in all patients in the recovery room. Alfentanil consumptions of the Group 1 and 2 were lower than that of the Group 3 (p < 0.05). Postoperative morphine consumption of Group 2 was lower than that of the Group 3 two and three hours after surgery (p < 0.05). We conclude that addition of ketamine or magnesium sulfate to general anesthesia may decrease intraoperative analgesic requirements and administration of ketamine reduces postoperative morphine requirement. Our results indicate that a bolus of ketamine 0.5 mg/kg and subsequent infusion of 0.15 mg/kg/h is more efficient than a bolus of magnesium sulfate 50 mg/kg, and subsequent infusion of 8 mg/kg/h for postoperative pain management.


Papaziogas et al 2001

Preincisional intravenous low-dose ketamine and local infiltration with ropivacaine reduces postoperative pain after laparoscopic cholecystectomy.

Papaziogas B, Argiriadou H, Papagiannopoulou P, Pavlidis T, Georgiou M, Sfyra E, Papaziogas T.

Surg Endosc 2001;15(9):1030–1033.

BACKGROUND: The preincisional use of ketamine combined with local tissue infiltration with Ropivacaine may reduce noxious input during surgery. The goal of this study was to examine whether this combination improves postoperative pain control after laparoscopic cholecystectomy. METHODS: A total of 55 patients were randomly assigned to one of three groups. Group 1 received placebos preincisional. Group 2 received preincisional saline IV and local infiltration with 20 ml ropivacaine (10 mg/ml). Group 3 received preincisional ketamine 1 mg/kg IV and local infiltration with 20 ml ropivacaine (10 mg/ml). Postoperative pain was rated at 0, 3, 6, 12, 24, and 48 h postoperatively by visual analogue scale scores (VAS). Cumulative analgesic consumption and time until first analgesic medication request were recorded. RESULTS: Group 3 experienced significantly (p < 0.05) less pain than group 2 at 6 h and 12 h postoperatively. Groups 2 and 3 did not differ significantly by VAS at 0 h, 3 h, 24 h, and 48 h. Group 1 had significantly higher VAS scores than groups 2 and 3 at 0 h, 3 h, 6 h, 12 h, and 24 h postoperatively. The consumption of analgesics was significantly higher in group 1 than in groups 2 and 3. Although the consumption of analgesics was higher in group 3 than in group 2, this difference did not reach statistical significance. The time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistical difference between groups 2 and 3. Conclusion: Preincisional treatment with low-dose IV ketamine and local infiltration with ropivacaine 1% reduces postoperative pain after laparoscopic cholecystectomy.


Ayoglu et al 2005

The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy

Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O

The Pain Clinic 2005;17(1):45–53

In this randomized, double blind study, we investigated the analgesic effect of ketamine and magnesium sulfate in patients scheduled for laparoscopic cholecystectomy. Sixty patients were randomly assigned into three groups. Before the induction of anesthesia, Group 1 received a bolus of magnesium sulfate 50 mg/kg, and an infusion of 8 mg/kg/h for the next 4 h; Group 2 received a bolus of ketamine 0.5 mg/kg and an infusion of 0.15 mg/kg/h for the next 4 h; Group 3 received the same volume of saline solution. Intraoperative pain was treated with bolus alfentanil. Patient controlled analgesia (PCA) was used in all patients in the recovery room. Alfentanil consumptions of the Group 1 and 2 were lower than that of the Group 3 (p < 0.05). Postoperative morphine consumption of Group 2 was lower than that of the Group 3 two and three hours after surgery (p < 0.05). We conclude that addition of ketamine or magnesium sulfate to general anesthesia may decrease intraoperative analgesic requirements and administration of ketamine reduces postoperative morphine requirement. Our results indicate that a bolus of ketamine 0.5 mg/kg and subsequent infusion of 0.15 mg/kg/h is more efficient than a bolus of magnesium sulfate 50 mg/kg, and subsequent infusion of 8 mg/kg/h for postoperative pain management. copyright 2005 VSP.


Mathisen et al 1999

Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy.

Mathisen LC, Aasbo V, Raeder J.

Acta Anaesthesiol Scand 1999;43:220–4.

AIM: This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) (R)-ketamine in laparoscopic cholecystectomy. (R)-ketamine was used due to the lower incidence of side-effects. METHODS: Sixty patients who underwent surgery under general anesthesia were randomly allocated to 3 groups and studied in a double-blind manner. Two i.v. injections were administered: one after induction of anesthesia, approximately 3 min before surgery, and one after surgery. The placebo group (PLA, n = 20) received saline in both injections. The preoperative group (PRE, n = 20) received (R)-ketamine 1 mg/kg and then saline. The postoperative group (POST, n = 20) received saline and then (R)-ketamine 1 mg/kg. Postoperatively, the patients used a patient-controlled analgesia (PCA) pump. Pain was evaluated with a visual analog scale (VAS) at 30 min and every hour for 4 h and with a verbal rating scale (VRS) at 24 h and after 7 days. RESULTS: There were no occurrence of side-effects from (R)-ketamine. VAS and VRS at 1, 2, 3, and 4 h postoperatively showed no statistical differences. In the POST group, extubation was delayed and pain score (VAS) at 30 min postoperatively was significantly lower (p < 0.05) than the two other groups. There were no statistical differences in meperidine consumption during the first 4 h postoperatively and no differences in consumption of analgesics at 24 h and 7 days. CONCLUSION: In this study a 1 mg/kg dose of (R)-ketamine given at the end of surgery exerted a short-lasting hypnotic and analgesic effect. The same dose given preoperatively did not show postoperative analgesic effect or pre-emptive effect.


Bell et al 2006

Perioperative ketamine for acute postoperative pain

Bell RF, Dahl JB, Moore RA, Kalso E.

Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004603

BACKGROUND: Postoperative pain management is often limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. OBJECTIVES: To evaluate the effectiveness and tolerability of ketamine administered perioperatively in the treatment of acute postoperative pain in adults. SEARCH STRATEGY: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by handsearching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer) provided search results from their in-house database, PARDLARS. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adult patients undergoing surgery, being treated with perioperative ketamine or placebo. Studies where ketamine was administered in addition to a basic analgesic (such as morphine or NSAID) in one study group, and compared with a group receiving the same basic analgesic (but without ketamine) in another group, were also included. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified fifty five RCTs for potential inclusion. Quality and validity assessment was performed by two independent reviewers. In the case of discrepancy, a third reviewer was consulted. Patient reported pain intensity and pain relief was assessed using visual analogue scales or verbal rating scales and adverse effects data were collated. MAIN RESULTS: Thirty-seven trials were included (2240 participants). Eighteen trials were excluded.Twenty-seven of the 37 trials found that perioperative subanaesthetic doses of ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24 hour PCA morphine consumption and postoperative nausea or vomiting (PONV). Adverse effects were mild or absent. AUTHORS' CONCLUSIONS: Ketamine in subanaesthetic dose (that is a dose which is below that required to produce anaesthesia) is effective in reducing morphine requirements in the first 24 hours after surgery. Ketamine also reduces postoperative nausea and vomiting. Adverse effects are mild or absent.


Seyhan et al 2006

Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery.

Seyhan TO, Tugrul M, Sungur MO, Kayacan S, Telci L, Pembeci K, Akpir K.

Br J Anaesth. 2006; 96: 247–52.

BACKGROUND: In this double-blind, randomized, placebo-controlled study we compared the effects of three different dose regimens of magnesium on intraoperative propofol and atracurium requirements, and postoperative morphine consumption in patients undergoing gynaecological surgery. METHODS: Eighty women were allocated to four equal groups. The control group received normal saline; magnesium groups received 40 mg kg(-1) of magnesium before induction of anaesthesia, followed by i.v. infusion of normal saline, magnesium 10 mg kg(-1) h(-1) or magnesium 20 mg kg(-1) h(-1) for the next 4 h. Propofol infusion was targeted to keep bispectral index values between 45 and 55. Postoperative analgesia was achieved using PCA with morphine. RESULTS: Magnesium groups required significantly less propofol [mean (sd) 121.5 (13.3), 102.2 (8.0) and 101.3 (9.7) microg kg(-1) min(-1) respectively] than the control group (140.7 (16.5) microg kg(-1) min(-1)). Atracurium use was significantly higher in the control group than magnesium groups [0.4 (0.06) vs 0.34 (0.06), 0.35 (0.04), 0.34 (0.06) mg kg(-1) h(-1) respectively]. Morphine consumption was significantly higher in control group than magnesium groups on the first postoperative day [0.88 (0.14) vs 0.73 (0.17), 0.59 (0.23), 0.53 (0.21) mg kg(-1) respectively]. The heart rate was lower in magnesium groups and 20 mg kg(-1) h(-1) infusion group demonstrated the lowest values. CONCLUSION: Magnesium 40 mg kg(-1) bolus followed by 10 mg kg(-1) h(-1) infusion leads to significant reductions in intraoperative propofol, atracurium and postoperative morphine consumption. Increasing magnesium dosage did not offer any advantages, but induced haemodynamic consequences.

 


Helmy + Bali 2001

The effect of the preemptive use of the NMDA receptor antagonist dextromethorphan on postoperative analgesic requirements

Helmy SA, Bali A

Anesth Analg 2001;92(3):739–44

Both central sensitization after peripheral tissue injury and the development of opiate tolerance involve activation of N-methyl-D-aspartate receptors. In this double-blinded, randomized study, we investigated the preemptive versus postincisional effects of dextromethorphan, an N-methyl-D-aspartate receptor antagonist, on postoperative pain management. Sixty ASA I and II patients undergoing elective upper abdominal surgery were randomly allocated to three equally sized groups. The Preincisional group patients received dextromethorphan (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min before the end of surgery. The Postincisional group received the same dose of dextromethorphan 30 min before the end of surgery and a placebo 30 min before skin incision, and the Control group received a placebo both 30 min before skin incision and 30 min before the end of surgery. A standard general anesthetic technique including fentanyl, propofol, isoflurane, and atracurium was used. Postoperative meperidine patient-controlled analgesia (PCA) was used. There were no significant group differences in the median pain scores except in the visual analog scale at 6 h both at rest and on movement; these were significantly lower in the Preincisional group than the other two groups (P < 0.05). The mean time to initiation of PCA was significantly longer in the Preincisional than in the Postincisional and Control groups (mean [SD]: 10.7 [2.2 h], 5.4 [2.1 h], and 3.7 [1.6 h], respectively; P < 0.001]. The 24-h PCA-meperidine consumption was significantly less in the Preincisional than in the Postincisional and Control groups (mean [SD]: 140 [60 mg], 390 [80 mg], and 570 [70 mg], respectively; P < 0.001]. The incidence of postoperative hypoxemia (SpO(2) < 90%) and nausea was significantly less in the Preincisional group (P < 0.05). In conclusion, preincisional IM 120 mg dextromethorphan compared with the same postincisional dose significantly reduced postoperative meperidine consumption. IMPLICATIONS: IM administration of preincisional dextromethorphan (120 mg), allowing the use of a larger dose sufficient to block the central sensitization caused by activation of the N-methyl-D-aspartate receptors, provides preemptive analgesia and has a supportive role in postoperative pain relief, as shown by a significant decrease in 24-h meperidine consumption.


Wu et al 2000

Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery

Wu CT, Yu JC, Liu ST, Yeh CC, Li CY, Wong CS

World J Surg 2000;24(5):512–7

Previous studies showed that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, provides a preemptive analgesic effect and preemptive analgesia improves postoperative pain management. The aim of this study was to examine whether premedication with dextromethorphan (DM) improves postoperative pain management after upper abdominal surgery. Sixty (American Society of Anesthesiologists class 1 and 2 of either gender) patients scheduled for upper abdominal surgery were included in the study. Patients were randomly assigned to one of four groups: control, DM-10, DM-20, and DM-40. In the control group, chlorpheniramine maleate (CPM, 20 mg) was injected immediately before induction of anesthesia intramuscularly (IM). In the DM-10, DM-20, and DM-40 groups, patients were premedicated with DM 10 mg, 20 mg, and 40 mg IM, respectively. After operation, patient-controlled analgesia (PCA) with morphine was given for pain relief. The time to the first PCA trigger, morphine consumption, pain scores, and analgesic-related side effects were recorded at 1, 2, 4, 24, 48, and 72 hours after surgery. The time to first PCA trigger for the control group was 17.8 +/- 1.4 minutes, for group DM-10 20.2 +/- 1.6 minutes, for group DM-20 32.4 +/- 1.9 minutes, and for DM-40 77.9 +/- 6.5 minutes. The morphine delivered and PCA triggering frequency were 5.5 +/- 0.5/11.3 +/- 0.8 times for the controls, 5.5 +/- 0.4/ 14.1 +/- 1.3 times for DM-10, 3.1 +/- 0.3/6.3 +/- 1.2 times for DM-20, and 0.2 +/- 0.1/0.3 +/- 0.2 times for DM-40 during the first hour after operation. For the first day, the figures are 19.9 +/- 1.2/23.9 +/- 1.4 for the controls, 15.6 +/- 1.2/17.3 +/- 2.4 for DM-10, 12.6 +/- 0.7/15.9 +/- 1.6 for DM-20, and 5.0 +/- 0.21/5.6 +/- 0.9 for DM-40. On the first day, the cough pain scores were 6.67 +/- 0.23, 6.53 +/- 0.16, 6.67 +/- 0.23, and 5.73 +/- 0.18 for the controls, DM-10, DM-20, and DM-40 groups, respectively. All data showed dose-dependent better pain relief in DM-premedicated patients. We conclude that DM premedication offers preemptive analgesia and reduces postoperative pain and morphine requirement.


Grace et al 1998

Preoperative dextromethorphan reduces intraoperative but not postoperative morphine requirements after laparotomy

Grace RF, Power I, Umedaly H, Zammit A, Mersiades M, Cousins MJ, Mather LE

Anesth Analg 1998;87(5):1135–8

N-methyl-D-aspartate (NMDA) antagonists combined with opioids are thought to be effective in the control of pain states. We evaluated morphine use and analgesia in 37 patients postlaparotomy. Patients received 60 mg of oral dextromethorphan or placebo the night before and again 1 h before surgery. Morphine was titrated intraoperatively to maintain blood pressure and heart rate within 20% of baseline and postoperatively via patient-controlled analgesia (PCA). The dextromethorphan and placebo groups were compared for morphine use intraoperatively, in recovery, via PCA in the first 4 and 24 h, and total use over the study period. Pain scores at rest and on activity for the first 4 and 24 h were also compared. Intraoperatively, the dextromethorphan group required less morphine: 13.1+/-4.3 vs 17.6+/-6.0 mg (P = 0.012). Postoperatively, there was no significant difference between the dextromethorphan and placebo groups for morphine use: in the recovery room 10.9+/-7.7 vs 12.1+/-7.7 mg; the first 4 h of PCA 15.9+/-9.3 vs 12.7+/-5.1 mg; the first 24 h of PCA 76.4+/-44.7 vs 61.8+/-27.5 mg; or in total morphine use 100.4+/-49.5 vs 91.5+/-3.1 mg. Pain scores for the two groups were not statistically different throughout the study period. We conclude that 60 mg of oral dextromethorphan given the night before and repeated an hour before surgery does not provide a postoperative morphine-sparing effect or improve analgesia after laparotomy. IMPLICATIONS: Patients given dextromethorphan before surgery had significantly reduced intraoperative morphine requirements. However, postoperative morphine requirements were unaltered. Dextromethorphan may need to be continued postoperatively to improve postoperative analgesia.


Duedahl et al 2006

A qualitative systematic review of peri-operative dextromethorphan in post-operative pain

Duedahl TH, Romsing J, Moiniche S, Dahl JB

Acta Anaesthesiol Scand 2006;50(1):1–13

BACKGROUND: The N-methyl-D-aspartate (NMDA) receptor antagonist, dextromethorphan (DM), has received interest as an adjunctive agent in post-operative pain management. Clinical trials have been contradictory. This systematic review aims to evaluate the available literature examining the analgesic efficacy of DM in post-operative patients. METHODS: Twenty-eight randomized, double-blind, clinical studies, with 40 comparisons, including a variety of dosing regimens comparing DM treatment with placebo, were included. Meta-analysis was intended but deemed to be inappropriate because of the substantial difference in methodology and reporting between trials. The outcome measures (pain scores at rest, time to first analgesic request and supplemental analgesic consumption) were evaluated qualitatively by significant difference (P<0.05) as reported in the original investigations. RESULTS: DM did not reduce the post-operative pain score with a clinically significant magnitude. The time to first analgesic request was significantly prolonged in most comparisons with DM. Significant decreases in supplemental opioid consumption were observed in the majority of parenteral DM studies and in about one-half of the oral studies. The decreases were of questionable clinical importance in most comparisons, although a relationship between a decrease in opioid consumption and opioid-related side-effects was established in some studies. CONCLUSION: Based on the studies available, DM has the potential to be a safe adjunctive agent to opioid analgesia in post-operative pain management, but the consistency of the potential opioid-sparing and pain-reducing effect must be questioned. Consequently, it is not possible to recommend dose regimens or routine clinical use of DM in post-operative pain. The route of administration may be important for the beneficial effect.


Burstal et al 2001

PCA ketamine and morphine after abdominal hysterectomy.

Burstal R, Danjoux G, Hayes C, Lantry G.

Anaesth Intensive Care 2001;29(3):246.

Following a standardized general anaesthetic for total abdominal hysterectomy, patients received either patient controlled analgesia (PCA) with morphine 1 mg/ml (group M, n = 33) or morphine 1 mg/ml plus ketamine 2 mg/ml (group K, n = 37) for 48 hours in a randomized, double-blind fashion. In 43 women the area of allodynia around the scar was mapped as a measure of the degree of central sensitization. A significant reduction in the area of allodynia was found in those receiving ketamine with morphine (42 cm2 [interquartile range (IQR) 57] compared with 57 cm2 [IQR 82] z = -2.0, P = 0.04) in those receiving morphine alone. There were no significant differences between the two groups with respect to age, or weight, or between the subgroups within which the area of allodynia was measured with respect to length of incision. No significant differences were found between the groups with respect to pain scores, total or hourly drug consumption, patient satisfaction, nausea scores or antiemetic use. Patients in group K were more likely to require PCA for a shorter period than those in group M (median 40 hours, IQR 26 versus 48 hours IQR 7). Ten patients in group K were withdrawn because of side-effects (dysphoria n = 4, nausea n = 2, pruritus n = 4) compared with one in group M (nausea n = 1) (P = 0.006). The potential usefulness of ketamine after hysterectomy was offset by a high incidence of adverse effects and a lack of opioid-sparing effects, such that combined intravenous ketamine and morphine PCA as used in this study cannot be recommended for routine care.


Munoz et al 2002

Effect of timing of morphine administration during remifentanil-based anaesthesia on early recovery from anaesthesia and postoperative pain.

Munoz HR, Guerrero ME, Brandes V, Cortinez LI

Br J Anaesth 2002;88(6):814–818.

BACKGROUND: Since the time to peak analgesic effect of intravenous morphine can be longer than 40-60 min in volunteers, the goal of this study was to evaluate the effect of the timing of intraoperative morphine administration on early postoperative pain. METHODS: A total of 120 adult patients undergoing laparoscopic cholecystectomy were studied. Anaesthesia was induced with remifentanil and etomidate and maintained with remifentanil and sevoflurane/nitrous oxide. Morphine 150 µgkg-1was given randomly at three different times during surgery, and a fourth group received placebo. Times to eyes opening and extubation were measured, and pain was evaluated in the post-anaesthesia care unit (PACU) using a visual analogue scale (VAS). Morphine 2–3 mg was given when the VAS score was > or = 50 mm. The four groups were, according to the time elapsed from morphine administration to the end of surgery, group 1 (n = 30): placebo; group 2 (n = 33): < 20 min; group 3 (n = 30): 20-40 min; group 4 (n = 27): > 40 min. RESULTS: Recovery from anaesthesia and pain scores were similar in all groups. However, mean (SD) morphine consumption was 5.7 (4.7) mg in group 1, 4.4 (4.2) mg in group 2, 4.7 (4.7) mg in group 3, and 2.2 (4.0) mg in group 4 (p < 0.05, group 1 vs. 4). Morphine was required in only 38% of patients in group 4 compared with 83%, 67% and 69% in groups 1, 2, and 3, respectively (p < 0.01, group 1 vs. 4). CONCLUSIONS: The timing of intraoperative morphine administration did not affect the early recovery from anaesthesia. However, the reduction in the number of patients requiring morphine in the PACU when morphine had been given more than 40 min before the end of surgery supports this practice, rather than administration closer to the end of surgery.


Damen et al 2004

The Effects of Remifentanil and Sufentanil on the Quality of Recovery after Day Case Laparoscopic Cholecystectomy: A Randomized Blinded Trial.

Damen SL, Nieuwenhuijs VB, Joosten W, Houweling PL, Clevers GJ

Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A 2004;14(2):87–92

Background: Duration of hospitalization after laparoscopic cholecystectomy (LC) is mainly determined by temporary side effects such as pain, nausea, and vomiting. In this study we compared remifentanil, a short acting opioid, and sufentanil, a longer acting opiold, on their ability to reduce these postoperative effects and facilitate LC in day case surgery. Method: Seventy patients scheduled for elective LC were randomized in two groups. Remifentanil was used in group 1 as part of the anesthetic protocol, sufentanil was used in group 2. After surgery, patients were asked to evaluate pain and nausea on a verbal rate scale (VRS). Frequency of vomiting and analgesic medication consumption was registered. Time between surgery and to the start of micturition, drinking, mobilization, dressing, and discharge was recorded. Patients registered their satisfaction on a VRS. Details of any other adverse events throughout the study were recorded. Results: Twenty-two patients (63%) of group 1 were treated as day cases vs. 27 (77%) in group 2 (P = NS). All patients who were not discharged as day cases left the hospital one day postoperatively. Immediately after surgery, patients in group 2 reported significantly less pain. There were no other significant differences between groups. Conclusion: The majority of patients scheduled for LC can be safely discharged on the day of surgery. Reported satisfaction one week postoperatively was high for all patients. We found no major relevant differences between the two anesthetic protocols.


McQuay et al 1999

Injected morphine in postoperative pain: a quantitative systematic review.

McQuay HJ, Carroll D, Moore RA.

J Pain Symptom Manage 1999;17(3):164–174.

This systematic review of single-dose, placebo-controlled, randomized trials assessed pain relief from subcutaneous, intramuscular or intravenous morphine compared with placebo in postoperative pain. Pain relief or pain intensity difference over 4 to 6 hours was extracted and converted into the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. In 15 trials, comparing intramuscular morphine 10 mg (486 patients) with placebo (460 patients) morphine had an NNT of 2.9 (95% confidence interval 2.6-3.6). This meant that one of every three patients with moderate or severe postoperative pain treated with 10 mg intramuscular morphine had at least 50% pain relief, and would not have achieved this had they been given placebo. Minor adverse effects were more common with morphine (34%) than with placebo (23%) (relative risk 1.49 [1.09-2.04]), but drug related study withdrawal was rare (1.2% overall) and no different from placebo.


Wheeler et al 2002

Adverse events associated with postoperative opioid analgesia: a systematic review.

Wheeler M, Oderda GM, Ashburn MA, Lipman AG.

J Pain 2002;3(3):159–180.


Naguib et al 1998

Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine.

Naguib M, Seraj M, Attia M, Samarkandi AH, Seet M, Jaroudi R.

Can J Anaesth 1998;45(12):1168–75.

PURPOSE: To compare the efficacy of tramadol and morphine for intra- and postoperative analgesia in patients undergoing laparoscopic cholecystectomy. METHODS: In a prospective, randomized, double-blind study 100 patients were allocated randomly into two groups. Ten minutes before induction of anaesthesia, patients in group 1 received 100 mg tramadol and those in group 2 received 10 mg morphine i.v. Anaesthesia was induced with 5 mg/kg thiopental and was maintained with O2, N2O plus isoflurane with additional doses of tramadol or morphine as decided by the attending anaesthetist. Postoperatively, patients in group 1 and group 2 received tramadol and morphine, respectively, from a patient-controlled analgesia (PCA) device. Pain, analgesic consumption, vital signs and side effects were recorded postoperatively for 24 hr. RESULTS: Intraoperative consumption of tramadol and morphine were 137 +/- 37 and 12.2 +/- 3 mg, respectively. Compared with morphine, patients receiving tramadol had higher blood pressures and required greater mean ETisQ to control haemodynamic variables (p < 0.05). Postoperatively, there were no differences in observer pain score or visual analogue pain score during the first 24 hr between groups except at 30, 45, and 90 min where patients in the tramadol group reported higher pain scores (P < 0.05). The cumulative, 24 hr PCA consumption was 111 +/- 93 and 7.5 +/- 6.6 mg of tramadol and morphine, respectively. CONCLUSIONS: There was no difference between the use of tramadol and morphine to treat pain after laparoscopic cholecystectomy from 90 min after the end of surgery. Morphine was more effective than tramadol as an intraoperative analgesic.


Moore et al 1997

Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics.

Moore RA, McQuay HJ.

Pain. 1997; 69: 287–94.

The analgesic effectiveness and safety of oral tramadol were compared with standard analgesics using a meta-analysis of individual patient data from randomised controlled trials in patients with moderate or severe pain after surgery or dental extraction. Calculation of %maxTOTPAR from individual patient data, and the use of > 50%maxTOTPAR defined clinically acceptable pain relief. Number-needed-to-treat (NNT) for one patient to have > 50%maxTOTPAR compared with placebo was used to examine the effectiveness of different single oral doses of tramadol and comparator drugs. Eighteen randomised, double-blind, parallel-group single-dose trials with 3453 patients using categorical pain relief scales allowed the calculation of %maxTOTPAR. The use of > 50%maxTOTPAR was a sensitive measure to discriminate between analgesics. Tramadol and comparator drugs gave significantly more analgesia than placebo. In postsurgical pain tramadol 50, 100 and 150 mg had NNTs for > 50%maxTOTPAR of 7.1 (95% confidence intervals 4.6-18), 4.8 (3.4-8.2) and 2.4 (2.0-3.1), comparable with aspirin 650 mg plus codeine 60 mg (NNT 3.6 (2.5-6.3)) and acetaminophen 650 mg plus propoxyphene 100 mg (NNT 4.0 (3.0-5.7)). With the same dose of drug postsurgical patients had more pain relief than those having dental surgery. Tramadol showed a dose-response for analgesia in both postsurgical and dental pain patients. With the same dose of drug postsurgical pain patients had fewer adverse events than those having dental surgery. Adverse events (headache, nausea, vomiting, dizziness, somnolence) with tramadol 50 mg and 100 mg had a similar incidence to comparator drugs. There was a dose response with tramadol, tending towards higher incidences at higher doses. Single-patient meta-analysis using more than half pain relief provides a sensitive description of the analgesic properties of a drug, and NNT calculations allow comparisons to be made with standard analgesics. Absolute ranking of analgesic performance should be done separately for postsurgical and dental pain.

 


McQuay H et al 2003

Meta-analysis of single dose oral tramadol plus acetaminophen in acute postoperative pain.

McQuay H, Edwards J.

Eur J Anaesthesiol 2003;20 Suppl 28:19–22.

BACKGROUND AND OBJECTIVE: Trials in acute postoperative pain are usually small. Pooling homogenous data from a number of trials in a meta-analysis enables a truer estimate of efficacy. The aims of the present meta-analysis were to assess the analgesic efficacy and adverse effects of single-dose oral tramadol plus acetaminophen (paracetamol) in acute postoperative pain, and to demonstrate the efficacy of the combination formulation compared with its components. METHODS: Individual data from > 1400 adult dental or gynaecologic/orthopaedic patients with moderate-to-severe pain were taken from seven randomised, double-blind, placebo controlled trials of tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) with identical methods. The primary outcome measure was the number of patients needed to be treated (NNT) for one patient to obtain at least 50% pain relief. Information on adverse effects was also collected and the number needed to harm (NNH) was estimated. RESULTS: The tramadol/acetaminophen combination was more effective than either of its two components administered alone. For dental patients, who formed the bulk of the population, the combination formulation also had a significantly lower (better) NNT (approximately 3) than the components al one (approximately 8-12), comparable to ibuprofen 400 mg. The adverse effects associated with tramadol/acetaminophen were similar to those associated with the components alone. The commonest were dizziness, drowsiness, nausea, vomiting and headache. CONCLUSIONS: Meta-analysis confirmed the analgesic superiority of the combination treatment over its components, without additional toxicity. Combination analgesic formulations are an important and effective means of pain relief, and should prove useful in treating elderly and other groups of patients who often cannot tolerate non-steroidal anti-inflammatory drugs, including the newer COX-2 inhibitors.


Collins et al 2000

Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain

Collins SL, Edwards JE, Moore RA, McQuay HJ

Cochrane Database Syst Rev 2000; CD001440(2)

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Dextropropoxyphene is one example of an opioid analgesic in current use, and is widely prescribed for pain relief in combination with paracetamol under names such as Co-proxamol and Distalgesic. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single dose oral Dextropropoxyphene alone and in combination with paracetamol (acetaminophen) for moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from: Medline (1966 - November 1996), Biological Abstracts (1985 - 1996), Embase (1980 - 1996), the Cochrane Library (Issue 4 1996), and the Oxford Pain Relief Database (1954 - 1994). Additional studies were identified from the reference lists of retrieved reports. Date of the most recent searches: July 1998. SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included dextropropoxyphene and placebo or a combination of dextropropoxyphene plus paracetamol and placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Six trials (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. For a single dose of dextropropoxyphene 65 mg in postoperative pain the NNT for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 hours. For the equivalent dose of dextropropoxyphene combined with paracetamol 650 mg the NNT was 4.4 (3.5 to 5.6) when compared with placebo. These results were compared with those for other analgesics obtained from equivalent systematic reviews. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol compared with placebo. REVIEWER'S CONCLUSIONS: The combination of dextropropoxyphene 65 mg with paracetamol 650 mg shows similar efficacy to tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of adverse effects. The same dose of paracetamol combined with 60 mg codeine appears more effective but, with the slight overlap in the 95% confidence intervals, this conclusion is not robust. Adverse effects of both combinations were similar. Ibuprofen 400 mg has a lower (better) NNT than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.


Moore et al 2000

Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain.

Moore A, Collins S, Carroll D, McQuay H, Edwards J.

Cochrane Database Syst Rev. 2000;(2):CD001547

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Paracetamol (acetaminophen) is an important non-opiate analgesic, commonly prescribed, as well as being available for retail sale. This review seeks to examine the efficacy of paracetamol alone and in combination with codeine, and also considers adverse effects. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single dose of oral paracetamol (acetaminophen) alone and in combination with codeine for moderate to severe postoperative pain. SEARCH STRATEGY: Published trials were identified from: Medline (1966 to May 1996), Embase (1980 to 1996), Cochrane Library (Issue 2 1996) and the Oxford Pain Relief Database (1950 to 1994). Additional trials were identified from reference lists of retrieved studies. Date of most recent searches: July 1998. SELECTION CRITERIA: Inclusion criteria were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared paracetamol with placebo or a combination of paracetamol and codeine with either placebo or the same dose of paracetamol alone. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief over 4 to 6 hours compared with placebo. Adverse effects were used to calculate relative risk and number-needed-to-harm (NNH). MAIN RESULTS: We found 40 trials of paracetamol against placebo (4171 patients), 22 trials of paracetamol plus codeine against placebo (1407 patients) and 12 trials of paracetamol plus codeine against the same dose of paracetamol (794 patients). In postoperative pain paracetamol 1000 mg had an NNT of 4.6 (3.8-5.4) for at least 50% pain relief when compared with placebo, and paracetamol 600/650 mg had an NNT of 5.3 (4.1-7.2). Paracetamol 600/650 mg plus codeine 60 mg had an NNT of 3. 6 (2.9-4.5). Comparing paracetamol plus codeine 60 mg with the same dose of paracetamol alone gave an NNT of 7.7 (5.1-17) for at least 50% pain relief. Adverse effects: Relative risk estimates for paracetamol 600/650 mg plus codeine 60 mg versus placebo showed a significant difference for 'drowsiness'/somnolence (NNH 11 (7.5- 0)) and dizziness (NNH 27 (15-164)) but no significant difference for nausea/vomiting. REVIEWER'S CONCLUSIONS: Paracetamol is an effective analgesic with a low incidence of adverse effects. The addition of codeine 60 mg to paracetamol produces additional pain relief even in single oral doses, but may be accompanied by an increase in drowsiness and dizziness.


Rømsing et al 2002

Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia.

Rømsing J, Moiniche S, Dahl JB.

Br J Anaesth 2002;88(2):215–226.

BACKGROUND: We have reviewed the analgesic efficacies of rectal and parenteral paracetamol and tested the evidence for a possible additive analgesic effect of the combination of paracetamol with a non-steroidal anti-inflammatory drug (NSAID) in postoperative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia. RESULTS: Eight studies compared rectal paracetamol with placebo. One study of single-dose administration of rectal paracetamol 40–60 mg/kg and three studies of repeat dosing with 14–20 mg/kg showed significant analgesic efficacy, while studies of a single dose of 10–20 mg/kg were negative. Ten studies compared parenteral paracetamol with placebo and eight studies showed improved pain relief with paracetamol. Of the nine studies comparing paracetamol with a combination of paracetamol and an NSAID, six studies showed improved pain relief for the combination while only two of the six studies comparing an NSAID with a combination of an NSAID and paracetamol showed improved pain relief for the combination. CONCLUSIONS: Considering the few studies available, evidence was found of a clinically relevant analgesic effect of rectal and parenteral paracetamol. Concurrent use of paracetamol and an NSAID was superior to paracetamol alone but no evidence was found of superior analgesic effect of the combination compared with the NSAID alone.


Remy 2005

Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials.

Remy C, Marret E, Bonnet F.

Br J Anaesth 2005;94(4):505–13.

BACKGROUND: Acetaminophen is commonly used for the management of perioperative pain. However, there is a marked discrepancy between the extent to which acetaminophen is used and the available evidence for an analgesic effect after major surgery. The aim of this systematic review is to determine the morphine-sparing effect of acetaminophen combined with patient-controlled analgesia (PCA) with morphine and to evaluate its effects on opioid-related adverse effects. METHODS: MEDLINE and the Cochrane Library were searched to select randomized controlled trials which compared PCA morphine alone with PCA morphine plus acetaminophen administered orally or intravenously. Studies were evaluated for their quality based on the Oxford Quality Scale. Outcome measures were morphine consumption over the first 24 h after surgery, patient satisfaction and the incidence of morphine side-effects, including nausea and vomiting, sedation, urinary retention, pruritus and/or respiratory depression. RESULTS: Seven prospective randomized controlled trials, including 265 patients in the group with PCA morphine plus acetaminophen and 226 patients in the group with PCA morphine alone, were selected. Acetaminophen administration was not associated with a decrease in the incidence of morphine-related adverse effects or an increase in patient satisfaction. Adding acetaminophen to PCA was associated with a morphine-sparing effect of 20% (mean, -9 mg; CI -15 to -3 mg; P=0.003) over the first postoperative 24 h. CONCLUSION: Acetaminophen 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.


Altman 2004

A rationale for combining acetaminophen and NSAIDs for mild-to-moderate pain.

Altman RD.

Clin Exp Rheumatol 2004;22(1):110–7.

Analgesic therapy that combines individual agents with different mechanisms of action has potential advantages for the management of mild-to-moderate pain in the outpatient setting. Theoretically, this approach can lead to greater efficacy and fewer adverse events. While the precise mechanism of action for the analgesic effect of acetaminophen remains uncertain, accumulating evidence suggests that its activity resides primarily in the central nervous system. In contrast, the site of action for the analgesic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is predominantly peripheral, within injured or inflamed tissue. Several controlled clinical studies among patients with musculoskeletal conditions, dental pain, or postoperative pain have shown that combinations of acetaminophen and NSAIDs provide additive pain-relieving activity, thereby leading to dose-sparing effects and improved safety. Further studies are warranted to determine the clinical utility and safety of acetaminophen/NSAID combinations as analgesic therapy for common conditions associated with mild-to-moderate pain.


Sarac et al 1996

The effect and timing of local anesthesia in laparoscopic cholecystectomy.

Sarac AM, Aktan AO, Baykan N, Yegen C, Yalin R.

Surg Laparosc Endosc 1996;6(5):362–066.

Although postoperative pain following laparoscopic cholecystectomy (LC) is less intense than that after open surgery, postoperative morbidity nonetheless increases with LC. The aim of this study was to investigate whether local anesthetic infiltration of trocar sites during LC decreased postoperative pain and, if so, to find the optimum timing for local anesthesia (LA). Seventy patients undergoing LC were randomized into three groups. In the first (control group, n = 25) 3 ml of 0.9% NaCl was subcutaneously infiltrated around each 5-mm trocar site, 4 ml around each 10-mm site. In the second group (n = 20), the same volume of local anesthetic was administered in the same manner prior to surgery, and in the third group (n = 25) an identical dose of local anesthetic was infiltrated at the end of surgery. A visual analog scale was given to all patients, who were asked to record their pain intensity at 1, 3, 5, 7, and 12 h postoperatively. Pethidine HCl 1 mg/kg i.m. was given to those whose pain intensities were greater than 5. The mean pain intensities were 7.6, 5.9, and 5.1 in the control, preoperative, and postoperative LA groups, respectively. In the preoperative LA group, 50% of patients and in the postoperative LA group 28% of patients required analgesics compared with 76% in the control group. The main pain intensities and analgesic requirements were significantly lower in the postoperative LA group compared with other groups. We conclude that local anesthesia during LC reduces postoperative pain and that infiltration of trocar sites following surgery offers better pain relief than local anesthetic given just before the incision.


Alexander et al 1996

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy.

Alexander DJ, Ngoi SS, Lee L, So J, Mak K, Chan S, Goh PM.

Br J Surg 1996;83:1223–1225.


Ure et al 1993

Preincisional local anesthesia with bupivacaine and pain after laparoscopic cholecystectomy. A double-blind randomized clinical trial.

Ure BM, Troidl H, Spangenberger W, Neugebauer E, Lefering R, Ullmann K, Bende J

Surg Endosc 1993;7(6):482–8

The aim of this study was to investigate whether local anesthesia of abdominal wall wounds prior to laparoscopic cholecystectomy leads to decreased pain beyond the immediate postoperative period and thus improves the comfort of the patient. In a randomized, double-blind study 50 patients scheduled for laparoscopic cholecystectomy were divided into two groups. In one group (n = 25) the skin, subcutis, fascia, muscle, and preperitoneal space were infiltrated with 8 ml of bupivacaine 0.5% 5 min before each abdominal wall incision. The control group (n = 25) received normal saline. The intensity of pain was assessed by a 100-point visual analogue scale (VAS) at rest and during movement and by the consumption of analgesics. Analgesic therapy was provided by on-demand analgesia with piritramide intravenously for 24 h and continued by ibuprofen orally on request. The mean intensity of pain at rest and during movement was lower but not statistically significant in patients who received bupivacaine compared to the control group up to the second postoperative day. The difference was between 4 and 9 VAS points and therefore of doubtful clinical relevance. Similar statistically nonsignificant results were found for the mean consumption of piritramide up to 16 h after the operation. Three patients (12%) in the bupivacaine group localized the most severe pain up to the second postoperative day to the right lower abdominal wall wound where the gallbladder had been extracted compared to 11 patients (44%) of the control group (P = 0.012). These results indicate that bupivacaine was effective at the site where it was administered.(ABSTRACT TRUNCATED AT 250 WORDS)


Dath and Park 1999

Randomized, controlled trial of bupivacaine injection to decrease pain after laparoscopic cholecystectomy.

Dath D, Park AE.

JCC 1999;42(4):284–8.

OBJECTIVES: To determine if intraoperative instillation of bupivacaine would decrease early postoperative pain after laparoscopic cholecystectomy, if the patients would consequently require less narcotic postoperatively and if such patients would elect to be discharged on the day of operation if given the choice. DESIGN: Double-blind, randomized, controlled trial. SETTING: A tertiary care hospital in Hamilton, Ont. PATIENTS: Fifty patients underwent laparoscopic cholecystectomy. Day-surgery patients had the choice of staying overnight for discharge the following day. They were compared with a control group of 47 patients who had laparoscopic cholecystectomy but did not receive bupivacaine. INTERVENTION: Instillation of 20 ml of 0.5% bupivacaine with epinephrine into laparoscopic cholecystectomy port sites intraoperatively before closure. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) pain scores assessed 4 times postoperatively, the choice of patients to leave hospital the same day or to remain in the hospital overnight; the level of postoperative narcotic usage. MAIN RESULTS: Mean VAS pain scores (range 0 [no pain] to 5 [severe pain]) at less than 2 hours and at 6 hours after surgery were 2.9 and 2.9, respectively, in the bupivacaine group compared with 4.5 and 4.0, respectively, in the control group (p = 0.001 and 0.025). VAS scores at 10 hours postoperatively and the next morning did not differ between the groups. More patients in the bupivacaine group elected to go home on the day of surgery (p = 0.034). Narcotic usage was not significantly different. CONCLUSION: Instillation of bupivacaine into port sites should be standard practice for elective laparoscopic cholecystectomy.


Lee et al 2001

Pain after laparoscopic cholecystectomy: the effect and timing of incisional and intraperitoneal bupivacaine.

Lee I, Kim S, Kong M, Lee M, Kim N, Choi Y, Lim S.

Can J Anaesth 2001;48(6):545–50.

PURPOSE: To examine the combined preemptive effects of somatovisceral blockade during laparoscopic cholecystectomy (LC). METHODS: One hundred fifty-seven patients under general anesthesia receiving local infiltration and/or topical peritoneal local anesthesia were studied. Patients were randomized to receive a total of 150 mg (0.25% 60 mL) bupivacaine via periportal (20 mL) and intraperitoneal (40 mL with 1:200,000 epinephrine) administration of each. Group A received preoperative periportal bupivacaine before incision and intraperitoneal bupivacaine immediately after the pneumoperitoneum. Group B received periportal and intraperitoneal bupivacaine at the end of the operation. Group C (preoperative) and Group D (postoperative) received only periportal bupivacaine and Group E (preoperative) and Group F (post-operative) received only intraperitoneal bupivacaine. The control group received no treatment. Pain and nausea were recorded at one, two, three, six, nine, 12, 24, 36, and 48 hr postoperatively. RESULTS: Throughout the postoperative 48 hr, incisional somatic pain dominated over other pain localizations in the control group (P <0.05). The incisional pain of groups A, B, C and D was significantly lower than that of the control group in the first and second hours. The incisional pain of groups A and C was significantly lower than that of the control group in the first three hours. CONCLUSION: Incisional pain dominated during the first two post-operative days after LC. Preoperative somato-visceral or somatic local anesthesia reduced incisional pain during the first three post-operative hours. A combination of somato-visceral local anesthetic treatment did not reduce intraabdominal pain, shoulder pain or nausea more than somatic treatment alone. Preoperative incisional infiltration of local anesthetics is recommended.


Lepner et al 2003

Postoperative pain relief after laparoscopic cholecystectomy: A randomised prospective double-blind clinical trial.

Lepner U, Goroshina J, Samarutel J

Scandinavian Journal of Surgery: SJS 2003;92(2):121–124

Background and Aims: The clinical value of infiltration of wounds with local anaesthetics (LA) and their intraperitoneal application for treating pain after laparoscopic cholecystectomy (LC) still remain controversial. In this study the use of intraincisional and intraperitoneal LA was evaluated. Material and Methods: Eighty patients were prospectively randomised into four groups. In the control group (G1) LA was not used. In G2 all wounds were infiltrated with 80 ml of 0.125% Bupivacaine containing 5 mg of Phenylephrine. In G3 the wounds were infiltrated with 80 ml of 0.9 % NaCl. In G4, in addition to wound infiltration with Bupivacaine/Phenylephrine, 200 ml of normal saline, containing 0.15% of Lidocaine, was left intraperitoneally under the right diaphragm. Postoperative abdominal and shoulder pain scores were recorded on a visual analogue scale (VAS) during 24 hours after LC. Narcotic analgesic consumption was also recorded. Results: The mean abdominal pain scores were significantly lower in G2, compared with G3, 3 to 24 hours after operation, compared with G4, 3 to 6 hours and compared with G1, 3 to 24 hours (except at hour 12) after surgery. The incidence of shoulder pain was 30%. There were no significant differences in the mean shoulder pain scores between the groups. The mean dosage and the total amount of Pethidine at 24 hours were significantly lower in G2 compared with G1. Conclusions: Intraincisional infiltration with a Bupivacaine/Phenylephrine mixture reduces significantly abdominal postoperative pain (for up to 24 h) and narcotic analgesic consumption after LC. An intraperitoneal subdiaphragmatic dilute solution of Lidocaine was not effective in reducing overall pain and shoulder pain after LC.


Papagiannopoulou et al 2003

Preincisional local infiltration of levobupivacaine vs ropivacaine for pain control after laparoscopic cholecystectomy.

Papagiannopoulou P, Argiriadou H, Georgiou M, Papaziogas B, Sfyra E, Kanakoudis F

Surgical Endoscopy 2003;17(12):1961–4

BACKGROUND: Postoperative pain is less intense after laparoscopic surgery than after open surgery. However, patients may gain additional benefit from a preincisional local infiltration of anesthetic. The aim of this study was to compare the analgesic efficacy of two local anesthetics, ropivacaine and levobupivacaine, for tissue infiltration as a means of improving postoperative pain control after laparoscopic cholecystectomy. METHODS: Using a randomized, double-blind study design, 57 American Society of Anesthesiologists (ASA) I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive local infiltration with 0.9% saline solution (Placebo group, n = 18), ropivacaine 1% (Rop group, n = 20), or levobupivacaine 0.5% (Lev group, n = 19). The local anesthetic was administered, prior to trocar placement, using the same technique and delivering the same volume (20 ml) for all three groups. The anesthetic technique was standardized for all groups. Postoperative pain was rated at 2 h, 4 h, and 24 h postoperatively by visual analogue scale (VAS) score. Cumulative analgesic consumption and adverse effects were also recorded. Data were analyzed by analysis of variance (ANOVA), followed by a post hoc test. RESULTS: The Lev and Rop groups did not differ significantly in their VAS scores at 2 h postoperatively, but the Lev group experienced significantly ( p < 0.001) less pain than the Placebo and Rop groups at 4 h and 24 h postoperatively. The Rop group registered significantly lower VAS scores ( p < 0.001) than the Placebo group at 4 h postoperatively. Additionally, the consumption of analgesics was significantly lower in the Lev group than in the Rop ( p < 0.01) and Placebo ( p < 0.001) groups, and patients in the Rop group consumed significantly less analgesics ( p < 0.001) than the to patients in the Placebo group. CONCLUSION: Local tissue infiltration with levobupivacaine is more effective than ropivacaine in reducing the postoperative pain associated with laparoscopic cholecystectomy.


Zajaczkowska et al 2004

Peripheral opioid analgesia in laparoscopic cholecystectomy.

Zajaczkowska R, Wnek W, Wordliczek J, Dobrogowski J

Regional Anesthesia & Pain Medicine 2004;29(5):424–429

Recent research has revealed that opioids can act directly on the peripheral terminals of afferent nerves to mediate antinociception. The aim of this study was to assess the influence of peripheral morphine administration on the nociception process in the postoperative period. One hundred fifty patients for laparoscopic cholecystectomy were randomly divided into 5 groups. Group M patients (n = 30) received local infiltration at trocar insertion points with 2 mg morphine in 20 mL of 0.9% NaCl solution (5 mL of solution per point) 10 minutes before the operation. For group B patients (n = 30), the solution used for infiltration was 20 mL of 0.25% bupivacaine; for group M+B patients (n = 30), the solution was 2 mg morphine in 20 mL of 0.25% bupivacaine; and for group S patients (n = 30), the solution was 20 mL 0.9% NaCl. For group S+M patients (n = 30), trocar insertion points were infiltrated with 20 mL of 0.9% NaCl, and patients in this group were given 2 mg of subcutaneous morphine 10 minutes before the surgery. Postoperative analgesic therapy was provided by on-demand analgesia with tramadol. After surgery, the following were measured: pain intensity scored on the visual analog scale, total tramadol requirement, time from the end of the surgical procedure to the administration of the first dose of tramadol, and the frequency of undesirable side effects (sedation, nausea, and vomiting). Pain intensity and total tramadol requirement after surgery were lower in groups M, B, and M+B compared with groups S and S+M, but these differences were not statistically significant. The time from the completion of the operation to the administration of the first dose of tramadol was significantly longer in groups M, B, and M+B compared with groups S and S+M. Results of the study confirm the possibility of modifying the nociception process in the postoperative period through peripheral opioid administration.


Møiniche et al 2000

Local anesthetic infiltration for postoperative pain relief after laparoscopy: A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block.

Møiniche S, Jorgensen H, Wetterslev J, Dahl JB

Anesth Analg 2000; 90: 899–912.

In a systematic review, we evaluated randomized controlled trials (RCTs) of peripheral local anesthetics (LA) compared with placebo or no treatment in the control of postoperative pain after laparoscopic surgery. A total of 41 trials with data from 2794 patients were considered appropriate for analysis. Of these 41 RCTs, 13 evaluated intraperitoneal LA after cholecystectomy, four RCTs assessed intraperitoneal LA after other procedures, eight RCTs evaluated port-site infiltration after various procedures, 12 RCTs evaluated mesosalpinx or fallopian tube block after sterilization, and four RCTs considered combined LA regimens. Outcome measures were pain scores, analgesic consumption, and time to first analgesic request. Efficacy was estimated by significant difference (P < 0.05), as reported in the original reports, and by calculation of the weighted mean difference of visual analog scale pain scores between treatment groups. Improved pain relief was observed in seven of the 13 RCTs of intraperitoneal LA after cholecystectomy and in four RCTs of other procedures. A statistically significant weighted mean difference of -13 mm visual analog scale (95% confidence intervals [CI]: -20 to -6) in favor of the treatment groups was observed after cholecystectomy. Three of eight trials of port-site infiltration showed significant differences but questionable clinical importance and validity in two; weighted mean difference was not statistically significant between treatment groups (95% CI -9 to 1). All RCTs of mesosalpinx or fallopian tube block after sterilization showed improved pain relief with a statistically significant weighted mean difference of -19 mm (95% CI -25 to -14) in favor of treatment groups. Data of combined regimens were positive, however, sparse. We conclude that there was evidence for a statistically significant but clinically questionable, important effect of intraperitoneal LA for postoperative pain control. There was evidence for a significant but short-lasting effect of mesosalpinx/fallopian tube block after sterilization, but there was a lack of evidence for any important effect of port-site infiltration. Data from combined regimens were too sparse for conclusions. IMPLICATIONS: A systematic review summarizes, through transparent methodology, available information from randomized, controlled trials to produce the best available evidence-based estimate of a "true" clinical effect of an intervention. This systematic review confirms intraperitoneal and mesosalpinx local anesthetic block, not port-site infiltration, to have some impact on postoperative pain after laparoscopy.


Møiniche et al 1998

A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations.

Møiniche S, Mikkelsen S, Wetterslev J, Dahl JB.

Br J Anaesth 1998; 81: 377–383.

In a qualitative systematic review, we have evaluated randomized controlled trials (RCT) of incisional local anaesthesia compared with placebo or no treatment in the control of postoperative pain after open abdominal operations. Twenty-six studies with data from 1211 patients were considered appropriate for analysis. Five RCT considered inguinal herniotomy, four hysterectomy, eight cholecystectomy and nine studies a variety of surgical procedures. Outcome measures were pain scores, supplementary analgesics and time to first analgesic request. Efficacy was estimated by significant difference (P < 0.05), as reported in the original investigation. All studies of herniotomy showed a 2-7-h duration of clinically relevant improved pain relief. Results of hysterectomy studies were inconclusive, with two being negative. Five of the cholecystectomy studies showed significant differences but questionable clinical importance and validity in three. In various other procedures results were inconsistent and in some of minor clinical importance. Except for herniotomy, there was a lack of evidence for effect of incisional local anaesthesia on postoperative pain and further standardized studies are needed before recommendations can be made.


Naja et al 2004

General anaesthesia combined with bilateral paravertebral blockade (T5-6) vs. general anaesthesia for laparoscopic cholecystectomy: A prospective, randomized clinical trial.

Naja MZ, Ziade MF, Lonnqvist PA.

European Journal of Anaesthesiology 2004;21(6):489–495.

Background and objective: The efficiency of bilateral paravertebral blockade combined with general anaesthesia (active) vs. general anaesthesia alone (control) in reducing postoperative pain following laparoscopic cholecystectomy was evaluated using a prospective randomized study design. Methods: Patients were randomly assigned to either group. Nerve-stimulator guided paravertebral blockade at the T5-6 level was performed with a local anaesthetic mixture (0.30 mL kg-1). Twenty millilitres of the mixture contained lidocaine 2% 6 mL; lidocaine 2% 6 mL with epinephrine 1/200 000; bupivacaine 0.5% 5 mL; fentanyl 1 mL (50 [mu]g mL-1) and clonidine 2 mL (150 [mu]g mL-1). Postoperative pain and consumption of opioids were assessed during the first 72 h. Results: Two-times 30 patients were analysed. Patient characteristics data, and pre- and peroperative variables were similar in both groups. Mean pain scores visual analogue scale were significantly less with active compared with control (P < 0.05) at 6h (1.56 +/- 1.58 vs. 4.78 +/- 1.67), at 12 h (1.52 +/- 1.58 vs. 3.81 +/- 1.63), at 24 h (1.16 +/- 1.34 vs. 2.71 +/- 1.50), at 36 h (0.68 +/- 1.02 vs. 2.29 +/- 1.41), at 48 h (0.60 +/- 1.04 vs. 1.61 +/- 1.33) and at 72 h (0.40 +/- 0.86 vs. 1.19 +/- 1.16). The number of patients consuming supplemental analgesics was significantly less (P < 0.05) with active compared with control, at 6 h (6 vs. 29), at 12 h (2 vs. 26), at 24 h (1 vs. 23) and at 36 h (2 vs. 15). More patients were free from nausea (P < 0.05) with active compared with control at 6 h (23 vs. 9) and at 12 h (29 vs. 19). Conclusion: When used as a complement to general anaesthesia, bilateral nerve-stimulator guided paravertebral blockade with lidocaine, bupivacaine, fentanyl and clonidine may improve postoperative pain relief.


Naja et al 2002

Bilateral paravertebral somatic nerve block for ventral hernia repair.

Naja Z, Ziade MF, Lonnqvist PA.

Eur J Anaesthesiol 2002;19(3):197–202.

Eur J Anaesthesiol 2002;19(3):197–202.BACKGROUND AND OBJECTIVE: Unilateral paravertebral nerve blockade has been reported to produce excellent afferent nerve block, reduce the incidence of postoperative nausea and vomiting, and reduce hospital stay following inguinal hernia repair. The aim was to compare the use of bilateral paravertebral blocks to regular general anaesthesia for ventral hernia repair. METHODS: Sixty patients were prospectively allocated to receive either bilateral paravertebral nerve blockade (midazolam for block; supplemented with light intraoperative sedation if needed) or general anaesthesia for ventral hernia repair. The end-points of the study were length of hospital stay, postoperative analgesia (visual analogue scale, supplemental opioid requirement) and incidence of postoperative nausea and vomiting. RESULTS: The duration of hospital stay was observed to be shorter in patients handled with bilateral paravertebral nerve blockade (2.3 [SD 1.3] days) compared with patients receiving general anaesthesia (4.1 (3.0) days). Paravertebral analgesia resulted in both lower visual analogue scores and a significantly reduced need for supplemental opioid administration during the first 48 h postoperatively compared with general anaesthesia (P < 0.001). The rate of postoperative nausea and vomiting in the paravertebral nerve blockade group was only 3.3%, while 26.7% of patients in the general anaesthesia group suffered from postoperative nausea and vomiting (P < 0.05). Paravertebral nerve blockade was associated with good patient acceptance in 90% of patients. CONCLUSIONS: Bilateral paravertebral blockade combined with light intravenous sedation was superior to general anaesthesia for ventral hernia repair. Paravertebral blockade was associated with shorter hospital stay, improved analgesia and less postoperative nausea and vomiting. It is suggested that this technique deserves more widespread use in patients undergoing ventral hernia repair.


Motamed et al 2000

Analgesic effect of low-dose intrathecal morphine and bupivacaine in laparoscopic cholecystectomy.

Motamed C, Bouaziz H, Franco D, Benhamou D.

Anaesthesia 2000;55:118–124.

We assessed the peri-operative analgesic efficiency of low-dose intrathecal morphine combined with a low dose of bupivacaine after elective laparoscopic cholecystectomy since postoperative pain in such procedures, although less than after a conventional open technique, may be significant, particularly during the first 12-24 h. After informed consent, 34 ASA I or II patients were randomly allocated to one of two groups to receive either a lumbar intrathecal injection of morphine (75 or 100 microg) combined with 5 mg of isobaric bupivacaine (spinal group) or a subcutaneous injection of a saline solution (control group). Intra-operatively, opioid requirements, blood pressure response and heart rate changes after insufflation were recorded. Postoperatively, morphine requirements, pain scores and opioid-related side-effects were assessed by a physician blinded to the randomisation. Intra-operative opioid requirements did not differ significantly between groups. Mean (SD) postoperative morphine requirements were significantly lower in the spinal group [13 (10) vs. 23 (10) mg; p = 0.04] as were postoperative pain scores (p < 0.001). Side-effects were of comparable incidence and severity between groups. Low-dose intrathecal morphine combined with low-dose bupivacaine provided effective postoperative analgesia for elective laparoscopic cholecystectomy.


Chaney 1995

Side effects of intrathecal and epidural opioids.

Chaney MA.

Can J Anaesth. 1995;42:891–903.

The purpose of this article is to review the literature on the side effects of intrathecal and epidural opioids. English-language articles were identified through a MEDLINE search and through review of the bibliographies of identified articles. With the increasing utilization of intrathecal and epidural opioids in humans during the 1980s, a wide variety of clinically relevant side effects have been reported. The four classic side effects are pruritus, nausea and vomiting, urinary retention, and respiratory depression. Numerous other side effects have also been described. Most side effects are dose-dependent and may be more common if the opioid is administered intrathecally. Side effects are less common in patients chronically exposed to either intrathecal, epidural, or systemic opioids. Some side effects are mediated via interaction with specific opioid receptors while others are not. It is concluded that the introduction of intrathecal and epidural opioids marks one of the most important breakthroughs in pain management in the last two decades. However, a wide variety of clinically relevant non-nociceptive side effects may occur. All physicians utilizing intrathecal and epidural opioids must be aware of these side effects, for while most are minor, others are potentially lethal.


Bisgaard et al 2004

Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy.

Bisgaard T, Kristiansen VB, Hjortso NC, Jacobsen LS, Rosenberg J, Kehlet H

British Journal of Surgery 2004;91(2):151–158

Background: Preoperative oral carbohydrate can attenuate postoperative insulin resistance and catabolism, and may have the potential to improve postoperative recovery. There are no data from randomized studies on postoperative clinical outcome after specific surgical procedures. This study evaluated the clinical effects of a preoperative carbohydrate beverage in patients undergoing laparoscopic cholecystectomy. Methods: Ninety-four patients undergoing laparoscopic cholecystectomy were included in a randomized clinical trial. Patients were randomized to receive 800 ml of an iso-osmolar 12.5 per cent carbohydrate-rich beverage the evening before operation (100 g carbohydrate) and another 400 ml (50 g carbohydrate) 2 h before initiation of anaesthesia, or the same volume of a placebo beverage. The primary endpoint was general well-being the day after operation. Patients were evaluated from 5 days before to 5 days after operation. Daily scores of general well-being, fatigue, appetite and pain, computerized measurements of physical activity and sleep (actigraphy), and subjective sleep quality were recorded. Nausea and vomiting were assessed twice within the first 24 h after surgery. Results: Data from 86 patients were available for statistical analysis, 43 in each treatment group. No significant intergroup differences in general well-being or any other outcome variable were found. Conclusion: A preoperative carbohydrate beverage did not improve clinical outcome after laparoscopic cholecystectomy.


Hausel et al 2005

Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy.

Hausel J, Nygren J, Thorell A, Lagerkranser M, Ljungqvist O

Br J Surg 2005;92(4):415–21

BACKGROUND: A carbohydrate-rich drink (CHO) has been shown to reduce preoperative discomfort. It was hypothesized that it may also reduce postoperative nausea and vomiting (PONV). METHODS: Patients undergoing elective laparoscopic cholecystectomy under inhalational anaesthesia (127 women and 45 men; mean(s.d.) 48(15) years) were randomized to either preoperative fasting, intake of CHO (50 kcal/100 ml, 290 mOsm/kg) or placebo. The non-fasting groups were double-blinded; patients ingested 800 ml of liquid on the evening before surgery and 400 ml 2 h before anaesthesia. Nausea and pain scores on a visual analogue scale (VAS) and episodes of PONV were recorded up to 24 h after surgery. RESULTS: The incidence of PONV was lower in the CHO than in the fasted group between 12 and 24 h after surgery (P = 0.039). Nausea scores in the fasted and placebo groups were higher after operation than before admission to hospital (P = 0.018 and P < 0.001 respectively), whereas there was no significant change in the CHO group. No intergroup differences in VAS scores were seen. The use of anaesthetics, opioids, antiemetics and intravenous fluids was similar in all groups. CONCLUSION: CHO may have a beneficial effect on PONV 12-24 h after laparoscopic cholecystectomy.


Fredman et al 1995

A comparative study of ketorolac and diclofenac on post-laparoscopic cholecystectomy pain.

Fredman B, Olsfanger D, Jedeikin R.

Eur J Anaesthiol 1995;12:501–504.

In a randomized, double-blind, placebo-controlled study designed to assess the post-operative analgesic efficacy and cost-effectiveness of ketorolac and diclofenac 60 ASA I and II patients undergoing laparoscopic cholecystectomy were studied. Prior to concluding the operative procedure, an injection (i.m.) of an equal volume of either saline 3 mL, ketorolac 60 mg, or diclofenac 75 mg was administered. All patients received intravenous morphine via a patient-controlled analgesia device (PCA). Post-operative pain intensity was assessed hourly for 4 h, by recording visual analogue score (VAS) for pain, PCA demands and actual morphine administered. PCA demands (mean +/- SD) were greater in the saline treatment group (115 +/- 90) when compared with both the ketorolac (42 +/- 44) and diclofenac groups (74 +/- 77). Furthermore, the saline treatment group received significantly (p < 0.05) more PCA morphine compared with both the ketorolac and diclofenac groups (12.2 mg +/- 5.0 vs. 8.6 mg +/- 5.2 vs. 8.9 mg +/- 4.8). Improved pain scores were demonstrated in both the ketorolac and diclofenac groups compared with the saline group. PCA demands and post-operative morphine requirements were similar in the ketorolac and diclofenac groups. Diclofenac has the added advantage, in our institution, of being 60% less expensive than ketorolac. We conclude that both ketorolac and diclofenac are effective post-operative analgesic drugs. However, economic considerations may favour diclofenac administration.


Bhatia et al 2004

Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy

Bhatia A, Kashyap L, Pawar DK, Trikha A

J Clin Anesth 2004;16(4):262–5

STUDY OBJECTIVE: To study the role of magnesium sulphate (MgSO4) on analgesic requirement, pain, discomfort, and sleep during perioperative period. DESIGN: prospective, double-blinded, randomized study. SETTINGS: Operating room and recovery ward at a university teaching hospital. PATIENTS: 50 ASA physical status I and II patients scheduled for elective open cholecystectomy with general anesthesia. INTERVENTIONS: patients were randomly allocated to receive MgSO4 or saline intravenously (i.v.). Patients in the magnesium group received 50% MgSO4 (50 mg kg(-1)) in 100 mL saline and those in the control group received an equal volume of saline i.v. during the preoperative period followed by 50 mL hr(-1) infusion of either MgSO4 (15 mg kg(-1) hr(-1)) or saline until the end of surgery. MEASUREMENTS AND MAIN RESULTS: Morphine requirement, pain during rest and on coughing, discomfort, and insomnia were assessed during the postoperative period for 24 hours. Intravenous morphine 40 microg kg(-1) increments were given to all patients in the postoperative period for analgesia. Patients in the magnesium and control groups had similar morphine requirement during the first 24 hours postoperatively (p = 0.07). Patients in the magnesium group experienced less discomfort during the first hour after the operation. They also had better sleep quality during the first postoperative night than did the control group patients (p < 0.05). The frequency of side effects was similar in the two groups. CONCLUSION: Administration of intraoperative MgSO4 as an adjuvant analgesic in patients undergoing open cholecystectomy resulted in better pain relief and comfort in the first postoperative hour, but it did not significantly decrease the postoperative morphine requirement. Magnesium sulphate resulted in better sleep quality during the postoperative period, without any significant adverse effects. The role of MgSO4 as an adjuvant analgesic in open cholecystectomy needs to be studied further.


Johnson et al 1999

Ideal pain relief following laparoscopic cholecystectomy.

Johnson RC, Hedges AR, Morris R, Stamatakis JD

Int J Clin Pract 1999;53(1):16–8

In a previous report the effectiveness of intraperitoneal bupivacaine in reducing pain following laparoscopic cholecystectomy was demonstrated. Other methods of pain relief are commonly used but none has been compared following laparoscopic cholecystectomy. In two further studies we have compared the analgesic effect of intraperitoneal bupivacaine against wound infiltration with bupivacaine, and against intraperitoneal bupivacaine with the addition of a non-steroidal anti-inflammatory drug (NSAID) in patients undergoing laparoscopic cholecystectomy. Two consecutive studies were performed. In the first, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine injected into the trocar wounds. In the second study, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity and a diclofenac suppository (100 mg) one hour before surgery. Postoperative pain was assessed with a visual analogue pain scale. There was no difference in pain scores in the two groups in either study. Intraperitoneal bupivacaine is as effective as wound infiltration. The addition of an NSAID makes no difference in the reduction of postoperative pain following laparoscopic cholecystectomy.


Bisgaard et al 1999

Multi-regional local anesthetic infiltration during laparoscopic cholecystectomy in patients receiving prophylactic multi-modal analgesia: a randomized, double-blinded, placebo-controlled study.

Bisgaard T, Klarskov B, Kristiansen VB, Callesen T, Schulze S, Kehlet H, Rosenberg J.

Anesth Analg 1999;89:1017–24.

Pain is the dominant complaint after laparoscopic cholecystectomy. No study has examined the combined effects of a somato-visceral blockade during laparoscopic cholecystectomy. Therefore, we investigated the effects of a somato-visceral local anesthetic blockade on pain and nausea in patients undergoing elective laparoscopic cholecystectomy. In addition, all patients received multi-modal prophylactic analgesic treatment. Fifty-eight patients were randomized to receive a total of 286 mg (66 mL) ropivacaine or 66 mL saline via periportal and intraperitoneal infiltration. During the first 3 postoperative h, the use of morphine and antiemetics was registered, and pain and nausea were rated hourly. Daily pain intensity, pain localization, and supplemental analgesic consumption were registered the first postoperative week. Ropivacaine reduced overall pain the first two hours and incisional pain for the first three postoperative hours (p < 0.01) but had no apparent effects on intraabdominal or shoulder pain. During the first 3 postoperative h, morphine requirements were lower (p < 0.05), and nausea was reduced in the ropivacaine group (p < 0.05). Throughout the first postoperative week, incisional pain dominated over other pain localizations in both groups (p < 0.01). We conclude that the somato-visceral local anesthetic blockade reduced overall pain during the first 2 postoperative h, and nausea, morphine requirements, and incisional pain were reduced during the first 3 postoperative h in patients receiving prophylactic multi-modal analgesic treatment. IMPLICATIONS: A combination of incisional and intraabdominal local anesthetic treatment reduced incisional pain but had no effect on deep intraabdominal pain or shoulder pain in patients receiving multimodal prophylactic analgesia after laparoscopic cholecystectomy. Incisional pain dominated during the first postoperative week. Incisional infiltration of local anesthetics is recommended in patients undergoing laparoscopic cholecystectomy.


Busley et al 1999

Intraperitoneal local anesthetics via subphrenic catheter following laparoscopic cholecystectomy: pain relief and pulmonary function.

Busley R, Blobner M, Jelen-Essenborn S, Feussner H, Kochs E.

Min Invas Ther & Allied Technol 1999;8(4):219–25.

Pain and pulmonary impairment continue to be major issues in the postoperative management of day-care laparoscopic cholecystectomy. 33 patients undergoing laparoscopic cholecystectomy were randomly assigned to one of two groups of postoperative pain management. The first group received prilocaine and bupivacaine via a subphrenic catheter inserted through a trocar incision at the end of laparoscopy. The second group received i.v. piritramid on request. Pain and alertness were assessed by visual analogue acales, pulmonary function by bedside spirometry and arterial blood gas analysis. There was no difference in pain scoring between groups, but pain relief was significantly faster in Group 1. No differences were found between groups in impaired postoperative forced vital capacity and peak expiratory flow, but only group 2 patients developed hypercarbia. It is concluded that postoperative pain relief via a subphrenic catheter is faster, equally effective and associated with greater alertness and no hypercarbia. Impaired pulmonary function cannot be improved when applying prilocaine and bupivacaine via the subphrenic catheter, instead of giving i.v. piritramid.


Paulson et al 2003

The use of intraperitoneal bupivacaine to decrease the length of stay in elective laparoscopic cholecystectomy patients.

Paulson J, Mellinger J, Baguley W

Am Surg 2003;69(4):275-8; discussion 278–9

This prospective, double-blind, randomized, and placebo-controlled study evaluates the effectiveness of intraperitoneal bupivacaine in decreasing the length of stay for elective laparoscopic cholecystectomy patients. Seventy-seven patients undergoing elective laparoscopic cholecystectomy before noon at a single institution and by a single group of surgeons were entered into the study. The pharmacy randomly assigned each patient to one of four study groups (control, predissection, postdissection, and both). Two syringes (A and B) containing 15 cm3 of either normal saline or 0.5 per cent bupivacaine were sent with the patient to surgery. Syringe A was sprayed over the perihepatic area before any dissection, and B was sprayed over the perihepatic area just before port removal. Preoperative, intraoperative, and postoperative data were collected. Sixty-six patients completed the study: control, 14; predissection, 18; postdissection, 15; and both, 19. There was no statistical difference between the predissection, postdissection, and both groups regarding same-day discharge. Therefore, these groups were combined for comparison against the control group. The study found that patients receiving bupivacaine at any time during the surgery were more likely to go home the same day as their procedure (79% vs 43%, respectively: P < 0.02).


Bisgaard 2006

Analgesic treatment after laparoscopic cholecystectomy: a critical assessment of the evidence.

Bisgaard T.

Anesthesiology 2006;104(4):835-46.

Acute pain after laparoscopic cholecystectomy is complex in nature. The pain pattern does not resemble pain after other laparoscopic procedures, suggesting that analgesic treatment might be procedure specific and multimodal. Randomized trials of analgesia after laparoscopic cholecystectomy were identified by systematic electronic literature searches (1985 to June 2005) supplemented with manual searching. The trials were categorized by well-defined criteria into high, moderate, or poor methodologic quality. Conclusions were based on trials of high and moderate methodologic quality. In total, 64 randomized analgesic trials were identified, comprising a total of 5,018 evaluated patients. The literature suggests a multimodal analgesic regimen consisting of a preoperative single dose of dexamethasone, incisional local anesthetics (at the beginning or at the end of surgery, depending on preference), and continuous treatment with nonsteroidal antiinflammatory drugs (or cyclooxygenase-2 inhibitors) during the first 3-4 days. Opioids should be used only when other analgesic techniques fail.


Elhakim et al 2000

Intraperitoneal lidocaine for postoperative pain after laparoscopy.

Elhakim M, Elkott M, Ali NM, Tahoun HM

Acta Anaesthesiol Scand 2000;44(3):280–4

BACKGROUND: A controversy exists over the effectiveness and clinical value of intraperitoneal local anaesthetics for treating pain after laparoscopic cholecystectomy. The use of intraperitoneal lidocaine was evaluated in this study. METHODS: At the end of surgery, 200 ml saline containing 200 mg lidocaine, or the same volume of saline, were randomly splashed under the right diaphragmatic surface in 50 patients in a double-blind manner. Postoperative shoulder and abdominal pain intensity were recorded on a numeric grading scale and a visual analogue scale, respectively. Analgesic consumption was also recorded. Respiratory function tests were compared before and after surgery. Side effects and recovery variables were assessed by the nurses at 2-h intervals. RESULTS: The incidence, severity and duration of shoulder pain were reduced from 40% of patients scoring 3.9+/-0.2 for duration of 17.9+/-0.2 h in the control group to 12% scoring 2.5+/-0.5 for duration of 1.6+/-0.01 h in the lidocaine group. Lidocaine treated patients had significantly less abdominal postoperative pain immediately on return to the ward and during the first postoperative day (P<0.05). "No pain on deep inspiration" was reported by 72% of patients in the lidocaine group immediately on return to the ward compared to 8% of those in the control group. Analgesic consumption for 24 h after surgery was significantly less in the lidocaine group (P<0.05). There were no significant differences in respiratory function tests, recovery variables or incidence of side effects between the two groups. CONCLUSION: Intraperitoneal lidocaine is simple to use and results in a long-lasting reduction of pain after a single administration.


 


Scheinin et al 1995

Effect of intraperitoneal bupivacaine on pain after laparoscopic cholecystectomy.

Scheinin B, Kellokumpu I, Lindgren L, Haglund C, Rosenberg PH

Acta Anaesthesiol Scand 1995;39(2):195–8

The effect of intraperitoneal bupivacaine on postoperative pain was studied in 60 ASA 1-2 patients undergoing elective laparoscopic cholecystectomy. The patients were randomly selected (20 patients in each group) to receive in double-blind fashion 100 mo of either plain 0.15% bupivacaine (150 mg.100 ml-1) or the same solution with adrenaline (1.5 micrograms ml-1), or the same volume of saline into the right subdiaphragmatic space at the end of surgery. The patients were kept in the Trendelenburg's position for 20 min after the instillation. Venous blood samples for the determination of bupivacaine plasma concentrations were drawn up to 180 min. Plasma bupivacaine concentrations peaked at 30 min (highest individual value 2.6 micrograms ml-1) after instillation. Bupivacaine concentrations were significantly lower in the bupivacaine-adrenaline group. During the follow-up no difference between the groups occurred as to the time to first demand of analgesia, severity of postoperative pain, amount of consumed analgesics during 7 days, and length of hospitalization. In all groups, 30-45% of the patients complained of right shoulder pain. After the first 24 hours, pain at rest and during moving was reported as mild and was managed with oral ketoprofen. It is concluded that postsurgical intraperitoneal instillation of 150 mg bupivacaine in 100 ml of saline had no effect on pain after laparoscopic cholecystectomy.


Pasqualucci et al 1994

The effects of intraperitoneal local anesthetic on analgesic requirements and endocrine response after laparoscopic cholecystectomy: a randomized double-blind controlled study.

Pasqualucci A, Contardo R, Da Broi U, Colo F, Terrosu G, Donini A et al AU - Sorrentino M AU - Pasetto A AU - Bresadola F.

J Laparoendosc Surg 1994;4(6):405–12.

This randomized double-blind placebo-controlled study was designed to evaluate the effects on postoperative pain of the local anesthetic, 0.5% bupivacaine with epinephrine, sprayed hepatodiaphragmatically under the surgeon's direct view during laparoscopic cholecystectomy. Metabolic endocrine responses to surgery (glucose and cortisol) and nonsteroidal anti-inflammatory drug requirements were investigated, as well as the presence of nausea, vomiting, and sweating. Local anesthetics or placebo solutions were given as follows. Immediately following the creation of a pneumoperitoneum, surgeons sprayed the first 20 mL of solution (S1), and an additional 20 mL of solution (S2) was sprayed at the end of the operation. Patients were classified into three groups (14 patients per group). Group A received 20 mL of saline during both S1 and S2, group B received 20 mL of saline during S1 and 20 mL of bupivacaine during S2, and group C received 20 mL of bupivacaine during both S1 and S2. The degree of postoperative pain was assessed using the visual analogue scale (VAS) and the verbal rating scale (VRS) on arrival in the recovery room and subsequently at time intervals of 4 h, 8 h, 12 h, and 24 h. The results of this study indicate a significant decrease of postoperative pain in patients treated with local anesthetic. VAS and VRS pain scores, as well as respiratory rate and analgesic requirements, were significantly lower in group C. The postoperative plasma cortisol level in group C was significantly lower than in groups A and B.


Rademaker et al 1994

Intraperitoneal local anaesthetics after laparoscopic cholecystectomy: effects on postoperative pain, metabolic responses and lung function.

Rademaker BM, Kalkman CJ, Odoom JA, de Wit L, Ringers J.

Br J Anaesth 1994;72:263–266.

We have compared the efficacy of 0.9% NaCl 20 ml (n = 15), 0.25% bupivacaine 20 ml (n = 15) and 0.5% lignocaine 20 ml (n = 15), administered i.p., in reducing postoperative pain and opioid requirements, and modifying the metabolic response to surgery and postoperative lung function after laparoscopic cholecystectomy. There were no differences in postoperative pain scores (visual analogue scale and verbal rating scale) between the three groups in the first 4 h after operation and in analgesic requirements during the first 24 h. In all groups, forced vital capacity, peak expiratory flow and forced expiratory volume in 1 s decreased 2 h after surgery (P < 0.001). Ventilatory values recovered only partially in the first 2 days after operation (P < 0.05), with no significant differences between groups. Plasma concentrations of glucose and cortisol increased after surgery (P < 0.05). Cortisol concentrations returned to baseline 48 h after operation. There were no significant differences between the groups in any measured variable. These data suggest that the administration of 20 ml of local anaesthetics i.p. is not effective in reducing postoperative pain, improving lung function, or attenuating the metabolic endocrine response after laparoscopic cholecystectomy.


Pasqualucci et al 1996

Preemptive analgesia: intraperitoneal local anesthetic in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study.

Pasqualucci A, De Angelis V, Contardo R, Colo F, Terrosu G, Donini A, Pasetto A, Bresadola F.

Anesthesiology 1996;85:11–20.

BACKGROUND: A controversy exists over the effectiveness and clinical value of preemptive analgesia. Additional studies are needed to define the optimum intensity, duration, and timing of analgesia relative to incision and surgery. METHODS: One hundred twenty patients undergoing laparoscopic cholecystectomy under general anesthesia plus topical peritoneal local anesthetic or saline were studied. Local anesthetic (0.5% bupivacaine with epinephrine) or placebo solutions were given as follows: immediately after the creation of a pneumoperitoneum (blocking before surgery), and at the end of the operation (blocking after surgery). Patients were randomly assigned to one of four groups of 30 patients each. Group A (placebo) received 20 ml 0.9% saline both before and after surgery, group B received 20 ml 0.9% saline before surgery and 20 ml local anesthetic after surgery, group C received 20 ml local anesthetic both before and after surgery, group P received 20 ml local anesthetic before and 20 ml 0.9% saline after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 0, 4, 8, 12, and 24 h after surgery. Metabolic endocrine responses (blood glucose and cortisol concentrations) and analgesic requirements also were investigated. RESULTS: Pain intensity (visual analog and verbal rating scales) and analgesic requirements were significantly less in the group receiving bupivacaine after surgery compared to placebo. However, in the groups receiving bupivacaine before surgery, both pain intensity and analgesic consumption were less than in the group receiving bupivacaine only after surgery. Blood glucose and cortisol concentrations 3 h after surgery were significantly less in groups receiving bupivacaine before surgery. CONCLUSIONS: The results indicate that intraperitoneal local anesthetic blockade administered before or after surgery preempts postoperative pain relative to an untreated placebo-control condition. However, the timing of administration is also important in that postoperative pain intensity and analgesic consumption are both lower among patients treated with local anesthetic before versus after surgery.


Jabbour-Khoury et al 2005

Intraperitoneal and intravenous routes for pain relief in laparoscopic cholecystectomy.

Jabbour-Khoury SI, Dabbous AS, Gerges FJ, Azar MS, Ayoub CM, Khoury GS

Jsls 2005;9(3):316–21

BACKGROUND: Postoperative abdominal and shoulder pain are the most common complaints after elective laparoscopic cholecystectomy. Postoperative pain is multifactorial in origin, and therefore multimodal therapy may be needed to optimize pain relief. METHODS: We conducted a double-blind study where patients were randomly allocated to 1 of 5 groups of 20 patients each. Statistical significance was considered P<0.05. Group 1 received 40 mL bupivacaine 0.25% intraperitoneal spray. Group 2 received 40 mL bupivacaine 0.25% intraperitoneal spray mixed with 200 mg ketoprofen. Group 3 received 40 mL bupivacaine 0.25% intraperitoneal spray and intravenous 200 mg ketoprofen. Group 4 received 200 mg ketoprofen intravenously. Group 5 was the control group. RESULTS: Demographic data were similar in the 5 groups. As compared with the control group, group 1 had significantly lower abdominal pain scores at 6 hours; group 2 at 0, 1, 2, and 6 hours; group 3 at 0, 1, 2, 6, 12, and 24 hours; and group 4 at 2 hours. Group 1 had significantly lower shoulder pain scores at 1 and 6 hours; group 2 at 0 and 6 hours; and groups 3 and 4 at 0, 1, and 6 hours. The number of patients requiring postoperative rescue analgesics and the incidence of postoperative vomiting were significantly lower in group 3 only. CONCLUSIONS: A multimodal approach to pain management following elective laparoscopic cholecystectomy is best achieved with a combination of 40 mL bupivacaine 0.25% intraperitoneal spray and 200 mg intravenous ketoprofen, achieving the least incidence of postoperative vomiting.


Hernandez-Palazon et al 2001

Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery

Hernandez-Palazon J, Tortosa JA, Martinez-Lage JF, Perez-Flores D.

Anesth Analg 2001;92(6):1473–1476.

We sought to determine the analgesic efficacy, opioid-sparing effects, and tolerability of propacetamol, an injectable prodrug of acetaminophen, in combination with morphine administered by patient-controlled analgesia (PCA) after spinal fusion surgery. Forty-two patients undergoing spinal stabilization surgery were randomized into two groups, which were given either an IV placebo or an IV injection of 2 g propacetamol every 6 h for 3 days after surgery. The postoperative opioid analgesic requirement was assessed with a PCA device used to self-administer morphine. Pain relief was evaluated by a visual analog pain scale and by verbal rating scores of pain relief at 8-h intervals for up to 72 h after surgery. The cumulative dose of morphine at 72 h was smaller in the Propacetamol group than in the Placebo group (60.3 +/- 20.5 vs 112.2 +/- 39.1 mg; p<0.001). The pain scores were significantly lower in the Propacetamol group measured at two intervals of the study, although visual analog scale pain intensity scores were smaller than 3 in both groups. Most patients in the Placebo group obtained a greater degree of sedation on postoperative Day 3 (p<0.05). This study demonstrates the usefulness of propacetamol as an adjunct to PCA morphine in the treatment of postoperative pain after spinal fusion.


Tsimoyiannis et al 1998

Intraperitoneal normal saline and bupivacaine infusion for reduction of postoperative pain after laparoscopic cholecystectomy.

Tsimoyiannis EC, Glantzounis G, Lekkas ET, Siakas P, Jabarin M, Tzourou H.

Surg Laparosc Endosc 1998;8(6):416–20.

After laparoscopic cholecystectomy, CO2 remains within the peritoneal cavity, commonly causing pain. This prospective randomized study was performed to determine the efficacy of intraperitoneal normal saline and bupivacaine infusion on postoperative pain after laparoscopic cholecystectomy. Three hundred patients were randomly assigned to one of six groups of 50 patients each. Group A patients served as controls. In group B patients, normal saline was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated. After suction, a subhepatic closed drain was left for 24 h. In group C patients, bupivacaine 1.5 mg/kg in solution 2.5 mg/ml, minus 15 ml of this solution, which was infiltrated in the trocar wounds, was infused under the right hemidiaphragm at the end of the cholecystectomy. In group D patients, bupivacaine was given as in group C, but a subhepatic drain was left for 24 h. In group E patients, normal saline was used as in group B plus bupivacaine as in group C. Group F patients were treated as in group E, but a subhepatic drain was left for 24 h. In all groups, 15 ml of a 2.5 mg/ml bupivacaine solution was infiltrated in the trocar wounds. Postoperatively, analgesic medication usage, nausea, vomiting, and pain scores were recorded at 2, 6, 12, 24, 36, 48, and 72 h. Postoperative pain was reduced significantly in the patients of the treatment groups vs. the controls. Between treatment groups, patients in groups B, E, and F had the best results, while those in groups C and D had significantly greater pain than those in groups B, E, and F. It is concluded that postoperative pain after laparoscopic cholecystectomy can be significantly reduced by intraperitoneal normal saline infusion subdiaphragmatically and after its postdeflation suction, bupivacaine infusion in the same area, or without bupivacaine in case a subhepatic drainage has been needed.


Abdel-Raouf + Amer 2004

Postoperative analgesic effects of intraperitoneal NMDA receptor antagonists (ketamine and magnesium) in patients undergoing laparoscopic cholecystectomy

Abdel-Raouf M, Amer H

Eg J Anaesth 2004:20(2);107-111

Background: This study was designed to evaluate the analgesic efficacy of intraperitoneal magnesium sulphate or ketamine added to bupivacaine in patients undergoing laparoscopic cholecystectomy. Methods: The study included 80 female patients and a standardized general anaesthetic including fentanyl, thiopentone, N2O, isoflurane, and vecuronium for muscle relaxation. At the end of surgery 50 ml of the studied solution were injected intraperitoneally under both copulae of diaphragm guided by the surgical camera. Patients were randomly allocated into one of four equal groups (n = 20 each), according to the composition of the intraperitoneal solution: normal saline 0.9% in the control group (Group C), bupivacaine 0.25% (Group B), 30 mg/kg magnesium sulphate in bupivacaine 0.25% (Group MB), and 1 mg/kg ketamine in bupivacaine 0.25% (Group KB). The following parameters were evaluated in all studied groups: 1) time to first request of analgesia (time between extubation and first analgesic dose); 2) postoperative shoulder and arm pain for 24 hours; and 3) the amount of postoperative patient-controlled analgesia (PCA) morphine consumed in 0–6 h, 6–12 h, 12–18 h, 18–24 h, and 0–24 h following extubation. Results: Time to first request of analgesia in groups C, B, MB, and KB were 15.33 (5.1) min, 35.23 (4.8) min, 130.34 (6.8) min and 132.13 (5.9) min, respectively, with significantly longer duration (P < 0.05) in groups MB and KB compared to either group C or group B. Dose of intravenous PCA morphine consumed at 0–6 h, 6–12 h, 12–18 h, 18–24 h, and 0–24 h following extubation were significantly lower in groups MB and KB compared to either group C or group B (P < 0.05). The incidence and severity of shoulder pain were significantly reduced in groups MB and KB (P < 0.05). Conclusion: Intraperitoneal co-administration of either magnesium sulphate or ketamine with bupivacaine 0.25% at the end of surgery is effective in reducing postoperative shoulder pain and analgesic requirement following laparoscopic cholecystectomy.


Elhakim et al 2000a

Effects of intraperitoneal lidocaine combined with intravenous or intraperitoneal tenoxicam on pain relief and bowel recovery after laparoscopic cholecystectomy.

Elhakim M, Amine H, Kamel S, Saad F.

Acta Anaesthesiol Scand 2000;44:929–933.

BACKGROUND: Previous work has demonstrated that intraperitoneal (i.p.) lidocaine may provide analgesia after laparoscopic cholecystectomy. The aim of this prospective, randomized, double-blind study was to compare pain relief, recovery variables, and side effects after i.p. instillation of lidocaine plus tenoxicam given either i.v. or i.p. after laparoscopic cholecystectomy. METHODS: Ninety patients were randomly allocated to one of three groups to receive either 200 ml normal saline i.p. and 2 ml of normal saline i.v. (saline group), 200 ml lidocaine 0.1% i.p. and 2 ml tenoxicam 20 mg i.v. (tenoxicam i.v. group), or 200 ml lidocaine 0.1% with 20 mg tenoxicam i.p. and 2 ml of normal saline i.v. (tenoxicam i.p. group). The i.p. instillation was made under the right diaphragm and on the gall bladder bed. VAS pain scores at rest, on movement and during coughing, were measured 2, 4, 6, 12, and 24 h after operation. The time to first demand of analgesia, total analgesic requirement, recovery variables, and side effects were investigated. RESULTS: In the tenoxicam i.p. group, pain scores were significantly lower both at rest and on movement and analgesic consumption was reduced compared with the saline group (p < 0.05). In the tenoxicam i.v. group, pain scores at rest were significantly lower compared with the saline group. Although recovery of bowel function was significantly faster in the tenoxicam i.p. group (p < 0.05), there were no differences in any other recovery characteristics or incidence of nausea between the groups. CONCLUSION: Combination of intraperitoneal lidocaine and tenoxicam provided better analgesia on movement, and faster return of bowel function compared with i.p. lidocaine and i.v. tenoxicam during the 24 h period after surgery.


Hernandez-Palazon et al 2003

Intraperitoneal application of bupivacaine plus morphine for pain relief after laparoscopic cholecystectomy.

Hernandez-Palazon J, Tortosa JA, Nun~o de la Rosa V, Gimenez-Viudes J, Ramirez G, Robles R

European Journal of Anaesthesiology 2003;20(11):891–896

Background and objective: Intraperitoneal administration of a local anaesthetic in combination with an opioid, for the relief of postoperative pain, has already been reported except after laparoscopic cholecystectomy. This study was aimed at assessing the analgesic effect of the intraperitoneal administration of bupivacaine and morphine in patients undergoing laparoscopic cholecystectomy. Methods: At the end of laparoscopic cholecystectomy, in a double-blind, randomized manner, one of the following injections was given intraperitoneally. There were 30 patients in each group: Group 1, physiological saline 30 mL; Group 2, bupivacaine 0.25% 30 mL; Group 3, bupivacaine 0.25% 30 mL plus morphine 2 mg. In addition, Group 2 received 2 mg intravenous (i.v.) morphine in 2 mL saline, and Groups 1 and 3, 2 mL saline intravenously. Patients' postoperative pain was evaluated using a visual analogue scale and a verbal rating score. The postoperative analgesic requirement was assessed by the total dose of metamizol administered by an i.v. patient-controlled analgesia (PCA) device. Pain, vital signs, supplemental analgesic consumption and side-effects were recorded for all patients for 24 h. Results: There were no differences between the three groups regarding pain scores (at rest and coughing) during the study except in the first 2 h, when scores were lower for patients receiving intraperitoneal bupivacaine plus i.v. morphine (P < 0.05). Supplemental consumption of metamizol was significantly lower (P < 0.05) in Group 3 than in Group 1 during the first 6 h after surgery. However, the cumulative doses of metamizol were also lower in Group 2 than in Groups 1 and 3 over the entire study (2025 +/- 1044 mg vs. 4925 +/- 1238 and 4125 +/- 1276 mg; P < 0.05). Conclusions: In patients undergoing laparoscopic cholecystectomy, the intraperitoneal administration of morphine plus bupivacaine 0.25% reduced the analgesic requirements during the first 6 postoperative hours compared with the control group. However, the combination of intraperitoneal bupivacaine 0.25% and i.v. morphine was more effective for treatment of pain after laparoscopic cholecystectomy.


Labaille et al 2002

The clinical efficacy and pharmacokinetics of intraperitoneal ropivacaine for laparoscopic cholecystectomy.

Labaille T, Mazoit JX, Paqueron X, Franco D, Benhamou D.

Anesth Analg 2002;94:100–105.

Postoperative pain after laparoscopic surgery is less than after laparotomy, and patients may benefit from an intraperitoneal injection of local anesthetic. Thirty-seven ASA physical status I or II patients received in double-blinded fashion 20 mL of 0.9% saline solution (placebo), ropivacaine 0.25% (Rop 0.25%), or ropivacaine 0.75% (Rop 0.75%) immediately after trocar placement and at the end of surgery. We measured pain and morphine consumption until 20 h after surgery. Plasma ropivacaine concentrations were measured. The three groups were comparable for shoulder pain, parietal pain, and incidence of side effects. Visceral pain at rest, during cough, and on movement and total consumption of morphine were significantly smaller in Groups Rop 0.25% and Rop 0.75% when compared with Placebo. Although no adverse effect occurred in any patient, the largest dose led to large plasma concentrations of ropivacaine (2.93 +/- 2.46 microg/mL and 3.76 +/- 3.01 microg/mL after the first and second injection, respectively). We conclude that intraperitoneal administration of ropivacaine before and after surgery significantly decreases postoperative pain. Because the smaller dosage (2 x 50 mg) provided similar analgesia and was associated with significantly smaller plasma concentrations than the larger dosage (2 x 150 mg), this smaller dosage seems more appropriate. IMPLICATIONS: Intraperitoneal ropivacaine 100 mg injected during laparoscopic cholecystectomy significantly decreased postoperative pain when compared with injection of intraperitoneal placebo. At this dose, plasma concentrations remained in the nontoxic range.


Raetzel et al 1995

Intraperitoneal application of bupivacaine during laparoscopic cholecystectomy - Risk or benefit?

Raetzel M, Maier C, Schroder D, Wulf H.

Anesth Analg 1995;81:967–972.

We investigated, in a double-blind study, the effects of intraperitoneal local anesthetics during laparoscopic cholecystectomy. In Part A of the study 30 patients received 50 mL saline 0.9% (A 0), bupivacaine 0.125% (A 125), or bupivacaine 0.25% (A 25) intraperitoneally at the end of surgery. Mean maximum plasma concentrations of bupivacaine reached 0.48 mg/L (range 0.15-0.90 mg/L) in Group A 125 and 1.0 mg/L (0.35-2.10 mg/L) in Group A 25 within 15 min (range, 5-30 min). There was no significant difference in pain scores or opioid consumption (patient-controlled analgesia with piritramid): 24, 28, and 13 mg/24 h among the study groups, respectively (not significant). Postoperative respiratory function deteriorated in comparison to preoperative values in all study groups, but the forced vital capacity was significantly more impaired in Group A .25. In Part B, 24 patients received placebo (B 0) or bupivacaine 0.25% (B 25). Postoperative hypoxemic periods (oxygen saturation < 92%) were significantly more frequent in Group B 25. Considering the questionable benefits and the potential risks, we would not recommend the application of intraperitoneal bupivacaine during laparoscopic cholecystectomy.


Narchi 1995

[New routes for infiltration: intraperitoneal injections].

Narchi P.

Cah Anesthesiol 1995;43(3):267–272.

Intraperitoneal administration of local anaesthetics is frequently used during gynaecological laparoscopy and especially after laparoscopic sterilization where the solution may be instilled, sprayed or infiltrated around the clip or the rings. In addition, the subdiaphragmatic instillation of local anaesthetics by the surgeon during laparoscopy is followed by a decrease in the intensity of postoperative scapular pain which is known to last 2-3 days and is due to some degree of residual pneumoperitoneum. After laparoscopic cholecystectomy, the analgesic effects of the administration of local anaesthetics via the intraperitoneal route remain controversial. The pharmacokinetic data available which confirm the safety of doses up to 100 mg of bupivacaine or 800 mg of lidocaine, should encourage the use of larger doses, especially after cholecystectomy.


Dreher et al 2000

Pain relief following day case laparoscopic tubal ligation with intra-peritoneal ropivacaine: a randomised double blind control study

Dreher JK, Nemeth D, Limb R

Aust N Z J Obstet Gynaecol 2000;40(4):434-7

The aim of this study was to examine the effectiveness of ropivacaine administered by a simple intraperitoneal technique in relieving pain following laparoscopic application of Filshie clips. Nineteen patients were randomised to receive either ropivacaine (200 mg) or normal saline through the umbilical port following clip application. Using a visual analogue scale women receiving ropivacaine had significantly lower pain scores 2 hours post operatively (0.97 vs 2.03 p < 0.05). The mean total postoperative fentanyl use was also significantly lower on the ropivacaine group (40 microg vs 104 microg p < 0.02). Only 10% (1/10) of the women in the ropivacaine group complained of nausea compared with 44% (4/9) in the control group. Furthermore, 80% (8/10) of women in the ropivacaine group were either very or totally satisfied with their pain relief. Only 56% (5/9) of the women in the control group were very or totally satisfied with their pain relief. Ropivacaine administered by a simple intraperitoneal technique following laparoscopic sterilisation significantly reduces postoperative pain and parenteral analgesic requirements. It would be reasonable to consider this method as standard practice following laparoscopic tubal ligation.


Karsli et al 2003

The effects of intraperitoneal tramadol, tenoxicam and bupivacaine on pain relief after laparoscopic gynecological procedures

Karsli B, Kayacan N, Zorlu G, Arici G, Erman M

The Pain Clinic 2003;15(3):281–286

Purpose: Patients undergoing laparoscopic procedures may experience postoperative pain. We conducted a randomized, double-blinded, placebo-controlled trial to evaluate the effectivenesses of peritoneal tramadol as an opioid analgesic, tenoxicam as an anti-imflammatory drug and bupivacaine as a local anesthetic. Methods: Patients were randomly assigned to one of four groups of 20 patients each. Group A received 50 mg tramadol (in 20 ml volume with 0.9% saline), group B received 20 mg tenoxicam (in 20 ml volume with 0.9% saline), group C received 20 ml 0.9% saline and group D received 50 mg bupivacaine HCl in 20 ml volume (10 ml 0.5% bupivacaine with 10 ml 0.9% saline) after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 30 and 60 min, and 2 and 4 h after surgery. Results: Pain intensity and analgesic requirements were significantly less in the group receiving intraperitoneal tramadol, tenoxicam and bupivacaine compared to placebo group. The pain scores of tenoxicam group at 30 and 60 min, and 2 h after surgery were significantly lower than those of the group B, C and D. There was no statistically significant difference in any group at 4 h after surgery. Conclusion: The results indicate that intraperitoneal application of tramadol, tenoxicam and bupivacaine is simple, cheap and effective for reducing pain after laparoscopic gynecological operations.


Keita et al 2003

Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement.

Keita H, Geachan N, Dahmani S, Couderc E, Armand C, Quazza M, Mantz J, Desmonts JM.

Br J Anaesth 2003;90(1):53–57.

BACKGROUND: The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR). METHODS: Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery. RESULTS: The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups. CONCLUSIONS: We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.


Schulte-Steinberg et al 1995

Intraperitoneal versus interpleural morphine or bupivacaine for pain after laparoscopic cholecystectomy.

Schulte-Steinberg H, Weninger E, Jokisch D, Hofstetter B, Misera A, Lange V, Stein C.

Anesthesiology 1995;82:634–640.

BACKGROUND: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions. METHODS: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h. RESULTS: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred. CONCLUSIONS: Interpleural bupivacaine (0.25%) produces analgesia after laparoscopic cholecystectomy. We attribute the lack of effect of intraperitoneal injections to the small dose and to a rapid dilution within the peritoneal cavity. The fact that interpleural morphine (0.005%) is ineffective may be due to an intact perineurial barrier in the noninflamed pleural cavity, which restricts the transperineurial passage of morphine to opioid receptors on intercostal nerves.


O'Hanlon et al 2002

Intraperitoneal pethidine versus intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: randomized trial.

O'Hanlon DM, Colbert S, Ragheb J, McEntee GP, Chambers F, Moriarty DC

World J Surg 2002;26(12):1432–6

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary endpoints were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6 +/- 0.8 vs. 2.4 +/- 0.9 cm; p < 0.001; pain upon movement at 4 hours: 2.1 +/- 0.9 vs. 3.1 +/- 1.2 cm; p < 0.001). The total dose of pethidine administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9 +/- 3.9 vs. 55.9 +/- 4.4 mg; p < 0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.


Colbert et al 2000

An assessment of the value of intraperitoneal meperidine for analgesia postlaparoscopic tubal ligation

Colbert ST, Moran K, O'Hanlon DM, Chambers F, Moriarty DC, Blunnie WP

Anesth Analg 2000;91(3):667–70

Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.


Munoz et al 2005

The effect of different isoflurane-fentanyl dose combinations on early recovery from anesthesia and postoperative adverse effects.

Munoz HR, Altermatt FR, Gonzalez JA, Leon PJ

Anesth Analg 2005;101(2):371–6

We evaluated the effect of different combinations of fentanyl-isoflurane on early recovery from anesthesia in 80 adult patients undergoing laparoscopic cholecystectomy. Anesthesia was induced with fentanyl 2 microg/kg and thiopental 5 mg/kg. Nitrous oxide was not used and patients were randomly assigned to one of four groups: Group 1 (n = 20) received 0.6% end-tidal isoflurane plus fentanyl, Group 2 (n = 20) received 1.2% end-tidal isoflurane plus fentanyl, Group 3 (n = 20) received 1.8% end-tidal isoflurane plus fentanyl, and Group 4 (n = 20) received only isoflurane. In Groups 1, 2 and 3 isoflurane concentration was kept constant and fentanyl was given as necessary to maintain the mean arterial blood pressure within +/- 10% of the minimum mean arterial blood pressure measured in the ward. In Group 4, isoflurane concentration was adjusted to maintain mean arterial blood pressure as above. At the end of skin closure isoflurane was discontinued and the time to spontaneous breathing (TSB), time to extubation (TE) and time to eye opening (TEO) were recorded. In the postanesthesia care unit, the degree of sedation, respiratory rate, Spo(2), emesis, pain, and morphine consumption were evaluated every 15 min for 1 h, and thereafter every 30 min until discharge. Fentanyl requirements were 8.3 +/- 4.5 microg/kg (mean +/- sd) in Group 1, 3.8 +/- 1.3 microg/kg in Group 2, and 3.0 +/- 0.7 microg/kg in Group 3 (P < 0.001), whereas in Group 4 the mean end-tidal concentration of isoflurane was 2.0% +/- 0.4%. Although the mean TSB was <5.5 min in all groups, TE increased from 7.3 +/- 5.1 min in Group 1 to 20.6 +/- 10.7 min in Group 4 (P < 0.001), and TEO increased from 7.4 +/- 5.1 min in Group 1 to 25.8 +/- 9.4 min in Group 4 (P < 0.001). There were no differences among the groups in any of the variables measured in the postanesthesia care unit. This study shows that the combination of a small concentration of isoflurane and a relatively larger dose of fentanyl results in a faster recovery from anesthesia than the inverse combination of doses. IMPLICATIONS: A fast recovery from anesthesia increases patient safety. This study shows that the combination of a small concentration of isoflurane and a relatively larger dose of fentanyl results in a faster recovery from anesthesia than the inverse combination of doses.


Luchetti et al 1996

Effectiveness and safety of combined epidural and general anesthesia for laparoscopic cholecystectomy.

Luchetti M, Palomba R, Sica G, Massa G, Tufano R.

Reg Anesth 1996;21(5):465–469.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the efficacy and safety of two anesthesia techniques, combined epidural/general anesthesia (CEGA) versus total intravenous anesthesia (TIVA), for laparoscopic cholecystectomy. METHODS: Forty patients were randomly assigned to one of two different groups: group A received TIVA and group B received CEGA. At preset times during the operation, systolic and diastolic arterial pressure, heart rate, oxygen saturation (SaO2) and end-tidal carbon dioxide (EtCO2) were monitored. Postoperatively, recovery (Steward's test) and analgesia (visual analog scale [VAS] pain scores) were assessed, as well as the incidence of adverse effects. RESULTS: The groups were comparable as to demographic data and duration of surgery and of anesthesia. Intraoperative parameters also showed no statistical differences. Both groups had a rapid recovery (Steward score of 6 within 12 minutes), but group B showed better recovery scores at 4 minutes. Postoperative pain was well controlled in both groups, but group B exhibited better scores at postoperative hour 2. The incidence of postoperative side effects was low in both groups. CONCLUSIONS: The use of CEGA for laparoscopic cholecystectomy seems to be effective and safe and to offer some advantages as compared to TIVA alone. CEGA can control pain due to CO2-induced peritoneal irritation, providing excellent intra- and postoperative analgesia. CEGA does not require the use of intraoperative intravenous opioids and shortens recovery time, without increasing the incidence of side effects.


Usmani et al 2004

Comparison of butorphanol and fentanyl for balanced anaesthesia in patients undergoing laparoscopic cholecystectomy.

Usmani H, Quadir A, Jamil SN, Bahl N, Rizvi A

Journal of Anaesthesiology Clinical Pharmacology 2004;20(3):251–254

Equianalgesic doses of butorphanol (40mcg kg-1) and fentanyl (2.0mcg kg-1) were compared in 60 adult female patients (ASA I and II) undergoing laparoscopic cholecystectomy under general anaesthesia. The patients were divided into two groups of 30 each (n=30). One of the study drugs (butorphanol or fentanyl) were given just prior to induction of anaesthesia in a double blind fashion. Following induction with a standard dose of propofol and tracheal intubation using vecuronium bromide, anaesthesia was maintained with nitrous oxide-oxygen and titrated concentration of halothane to keep the heart rate and blood pressure +/-20% of base line. The proportion of patients with moderate-severe pain during postoperative period was significantly higher in fentanyl group as compared to butorphanol group. Time to first rescue analgesic (tramadol hydrochloride) was also significantly prolonged in butorphanol group as compared to fentanyl group. The incidence of side effects was comparable in both the groups. Thus, butorphanol is an effective analgesic for patients undergoing laparoscopic cholecystectomy under general anaesthesia.


Grundmann et al 2001

Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy.

Grundmann U, Silomon M, Bach F, Becker S, Bauer M, Larsen B, Kleinschmidt S

Acta Anaesthesiol Scand 2001;45(3):320–6

BACKGROUND: Nitrous oxide (N2O) has been suggested to contribute to bowel distension, resulting in worsened operating conditions for laparoscopic surgery, and to increase incidence of postoperative nausea and vomiting. Therefore, our objective was to assess the feasibility of two remifentanil-based anaesthetic regimens free from N2O with special regard to recovery profile, postoperative analgesic demand and side effects in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients (ASA I-II, 23-65 yr) were randomly assigned to receive remifentanil-based anaesthesia in conjunction with propofol (group R/P) or desflurane (group R/D). After standardised induction of anaesthesia, analgesia was continued with remifentanil in all patients. For maintenance of hypnosis, propofol or desflurane were used in concentrations to ensure loss of consciousness, lack of awareness, and maintenance of heart rate and blood pressure within +/- 25% of initial values. At the end of surgery all anaesthetics were discontinued without tapering and early emergence and recovery were recorded. Pain scores were assessed by using a visual analogue scale. Patient-controlled analgesia with i.v. piritramide was used for treatment of postoperative pain and recorded for 90 min in the postanaesthesia care unit (PACU). In addition, side effects were noted. RESULTS: Early emergence from anaesthesia did not differ between the groups. In group R/P, time to eye opening, spontaneous respiration and extubation was 4.4 +/- 2.9 min, 5.2 +/- 3.4 min and 5.5 +/- 3.3 min respectively, compared with 4.7 +/- 2.7 min, 5.3 +/- 2.4 min and 5.7 +/- 2.5 min in group R/D. While pain scores did not differ between both groups on admission to the PACU, patients receiving desflurane required more i.v. piritramide as compared to those receiving propofol, 22.0 +/- 6.5 mg and 17.9 +/- 7.0 mg, respectively (P<0.05). Nausea was less frequent after propofol (16% vs. 48%, P<0.05). CONCLUSION: In patients undergoing laparoscopic cholecystectomy, remifentanil-based anaesthetic regimens in conjunction with propofol or desflurane are suitable and allow for rapid recovery from anaesthesia. However, the use of propofol results in less postoperative analgesic consumption and nausea as compared to desflurane.


Vezakis et al 1999

Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy.

Vezakis A, Davides D, Gibson JS, Moore MR, Shah H, Larvin M, McMahon MJ.

Surg Endosc 1999;13:890–893.

BACKGROUND: Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery. METHODS: Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser). RESULTS: The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p = 0.01). CONCLUSIONS: Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease.


Larsen et al 2001

Randomized comparison of conventional and gasless laparoscopic cholecystectomy: operative technique, postoperative course, and recovery.

Larsen JF, Ejstrud P, Kristensen JU, Svendsen F, Redke F, Pedersen V.

J Gastrointest Surg 2001;5:330–335.

The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular, neuroendocrine, and renal changes. Concern about these pathophysiologic changes has led to the introduction of a gasless technique. Fifty consecutive patients with symptomatic gallstones were randomized to conventional (CLC) or gasless laparoscopic cholecystectomy (GLC), with special reference to overall patient satisfaction, technical difficulties, duration of surgery, postoperative pain, and recovery. The overall exposure of the operative field was extremely poor in the GLC group, whereas the duration of surgery, steps involved in the cholecystectomy technique, length of hospital stay, and postoperative pain score did not differ significantly. After discharge, the median time to complete relief of pain tended to be shorter in the gasless group (5 days [range 1 to 15]) vs. the conventional group (8 days [range 1 to 15]). The period to return to normal activity was shorter in the GLC group (6 days [range 1 to 15]) compared to the CLC group (8.5 days [range 1 to 15]) (p = 0.031). No differences were found in terms of fatigue, dizziness and nausea, and overall satisfaction with the outcome. This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique. Exposure of the operative field was less than optimal using the gasless technique.


Lindgren et al 1995

Conventional pneumoperitoneum compared with abdominal wall lift for laparoscopic cholecystectomy.

Lindgren L, Koivusalo AM, Kellokumpu I

Br J Anaesth 1995;75(5):567–72

We have compared, in a randomized study, conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy. Intra-abdominal pressure (IAP) (11 (SD 2) mm Hg vs 2.7 (9) mm Hg) (P < 0.01) and total amount of carbon dioxide used (40 (23) litre vs 9 (7) litre) (P < 0.001) were significantly less with abdominal wall lift. Pulmonary compliance was significantly greater (P < 0.01) in the abdominal wall lift group throughout operation. During the first 15 min of insufflation, arterial pressures were lower with abdominal wall lift (P < 0.05). In the conventional pneumoperitoneum group, femoral vein pressure increased (P < 0.01) and remained elevated for 3 h in the recovery room. Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group (98 (46) min vs 13 (34) min) (P < 0.01). Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum (P < 0.05). We conclude that the benefits of abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP.


Uen et al 2002

Randomized comparison of conventional carbon dioxide insufflation and abdominal wall lifting for laparoscopic cholecystectomy.

Uen YH, Liang AI, Lee HH

J Laparoendosc Adv Surg Tech A 2002;12(1):7–14

BACKGROUND: Gasless laparoscopy using abdominal wall lifting (AWL) has been developed in an attempt to avoid the adverse effects of carbon dioxide pneumoperitoneum that may occur in conventional laparoscopy. However, lifting has been criticized for its poor operative space and surgical invasiveness. This study compared the AWL method with conventional CO2 pneumoperitoneum for laparoscopic cholecystectomy with respect to operation performance, postoperative course, and stress response. PATIENTS AND METHODS: During a 6-month period, 95 patients with symptomatic gallstones were randomly assigned to receive laparoscopic cholecystectomy with conventional CO2 pneumoperitoneum (CO2 group; N = 47) or the AWL method (AWL group; N = 48). Operative results and operative time were recorded. Cardiopulmonary functions were assessed, and arterial blood gases were analyzed during surgery. Urinary cortisol, vanillylmandelic acid, metanephrines, and nitrogen loss; serum complement 3, C-reactive protein, and interleukin-6; postoperative pain; and the presence of nausea and vomiting were assessed for 48 hours after surgery. Postoperative time to recovery of flatus, tolerance of a full oral diet, and full activity were also determined. RESULTS: Only three significant differences were found. First, intraoperative ventilatory function deteriorated significantly less in the AWL group. Second, arterial blood gas determinations and capnography showed a greater decrease in intraoperative arterial pH and compliance with CO2 retention and an increase in peak airway pressure in the CO2 group (P < 0.05), reflecting poorer ventilatory performance. Third, preparation time and total operating time were significantly greater with the AWL method (P < 0.05). CONCLUSIONS: Although AWL required a longer operation time, our results suggest that the technique may still have value in high-risk patients with cardiorespiratory diseases.


Schulze et al 1999

Cardiovascular and respiratory changes and convalescence in laparoscopic colonic surgery: comparison between carbon dioxide pneumoperitoneum and gasless laparoscopy.

Schulze S, Lyng KM, Bugge K, Perner A, Bendtsen A, Thorup J, Nielsen HJ, Rasmussen V, Rosenberg J.

Arch Surg 1999;134(10):1112–1118.

HYPOTHESIS: Gasless laparoscopy produces smaller cardiopulmonary and systemic changes than carbon dioxide (CO2) laparoscopy during colonic surgery. DESIGN: Prospective randomized trial. SETTING: Department of Surgery in a university hospital. PATIENTS: Twenty-two patients scheduled for laparoscopic colonic resection; 5 patients were excluded because of conversion to open surgery (N = 17). INTERVENTIONS: Patients were randomized to either gasless (n = 9) or conventional CO2 (n = 8) surgery. MAIN OUTCOME MEASURES: Intraoperative assessment of hemodynamic factors and pulmonary function, and postoperative assessment of pain, pulmonary function, convalescence, and various injury factors were done several times until 30 days after surgery. Surgical complications were noted. RESULTS: Descending aorta blood flow after 30 minutes (P=.03) and heart rate after 150 minutes were higher in the CO2 group (P=.009). Central venous pressure, PaCO2 inspiration pressure, and end tidal CO2 level were significantly higher in the CO2 group (P = .05, .03, .04, and .01, respectively). Patients in the CO2 group had less pain during mobilization and coughing (P = .008 and .006, respectively), and were significantly more fatigued (P = .04). No other important differences were observed in intraoperative hemodynamic factors, postoperative convalescence, immunocompetence, or pulmonary function. CONCLUSION: No clinically important differences in cardiovascular and systemic response were observed between patients undergoing CO2 or gasless laparoscopy for colonic disease.


Johnson et al 1997

Laparoscopy. Gasless vs. CO2 pneumoperitoneum.

Johnson PL, Sibert KS

J Reprod Med. 1997; 42: 255–9

OBJECTIVE: To compare gasless laparoscopy with conventional laparoscopy using CO2 pneumoperitoneum. STUDY DESIGN: Women undergoing bilateral laparoscopic tubal coagulation (LTC) were randomly assigned to one of two laparoscopy procedures: (1) a gasless laparoscopy system consisting of an intraabdominal fan retractor and electrically powered mechanical arm, and (2) standard CO2 pneumoperitoneum laparoscopy. The two laparoscopic procedures were compared on the basis of intraoperative visualization, operation duration, procedural difficulty, ventilatory parameters, hemodynamic stability, and postoperative pain and nausea. RESULTS: Significant disadvantages for the surgeon (increased technical difficulty, poorer visualization, longer operative times) and patient (greater postoperative pain and nausea) were seen with the gasless system. Because of these findings, the study was prematurely terminated after only 18 patients had participated. Intraoperative ventilatory and hemodynamic parameters were more stable in the gasless laparoscopy groups; however, the differences were not clinically significant in this population of healthy patients. CONCLUSION: The markedly increased technical difficulty and absence of clear clinical benefits for the healthy patient led to the conclusion that laparoscopy with CO2 pneumoperitoneum is preferable for routine LTC and most laparoscopic procedures in the pelvis. Gasless laparoscopy may be of benefit for the fragile patient with a compromised cardiovascular system who may suffer complications from hypercarbenemia.


Guido et al 1998

A randomized, prospective comparison of pain after gasless laparoscopy and traditional laparoscopy

Guido RS, Brooks K, McKenzie R, Gruss J, Krohn MA

J Am Assoc Gynecol Laparosc 1998;5(2):149–53

STUDY OBJECTIVE: To compare pain after laparoscopic tubal ligation by gasless laparoscopy versus carbon dioxide (CO2) pneumoperitoneum. DESIGN: Prospective, randomized, single-blind comparison (Canadian Task Force classification I). SETTING: Private obstetric-gynecology hospital associated with a university resident teaching program. PATIENTS: Women age 21 to 42. INTERVENTION: Single-puncture laparoscopic tubal ligation was performed with a silicone elastomer band. Gasless laparoscopy was performed with a Laprolift and traditional laparoscopy with CO2 pneumoperitoneum. Postoperative pain in the shoulder and periumbilical and lower pelvic regions was measured by visual analog scale on the day of surgery and postoperative days 1, 2, 3, 7, and 14. MEASUREMENTS and MAIN RESULTS: Of the 67 patients, 54 provided visual analog scales for analysis, 30 in the gasless group and 24 in the traditional group. No statistical difference was seen in scores for shoulder, periumbilical, and pelvic pain between techniques. CONCLUSION: Patients undergoing gasless laparoscopy and traditional laparoscopy experience similar postoperative pain.


Barczynski and Herman 2003

A prospective randomized trial on comparison of low-pressure (LP) and standard-pressure (SP) pneumoperitoneum for laparoscopic cholecystectomy

Barczynski M, Herman RM.

Surg Endosc 2003;17(4):533–538.

AIM: This study aimed to investigate the advantages and disadvantages of LP (7 mmHg) in comparison to SP (12 mm Hg) pneumoperitoneum in a prospective randomized clinical trial. MATERIALS AND METHODS: 148 consecutive patients qualified for laparoscopic cholecystectomy (LC) due to uncomplicated symptomatic gallstones were randomized to either SPLC or LPLC. The same experienced team of surgeons performed all the procedures. The statistical analysis included sex, mean age, body mass index, ASA grade, operative time, complication rate, conversion rate, postoperative pain assessed by the Visual Analogue Scale of Pain (VAS) including the incidence of shoulder-tip pain, postoperative hospital stay, recovery time, and the quality of life (QOL) within 7 days following the operation. p <0.05 was considered as indicative of significance. RESULTS: Neither conversion to an open procedure nor major complications occurred in either group. The operative time was similar in both groups (LP 55.7 +/- 8.6 min vs. SP 51.9 +/- 8.3 min). The mean postoperative pain score was 6.18 +/- 3.48 lower after LP than SPLC and the difference amounted to 22.2% (p <0.005). The incidence of shoulder-tip pain was 2.1 times lower after LP than SPLC (p <0.05). QOL within 7 days following the operation was remarkably better after LPLC than after SPLC (p <0.01). CONCLUSIONS: LP pneumoperitoneum is superior to SP pneumoperitoneum in terms of lower postoperative pain, a lower incidence of shoulder-tip pain, and a better QOL within 5 days following the operation. LP should be used for LC in cases of uncomplicated symptomatic gallstones as a recommended procedure as long as an adequate exposure is obtained with this technique.


Wallace et al 1997

Randomized trial of different insufflation pressures for laparoscopic cholecystectomy.

Wallace DH, Serpell MG, Baxter JN, Dwyer PJ.

Br J Surg 1997;84:455–458.

BACKGROUND: The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood. The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg. METHODS: Forty patients with similar preoperative characteristics were randomized, 20 to each group. RESULTS: There were no significant differences in intraoperative heart rate or cardiac index although the latter fell significantly soon after insufflation in both groups. The fall in cardiac index lasted longer (7 versus 2 min) and coincided with a slower rise in mean arterial pressure in those having 15 mmHg insufflation. Changes in peak airway pressure, end-tidal carbon dioxide and arterial blood gases were similar. After operation the low-pressure group had significantly less pain, better preservation of pulmonary function and were discharged home sooner (P = 0.015). CONCLUSIONS: Insufflation pressure significantly affects the haemodynamic changes and postoperative pain associated with laparoscopic cholecystectomy.


Mouton et al 1999

A randomized controlled trial assessing the benefit of humidified insufflation gas during laparoscopic surgery.

Mouton WG, Bessell JR, Millard SH, Baxter PS, Maddern GJ.

Surg Endosc 1999;13:106–108.

Background: We conducted a randomized controlled trial during laparoscopic cholecystectomy to determine the extent of heat preservation and postoperative pain reduction using humidified carbon dioxide (CO2) gas insufflation instead of standard dry insufflation gas. Methods: Forty consecutive patients were randomized. Twenty patients received humidified CO2, and 20 control patients received standard CO2 insufflation. A sample of 16 patients from each group was evaluated for postoperative pain levels. Results: No adverse effects from the humidification of insufflated gas were observed. There was no significant difference in core body temperature between the two groups for this brief operation. Pain, as assessed by the Analogue Pain Score (APS) was significantly less for the group with humidified gas insufflation than for the control group at 6 h postoperatively as well as on the 1st, 2nd, and 3rd postoperative day and at follow-up 10 days after the operation. In the humidified group, the mean time to return to normal activities was significantly less-5.9 days, as compared to 10.9 days in the control group. Conclusions: The use of humidified insufflation gas reduces postoperative pain following laparoscopic cholecystectomy, but except for these relatively brief procedures, the heat-preserving effect of humidified gas insufflation is not significant.


Farley et al 2004

Double-blind, prospective, randomized study of warmed, humidified carbon dioxide insufflation vs standard carbon dioxide for patients undergoing laparoscopic cholecystectomy.

Farley DR, Greenlee SM, Larson DR, Harrington JR

Archives of Surgery 2004;139(7):739–43; discussion 743–4

HYPOTHESIS: Patients undergoing warmed, humidified carbon dioxide (CO2) insufflation for laparoscopic cholecystectomy will (1) maintain a warmer intraoperative core temperature, (2) have their surgeon experience less fogging of the camera lens, and (3) have less postoperative pain than patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation. DESIGN: A double-blind, prospective, randomized study comparing patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation vs those receiving warmed, humidified CO2 (Insuflow Filter Heater Hydrator; Lexion Medical, St Paul, Minn) was performed. Main variables included patient core temperature, postoperative pain, analgesic requirements, and camera lens fogging. RESULTS: One hundred one blinded patients (69 women, 32 men) undergoing laparoscopic cholecystectomy were randomized into 2 groups-52 receiving standard CO2 insufflation (group A) and 49 receiving warmed, humidified CO2 (group B). Mean patient intraoperative core temperature change (group A decreased by 0.03 degrees C, group B increased by 0.29 degrees C, P =.01) and mean abdominal pain (Likert scale, 0-10) at 14 days postoperatively (group A, 1.0; group B, 0.3; P =.02) were different. Other variables (camera lens fogging, early postoperative pain, narcotic requirements, recovery room stay, and return to normal activities) between groups were similar. CONCLUSION: While patients undergoing laparoscopic cholecystectomy with warmed, humidified CO2 had several advantages that were statistically significant, no major clinically relevant differences between groups A and B were evident.


Slim et al 1999

Effect of CO2 gas warming on pain after laparoscopic surgery: A randomized double-blind controlled trial.

Slim K, Bousquet J, Kwiatkowski F, Lescure G, Pezet D, Chipponi J.

Surg Endosc 1999;13:1110–14.

BACKGROUND: Previous studies have suggested that gas temperature has an influence on postlaparoscopy pain. This trial therefore was conducted to study the effect of gas warming on pain after upper abdominal laparoscopic surgery. METHODS: Patients who underwent laparoscopic cholecystectomy, fundoplication, or Heller's myotomy were included and randomly allocated to receive either warm or cold gas. Primary end point was shoulder tip pain, and secondary end points were subcostal, trocar wound, and visceral pains, as well as other postoperative events. Criteria of pain assessment were the visual analog scale, verbal rating scale, and amount of analgesics. RESULTS: A total of 100 patients were suitable for postoperative evaluation. The groups were well matched. Shoulder tip and subcostal pains were significantly more intense after gas warming (p < 0.05). The three assessment criteria showed the same differences. No difference was observed concerning trocar wound and visceral pains and the other secondary end points. Subdiaphragmatic temperature was not significantly different (34.4 degrees with warming vs. 34 degrees without warming). CONCLUSIONS: Gas warming does not reduce, and probably increases, postoperative shoulder tip and subcostal pains.


Beste et al 2006

Humidified compared with dry, heated carbon dioxide at laparoscopy to reduce pain.

Beste TM, Daucher JA, Holbert D.

Obstet Gynecol. 2006;107:263–8

OBJECTIVE: To study whether using 95% humidified, heated carbon dioxide (CO(2)) at laparoscopy reduces pain compared with dry, heated CO(2). METHODS: Patients were randomly assigned to either heated, 95% humidified CO(2) (study group) or heated, dry CO(2) (control group) during laparoscopy. Pain control was achieved per standard protocols. Pain scales were administered the first 4 hours and 24 and 48 hours postoperatively. RESULTS: The 89 patients available in the intent-to-treat model revealed a decrease in total morphine equivalents and a decrease in pain scores at 1, 2, and 24 hours in the study group (directional P values < .05). Subgroup analysis in patients without chronic pelvic pain revealed lower mean pain scores at 1, 2, 24, and 48 hours and decreases in postoperative and total morphine equivalents (directional P values < .05) in the study group. CONCLUSION: At laparoscopy, heated, 95% humidified CO(2) effectively decreases postoperative pain and narcotics usage compared with heated, dry CO(2). LEVEL OF EVIDENCE: II-2.


Demco 2001

Effect of heating and humidifying gas on patients undergoing awake laparoscopy.

Demco 2001

J Am Assoc Gynecol Laparosc. 2001;8:247–51.

STUDY OBJECTIVE: To determine the effect of heating and humidifying CO2 on the tolerance of awake laparoscopy and frequency of shoulder pain and patient recovery. DESIGN: Randomized, controlled study (Canadian Task Force classification I). SETTING: University-affiliated hospital. PATIENTS: Forty consecutive women. INTERVENTION: Awake laparoscopy with and without heating and humidifying CO2. MEASUREMENTS AND MAIN RESULTS: Heating and humidifying CO2 decreased the frequency of shoulder pain and increased tolerance of the procedure. Thirty percent of patients required no intravenous sedation and did not experience shoulder pain when 3 L of gas or 15 mm Hg pressure was achieved. When shoulder pain did occur with heated and humidified gas, it was brief. CONCLUSION: Heating and humidifying CO2 increases tolerance of awake laparoscopy and decreases the frequency and duration of shoulder pain.


Ott et al 2003

Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery.

Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, Hubbard RC, Hsu PH, Saidman LJ, Manga

J Thorac Cardiovasc Surg 2003;125(6):1481–1492.

OBJECTIVE: Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients. We prospectively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a randomized clinical trial. METHODS: A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States, Canada, Germany, and the United Kingdom participated in this multicenter, phase III, placebo-controlled, double-blind, randomized, parallel-group trial. Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively. Intravenous study drug (40 mg) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days. Subsequently, oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days. Patient-controlled analgesia with morphine, oral opioids, or acetaminophen was available as required. Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use. Additional efficacy evaluations included daily pain intensity, patient and physician global evaluation of study medication, and pain effect on quality of life. Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period. RESULTS: Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour (p =.009), 24- to 48-hour (p = 0.017), 72- to 96-hour (p = 0.002), 96- to 120-hour (p = 0.004), and 120- to 144-hour (p = 0.037) periods. Both patients (p < 0.001) and physicians (p < 0.001) evaluated the study medication as significantly better than control therapy. The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days. Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19.0%, 59/311 patients) than in control patients (9.9%, 15/151 patients; p = 0.015). Regarding individual serious adverse events, a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients (10 [3.2%]) versus control patients (0 [0%]) (p = 0.035). The incidences of other individual serious adverse events, including cerebrovascular complications, myocardial infarction, and renal dysfunction, were proportionally greater but not significantly different between the groups. CONCLUSIONS: In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.


Kissler et al 2004

Effect of humidified and heated CO2 during gynecologic laparoscopic surgery on analgesic requirements and postoperative pain

Kissler S, Haas M, Strohmeier R, Schmitt H, Rody A, Kaufmann M, Siebzehnruebl E

J Am Assoc Gynecol Laparosc 2004;11(4):473-7

STUDY OBJECTIVE: To determine the effect of humidified and heated CO(2) for pneumoperitoneum during laparoscopic surgery on analgesic requirements, postoperative pain, and patient satisfaction. DESIGN: Prospective, randomized, double-blind, controlled study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Ninety consecutive women scheduled for gynecologic laparoscopic surgery. INTERVENTION: Operative laparoscopic management of adnexa surgery or adhesiolysis. MEASUREMENTS AND MAIN RESULTS: Thirty consecutive patients were randomized into each study group. Group I received humidified, heated gas; group II dry, heated gas; and group III (control group) standard dry, cold gas. No significant difference in intraoperative and postoperative analgesic requirements or postoperative pain score between group I and group II was found. There was even a tendency (not significant) toward less pain and higher postoperative satisfaction in patients in the control group. Therefore, the evaluation was stopped after 53 patients. CONCLUSION: The use of humidified, heated gas did not reduce postoperative pain or intraoperative analgesic requirements and is thus not preferable to standard dry, cold gas in gynecologic laparoscopic surgery.


Neudecker et al 2002

The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery.

Neudecker J, Sauerland S, Neugebauer E, Bergamaschi R, Bonjer HJ, Cuschieri A, Fuchs KH, Jacobi Ch,

Surg Endosc 2002 Jul;16(7):1121–43

BACKGROUND: The pneumoperitoneum is the crucial element in laparoscopic surgery. Different clinical problems are associated with this procedure, which has led to various modifications of the technique. The aim of this guideline is to define the scientifically proven standards of the pneumoperitoneum. METHODS: Based on systematic literature searches (Medline, Embase, and Cochrane), an expert panel consensually formulated clinical recommendations, which were graded according to the strength of available literature evidence. RECOMMENDATIONS: Preoperatively, all patients should be assessed for the presence of cardiac, pulmonary, hepatic, renal, or vascular comorbidity. Presupposing appropriate perioperative measures and surgical technique, there is no reason to contraindicate pneumoperitoneum in patients with peritonitis or intraabdominal malignancy. During laparoscopy, monitoring of end tidal CO2 concentration is mandatory. The available data on closed- (Veress needle) and open-access techniques do not allow us to principally favor the use of either technique. Using 2 to 5-mm instead of 5 to 10-mm trocars improves cosmetic result and postoperative pain marginally. It is recommended to use the lowest intraabdominal pressure allowing adequate exposure of the operative field, rather than using a routine pressure. In patients with limited cardiac, pulmonary, or renal function, abdominal wall lifting combined with low-pressure pneumoperitoneum might be an alternative. Abdominal wall lifting devices have no clinically relevant advantages compared to low-pressure (5–7 mmHg) pneumoperitoneum. In patients with cardiopulmonary diseases, intra- and postoperative arterial blood gas monitoring is recommended. The clinical benefits of warmed, humidified insufflation gas are minor and contradictory. Intraoperative sequential intermittent pneumatic compression of the lower extremities is recommended for all prolonged laparoscopic procedures. For the prevention of postoperative pain a wide range of treatment options exists. Although all these options seem to reduce pain, the data currently do not justify a general recommendation.


Aitola et al 1998

Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectom

Aitola P, Airo I, Kaukinen S, Ylitalo P.

Surg Laparosc Endosc 1998;8(2):140–144.

To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.


Tsereteli et al 2002

Prospective randomized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery.

Tsereteli Z, Terry ML, Bowers SP, Spivak H, Archer SB, Galloway KD, Hunter JG.

J Am Coll Surg. 2002;195:173–9

BACKGROUND: Recent publications demonstrating the safety and advantages of N2O for pneumoperitoneum (PP) prompted us to reconsider N2O as an agent for PP in general surgical laparoscopy. The purpose of this prospective, double-blind, randomized clinical trial was to determine whether N2O PP has any benefits over CO2 PP. STUDY DESIGN: One hundred three patients received N2O (group I, n = 52) or CO2 (group II, n = 51) PP for elective laparoscopic surgery. Heart rate, mean arterial blood pressure, end-tidal CO2, minute ventilation, and O2 saturation were recorded before PP, during PP, and in the recovery room. Postoperative pain medication use was recorded. Pain was assessed by means of visual analog scale (VAS) at postoperative hours 2 and 4, and on day 1. RESULTS: There were no differences between groups I and II in patient age, gender, weight, anesthesia risk (American Society of Anesthesiologists Score > 2), operative time, duration of PP, or length of hospital stay. Mean end-tidal CO2 increase under anesthesia was greater in group II than group I (3.0 versus 0.5 mmHg, p < 0.001) despite a greater mean intraoperative increase in minute ventilation in group II than group I (0.7 versus -0.2 L/min p < 0.001). The patients who had N2O PP had less pain 2 hours postoperatively (VAS: 4.9 versus 5.7, p <0.05), 4 hours postoperatively (VAS: 3.3 versus 5.1, p < 0.01), and 1 day postoperatively (VAS: 1.7 versus 3.5, p < 0.01) than patients who had CO2 PP. Postoperative narcotic or ketorolac use was not statistically different between groups. There were no adverse events related to either N2O or CO2 pneumoperitoneum. CONCLUSIONS: These results suggest that the use of N2O PP has sufficient advantages over CO2 that it should be considered as the standard agent for therapeutic PP.


Sharp et al 1982

Comparison of CO2- and N2O-induced discomfort during peritoneoscopy under local anesthesia.

Sharp JR, Pierson WP, Brady CE 3rd.

Gastroenterology. 1982;82:453–6.

The most comfortable gas for peritoneoscopy has been the subject of debate. We subjected 46 patients to double-blind comparison of carbon dioxide and nitrous oxide during initial pneumoperitoneum. The discomfort from local anesthesia was similar in both patient groups. The patient's and the physician's assessment of discomfort during gas insufflation showed that carbon dioxide was more uncomfortable as perceived by the patient (p = 0.02), the physician (p = 0.0006), and objectively assessed by degree of abdominal splinting (p = 0.006). The presence of intraabdominal adhesions had no relationship to discomfort. We conclude that nitrous oxide is more comfortable for institution of pneumoperitoneum during peritoneoscopy under local anesthesia.


Lipscomb et al 1994

The effect of nitrous oxide and carbon dioxide pneumoperitoneum on operative and postoperative pain during laparoscopic sterilization under local anesthesia.

Lipscomb GH, Summitt RL Jr, McCord ML, Ling FW.

J Am Assoc Gynecol Laparosc. 1994;2:57–60


STUDY OBJECTIVE: To compare carbon dioxide and nitrous oxide pneumoperitoneum with respect to intraoperative and postoperative pain during laparoscopic sterilization under local anesthesia. DESIGN: Randomized, double-blind study of pain during surgery and at 15 minutes, 1 hour, and 24 hours postoperatively. SETTING: Regional Medical Center, Memphis, Tennessee. PATIENTS: Women scheduled for laparoscopic sterilization under local anesthesia. Interventions. Forty-nine patients were randomized to carbon dioxide and 56 to nitrous oxide pneumoperitoneum. MEASUREMENTS AND MAIN RESULTS: Pain was assessed using a modified McGill pain questionnaire. Intraoperative pain was measured by the amount of supplemental narcotic required. Analgesic use in the recovery room and during the first 24 hours postoperatively was compared. Demographics for both groups were similar. The groups had no statistical differences in pain during surgery or at any of the postoperative time periods. Recovery room analgesia requirement was similar, but the nitrous oxide group used fewer pain tables (0.98 vs 0.42 tablets) in the first 24 hours. CONCLUSIONS: There is no difference in intraoperative and postoperative pain between nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic sterilization


O'Boyle et al 2002

Helium vs carbon dioxide gas insufflation with or without saline lavage during laparoscopy: a randomized trial.

O'Boyle CJ, DeBeaux AC, Watson DI, Ackroyd R, Lafullarde T, Leong JY, et al AU - Williams JAR AU - J

Surg Endosc 2002;16:620–5.

BACKGROUND: Helium is an inert gas that, if used for insufflation during laparoscopy, may be followed by less postoperative pain than carbon dioxide (CO2) insufflation, due to a more limited effect on intraabdominal pH and metabolism. Saline lavage has also recently been shown to reduce postoperative pain following laparoscopic surgery. To evaluate these possibilities and to better define the clinical safety of helium insufflation, we undertook a prospective randomized trial comparing CO2 and helium insufflation with or without saline lavage in patients undergoing elective laparoscopic upper abdominal surgery. METHODS: From January to November 2000, 173 patients undergoing elective laparoscopic cholecystectomy or fundoplication were randomized to undergo laparoscopy with either CO2 or helium insufflation. Within each group, patients were further randomized to undergo peritoneal lavage with 2 L of 0.9% saline at the end of the surgical procedure. This yielded the following four patient groups; CO2 (group 1, n = 47), CO2 + saline lavage (group 2, n = 43), helium (group 3, n = 43) and helium + saline lavage (group 4, n = 40). Patients were blinded to their randomization, and post-operative assessment was also performed by a blinded investigator, who applied a standardized scoring system to assess postoperative pain. RESULTS: The study groups were well matched for age, sex, weight, American Society of Anesthesiologists (ASA) status, duration of surgery, and volume of gas utilized, and 81% of patients were discharged within 48 h. There were no differences in the incidence of postoperative complications among the study groups, and postoperative pain scores were not significantly different when all four groups were compared. When helium (groups 3 and 4) was compared with CO2 (groups 1 and 2), no differences in pain score were seen. When no lavage (groups 1 and 3) was compared with lavage (groups 2 and 4), less pain was found in the group undergoing saline peritoneal lavage (mean 4-h pain score, 5.9 vs 5.2; 24-h pain score, 4.8 vs 4.1; p > 0.05). CONCLUSIONS: The use of helium insufflation for laparoscopic surgery, while not associated with any significant adverse sequelae, was not associated with less postoperative pain in this trial. The use of saline peritoneal lavage was associated with less pain in the early postoperative period.


Bisgaard et al 2000

Pain after microlaparoscopic cholecystectomy. A randomized double-blind controlled study.

Bisgaard T, Klarskov B, Trap R, Kehlet H, Rosenberg J.

Surg Endosc 2000;14:340–4.

BACKGROUND: Laparoscopic cholecystectomy (LC) is traditionally performed with two 10-mm and two 5-mm trocars. The effect of smaller port incisions on pain has not been established in controlled studies. METHODS: In a double-blind controlled study, patients were randomized to LC or cholecystectomy with three 2-mm trocars and one 10-mm trocar (micro-LC). All patients received a multimodal analgesic regimen, including incisional local anesthetics at the beginning of surgery, NSAID, and paracetamol. Pain was registered preoperatively, for the first 3 h postoperatively, and daily for the 1st week. RESULTS: The study was discontinued after inclusion of 26 patients because five of the 13 patients (38%) randomized to micro-LC were converted to LC. In the remaining 21 patients, overall pain and incisional pain intensity during the first 3 h postoperatively increased in the LC group (n = 13) compared with preoperative pain levels (p < 0.01), whereas pain did not increase in the micro-LC group (n = 8). CONCLUSIONS: Micro-LC in combination with a prophylactic multimodal analgesic regimen reduced postoperative pain for the first 3 h postoperatively. However, the micro-LC led to an unacceptable rate of conversion to LC (38%). The micro-LC instruments therefore need further technical development before this surgical technique can be used on a routine basis for laparoscopic cholecystectomy.


Sarli et al 2003

Randomized clinical trial of laparoscopic cholecystectomy performed with mini-instruments.

Sarli L, Iusco D, Gobbi S, Porrini C, Ferro M, Roncoroni L

British Journal of Surgery 2003;90(11):1345–8

BACKGROUND: The outcomes after traditional laparoscopic cholecystectomy (LC; one 10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease were compared. METHODS: The study was a randomized, single-blind trial comparing LC with MLC. Only elective patients were eligible for inclusion. LC was a routine procedure at the institution in which the study was performed, whereas MLC was introduced after a short training period. The randomization period was from January to December 2001. RESULTS: Of 175 patients who had elective minimal access cholecystectomy during the randomization period, 135 entered the trial: 68 underwent LC and 67 underwent MLC. The groups were matched for age, sex and preoperative characteristics. Median (range) operating times for LC and MLC were similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and postoperative complication rates, the time for the patient to resume walking, eating and passing stools, and median hospital stay were the same in the two groups. The level of postoperative pain was lower in the MLC group at 1 h (P = 0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034). Patients who had MLC received fewer injections of analgesic (P = 0.036) and more patients in this group expressed satisfaction with the cosmetic result (P = 0.001). CONCLUSION: MLC took a similar time to perform and caused less postoperative pain than the standard laparoscopic procedure. Reducing the port size further enhanced the advantages of laparoscopic over open cholecystectomy.


Bresadola et al 1999

Elective transumbilical compared with standard laparoscopic cholecystectomy.

Bresadola F, Pasqualucci A, Donini A, Chiarandini P, Anania G, Terrosu G, Sistu MA, Pasetto A

Eur J Surg 1999;165(1):29–34

OBJECTIVE: To compare the transumbilical technique of laparoscopic cholecystectomy with standard laparoscopic cholecystectomy. DESIGN: Randomised open study. SETTING: Teaching hospital, Italy. SUBJECTS: 90 patients who required elective cholecystectomy under general anaesthesia. INTERVENTIONS: Standard laparoscopic cholecystectomy through 4 ports or transumbilical cholecystectomy through 2 ports. MAIN OUTCOME MEASURES: Amount of pain and analgesia, cost, side effects, and cosmesis. RESULTS: 25 patients were excluded from analysis (8 in the standard group because relevant data were not recorded; and 17 in the transumbilical group in 4 of whom relevant data were not recorded, and 13 for technical reasons). 32 patients who had standard, and 25 who had transumbilical cholecystectomy had operative cholangiograms. There were no complications, no side effects, and no conversions to open cholecystectomy. Those who had transumbilical cholecystectomy had significantly lower pain scores (p<0.05) and required significantly less analgesia during the first 24 hours (p<0.05) than those who had standard laparoscopic cholecystectomy. CONCLUSION: Once the learning curve has been completed, transumbilical cholecystectomy is possible without some of difficulties associated with standard laparoscopic cholecystectomy.


Ainslie et al 2003

Micropuncture cholecystectomy vs conventional laparoscopic cholecystectomy: A randomized controlled trial.

Ainslie WG, Catton JA, Davides D, Dexter S, Gibson J, Larvin M, McMahon MJ, Moore M, Smith S, Vezakis A.

Surgical Endoscopy 2003;17(5):766–772.

Background: The aim of this study was to compare micropuncture laparoscopic cholecystectomy (MPLC), with three 3.3-mm cannulas and one 10-mm cannula with conventional laparoscopic cholecystectomy (CLC). Methods: Patients were randomized to undergo either CLC or MPLC. The duration of each operative stage and the procedure were recorded. Interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), and vasopressin were sampled for 24 h. Visual analogue pain scores (VAPS) and analgesic consumption were recorded for 1 week. Pulmonary function and quality of life (EQ-5D) were monitored for 4 weeks. Statistical analysis was performed using the Mann-Whitney test or Fisher's exact test. Results are expressed as median (interquartile range). Results: Forty-four patients entered the study, but four were excluded due to unsuspected choledocholithiasis (n = 3) or the need to reschedule surgery (n = 1). The groups were comparable in terms of age, duration of symptoms, and indications for surgery. Total operative time was similar (CLC, 63 [52-81] min vs MPLC 74 [58- 95] min; p = 0.126). However, time to place the cannulas after skin incision (CLC, 5:42 [3:45-6:37] min vs MPLC, 7:38 [5:57-10:15] min; p = 0.015) and to clip the cystic duct after cholangiography (CLC, 1:05 [0:40-1:35] min vs MPLC, 3:45 [2:26-7:49] min; p < 0.001) were significantly longer for MPLC. Six CLC patients and one MPLC patient required postoperative parenteral opiates (p = 0.04). Oral analgesic consumption was similar in both groups (p = 0.217). Median VAPS were lower at all time points for MPLC, but this finding was not significant (p = 0.431). There were no significant differences in postoperative stay, IL-6, ACTH or vasopressin responses, pulmonary function, or EQ-5D scores. Conclusions: The thinner instruments did not significantly increase the total duration of the procedure. MPLC reduced the use of parenteral analgesia postoperatively, which may prove beneficial for day case patients, but it did not have a significant impact on laboratory variables, lung function or quality of life.


Lam et al 2000

Radially expanding trocar: A less painful alternative for laparoscopic surgery.

Lam TYD, Siu WL, Hing SS, Kwok SPY.

J Laparosc Adv Surg Techniques 2000;10(5):269–273.

BACKGROUND AND PURPOSE: One advantage of minimal-access surgery is that it produces less pain. A radially expanding trocar has been claimed to reduce pain further. We aimed to evaluate this claim. PATIENTS AND METHODS: This was a randomized controlled single-blind clinical trial. Fifty-four patients who underwent laparoscopic cholecystectomy at the Department of Surgery, United Christian Hospital, Hong Kong, between July 1997 and September 1998 were randomized into either the study group or the control group. The radially expanding 10-mm trocar was used for the epigastric port in the study group. The conventional 10-mm metal trocar was used similarly in the control group. The operation was otherwise performed with a standardized technique. Another conventional 10-mm metal trocar was used for the subumbilical port for all patients. Pain was measured using a visual analog scale. Pain scores for the epigastric port and subumbilical port were documented for 3 days after the surgery. RESULTS: There was no difference in age, sex, diagnoses, operating time, or conversion rate. There was consistently no difference in the pain experienced in the subumbilical wound, whereas pain at the epigastric wound was consistently less with the radially expanding trocar (p < 0.05). CONCLUSION: The radially expanding trocar produces less early postoperative pain than the conventional metal trocar.


Bhoyrul et al 2000

A randomized prospective study of radially expanding trocars in laparoscopic surgery.

Bhoyrul S, Payne J, Steffes B, Swanstrom L, Way LW.

J Gastrointest Surg 2000;4:392–397.

Trocar injury is one of the most serious and potentially preventable complications of laparoscopic surgery. Use of a blunt rather than a cutting trocar could be expected to lessen the likelihood of this injury. Therefore complications related to laparoscopic port design were studied by comparing conventional cutting trocars with radially expanding (blunt) trocars. A multicenter, prospective, randomized clinical trial was conducted in 250 adult patients undergoing elective laparoscopic procedures at tertiary care centers and community hospitals. The patients were randomly assigned to one of two groups: group C, conventional cutting trocars; or group S, radially expanding trocars. Sixteen surgeons performed 244 elective laparoscopic procedures; six patients were removed from the study. One hundred nineteen patients were assigned to group S and 125 to group C. The groups were similar with regard to age, sex, and type of procedure. The following data were collected: intraoperative complications related to the trocars, abdominal wall bleeding, visceral or vascular injury, other complications, fascial closure, procedure time, trocar site assessment at 4 and 24 hours postoperatively, and visual analog pain scores at 4, 8, 12, and 24 hours postoperatively. Fascial defects from 10 mm or larger trocars in group C were closed; the fascial defects in group S were not closed. The trocar sites were checked for incisional hernias at late follow-up. Mean operating time was not different between the two groups (group S, 92 +/- 73 minutes; group C, 100 +/- 74 minutes). There were no episodes of intraoperative cannula site bleeding in group S compared with 16 episodes in 13 patients (P < 0.001) in group C. Postoperative wound complications were fewer in group S (13 vs. 23; P < 0.05). Although the pain scores were generally lower in group S, the differences were not significant. Only 3% of the patients in group S had fascial defects of 10 mm or greater that had to be closed. Within a follow-up period of 6 to 18 months, there have been no incisional hernias in either group. This study shows that radially expanding trocars are safe and effective, and less likely than conventional trocars to result in intraoperative or postoperative complications. The defects created by the radially expanding trocars do not have to be routinely closed.


Yim + Yuen 2001

Randomized double-masked comparison of radially expanding access device and conventional cutting tip trocar in laparoscopy

Yim SF, Yuen PM

Obstet Gynecol 2001;97(3):435–8

OBJECTIVE: To compare postoperative wound pain associated with the radially expanding access device and the conventional disposable cutting-tip trocar. METHODS: Our randomized, double-masked, self-controlled study involved 34 women scheduled for laparoscopic adnexal surgery. In each, a 10-mm radially expanding access device was inserted laterally on one side of the lower abdomen and a size-matched disposable cutting-tip trocar was placed on the other side, using random assignment. Postoperative pain for each studied wound and patient satisfaction toward the wounds were assessed using a visual analog scale. Any bleeding complication associated with insertion of the trocar was also recorded. RESULTS: The radially expanding access device was associated with significant reduction in severity (median 1.4 versus 5.0, P <.001) and duration (median 11 versus 21 days, P <.001) of postoperative wound pain, shorter wound scars (14 versus 17 mm, P <.001), a lower incidence of wound induration (0 versus 9, P <.01), and a higher patient satisfaction (median 9.7 versus 6.2, P <.001). There were four inferior epigastric artery injuries, all at the conventional trocar wound. CONCLUSION: The radially expanding access device was associated with less postoperative wound pain and more patient satisfaction than the conventional cutting-tip trocar.


Kum et al 1996

Randomized comparison of pulmonary function after the 'French' and 'American' techniques of laparoscopic cholecystectomy.

Kum CK, Eypasch E, Aljaziri A, Troidl H

Br J Surg 1996;83(7):938–41

The 'French' and 'American' techniques of laparoscopic cholecystectomy, which differ in the position of the surgeon and ports, have not been compared directly. The authors' hypothesis was that the 'French' technique results in better postoperative pulmonary function than the 'American' technique. Patients undergoing elective cholecystectomy were randomized, 25 patients to have the 'French' method and 24 the 'American' method. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured before operation, and 6, 24 and 48 h after surgery. Postoperative pain and fatigue were also measured. Both FVC and FEV1 at 6 h, 24 h and 48 h after operation were significantly less in the 'American' group (FVC at 24 h: 71 versus 86 per cent of preoperative value; P = 0.001, Student's t test; 95 per cent confidence interval 7-24). Two cases of atelectasis occurred in the 'American' group and none in the 'French' group. Differences in access to Calot's triangle were also noted. One patient in the 'French' group sustained a diathermy injury of the duodenum, related to defective equipment. It is concluded that the 'French' method leads to less impairment of pulmonary function.


Scott et al 1992

Laparoscopic cholecystectomy: Laser or diathermy?

Scott HJ, Kelly S, Rosin RD

Minimally Invasive Therapy 1992;1(5):347–349

Laparoscopic cholecystectomy is becoming the favoured operation for symptomatic gallstones. The results of atrial comparing diathermy and laser for dissection of the gall bladder bed have demonstrated no difference in any of the parameters measured between the two groups. Both groups demonstrated a rise in bilirubin (laser [L], P = 0.03; diathermy [D], P = 0.001) and AST (L, P = 0.003; D, P = 0.002), and a fall in albumin (L, P = 0.0001; D, P = 0.002) and total protein (L, P = 0.0001; D, P = 0.0003). There was a corresponding fall in haemoglobin (L, P = 0.001; D, P = 0.008) and haematocrit (L, P = 0.002; D, P = 0.003) and rise in white cell count (L, P = 0.02; D, P = 0.006). There was no difference in pain assessment, operating time or hospital stay between the two groups. If used for cholecystectomy alone, the financial outlay for laser equipment is unjustified.


Cengiz et al 2005

Randomized trial of traditional dissection with electrocautery versus ultrasonic fundus-first dissection in patients undergoing laparoscopic cholecystectomy

Cengiz Y, Janes A, Grehn A, Israelsson LA

Br J Surg 2005;92(7):810–3

BACKGROUND: In laparoscopic cholecystectomy dissection can be with monopolar electrocautery or with ultrasonic shears, and can start at the triangle of Calot or at the fundus of the gallbladder. METHODS: Thirty-seven patients undergoing laparoscopic cholecystectomy were randomized to electrocautery dissection from the triangle of Calot and 43 to fundus-first dissection with ultrasonic shears. All procedures were strictly standardized, and patients and their postoperative carers were blinded to the operation performed. RESULTS: Ultrasonic fundus-first dissection was associated with a shorter duration of operation (mean 46 versus 61 min), fewer overnight hospital stays (two versus eight), lower pain scores 4 and 24 h after surgery, less nausea at 2, 4 and 24 h, and a shorter period of sick leave (mean 5.5 versus 9.3 days) compared with electrocautery from the triangle of Calot. CONCLUSION: Ultrasonic fundus-first dissection during laparoscopic cholecystectomy was quicker and associated with less nausea and pain than electrocautery dissection from the triangle of Calot.


Tsimoyiannis et al 1998c

Laparoscopic cholecystectomy using ultrasonically activated coagulating shears.

Tsimoyiannis EC, Jabarin M, Glantzounis G, Lekkas ET, Siakas P, Stefanaki-Nikou S

Surg Laparosc Endosc 1998;8(6):421-4

Ultrasonic energy has recently been used for surgical cutting and coagulating. A prospective randomized study was undertaken to determine the effectiveness of ultrasonic energy versus monopolar electrosurgery in human laparoscopic cholecystectomy. Two hundred patients were enrolled and randomized into two groups of 100 patients each. Group A patients underwent laparoscopic cholecystectomy with monopolar electrocautery. Group B patients underwent laparoscopic cholecystectomy with ultrasonically activated shears. In 18 cases of this group, the cystic artery was coagulated and cut without clips. Subhepatic closed drainage was left for 24 h in patients who were candidates for oozing of blood or leakage of bile. The median operating time was 45 min in group A and 37 min in group B. Subhepatic drainage was left in 37 patients of group A and 26 of group B. The median blood loss was 14 ml in group A and 2 ml in group B, while 3 patients of group A and none of group B had bile leakage from the bed of the gallbladder for 1, 1, and 6 days, respectively. Postoperative ultrasound examination showed a minor subhepatic fluid collection in 5 patients of group A and in 1 patient of group B. All these collections were treated without drainage. The length of hospital stay was 1.9 +/- 0.5 days in group A and 1.4 +/- 0.2 days in group B. Postoperative pain scores, nausea, and vomiting were equivalent in both groups. It is concluded that ultrasonically activated coagulating shears are safer, easier to use, faster, and less prone to intraoperative complications and postoperative morbidity than monopolar electrocautery in laparoscopic cholecystectomy.


Fredman 1994

Residual pneumoperitoneum: a cause of postoperative pain after laparoscopic cholecystectomy.

Fredman B 1994

Anesth Analg 1994;79:152–154.

After laparoscopic cholecystectomy, residual gas is inevitably retained in the peritoneal cavity. An active attempt is not always made to remove it. Using a double-blind prospective protocol in 40 healthy patients, we evaluated the effect of residual pneumoperitoneum on post-laparoscopic cholecystectomy pain intensity. On completion of surgery, prior to removal of the surgical instruments, the patients were randomly divided into two groups: in the active aspiration (AA) group an active attempt was made to remove as much gas as possible from the peritoneal cavity, while in the nonactive aspiration (NAA) group no such effort was made. Postoperative pain was assessed hourly over a 4-h period with a visual analog scale (VAS) and a patient-controlled analgesia (PCA) device. During the first postoperative hour, the NAA patients made significantly (P < 0.05) more demands (mean +/- SD) for morphine than those in the AA group (31.3 +/- 26.2 vs 15.3 +/- 15.7) and also received a borderline significantly (P = 0.056) larger dose (mean +/- SD) of PCA morphine (3.9 +/- 1.9 mg vs 2.7 +/- 1.3 mg). The VAS scores (mean +/- SD) over the 4-h study period were similar in both groups, being high during the first postoperative hour (AA = 5.1 +/- 2.1 vs NAA = 6.1 +/- 2.2) and then decreasing. We conclude that residual pneumoperitoneum is a contributing factor in the etiology of postoperative pain after laparoscopic cholecystectomy.


Hawasli and Brown 1994

The effect of drains in laparoscopic cholecystectomy.

Hawasli A, Brown E

J Laparoendosc Surg 1994;4(6):393–8

A prospective controlled randomized study was performed on 100 patients undergoing elective laparoscopic cholecystectomy to evaluate the benefit of routine drainage in simple uncomplicated procedures. The 100 patients were randomized into two groups. Group 1 patients (n = 50) had a drain placed through the epigastric trocar site. The drain was removed before their discharge unless bile or blood was present. Group 2 patients (n = 50) did not have a drain placed. Eleven patients in group 2 (no drain) (22%) were discharged on the same day of surgery (within 8 h), and the remaining 89 patients in both groups were discharged the day after surgery (within 23 h). There were no wound infections or postoperative fever in either group. There were minor but not statistically significant differences between the two groups in postoperative severity and duration of abdominal pain, shoulder pain, and nausea. Furthermore, the two groups were similar in respect to postoperative recovery time and return to work.


Tsimoyiannis et al 1998

Intraperitoneal normal saline infusion for postoperative pain after laparoscopic cholecystectomy.

Tsimoyiannis EC, Siakas P, Tassis A, Lekkas ET, Tzourou H, Kambili M.

World J Surg 1998;22:824–8.

After laparoscopic surgery carbon dioxide remains within the peritoneal cavity for a few days, commonly causing pain. This prospective randomized study was performed to determine the efficacy of intraperitoneal infusion of normal saline on postoperative pain after laparoscopic cholecystectomy. Altogether 300 patients were randomly assigned to one of five groups of 60 patients each. Group A: control group, no peritoneal infusion, no subhepatic drain. Group B: no peritoneal infusion but a subhepatic closed brain was left for 24 hours. Group C: normal saline 25 to 30 ml/kg body weight at a temperature of 37 degrees C was infused under the right hemidiaphragm and left in the peritoneal cavity. Group D: normal saline in a room temperature was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated. Group E: normal saline was infused and suctioned as in group D, but a subhepatic closed drain was left for 24 hours. Postoperatively, analgesic medication usage, nausea, vomiting, and pain scores were determined at 2, 6, 12, 24, 48, and 72 hours (during hospitalization and at home). Postoperative pain was reduced significantly (p < 0.001) in the patients of groups C, D, and E versus controls, whereas no difference was observed between groups A and B. Among groups C < D and E, group E (p < 0.01) had the best results followed by group D and then group C. Intraperitoneal normal saline offered a detectable benefit to patients undergoing laparoscopic cholecystectomy. The beneficial effect was better when the fluid was suctioned after deflation of the pneumoperitoneum and even better when a subhepatic closed drain continued fluid suction during the first postoperative hours.


Barczynski and Herman 2004

Low-pressure pneumoperitoneum combined with intraperitoneal saline washout for reduction of pain after laparoscopic cholecystectomy: A prospective randomized study.

Barczynski M, Herman RM

Surgical Endoscopy 2004;18(9):1368–1373

Background: We designed a prospective randomized clinical trial to investigate whether intraperitoneal saline washout combined with a low-pressure pneumoperitoneum (LPSW) was superior to low-pressure pneumoperitoneum (LP) alone as a means of reducing postoperative pain and analgesic consumption in the early recovery period after laparoscopic cholecystectomy (LC). Methods: A total of 124 consecutive patients undergoing LC due to uncomplicated symptomatic gallstones were randomized to the LP or LPSW group. In the LPSW group, normal saline at body temperature (25 ml/kg of body weight) was irrigated under the diaphragm. The fluid was evacuated via the passive-flow method through a 16-F closed drain left under the liver for 24 h. We then assessed the intensity of total abdominal postoperative pain using the Visual Analogue Scale (VAS), including the incidence of shoulder-tip pain (STP), total daily analgesia demand rate, analgesic consumption. Quality of life (QOL) within 7 days after the operation was assessed using the Medical Outcomes Study Short Form 36 Health Survey (SF-36). A p value of < 0.05 was considered significant. Results: The mean postoperative pain score was lower by 2.64 +/- 0.86 in the LPSW; the difference equaled 9.64% (p < 0.05). The incidence of STP was lower in the LPSW group (LP 11.29% vs LPSW 1.6%; p = 0.028). The analgesia demand rate was remarkably lower in LPSW vs LP within 24 and 48 h postoperatively (70.96% vs 90.32%; p = 0.006 and 64.51% vs. 83.87%; p = 0.013, respectively). After LPSW vs LP, QOL was better in terms of physical functioning, role limitations due to physical problems, and bodily pain (90.32% vs 77.42%; p = 0.05, 90.32% vs 75.8%; p = 0.03, 91.93% vs 74.19%; p = 0.008, respectively). Conclusion: In terms of lower postoperative pain and a better QOL within the early recovery period, LPSW is superior to LP alone. The saline washout procedure should be recommended during LC because it is a simple way to reduce pain intensity, even after LP operations.


Nursal et al 2003

Effect of drainage on postoperative nausea, vomiting, and pain after laparoscopic cholecystectomy.

Nursal TZ, Yildirim S, Tarim A, Noyan T, Poyraz P, Tuna N, Haberal M

Langenbecks Archives of Surgery 2003;388(2):95–100

Background: Laparoscopic cholecystectomy is associated with a high incidence of postoperative pain, nausea, and vomiting. Pneumoperitoneum created during the operation and residual gas after the operation are two of the factors in postoperative pain and nausea. We studied the effects of a subdiaphragmatic gas drain, which is intended to decrease the residual gas, on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy. Patients and methods: Seventy patients were randomized into two demographically and clinically comparable groups: drainage and control. Postoperative pain, nausea, and vomiting were measured by verbal grading and visual analog scale 2-72 h postoperatively. Analgesic and anti-emetic use and incidence of retching, vomiting and other complaints were also recorded. Results: Subdiaphragmatic drain effectively reduced the incidence and amount of subdiaphragmatic gas bubble. The incidence and severity of nausea was lower in the drainage group at 72 h. Although severity of pain was lower at 8 and 12 h in the drainage group, the difference was not significant. There was also no difference between the groups in regard to analgesic and antiemetic use. Conclusions: Subdiaphragmatic drain offers only minor, if any, benefit on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy, and this effect is probably clinically irrelevant.


Shen et al 2002

A prospective, randomized study of closed-suction drainage after laparoscopic-assisted vaginal hysterectomy

Shen CC, Huang FJ, Hsu TY, Weng HH, Chang HW, Chang SY

J Am Assoc Gynecol Laparosc 2002;9(3):346–52

STUDY OBJECTIVE: To estimate whether closed-suction drainage of the pelvis after laparoscopic-assisted vaginal hysterectomy reduces the risk of postoperative morbidity. DESIGN: Prospective, randomized study (Canadian Task Force classification 1). SETTING: Teaching medical center. PATIENTS: Three hundred twenty-four women. INTERVENTION: Laparoscopic-assisted vaginal hysterectomy. MEASUREMENTS AND MAIN RESULTS: The 160 women in group 1 had closed-suction (Jackson-Pratt) drains inserted into the peritoneal cavity and cul-de-sac, whereas the 164 in group 2 had no drains. Postoperative time to flatulence, hemoglobin, analgesic requirements, duration of hospital stay, rehospitalization, complications, febrile morbidity, and infection were studied. No statistically significant differences were seen between groups in demographics, outcome measures, postoperative infectious morbidity, or complications. The small power value may mean that no true differences existed for most tests. A statistically significant difference in analgesic requirement was found, with more oral analgesics taken by women in group 2. CONCLUSION: Prophylactic surgical drainage may not be necessary to prevent postoperative morbidity after laparoscopic-assisted vaginal hysterectomy when prophylactic and postoperative antibiotics are given. A drain still has its role in gynecologic laparoscopy in selected women, such as in those with persistent ooze from raw surfaces, bowel injury, or frank pus in the abdomen.


Holte et al 2004

Liberal versus restrictive fluid administration to improve recovery after laparoscopic cholecystectomy: a randomized, double-blind study.

Holte K, Klarskov B, Christensen DS, Lund C, Nielsen KG, Bie P, Kehlet H

Ann Surg 2004;240(5):892–9

OBJECTIVE: The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens. METHODS: In a double-blind study, 48 ASA I-II patients undergoing laparoscopic cholecystectomy were randomized to 15 mL/kg (group 1) or 40 mL/kg (group 2) intraoperative administration of lactated Ringer's solution (LR). All other aspects of perioperative management as well as preoperative fluid status were standardized. Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function (spirometry), exercise capacity (submaximal treadmill test), cardiovascular hormonal responses, balance function, pain, nausea and vomiting, recovery, and hospital stay. RESULTS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response (aldosterone, antidiuretic hormone, and angiotensin II). Nausea, general well-being, thirst, dizziness, drowsiness, fatigue, and balance function were also significantly improved, as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution. CONCLUSIONS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy.


Launo et al 2004

Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy.

Launo C, Bassi C, Spagnolo L, Badano S, Ricci C, Lizzi A, Molinino M

Minerva Anestesiol 2004;70(10):727-34; 734–8

AIM: Preemptive analgesia is currently in use in the management of postoperative pain and no more under search. The administration of ketamine as intraoperative analgesic agent is well-known since a long time; the analgesic properties of this drug are related to its actions as a non-competitive N-methyl-D-aspartate receptors antagonist; these receptors present an excitatory function on pain transmission and this binding seems to prevent or reverse the central sensitisation of every kind of pain, including postoperative pain. In literature, the use of this anesthetic for the preemptive analgesia in the management of postoperative pain is controversial; for this reason the aim of our study was the clinical evaluation of preemptive perioperative analgesia with low-doses ketamine. METHODS: This trial involved 40 patients undergoing laparoscopic cholecystectomy, with the same surgical operator; postoperative analgesia was performed with the intraoperative administration of ketamine (0.7 mg/kg) or tramadol (15 mg/kg). A randomized, double-blind study was performed; after an inhalatory/analgesic general anesthesia (sevofluorane + remifentanyl) the postoperative-pain control was clinically evaluated through algometric measurements (Visual Analog Scale, Verbal Rating Scale, Pain Intensity Difference); supplemental doses of tramadol were administered if required, also to quantify the adequacy of analgesia, and adverse effects were evaluated. RESULTS: The results show that preemptive intraoperative analgesia with ketamine produces a good analgesia at the awakening, despite low duration (approximately 1 hour), and upgrades the analgesic effect of tramadol in the postoperative period. Among the adverse effects, some (for example nausea) were related to the administration of both analgesics and to the kind of surgery, others (hallucinosis, nystagmus, photophobia, psychomotor excitation, psychotic symptoms) were due to ketamine, and others (respiratory depression and hypotension) could be related to tramadol. Although the adverse effects due to ketamine are more numerous than those related to tramadol, the second could potentially be more dangerous. CONCLUSION: Our study suggests that preemptive low-doses ketamine is able to produce an adequate postoperative analgesia and increases the analgesic effect of tramadol; furthermore, ketamine adverse effects could be reduced by intraoperative administration of benzodiazepines and/or antiemetic drugs, or by the association of ketamine and a peripheral analgesic (ketorolac).


Walder et al 2001

Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review.

Walder B, Schafer M, Henzi I, Tramer MR.

Acta Anaesthesiol Scand 2001;45(7):795–804.

BACKGROUND: The usefulness of intravenous patient-controlled analgesia (PCA) with opioids for postoperative analgesia is not well defined. METHODS: We systematically searched (MEDLINE, EMBASE, Cochrane Library, bibliographies, any language, to January 2000) for randomised trials comparing opioid-based PCA with the same opioid given intramuscularly, intravenously, or subcutaneously. Weighted mean differences (WMD) for continuous data, relative risks (RR) and numbers-needed-to-treat (NNT) for dichotomous data were calculated with 95% confidence intervals (CI) using fixed and random effects models. RESULTS: Data from 32 trials were analysed: 22 (1139 patients) were with morphine, five (682) with pethidine, three (184) with piritramide, one (47) with nalbuphine and one (20) with tramadol. In three morphine and one pethidine trial (352 patients), more patients preferred PCA (89.7% vs. 65.8%, RR 1.41 (95%CI 1.11 to 1.80), NNT 4.2). Combined dichotomous data on pain intensity and relief, and the need for rescue analgesics from eight morphine, one pethidine, one piritramide, and one nalbuphine trial (691 patients), were in favour of PCA (RR 1.22 (1.00 to 1.50), NNT 8). In two morphine trials (152), pulmonary complications were more frequently prevented with PCA (100% vs. 93.3%, RR 1.07 (1.01 to 1.14), NNT 15). There was equivalence for cumulative opioid consumption, pain scores, duration of hospital stay, and opioid-related adverse effects. CONCLUSION: These trials provide some evidence that in the postoperative pain setting, PCA with opioids, compared with conventional opioid treatment, improve analgesia and decrease the risk of pulmonary complications, and that patients prefer them.


Naguib et al 2000

Wound closure tramadol administration has a short-lived analgesic effect.

Naguib M, Attia M, Samarkandi AH.

Can J Anaesth 2000;47(8):815–818.

PURPOSE: To evaluate the effects of tramadol administration at wound closure on postoperative pain and analgesic requirements in patients undergoing laparoscopic cholecystectomy. METHODS: In a prospective, randomized, double-blind study 80 patients were allocated into two groups (n = 40 in each) to receive either 200 mg tramadol or placebo i.v. at the time of wound closure. Postoperatively, all patients received tramadol from a patient-controlled analgesia (PCA) device. Pain, analgesic consumption, vital signs and side effects were recorded postoperatively for 24 hr. RESULTS: Administration of 200 mg tramadol at the time of wound closure was associated with a short-lived (60 min) reduction in pain scores and PCA consumption compared with placebo. Although the time to first request for analgesia after surgery was longer in patients who received tramadol at wound closure, there was no difference between the two groups with respect to pain scores or to the requirements of postoperative analgesia over the next 23 hr. The cumulative PCA consumption of tramadol in 24 hr was 139.4+/-108 and 102.4+/-106 mg in the placebo and tramadol groups, respectively (p = 0.06). CONCLUSIONS: Wound closure administration of 200 mg tramadol had a short-lived (60 min) analgesic effect but did not affect the long-term pain scores or analgesic requirements after laparoscopic cholecystectomy.


Owen et al 1997

Pain control in the week following laparoscopic surgery: A comparison of sustained-release ibuprofen and paracetamol

Owen H, Plummer JL, Ilsley AH, Tordoff K, Toouli J

Minimally Invasive Therapy & Allied Technologies: Mitat 1997;6(3):235–240

This study compared pain relief and adverse events from sustained-release ibuprofen and paracetamol administered for a week after laparoscopic cholecystectomy. Patients were randomly assigned to receive sustained-release ibuprofen (2 x 800 mg once daily) or paracetamol (2 x 500 mg PRN up to 4 hourly). Oxycodone tablets (5 mg) were available for rescue analgesia. Patients kept a pain diary for 1 week and were assessed by the investigators 24 h after surgery and at the surgical follow-up clinic. Patients receiving ibuprofen (n = 46) reported lower pain scores (scale 0-4, where 0 = no pain and 4 = unbearable pain) than those receiving paracetamol (n = 44) (mean 1.07 vs 1.35) and consumed less oxycodone (mean 0.83 vs 1.67 tablets). Although these differences were not statistically significant (P = 0.057 and P = 0.12 respectively), the 95% confidence interval for the difference in mean pain scores was -0.01 to +0.55 indicating that sustained-release ibuprofen was equivalent or superior to paracetamol. Nineteen patients who received ibuprofen reported a total of 33 adverse events compared to 13 patients receiving paracetamol who reported 18 adverse events (P = 0.24). Sustained-release ibuprofen is as good as or better than paracetamol for the control of pain after laparoscopic surgery.


Chung et al 2004

Controlled-release codeine is equivalent to acetaminophen plus codeine for post-cholecystectomy analgesia.

Chung F, Tong D, Miceli PC, Reiz J, Harsanyi Z, Darke AC, Payne LW

Canadian Journal of Anaesthesia 2004;51(3):216–221

Purpose: Following ambulatory surgery, long-acting analgesics may provide advantages over short-acting analgesics. This study compared controlled-release codeine (CC) and acetaminophen plus codeine (A/C; 300 mg/30 mg) for pain control in the 48-hr period following laparoscopic cholecystectomy. Methods: Eligible patients were randomized to CC or A/C in a double-blind, double-dummy parallel group study. Unrelieved pain in hospital was treated with fentanyl iv bolus. Pain [100 mm visual analogue scale (VAS)] was assessed before the first dose of medication; at 0.5, one, two, three, and four hours post-dose; at discharge; and three times a day for 48 hr. Adverse events were recorded and measures of patient satisfaction were assessed at the end of the study. Results: Eighty-four patients were enrolled in the study; 42 patients in each group. There were no statistically significant differences between CC and A/C treatment. Mean VAS baseline pain was similar in both groups (P = 0.49) and there was no significant difference in the time to onset of analgesia (P = 0.17). At 0.5 hr, the mean VAS pain score was significantly reduced from baseline in both groups (P = 0.0001). The VAS pain scores at discharge were reduced 59% and 56% from baseline, respectively (P = 0.61). There was no difference between treatments in the incidence of adverse events and patients reported similar levels of satisfaction. Conclusions: Controlled-release codeine provides an equivalent onset of analgesia, reduction in postoperative pain, and level of patient satisfaction, to acetaminophen plus codeine, over 48 hr following cholecystectomy, with the advantage of less frequent dosing.


Gupta et al 2005

Wound instillation with 025% bupivacaine as continuous infusion following hysterectomy

Gupta S, Maheshwari R, Dulara SC.

Middle East journal of anesthesiology 2005;18(3):595-610

Postoperative pain relief was assessed by the effects of local anesthetic wound instillation on 100 patients who had undergone total abdominal hysterectomy with bilateral salpingo oophorectomy (TAH with BSO). Patients were divided into four groups of wound and non-wound instillation: Wound instillation Group A1 received diclofenac IM. Group A2 received diclofenac suppository. Non-wound instillation Group B1 received diclofenac IM. Group B2 received diclofenac suppository. A standard general anesthesia technique was administered. For would instillation, a multiholed (1 cm apart) 18G epidural catheter was placed above rectus sheath. This was connected to a pediatric regulated drip set with Dial-a flo to deliver 0.25% bupivacaine 10 ml /hour for 6 hours after a basal bolus of 10 ml. During first 6 hours after surgery rescue pentazocine 15 mg was administered to achieve VAS score < or = 30. Thereafter, rescue diclofenac was administered to patients. The requirement of rescue analgesic (pentazocine) was significantly less (P < 0.001) in wound instillation Groups A1 (13.80 mg +/- 13.64) and A2 (12.00 mg +/- 12.25) in comparison to non wound instillation Groups B1 (35.60 mg +/- 14.02) and B2 (31.80 mg +/- 15.80). Rescue diclofenac was not required in wound instillation groups as compared to 30 mg (B1) and 36 mg (B2) in non wound instillation groups. Nausea and vomiting was less in wound instillation groups. VAS score supine from 4th to 12th hours, VAS coughing during all time interval and VAS leg raising from 3rd to 12th hours was significantly lower (P < 0.001) in wound instillation group (A1, A2) in comparison to non wound instillation groups (B1, B2). We conclude that basal bolus infusion followed by continuous wound instillation of bupivacaine decreases analgesic requirement and pain scores in first 24 hours of postoperative period after TAH with BSO.


Gupta et al 2002

Postoperative pain relief using intermittent injections of 0.5% ropivacaine through a catheter after laparoscopic cholecystectomy.

Gupta A, Thorn SE, Axelsson K, Larsson LG, Agren G, Holmstrom B, Rawal N.

Anesth Analg 2002;95(2):450–456.

Postoperative pain has been an important limiting factor for ambulatory laparoscopic cholecystectomy. We anesthetized 40 ASA physical status I-II patients using propofol for the induction and sevoflurane in oxygen and air for the maintenance of anesthesia. At the end of the anesthesia, the patients were randomized into one of two groups: Group P (Placebo) and Group R (0.5% Ropivacaine). Twenty milliliters of normal saline or ropivacaine, respectively, were injected intraperitoneally at the end of surgery via a catheter placed in the bed of the gall bladder. Postoperatively, intermittent injections (10 mL) of the study solution were given when required for pain. Ketobemidone 1-2 mg was given i.v. as rescue medication. Pain was assessed using a visual analog scale at 1, 2, 3, 4, 8, 12, 16, and 20 h after surgery and once each day for 1 wk at rest (deep pain), shoulder and incision sites, and pain during coughing. Recovery was assessed by the time to transfer from Phase 1 to 2, the ability to walk, drink, and eat, and the ability to void. Plasma concentrations of ropivacaine were measured in eight patients. Time to ability to walk, defecation, driving a car, and return to normal activities were also recorded through a questionnaire sent home with the patient. During the first 4 postoperative h, patients in Group R had lower scores for deep pain and during coughing compared with Group P (P < 0.05). No differences were found in the postoperative consumption of ketobemidone. Median times to recovery at home were similar between the groups. By the seventh day, 93% of the patients had returned to normal activities of daily living. We conclude that the early postoperative pain after ambulatory laparoscopic cholecystectomy could be relieved using intermittent injections of ropivacaine 0.5% into the bed of the gall bladder. IMPLICATIONS: Early postoperative pain can be relieved by intermittent injections of ropivacaine 0.5% through a catheter placed in the bed of the gall bladder after ambulatory laparoscopic cholecystectomy.


Fujii et al 1998

Efficacy of thoracic epidural analgesia following laparoscopic cholecystectomy.

Fujii Y, Toyooka H, Tanaka H.

Eur J Anaesthiol 1998;15:342–344.

This study was undertaken to determine whether epidural analgesia has any benefit for post-operative pain relief in patients undergoing laparoscopic cholecystectomy. Patients were randomly assigned to receive post-operative epidural analgesia with a morphine-bupivacaine combination (Group A, n = 22) or placebo (saline) (Group B, n = 22). The same standard general anaesthetic technique, which consists of nitrous oxide and isoflurane in oxygen was used. Analgesia was assessed using visual analogue pain scores (0-10 cm). The evaluation was carried out 24 and 48 h post-operatively. At 24 h after anaesthesia, pain scores in Group A (2.3 +/- 1.2) were lower than those in Group B (4.4 +/- 1.5) (p < 0.05). However, at 48 h post-operatively, no difference in scores was observed between the two groups. In conclusion, epidural analgesia with a morphine-bupivacaine combination improves pain relief during the first 24 h following laparoscopic cholecystectomy.


Wu et al 2005

Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis

Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, Lin EE, Liu SS.

Anesthesiology 2005;103(5):1079–88

The authors performed a meta-analysis and found that epidural analgesia overall provided superior postoperative analgesia compared with intravenous patient-controlled analgesia. For all types of surgery and pain assessments, all forms of epidural analgesia (both continuous epidural infusion and patient-controlled epidural analgesia) provided significantly superior postoperative analgesia compared with intravenous patient-controlled analgesia, with the exception of hydrophilic opioid-only epidural regimens. Continuous epidural infusion provided statistically significantly superior analgesia versus patient-controlled epidural analgesia for overall pain, pain at rest, and pain with activity; however, patients receiving continuous epidural infusion had a significantly higher incidence of nausea-vomiting and motor block but lower incidence of pruritus. In summary, almost without exception, epidural analgesia, regardless of analgesic agent, epidural regimen, and type and time of pain assessment, provided superior postoperative analgesia compared to intravenous patient-controlled analgesia.


Ballantyne et al 1998

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

Ballantyne JC, Carr DB, deFerranti S, Suarez T, Lau J, Chalmers TC, Angelillo IF, Mosteller
F.

Anesth Analg 1998;86(3):598–612.

We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.33–0.85) and had a weak tendency to reduce the incidence of pulmonary infections (RR 0.53, 95% CI 0.18–1.53) and pulmonary complications overall (RR 0.51, 95% CI 0.20–1.33). Epidural local anesthetics increased PaO2 (difference 4.56 mm Hg, 95% CI 0.058–9.075) and decreased the incidence of pulmonary infections (RR 0.36, 95% CI 0.21–0.65) and pulmonary complications overall (RR 0.58, 95% CI 0.42–0.80) compared with systemic opioids. Intercostal nerve blockade tends to improve pulmonary outcome measures (incidence of atelectasis: RR 0.65, 95% CI 0.27–1.57, incidence of pulmonary complications overall: RR 0.47, 95% CI 0.18–1.22), but these differences did not achieve statistical significance. There were no clinically or statistically significant differences in the surrogate measures of pulmonary function (FEV1, FVC, and PEFR). These analyses support the utility of epidural analgesia for reducing postoperative pulmonary morbidity but do not support the use of surrogate measures of pulmonary outcome as predictors or determinants of pulmonary morbidity in postoperative patients. IMPLICATIONS: When individual trials are unable to produce significant results, it is often because of insufficient patient numbers. It may be impossible for a single institution to study enough patients. Meta-analysis is a useful tool for combining the data from multiple trials to increase the patient numbers. These meta-analyses confirm that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity.


Curet et al 2002

Laparoscopic cholecystectomy.

Curet MJ, Contreras M, Weber DM, Albrecht R

Surg Endosc 2002;16(3):453–7

BACKGROUND: This study was undertaken to determine if patients undergoing laparoscopic cholecystectomy may be discharged home 4 h postoperatively with similar outcomes as patients admitted overnight. METHODS: Patients were randomized to an outpatient group (OP), consisting of patients who were discharged after a 4-h stay in the Post Anesthesia Care Unit (PACU), or to an inpatient group. Variables compared between the two groups included patient demographics; degree of postoperative pain, nausea, vomiting, and patient satisfaction; amount of pain and nausea medication taken; and number of phone calls, readmissions, or complications. Statistical analysis was performed with students t-test, Fisher's exact test, and Wilcoxon's signed rank and rank sums tests as appropriate. RESULTS: Eighty patients were initially enrolled. Two were converted and 4 required admission after being randomized to the OP group. Patients in the OP group received more oral pain medication prior to PACU discharge. Degree of pain, number of phone calls, readmission and complication rates, and patient satisfaction were similar between both groups. Of the 4 unexpected admissions, all were identified within the 4-h PACU stay. CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy who are discharged home 4 h postoperatively will experience the same satisfaction with no increase in complications as patients admitted overnight.


Keulemans et al 1998

Laparoscopic cholecystectomy: day-care versus clinical observation.

Keulemans Y, Eshuis J, de Haes H, de Wit LT, Gouma DJ

Ann Surg 1998;228(6):734–40

OBJECTIVE: To determine the feasibility and desirability of laparoscopic cholecystectomy (LC) in day-care versus LC with clinical observation. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy has been performed regularly as outpatient surgery in patients with uncomplicated gallstone disease in the United States, but this has not been generally accepted in Europe. The main objections are the risk of early severe complications (bleeding) or other reasons for readmission, and the argument that patients might feel safer when observed for one night. Quality-of-life differences hitherto have not been investigated. METHODS: Eighty patients (American Society of Anesthesiology [ASA] I/II) with symptomatic gallstones were randomized to receive LC either in day-care or with clinical observation. Complications, (re)admissions, consultations of general practitioners or the day-care center within 4 days after surgery, use of pain medication, quality of life, convalescence period, time off from professional activities, and treatment preference were assessed. The respective costs of day-care and clinical observation were determined. RESULTS: Of the 37 patients assigned to the day-care group who underwent elective surgery, 92% were discharged successfully after an observation period of 5.7+/-0.2 hours. The remainder of the patients in this group were admitted to the hospital and clinically observed for 24 hours. For the 37 patients in the clinical observation group who underwent elective surgery, the observation time after surgery was 31+/-3 hours. Three patients in the day-care group and one patient in the clinical observation group had complications after surgery. None of the patients in either group consulted a general practitioner or the hospital during the first week after surgery. Use of pain medication was comparable in both groups over the first 48 hours after surgery. There were no differences in pain and other quality-of-life indicators between the groups during the 6 weeks of follow-up. Of the patients in the day-care group, 92% preferred day-care to clinical observation. The same percentage of patients in the clinical observation group preferred at least 24 hours of observation to day-care. Costs for the day-care patients were substantially lower (approximately $750/patient) than for the clinical observation patients. CONCLUSION: Effectiveness was equal in both patient groups, and both groups appeared to be satisfied with their treatment. Because no differences were found with respect to the other outcomes, day-care is the preferred treatment in most ASA I and II patients because it is less expensive.


Young and O'Connell 2001

Recovery following laparoscopic cholecystectomy in either a 23 hour or an 8 hour facility.

Young J, O'Connell B.

J Qual Clin Practice 2001;21:2–7.

Research confirms that laparoscopic cholecystectomy (LC) results in shorter lengths of hospital stay and earlier return to usual activity than the traditional cholecystectomy procedure. Research in this area, however, focuses more on the medical aspects of patient recovery, but very few studies have evaluated how these patients manage their recovery at home or what types of problems they encounter. A total of 28 LC patients were randomly assigned to two groups: (1) 23 h stay (overnight) in a general surgical ward or (2) day procedure unit (DPU) stay. Data was collected by a self-administered Postoperative Symptoms Diary and telephone interview. Results showed no significant difference between the two groups of patients recovery symptoms scores. Problems with mobility, pain and elimination recorded the highest mean scores for both groups of patients. Overnight patients also experienced problems with tiredness and eating. All DPU patients were able to manage their postoperative symptoms, compared to only 44% of patients who had stayed in overnight. Carer assistance was needed with regard to activities of daily living, child care and reassurance. Results showed that with careful selection of patients, LC cases performed as day procedures did not impact at all on the patients' recovery trajectory.


Mitchell + Harrow 1994

Costs and outcomes of inpatient versus outpatient hernia repair

Mitchell J B, Harrow B

Health Policy 1994:28(2);143–52

This study sought to compare treatment costs and outcomes for a large number of Medicare patients undergoing inpatient versus outpatient hernia repair around the country. Medicare physician and hospital claims were obtained for all Medicare enrollees residing in eleven states in 1987 and 1988, in order to take advantage of geographic variation in treatment location. All patients undergoing uncomplicated inguinal hernia repair were identified from the surgeon's bill; the location of surgery was then validated by the facility bill (n = 27,036). Over one-third of all hernia repairs in our sample were performed on an ambulatory basis, but with tremendous variation across states, ranging from 89.9% of cases in Washington in outpatient settings to almost none (6.3%) in Georgia. Treatment costs were 56% higher for hernias repaired on an inpatient basis, $2341 versus $1505 for those performed in outpatient settings. There were no detectable differences between inpatients and outpatients along such outcomes as complication rates, deaths and hernia recurrence, but readmission rates were higher for inpatients. The dramatic differences in costs, along with the apparent absence of adverse outcomes, suggests that Medicare should actively encourage surgeons to perform more hernia repairs on an outpatient basis.