Literature Reviews

Procedure-specific systematic review summary



Connelly et al 1999

Use of clonidine in hernia patients: intramuscular versus surgical site.

Connelly NR, Reuben SS, Albert M, Page D, Gibson CS, Moineau A, Dixon KL, Maciolek H.

Reg Anesth Pain Med 1999;24(5):422–425.

BACKGROUND AND OBJECTIVES: This study was designed to determine if administration of clonidine in hernia patients enhances analgesia. It was also designed to determine whether administration directly in the surgical site further improves the analgesia. METHODS: A randomized, double-blinded study was undertaken at a tertiary care hospital. Forty-five outpatients undergoing unilateral inguinal hernia repair by one of two surgeons (D.P. or M.A.) under local anesthesia with monitored anesthesia care were evaluated. Patients were invited to participate in this investigation at the time of the preoperative surgical visit. Patients who had a contraindication to the use of clonidine or who refused repair under local anesthesia with sedation were excluded. Patients were randomized to one of three groups: (a) clonidine 0.5 microg/kg intramuscularly and saline in the surgical site (mixed with the local anesthetic); (b) clonidine 0.5 microg/kg in the surgical site and saline intramuscularly; or (c) saline in both the surgical site and intramuscularly. The outcome measures included visual analog pain scores twice in the hospital, pain scores at rest and with movement 24 hours postoperatively, the time to first analgesic, and total analgesic requirement. RESULTS: The pain scores were lower in both clonidine groups at 2 hours postoperatively than in the control group (P <.03). No difference was observed with respect to the time to first analgesic, 24-hour analgesic use, or 24-hour pain scores among the groups. CONCLUSIONS: When clonidine is administered to patients undergoing hernia repair, the 2-hour pain scores are lowered. No difference was exhibited when clonidine was administered intramuscularly or directly into the hernia site.

Tan et al 2001

The effect of dexamethasone on postoperative pain and emesis after intrathecal neostigmine.

Tan PH, Liu K, Peng CH, Yang LC, Lin CR, Lu CY.

Anesth Analg 2001;92(1):228–232.

We evaluated the effect of a single dose of dexamethasone on the incidence and severity of postoperative nausea and vomiting (PONV) after intrathecal injection of tetracaine plus neostigmine. Sixty ASA physical status I patients scheduled for inguinal herniorrhaphy were studied with a randomized, double-blinded, placebo-controlled protocol. The dexamethasone group (Group D) received 10 mg of dexamethasone IV before performance of spinal anesthesia, whereas the placebo group (Group P) received saline. Spinal anesthesia was performed with intrathecal injection of 15 mg tetracaine plus neostigmine 100 microg in both groups. Pain, PONV, and other side effects were evaluated 24 h after surgery. The duration and severity of analgesia and the incidence of PONV were not significantly different between the two groups. Our results demonstrate that a single dose of dexamethasone (10 mg) did not potentiate the analgesic effect or reduce the incidence of PONV after intrathecal injection of tetracaine and neostigmine. Implications: The results of our evaluation of the effect of IV dexamethasone versus saline control on analgesia and nausea and vomiting after intrathecal neostigmine and tetracaine suggest that IV dexamethasone did not enhance the analgesic effect of neostigmine or reduce the incidence of emesis after intrathecal administration.

Tan et al 2001

Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery.

Tan PH, Chia YY, Lo Y, Liu K, Yang LC, Lee TH.

Can J Anaesth 2001;48(6):551–556.

PURPOSE: To compare the postoperative analgesic efficacy and safety of intrathecal (IT) neostigmine and IT morphine in patients undergoing total knee replacement under spinal anesthesia. METHODS: Sixty patients scheduled for elective total knee replacement under spinal anesthesia were randomly divided into three equal groups which received IT 0.5% hyperbaric bupivacaine 15 mg with either normal saline 0.5 mL, neostigmine 50 microg, or morphine 300 microg. The maximal level of sensory block, duration of analgesia, time to use of rescue analgesics, the overall 24-hr and four-hour interval visual analogue scale (VAS) pain score, and the incidence of adverse effects were recorded for 24 hr after administration. RESULTS: There was no significant difference in maximal level of sensory block among the three groups. The morphine group had a later onset of postsurgical pain and longer time to first rescue analgesics than the neostigmine group (P <0.05). Overall 24-hr VAS pain scores were significantly higher in the saline group vs the morphine and neostigmine groups (P <0.05). Motor block lasted significantly longer in the neostigmine group than in the morphine and saline groups (P <0.05). The incidence of adverse effects was similar in the neostigmine and morphine groups except for pruritus (70%) occurring more frequently in the morphine group than in the neostigmine and saline groups (0%; P <0.05). Overall satisfaction rates were better in the neostigmine group than in the morphine and saline groups (P <0.05). CONCLUSIONS: IT neostigmine 50 microg produced postoperative analgesia lasting about seven hours with fewer side effects and better satisfaction ratings than IT morphine 300 microg.

Apfel et al 2004

A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.

Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N.

N Engl J Med 2004;350(24):2441–2451.

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. METHODS: We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly. RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk. CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.

Ma et al 2004

Perioperative rofecoxib improves early recovery after outpatient herniorrhaphy.

Ma H, Tang J, White PF, Zaentz A, Wender RH, Sloninsky A, Naruse R, Kariger R, Quon R, Wood D, Carroll BJ.

Anesth Analg 2004;98(4):970–975.

Non-opioid analgesics have become increasingly popular as part of a multimodal regimen for pain management in the ambulatory setting. We designed this randomized, double-blind, placebo-controlled study to evaluate the effect of perioperative administration of the cyclooxygenase-2 inhibitor rofecoxib on patient outcome after inguinal herniorrhaphy procedures. Sixty consenting outpatients undergoing elective hernia repair surgery were randomly assigned to one of two treatment groups: control (vitamin C, 500 mg) or rofecoxib (rofecoxib, 50 mg). The first oral dose of the study medication was administered 30-40 min before entering the operating room, and a second dose of the same medication was given on the morning of the first postoperative day. Recovery times, postoperative pain scores, the need for "rescue" analgesics, and side effects were recorded at 1- to 10-min intervals before discharge from the recovery room. Follow-up evaluations were performed at 36 h, 7 days, and 14 days after surgery to assess postdischarge pain, analgesic requirements, resumption of normal activities, as well as patient satisfaction with their postoperative pain management. Rofecoxib significantly decreased the early recovery times, leading to an earlier discharge home after surgery (88 +/- 30 vs 126 +/- 44 min, P < 0.05). When compared with the control group, the patients' median [range] quality of recovery score was also significantly higher in the rofecoxib group (18 [14-18] vs 16 [13-18], P < 0.05). In the predischarge period, a significantly larger percentage of patients required rescue pain medications in the control group (67% vs 37% in the rofecoxib group, P < 0.05). At the 36-h follow-up assessment, rofecoxib-treated patients reported significantly reduced oral analgesic requirements (0 [0-20] vs 9 [1-33] pills, P < 0.05) and lower maximal pain scores, resulting in improved patient satisfaction with their postoperative pain management (3 [1-4] vs 2 [0-3], P < 0.05). However, there were no differences in the times required to resume their activities of daily living. In conclusion, perioperative rofecoxib, 50 mg per os, significantly decreased postoperative pain and the need for analgesic rescue medication, leading to a faster and improved quality of recovery after outpatient hernia surgery. However, perioperative use of rofecoxib failed to improve recovery end points in the postdischarge period. IMPLICATIONS: Rofecoxib (50 mg per os), given before and after surgery, was effective in improving postoperative pain management, as well as the speed and quality of recovery after outpatient inguinal herniorrhaphy. However, it failed to accelerate the postdischarge resumption of normal activities of daily living.

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.

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.

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.

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.

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 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.


Available at

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.

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.

Ben-David et al 1996

Is preoperative ketorolac a useful adjunct to regional anesthesia for inguinal herniorrhaphy?

Ben-David B, Baune-Goldstein U, Goldik Z, Gaitini L.

Acta Anaesthesiol Scand 1996;40(3):358–363.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) have become a popular component of analgesia regimens, particularly in combination with narcotics. We questioned whether there might also be a place for their use in conjunction with regional anesthesia and whether there was a preferable route for NSAID administration. METHODS: Ilioinguinal and field blocks were performed preoperatively on seventy patients undergoing outpatient inguinal hernia repair. Patients were divided into a control group who received no ketorolac and four study groups who received a preoperative dose of 30 mg ketorolac by one of the following routes: i.v., i.m., p.o., or intrawound (i.w.). The ketorolac in the i.w group was mixed in the syringe with the local anesthetic used for the field block. i.v. and i.m. groups also received ketorolac at the time of the preoperative regional anesthesia and the PO group received the dose at least one hour preoperatively. All patients received a similar general anesthetic intraoperatively. RESULTS: Postoperative pain scores and analgesic requirements were lowest for the i.m., i.v., and i.w. groups. Pain scores and analgesic requirements for the PO group were less than for the control group but more than for the other three groups. Analgesic efficacy therefore ranked: i.m. = i.v. = i.w. > p.o. > control. Though no differences were found between groups in the time to discharge from the recovery room, the ease of nursing care paralleled the findings for pain scores and analgesia requirements. CONCLUSION: Beyond the analgesia provided by the regional anesthesia of the ilioinguinal and field blocks, the preoperative use of ketorolac further reduced postoperative pain scores and the need for additional postoperative analgesic medication. Comparable outcomes for the i.v., i.m. and i.w. groups indicate the lack of any benefit to concentrating the non-steroidal anti-inflammatory drug at the wound (i.w.) or to achieving high blood levels rapidly (i.v.). In conclusion, ketorolac is a useful supplement to ilioinguinal plus field block regional anesthesia for hernia surgery and is most effective administered parenterally.

Dueholm et al 1989

Pain relief following herniotomy: a double-blind randomized comparison between naproxen and placebo.

Dueholm S, Forrest M, Hjortso E, Lemvigh E.

Acta Anaesthesiol Scand 1989;33(5):391–394.

Sixty consecutive out-patients were randomly assigned to have either a non-steroid anti-inflammatory drug (naproxen 500 mg) or an identical placebo administered as suppositories half an hour before unilateral herniotomy. Within 1.5 h after the end of surgery, pain scores were significantly improved in patients receiving naproxen (P less than 0.02). The long-term analgesic effect was measured indirectly by registering the postoperative requirement for supplementary analgesic doses of acetylsalicylic acid 1 g plus codeine 20 mg. The time elapsing before the first demand for additional analgesics was prolonged by median 1.5 h, and the need for further analgesic treatment during 24 h was significantly reduced (P less than 0.003) in the naproxen group (median, 2 doses) compared to the placebo group (median, 4 doses). No statistically significant difference was found between the groups with regard to the occurrence of side-effects.

Lin et al 1998

Comparison of local infiltration of tenoxicam and intravenous tenoxicam for postoperative analgesia in herniorrhaphy.

Lin CF, Wong KL, Chan YL, Wang JM, Wu KH, Wei TT.

Acta Anaesthesiol Sin 1998;36(1):23–29.

BACKGROUND: The major complaint of herniorrhaphy is postoperative pain which occurs during the first 24 h after operation. Tenoxicam has a long half-life of 60-80 h. Local infiltration of the drug concentrates the pain control effects in the local area. The local infiltration dose can be smaller than the recommended systemic dose needfully to reach the target area to be effective. Therefore we studied the effect of preoperative local infiltration of tenoxicam on postoperative pain. METHODS: Sixty patients, belonging to ASA classes I and II, undergoing unilateral herniorrhaphy, were randomly assigned to 4 groups. General anesthesia was induced with thiamylal 5 mg/kg, fentanyl 2 micrograms/kg, and atracurium 5 mg/kg. Group 1 (G1) patients were preoperatively injected with 10 mg of tenoxicam in 10 ml normal saline or distilled water, in the operative area. Group 2 (G2) and Group 3 (G3) patients were preoperatively given intravenous tenoxicam, 20 mg and 10 mg, respectively. Group 4 (G4) patients were not given preoperative local infiltration or intravenous tenoxicam to serve as control group. The pain score was assessed at 2 h, 9 h, 24 h postoperatively in all groups. We recorded the total amount of acetaminophen used and the form of administration of the analgesic drug. All patients received general anesthesia in uniform technique. RESULTS: Pain score and amount of analgesic drug required in G1 (local infiltration group) patients were significantly decreased compared with the other groups. The postoperative pain score of Visual Analog Scale (VAS) and analgesic requirement in the four groups were ranked as follows: G1 < G2 < G3 < G4. No significant difference was observed between G2, G3 and G4. Only the pain score in G2 patients significantly decreased (p < 0.05) during the late postoperative period (24 h) when compared with G4 patients. CONCLUSIONS: Preoperative local infiltration of tenoxicam can decrease postoperative pain score significantly during the most painful period (24 h) in herniorrhaphy.

Lau et al 2002

Prospective randomized trial of pre-emptive analgesics following ambulatory inguinal hernia repair: intravenous ketorolac versus diclofenac suppository.

Lau H, Wong C, Goh LC, Patil NG, Lee F.

ANZ J Surg 2002;72(10):704–707.

BACKGROUND: A pre-emptive non-steroidal anti-inflammatory drug is routinely given to patients undergoing ambulatory inguinal hernia repair. The present prospective randomized trial was undertaken to compare the efficacy of intravenous ketorolac and rectal diclofenac for ambulatory inguinal hernia repairs. METHODS: Between June 1999 and February 2001, a total of 108 patients who underwent ambulatory inguinal hernia repairs under general anaesthesia were recruited. Patients were randomized to receive either intravenous ketorolac 30 mg immediately prior to induction of general anaesthesia (n = 54) or rectal diclofenac 50 mg after signing consent at the Day Surgery Centre (n = 54). RESULTS: The demographic features, hernia types, anaesthetic time, dosage of anaesthetic medication and operative details of the two groups were comparable. There was no significant difference in total amount of analgesic consumption and linear analogue pain scores after operation. With regard to recovery variables, the respective times taken to regain ambulation and micturition were similar in both groups. CONCLUSION: Diclofenac suppository 50 mg and intravenous ketorolac 30 mg provided equivalent postoperative analgesia following ambulatory inguinal hernia repair under general anaesthesia. Diclofenac suppository is an economical alternative to intravenous ketorolac. In the interests of cost containment rectal diclofenac could be considered the non-steroidal anti-inflammatory drug of choice for pre-emptive analgesia.

Mixter et al 1998

Preemptive pain control in patients having laparoscopic hernia repair: a comparison of ketorolac and ibuprofen.

Mixter CG, 3rd, Meeker LD, Gavin TJ.

Arch Surg 1998;133(4):432–437.

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.

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.

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.

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.

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.

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.

Subramaniam et al 2004

Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review.

Subramaniam K, Subramaniam B, Steinbrook RA.

Anesth Analg 2004;99(2):482–495, table of contents.

Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n=11), continuous infusion (n=11), patient-controlled analgesia (PCA) (n=6), epidural ketamine with opioids (n=8), and studies in children (n=4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (p<0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.

Bugedo et al 1990

Preoperative percutaneous ilioinguinal and iliohypogastric nerve block with 0.5% bupivacaine for post-herniorrhaphy pain management in adults.

Bugedo GJ, Carcamo CR, Mertens RA, Dagnino JA, Munoz HR.

Reg Anesth 1990;15(3):130–133.

The safety, effectiveness and duration of a percutaneous ilioinguinal-iliohypogastric nerve block with 10 ml 0.5% bupivacaine, as a method for postoperative analgesia, were studied prospectively in adult patients undergoing unilateral inguinal herniorrhaphy under spinal anesthesia. Group I (n = 20) blocked patients were compared with Group II (n = 25), non-blocked control patients. A blinded observer assessed pain scores and analgesic requirements after surgery. Group I patients had less pain at 3, 6, 24 and 48 hours after surgery and also required less analgesics during the first two postoperative days. This technique appears to be a simple and safe method for providing effective and long-lasting postoperative analgesia following inguinal hernia repair in adults.

Dierking et al 1994

The effects of wound infiltration with bupivacaine versus saline on postoperative pain and opioid requirements after herniorrhaphy.

Dierking GW, Ostergaard E, Ostergard HT, Dahl JB.

Acta Anaesthesiol Scand 1994;38(3):289–292.

In a prospective, double-blind, placebo-controlled study, twenty-eight healthy, male patients, aged 20-69 years, scheduled for unilateral elective inguinal herniorrhaphy ad modum Bassini were randomized to receive postoperative infiltration of the surgical wound with either bupivacaine 0.25%, or isotonic saline. General anaesthesia was induced with thiopentone 3-5 and alfentanyl 10, and maintained with alfentanyl 5 15 min and N2O/O2. After herniorrhaphy, the internal fascia was infiltrated with bupivacaine 0.25% or saline, 10 ml. After closure of the external fascia, the subcutaneous tissue was infiltrated with bupivacaine 0.25% or saline, 15 ml on both sides of the surgical wound. Pain at rest, during mobilisation and during cough was significantly decreased in patients receiving bupivacaine compared to placebo. Median time to first request for morphine was increased from 25 min to 135 min, and the consumption of supplementary morphine during the 24 h study period reduced from four to two doses of 0.1 iv or 0.125 im, in patients who received bupivacaine compared to placebo.

Fischer et al 2000

Prospective double-blind randomised study of a new regimen of pre-emptive analgesia for inguinal hernia repair: evaluation of postoperative pain course.

Fischer S, Troidl H, MacLean AA, Koehler L, Paul A.

Eur J Surg 2000;166(7):545–551.

OBJECTIVE: To evaluate the effectiveness of a new regimen of pre-emptive analgesia on the development of postoperative pain after inguinal hernia repair. DESIGN: Prospective, double-blind, randomised study. SETTING: University Hospital, Germany. SUBJECTS: 70 consecutive patients who had primary unilateral inguinal hernia repairs. INTERVENTIONS: A new regimen of pre-emptive analgesia with bupivacaine that was infiltrated preoperatively, intraoperatively, and postoperatively was tested. The control group were given saline infiltrations at the same times. Pain was measured up to postoperative day 30 using the visual analogue scale (VAS), the verbal rating scale (VRS), and by recording patient-controlled use of ibuprofen suppositories. RESULTS: Pain was significantly less in the pre-emptive analgesia group than in the control group during the first 10 days postoperatively as assessed by VAS and VRS (p < 0.05). Analgesic consumption was also significantly reduced in the pre-emptive analgesia group (p < 0.05). Multivariate analysis showed that bupivacaine infiltration (pre-emptive analgesia) was associated with significantly less postoperative pain (p < 0.0001). CONCLUSION: This regimen of pre-emptive analgesia is an effective and safe method of reducing postoperative pain and analgesic consumption after inguinal hernia repair.

Dierking et al 1992

Effect of pre- vs postoperative inguinal field block on postoperative pain after herniorrhaphy. see comment.

Dierking GW, Dahl JB, Kanstrup J, Dahl A, Kehlet H.

Br J Anaesth 1992;68(4):344–348.

The analgesic effects of an identical inguinal field block, performed before or immediately after inguinal herniorrhaphy, were evaluated in 32 healthy patients in a double-blind, randomized study. During surgery, all patients received a light general anaesthesia with thiopentone, alfentanil and nitrous oxide in oxygen. After induction of general anaesthesia, patients were allocated randomly to receive an inguinal field block with lignocaine, either 15 min before operation or immediately after operation, after closure of the surgical wound, but before the patients were awake. Pain score on a visual analogue scale and on a verbal scale at rest, during mobilization from supine into sitting position and during cough was assessed 1, 2, 4, 6, 8 and 24 h, and 7 days after operation. No significant differences between the groups were observed in VAS scores or verbal pain scores during rest or ambulation at any time. There was no significant difference in time to first request for morphine or total morphine consumption. These results do not show pre-emptive analgesia with a conventional inguinal field block to be of clinical importance compared with a similar block administered after operation.

Bays et al 1991

The use of bupivacaine in elective inguinal herniorrhaphy as a fast and safe technique for relief of postoperative pain.

Bays RA, Barry L, Vasilenko P.

Surg Gynecol Obstet 1991;173(6):433–437.

The intraoperative use of local anesthetic agents to decrease postoperative pain has been used in many types of procedures. Most of these techniques involve needle injection of anesthetic and result in a low but troublesome incidence of complications. In this study, we evaluated the reliability, safety, and efficacy of a technique emphasizing bathing of tissues with anesthetic rather than needle injection for relieving postoperative pain. Thirty consecutive patients undergoing outpatient elective inguinal herniorrhaphy with general anesthetic were prospectively randomized into four treatment groups. Group 1 received 0.5 per cent bupivacaine plus epinephrine 1 to 200,000; group 2, 0.5 per cent bupivacaine; group 3, normal saline solution, and group 4, no treatment. At the end of the repair, one-third of the test solution (approximately 5 milliliters) was bathed along the spermatic cord throughout its length in the inguinal canal. The external oblique aponeurosis was closed superficial to the cord structures and another one-third of the solution was instilled into the wound. Just prior to the end of skin closure the remaining solution was instilled subcutaneously. No needles were used to instill the solutions and they were not suctioned or removed from the wound. Data collection consisted of an analog type of patient questionnaire allowing subjective assessment of postoperative pain at various time intervals during the first 20 hours postoperatively. Pain medication provided was propoxyphene, 100 milligrams and acetaminophen, 650 milligrams every three hours as needed. Total doses of pain medication for the study period and the time to first pain medication requirement were obtained. Results were analyzed using analysis of variance, and Wilcoxon ranked sums test. Patients in group 1 (0.5 per cent bupivacaine with epinephrine) exhibited significantly less pain than those in groups 3 (saline solution) and 4 (control) for more than 12 hours postoperatively. Patients in group 2 (0.5 per cent bupivacaine) likewise experienced less pain than those in groups 3 and 4 through seven hours. The patients receiving saline solution were not significantly different than those in the control group throughout. Objectively, groups 1 and 2 required fewer total doses of pain medication and waited longer before requesting oral pain medication postoperatively compared with those in the control group. No complications occurred that could be attributed to the technique. The results of this study indicate that the bathing of wounds with 0.5 per cent bupivacaine with or without epinephrine 1:200,000 is a safe and effective method of decreasing postoperative pain for several hours in patients undergoing elective inguinal herniorrhaphy.(ABSTRACT TRUNCATED AT 400 WORDS)

Spittal et al 1992

A comparison of bupivacaine instillation and inguinal field block for control of pain after herniorrhaphy.

Spittal MJ, Hunter SJ.

Ann R Coll Surg Engl 1992;74(2):85–88.

In a single-blind, randomised trial, 50 consecutive adult patients for inguinal herniorrhaphy under general anaesthesia received either an inguinal field block or bupivacaine instilled into the wound to provide postoperative analgesia. Bupivacaine instillation was found to be simple, safe and effective. The method is particularly appropriate for day-case surgery.

Nehra et al 1995

Pain relief after inguinal hernia repair: a randomized double-blind study. see comment.

Nehra D, Gemmell L, Pye JK.

Br J Surg 1995;82(9):1245–1247.

A randomized double-blind study was undertaken using 0.5 per cent bupivacaine ilioinguinal field block and oral papaveretum-aspirin tablets to assess pain relief after hernia surgery. A consecutive series of 200 men undergoing repair of a unilateral inguinal hernia underwent random allocation into one of the four groups to receive: bupivacaine and papaveretum-aspirin (group 1), bupivacaine and oral placebo (group 2), saline and papaveretum-aspirin (group 3), or saline and oral placebo (group 4). Patients were prescribed postoperative opiates to be given on demand. Pain levels and mobility were assessed at 6 and 24 h after operation. Patients in group 1 reported significantly less pain, required less additional opiates and had better mobility than those in group 4 (pain score P < 0.001 at 6 h and P = 0.002 at 24 h) and group 3 (P = 0.002 for pain and mobility scores at 6 h). Bupivacaine alone provided good immediate postoperative pain relief (P = 0.002 group 2 versus group 4 at 6 h). The combination of bupivacaine and papaveretum-aspirin provided the best results and is suitable for day-case postoperative analgesia.

Pavlin et al 2003

Preincisional treatment to prevent pain after ambulatory hernia surgery.

Pavlin DJ, Horvath KD, Pavlin EG, Sima K.

Anesth Analg 2003;97(6):1627–1632.

We designed this study as a randomized comparison of postoperative pain after inguinal hernia repair in patients treated with triple preincisional analgesic therapy versus standard care. Triple therapy consisted of a nonsteroidal antiinflammatory, a local anesthetic field block, and an N-methyl-D-aspartate inhibitor before incision. The treatment group (n = 17) received rofecoxib, 50 mg PO, a field block with 0.25% bupivacaine/0.5% lidocaine, and ketamine 0.2 mg/kg IV before incision; controls (n = 17) received a placebo PO before surgery. The anesthetic protocol was standardized. Postoperative pain was treated by fentanyl IV and oxycodone 5 mg/acetaminophen 325 mg PO as required for pain. Pain scores (0-10) and analgesic were recorded for the first 7 days after surgery. Pain scores were 47% lower in the treatment group before discharge (3.1 +/- 0.6 versus 5.9 +/- 0.6, P = 0.0026) (mean +/- SE) and 18% less in the first 24 h after discharge (5.6 +/- 0.4 versus 6.8 +/- 0.5, P = 0.05); oral analgesic use was 34% less in the treatment group (4.6 +/- 0.8 doses versus 7.1 +/- 0.7 doses, P = 0.02) in the first 24 h after surgery. We conclude that triple preincisional therapy diminishes pain and analgesic use after outpatient hernia repair, and encourage further evaluation of this technique. IMPLICATIONS: Outpatients undergoing inguinal hernia repair under general anesthesia report moderate-to-severe pain after surgery. Triple preincisional therapy that included rofecoxib, 50 mg PO, ketamine, 0.2 mg/kg IV, and local anesthetic field block reduced pain scores and analgesic use in the first 24 h after discharge.

Johansson et al 1997

Preoperative local infiltration with ropivacaine for postoperative pain relief after inguinal hernia repair. A randomised controlled trial.

Johansson B, Hallerback B, Stubberod A, Janbu T, Edwin B, Glise H, Solhaug JH.

Eur J Surg 1997;163(5):371–378.

OBJECTIVE: To assess the effect of preoperative local anaesthesia with ropivacaine and find out if there was a dose-response relationship with postoperative pain after inguinal hernia repair. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Two Swedish and two Norwegian hospitals. SUBJECTS: 131 Male patients undergoing elective inguinal hernia repair. INTERVENTION: Infiltration of the inguinal field before operation with 0.5% ropivacaine 40 ml (200 mg), 0.25% ropivacaine 40 ml (100 mg) or saline 40 ml. MAIN OUTCOME MEASURES: Wound pain at rest and during mobilisation, pressure exerted to reach pain threshold and maximum pain tolerance after 3, 6, 10, and 24 hours, and after 7 days; consumption of analgesics; and Quality of Life assessed by two independent questionnaires before and after operation. RESULTS: Pain scores after 3 hours were significantly lower in the ropivacaine groups compared with the saline group for all variables (p < 0.05). At 6 hours pain scores were significantly lower for ropivacaine 0.5% compared with saline for wound pain during mobilisation and pressure exerted to reach maximum pain tolerance. Patients given saline made their first request for analgesics significantly sooner than in the other two groups (p < 0.05), and a significantly larger percentage of them requested analgesics during the first 24 hours (p < 0.05). Evaluation of the Quality of Life questionnaires showed no significant differences between the groups. CONCLUSION: Ropivacaine has a significant, dose-related pain-reducing effect in the immediate postoperative period but we could find no support for the theory that preoperative infiltration analgesia reduces long term pain.

Erichsen et al 1995

Wound infiltration with ropivacaine and bupivacaine for pain after inguinal herniotomy.

Erichsen CJ, Vibits H, Dahl JB, Kehlet H.

Acta Anaesthesiol Scand 1995;39(1):67–70.

In a double-blind, randomized study, 32 patients scheduled for elective inguinal herniotomy under general anaesthesia received subcutaneous infiltration with 40 ml ropivacaine 2.5 mg/ml or bupivacaine. Postoperative pain intensity was assessed repeatedly for 24 hours at rest, during cough and movement on a visual analogue scale (VAS) and by means of pressure algometry. No differences between pain intensities or wound tenderness were found between the groups. The demand for analgesics was similar in the two groups. We conclude that incisional ropivacaine is as effective as bupivacaine in the management of post-herniotomy pain.

Ding et al 1995

Post-herniorrhaphy pain in outpatients after pre-incision ilioinguinal-hypogastric nerve block during monitored anaesthesia care.

Ding Y, White PF.

Can J Anaesth 1995;42(1):12–15.

The objective of this study was to evaluate the effect of an ilioinguinal-hypogastric nerve block (IHNB) with bupivacaine 0.25% on the postoperative analgesic requirement and recovery profile in outpatients undergoing inguinal herniorrhaphy with local anaesthetic infiltration. Thirty consenting healthy men undergoing elective unilateral inguinal herniorrhaphy procedures were randomly assigned to receive an IHNB with either saline or bupivacaine according to a double-blind, IRB-approved protocol. All patients received midazolam, 2 mg iv, and fentanyl 25 microgram iv, prior to injection of 30 ml of either bupivacaine 0.25% or saline through the oblique muscle approximately 1.5 cm medial to the anterior superior iliac spine. Subsequently, the surgeon infiltrated the incision site with a lidocaine 1% solution. Sedation was maintained during the operation with a variable-rate propofol infusion, 25-140 No significant differences were noted in the intraoperative doses of lidocaine, propofol and fentanyl in the two treatment groups. However, the pain visual analogue score at 30 min after entering the PACU was lower in the bupivacaine (versus saline) group (P < 0.05). Although the times to ambulation (86 +/- 18 vs 99 +/- 27 min) and being judged "fit for discharge" (112 +/- 49 vs 126 +/- 30 min) were similar in the two groups, the bupivacaine-treated (vs saline) patients required less oral analgesic medication after discharge (46% vs 85%). We concluded that the use of an ilioinguinal-hypogastric nerve block with bupivacaine 0.25% as an adjuvant during inguinal herniorrhaphy under monitored anaesthesia care decreased pain in the PACU and oral analgesic requirements after discharge from the day-surgery unit.

McCleane et al 1994

The addition of triamcinolone acetonide to bupivacaine has no effect on the quality of analgesia produced by ilioinguinal nerve block.

McCleane G, Mackle E, Stirling I.

Anaesthesia 1994;49(9):819–820.

In a study of 30 men undergoing elective inguinal hernia repair under general anaesthesia no difference in postoperative pain, patient rating score or morphine consumption was found between patients who had pre-operative ilioinguinal nerve block with bupivacaine 0.5% plain and those who received a similar block with bupivacaine 0.5% plain and triamcinolone acetonide 40 mg. Mean (SD) morphine requirements using a patient-controlled analgesia system were 37 (22.2) mg and 32 (20.3) mg in the bupivacaine and bupivacaine/triamcinolone groups respectively (p > 0.05). The addition of triamcinolone 40 mg to bupivacaine 0.5% offers no advantages over unsupplemented bupivacaine when used for ilioinguinal block.

Armstrong et al 1986

Local anaesthesia in inguinal herniorrhaphy: influence of dextran and saline solutions on duration of action of bupivacaine.

Armstrong DN, Kingsnorth AN.

Ann R Coll Surg Engl 1986;68(4):207–208.

Because recent clinical trials have shown that dextran solutions can prolong the local anaesthetic action of 0.25% bupivacaine, a prospective double blind trial was performed in patients (n = 50) undergoing uncomplicated elective inguinal herniorrhaphy under local anaesthesia alone. Patients were randomised prior to infiltration of local anaesthesia into 2 groups: 0.5% bupivacaine (30 ml) diluted with an equal volume of either 0.9% saline or an equal volume of dextran 110. There was no significant difference in duration nor degree of postoperative anaesthesia between the two groups. Dextran solutions were found to be significantly more acidic than saline solutions and the possible effects of this on bupivacaine kinetics are discussed.

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.

Deans et al 1998

Controlled trial of preperitoneal local anaesthetic for reducing pain following laparoscopic hernia repair. see comment.

Deans GT, Wilson MS, Brough WA.

Br J Surg 1998;85(7):1013–1014.

BACKGROUND: A prospective randomized trial was performed to determine whether local anaesthetic solutions injected into the preperitoneal space may provide additional pain relief following transabdominal preperitoneal laparoscopic hernia repair. METHODS: One hundred patients undergoing transabdominal preperitoneal laparoscopic hernia repair were allocated randomly to receive (1) bupivacaine 1.5 mg/kg, (2) bupivacaine 1.5 mg/kg with 1 in 200000 adrenaline, (3) bupivacaine 3 mg/kg or (4) saline instilled into the preperitoneal space at the end of the operation. An independent clinical assessor determined the level of pain using a visual analogue pain score and noted the parenteral and oral analgesia requirements at 4, 8, 12 and 24 h after operation. Results: At each of the time intervals, there was no significant difference between the groups for pain scores (at 24 h, P = 0.71) or the number of doses of either morphine (at 24 h, P = 0.73) or oral analgesia (at 24 h, P = 0.89). There was also no significant difference in the time to return to normal activity or work between the groups. CONCLUSION: This study suggests that instilling local anaesthetic into the preperitoneal space has no significant effect on postoperative pain relief requirement following laparoscopic hernia repair. Other methods of reducing postoperative pain should be sought that may facilitate day-case laparoscopic hernia surgery.

Klein et al 2002

Paravertebral somatic nerve block compared with peripheral nerve blocks for outpatient inguinal herniorrhaphy.

Klein SM, Pietrobon R, Nielsen KC, Steele SM, Warner DS, Moylan JA, Eubanks WS, Greengrass RA.

Reg Anesth Pain Med 2002;27(5):476–480.

BACKGROUND: Inguinal herniorrhaphy (IH) is a common outpatient procedure, yet postoperative pain and anesthetic side effects remain a problem. Paravertebral somatic nerve blocks (PVB) have the potential to offer unilateral abdominal wall anesthesia and long-lasting pain relief with minimal side effects. We compared PVB with peripheral neural blocks for outpatient IH. METHODS: Forty-six patients scheduled for IH were entered into this prospective, single-blind study. All patients underwent a standardized general anesthetic. Patients were randomly assigned to receive a PVB (levels T10-L2) preoperatively (n = 24) or an intraoperative peripheral block (PB) by the surgeon (n = 22), using 0.5% ropivacaine (40 mL). Opioid use, verbal analog pain scores, and side effects were documented for 72 hours. RESULTS: The use of opioids during surgery was less for the PVB group 162 +/- 70 mg than the PB group, 210 +/- 60 (P =.02). Need for opioids in PACU was less for the PVB group (39%) than the PB group (61%) (P =.002). Time until first pain after discharge was not different between groups, 312 +/- 446 minutes (PB) and 425 +/- 384 minutes (PVB) (P =.12). Of the PVB patients, 29% used no opioids at all compared with 18% of PB patients (P =.12). Mean time until first oxycodone use was similar between groups, 303 +/- 469 minutes (PB) and 295 +/- 225 minutes (PVB) (P =.18). Oxycodone use was also similar; 35 +/- 34 mg (PVB) versus 49 +/- 42 mg (PB) (P =.30). More patients in the PB group (50%) required antiemetic treatment in the postanesthesia care unit than the PVB group (21%) (P <.001). Side effects were similar at all other measurements. CONCLUSIONS: This study shows that PVB provides analgesia equivalent to extensive peripheral nerve block for inguinal herniorrhaphy, offering an alternative method of postoperative pain management and perhaps fewer side effects.

Connelly et al 1997

Use of preincisional ketorolac in hernia patients: intravenous versus surgical site.

Connelly NR, Reuben SS, Albert M, Page D.

Reg Anesth 1997;22(3):229–232.

BACKGROUND AND OBJECTIVES: This study was designed to determine whether administration of ketorolac directly in the surgical site results in enhanced analgesia. METHODS: A randomized double-blind study was undertaken at a university-affiliated tertiary care hospital. Thirty outpatients undergoing unilateral inguinal hernia repair by one of two surgeons under local anesthesia with sedation were evaluated. Patients were invited to participate in this investigation at the time of the preoperative surgical visit. Patients who had a contraindication to the use of ketorolac or who refused repair under local anesthesia with sedation were excluded. Patients received ketorolac 60 mg either via the parenteral route or directly in the surgical site (mixed with the local anesthetic). The outcome measures included visual analog pain scores, measured at two different times in the hospital, pain scores at rest and with movement 24 hours after surgery, time to first analgesic, and total analgesic requirement. RESULTS: The study revealed lower 24 hour movement-associated pain scores (P <.02), increased time to first analgesic (P <.03), and decreased oral analgesic consumption (P <.0002) in the surgical site group. CONCLUSIONS: Ketorolac provides enhanced patient comfort when it is administered in the surgical site in patients undergoing inguinal hernia repair. It is recommended that clinicians add ketorolac to the local anesthetic solution in such patients.

Rømsing et al 2000

Local infiltration with NSAIDs for postoperative analgesia: Evidence for a peripheral analgesic action.

Rømsing J, Moiniche S, Ostergaard D, Dahl JB.

Acta Anaesthesiologica Scandinavica 2000;44(6):672-683.

Background: In order to investigate the evidence for a peripheral analgesic effect of local infiltration with nonsteroidal anti-inflammatory drugs (NSAIDs) in postoperative pain, we conducted a systematic review. Methods: Randomised controlled and double-blind trials were evaluated. Outcome measures were pain scores, the use of supplementary analgesics, 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 pain scores between treatment groups. Results: Sixteen studies with data from 844 patients were considered appropriate for analysis. The NSAIDs were administered as intra-articular injections, as components of intravenous regional anaesthesia (IVRA), and by wound infiltration and were compared with systemic administration or placebo. In the four studies comparing intra-articular NSAIDs with systemic administration a statistically significant effect in favour of intra- articular NSAIDs was found. Only one study compared IVRA NSAID with systemic administration, showing a significant effect in favour of IVRA administration. No more than two of the five studies comparing intrawound NSAIDs with systemic administration showed Significant effect after intrawound administration. Most of the studies comparing local infiltration with placebo showed significant effect in favour of local infiltration. Conclusion: There is evidence for a clinically relevant peripheral analgesic action of intra-articular NSAIDs while results of IVRA and wound infiltration with NSAIDs in postoperative pain are inconclusive. Trials without a systemic control group were not considered to provide evidence for a local effect. (C) Acta Anaesthesiologica Scandinavica 44 (2000). <274> *COPYRIGHT ELSEVIER SCIENCE B.V. - ALL RIGHTS RESERVED* MULTIFILESEGMENT EMBASE

O'Hanlon et al 1996

Preoperative application of piroxicam gel compared to a local anaesthetic field block for postoperative analgesia.

O'Hanlon et al 1996

Acta Anaesthesiol Scand 1996;40(6):715–718.

The non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis and hence have an analgesic action. Following topical administration, the drug is concentrated in the tissues and so can have a local analgesic effect. This study investigated the effect of the preoperative application of topical piroxicam on postoperative analgesic requirement compared to a placebo group and a conventional local anaesthetic field block. Forty-two patients presenting for in-patient inguinal hernia repair were randomly allocated on a double-blind basis to have either piroxicam gel 15gm applied preoperatively, or an inguinal field block with 20 ml of 0.375% bupivacaine following induction of anaesthesia, or no treatment. Postoperative Visual Analogue Scores for pain on moving in group P, I or C on admission at 1h, 2h, and 4 h following surgery were: 2 vs 1 vs 6.5; 3 vs 3 vs 5; 3 v 2 vs 4.5; 3 vs 2 vs 5.0, respectively (P < 0.005). Median(range) time to first analgesia was 25.4(15-70) min in group I, 30.3(10-49) min in group P; this was not significantly different from group C21.5(7-70) min. Over the first 24 hours the postoperative morphine requirement was significantly less in the two treatment groups 30(20)mg in group I and 34(17) mg in group P and 71(15) in group C, P < 0.0001. There were no apparent NSAID-induced side-effects, or effects on wound healing. The preoperative administration of piroxicam (15gm) topically compared favourably with a preoperative local anaesthetic field block with respect to VAS scores, time to first analgesia and total morphine consumption. And both treatment groups provided significantly superior analgesia than the control group.

Elliott et al 1997

Does the addition of clonidine affect duration of analgesia of bupivacaine wound infiltration in inguinal hernia surgery?

Elliott S, Eckersall S, Fligelstone L, Jothilingam S.

Br J Anaesth 1997;79(4):446–449.

We conducted a prospective, randomized, double-blind study to compare analgesia obtained by wound infiltration using 29 ml of 0.25% bupivacaine alone, or with the addition of clonidine hydrochloride 150 micrograms. A third group received bupivacaine wound infiltration with clonidine 150 micrograms i.m. to control for the systemic effects caused by absorption of clonidine. We studied 46 adults undergoing elective inguinal hernia repair. The general anaesthetic technique, postoperative analgesia and wound infiltration technique were standardized. There was no difference in time to first analgesic request or to total analgesic consumption between the three groups during the 24-h study. Visual analogue scores (VAS) at rest and after coughing were noted over a 24-h period. The only difference was higher VAS scores at rest at 24 h in the control group who received i.m. clonidine. We conclude that for elective inguinal hernia repair, postoperative analgesia obtained by bupivacaine wound infiltration was not improved by the addition of clonidine 150 micrograms.

Rømsing et al 2001

Postoperative analgesia is not different after local vs systemic administration of meloxicam in patients undergoing inguinal hernia repair.

Rømsing J, Mysager S, Vilmann P, Sonne J, Larsen NE, Stergaard D.

Can J Anaesth 2001;48(10):978–984.

PURPOSE: To distinguish between local and systemic drug effects, we compared pain scores, analgesic consumption and plasma concentrations after local vs i.v. administration of meloxicam 7.5 mg in patients with inguinal hernia repair. METHODS: In a double-blind, randomized study 56 patients received either local or i.v. meloxicam 7.5 mg. Postoperative pain was assessed with a visual analogue scale (VAS) at rest, on mobilization, and on coughing, the need for supplementary analgesics (fentanyl i.v. and/or acetaminophen-codeine tablets) was recorded, and blood samples were drawn during 24 hr after meloxicam administration. RESULTS: No significant differences were found between groups with respect to pain scores, or in the consumption of supplementary analgesics. Following local application of meloxicam, the peak plasma concentration (C(max)) of 0.5 +/- 0.2 mg*L(-1) achieved after 1.8 +/- 0.5 hr was much lower than the C(max) of 2.5 +/- 0.9 mg*L(-1) achieved immediately after i.v. administration (P <0.05). Mean meloxicam plasma concentration after infiltration was significantly lower than after i.v. doses for the first three hours after administration (P <0.05). CONCLUSION: We showed no differences in pain scores and analgesic consumption between local and i.v. administration of meloxicam 7.5 mg during the first 24 hr after herniorrhaphy, while plasma concentration of meloxicam was lower after local administration. These results indicate a lack of difference in pain relief after concentrating meloxicam at the hernia wound or after achieving high blood levels rapidly (i.v.). Local administration of meloxicam may confer an advantage over systemic administration by eliciting lower incidences of systemic adverse effects.

Rosenstock et al 1996

Analgesic effect of incisional morphine following inguinal herniotomy under spinal anesthesia.

Rosenstock C, Andersen G, Antonsen K, Rasmussen H, Lund C.

Reg Anesth 1996;21(2):93–98.

BACKGROUND AND OBJECTIVES. Opioids have been shown to possess antinociceptive effects after peripheral administration in experimental and clinical studies. The results of clinical studies on intra-articularly administered morphine are, however, conflicting. The objective of this study was to examine a possible analgesic effect of incisionally administered morphine on postoperative pain in patients undergoing inguinal herniotomy. METHODS. Forty outpatients were included in a double blind randomized, placebo-controlled study. The patients had spinal anesthesia with 1.5-2.0 mL hyperbaric 5% lidocaine. At conclusion of herniotomy morphine 5 mg was injected incisionally in 10 patients, intravenously in 10, and subcutaneously in 10. The placebo group of 10 patients had saline injected in the incision. Postoperative pain was assessed with a visual analog scale at rest and during mobilization. Assessments were made immediately before and at 0, 2, 4, and 6 hours after herniotomy and on the second and seventh postoperative days. At the same times morphine and acetaminophen consumptions were recorded. RESULTS. There were no significant differences in postoperative visual analog scores between the groups. Except for the cumulative morphine requirement from the second to the seventh postoperative day, which was significantly higher in the placebo group than in other groups, no significant differences in cumulative morphine and acetaminophen requirements were found between the groups. CONCLUSIONS. A single 5-mg dose of morphine injected in the herniotomy wound did not affect pain scores or supplementary analgesic requirements, which argues against a role of peripheral opioid receptors in mediating analgesia.

Aasbo et al 2002

Improved long-lasting postoperative analgesia, recovery function and patient satisfaction after inguinal hernia repair with inguinal field block compared with general anesthesia.

Aasbo V, Thuen A, Raeder J.

Acta Anaesthesiol Scand 2002;46(6):674–678.

BACKGROUND: Inguinal hernia repair is a common surgical procedure, and different types of anesthetic techniques are in use. We wanted to test if preoperative inguinal field block (IFB) with ropivacaine would provide benefits in the postoperative period compared with general anesthesia and wound infiltration. METHODS: Sixty patients scheduled for inguinal hernia repair were randomized to receive general anesthesia with wound infiltration postoperatively, or inguinal field block (IFB) before surgery, with no or only light sedation intraoperatively. General anesthesia was induced with midazolam, fentanyl and propofol, maintained with propofol and alfentanil, and supplemented with nitrous oxide in oxygen through a laryngeal mask. The IFB was performed by an anesthesiologist, with 50–60 ml ropivacaine and 5 mg/ml with a dedicated technique. RESULTS: All significant differences were in favor of the IFB group: less pain (visual analog scale, verbal pain score) postoperatively and until day 7, faster mobilization with less pain, lower analgesic consumption, and higher patient satisfaction. CONCLUSION: Preoperative inguinal field block for hernia repair provides benefits for patients in terms of faster recovery, less pain, better mobilization and higher satisfaction throughout the whole first postoperative week.

Özgün et al 2002

Comparison of local, spinal, and general anaesthesia for inguinal herniorrhaphy.

Özgün et al 2002

Eur J Surg 2002;168(8–9):455–459.

OBJECTIVE: To compare local, spinal, and general anaesthesia for inguinal hemiorraphy in otherwise healthy patients with respect to duration of operation, time in operating room, postoperative pain, complications, rehabilitation, and satisfaction. DESIGN: Prospective randomised controlled trial. SETTING: University hospital, Turkey. SUBJECTS: Seventy-five men with unilateral primary inguinal hernias, Nyhus type II and III, and ASA I and II. INTERVENTIONS: Lichtenstein repairs with standard local, spinal, or general anaesthesia. MAIN OUTCOME MEASURES: Duration of operation and anaesthesia, postoperative pain scores, analgesic requirements, complications, length of hospital stay, postoperative rehabilitation, and satisfaction. RESULTS: With local anaesthesia, we recorded shorter time spent in the operating room, lower incidence of nausea and urinary retention, and more satisfaction. In the local and spinal anaesthetic groups, postoperative analgesic requirements and length of hospital stay were less than in the general anaesthesia group. CONCLUSIONS: Local anaesthesia is suitable for day-case hernia repair with fewer postoperative problems and less analgesia requirement. Patients also reported greater satisfaction. Local anaesthesia may be preferred to other methods.

Song et al 2000

Recovery profiles and costs of anesthesia for outpatient unilateral inguinal herniorrhaphy.

Song D, Greilich NB, White PF, Watcha MF, Tongier WK.

Anesth Analg 2000;91(4):876–881.

The use of an ilioinguinal-hypogastric nerve block (IHNB) as part of a monitored anesthesia care (MAC) technique has been associated with a rapid recovery profile for outpatients undergoing inguinal herniorrhaphy procedures. This study was designed to compare the cost-effectiveness of an IHNB-MAC technique with standardized general and spinal anesthetics techniques for inguinal herniorrhaphy in the ambulatory setting. We randomly assigned 81 consenting outpatients to receive IHNB-MAC, general anesthesia, or spinal anesthesia. We evaluated recovery times, 24-h postoperative side effects and associated incremental costs. Compared with general and spinal anesthesia, patients receiving IHNB-MAC had the shortest time-to-home readiness (133+/-68 min vs. 171+/-40 and 280+/-83 min), lowest pain score at discharge (15+/-14 mm vs. 39+/-28 and 34+/-32 mm), and highest satisfaction at 24-h follow-up (75% vs. 36% and 64%). The total anesthetic costs were also the least in the IHNB-MAC group ($132.73+/-33.80 vs. $172.67+/-29.82 and $164.97+/-31.03). We concluded that IHNB-MAC is the most cost-effective anesthetic technique for outpatients undergoing unilateral inguinal herniorrhaphy with respect to speed of recovery, patient comfort, and associated incremental costs.

Nordin et al 2003

Local, regional, or general anaesthesia in groin hernia repair: multicentre randomised trial.

Nordin P, Zetterstrom H, Gunnarsson U, Nilsson E.

Lancet 2003;362(9387):853–858.

BACKGROUND: In specialised centres, local anaesthesia is almost always used in groin hernia surgery; whereas in routine surgical practice, regional or general anaesthesia are the methods of choice. In this three-arm multicentre randomised trial, we aimed to compare the three methods of anaesthesia and to determine the extent to which general surgeons can reproduce the excellent results obtained with local anaesthesia in specialised hernia centres. METHODS: Between January, 1999, and December, 2001, 616 patients at ten hospitals, were randomly assigned to have either local, regional, or general anaesthesia. Primary endpoints were early and late postoperative complications. Secondary endpoints were duration of surgery and anaesthesia, length of postoperative hospital stay, and time to normal activity. Analysis was by intention to treat. FINDINGS: Intraoperative tolerance for local anaesthesia was high. In the early postoperative period, local anaesthesia was superior to the other two types with respect to almost all endpoints. At 8 days' and 30 days' follow-up, there were no significant differences between the three groups. Although the mean duration of surgery was longer, the total anaesthesia time-ie, time from the start of anaesthesia until the patient left the operating room-was significantly shorter than it was for regional or general anaesthesia. INTERPRETATION: Local anaesthesia has substantial advantages compared with regional or general anaesthesia, such as shorter duration of admission, less postoperative pain, and fewer micturition difficulties. The favourable results obtained with local anaesthesia in specialised hernia centres can, to a great extent, be reproduced by general surgeons in routine surgical practice.

Gönüllü et al 2002

Comparison of local and general anesthesia in tension-free (Lichtenstein) hernioplasty: a prospective randomized trial.

Gönüllü NN, Cubukcu A, Alponat A.

Hernia 2002;6(1):29–32.

To compare pulmonary effects, postoperative pain and fatigue, morbidity, patient satisfaction, and cost of different anesthetic techniques for inguinal hernia repair, 50 patients were randomized to local and general anesthesia groups (LA and GA). All patients received the same premedications and the same postoperative analgesic regimen. The standardized postoperative analgesic, intramuscular pyroxicam 20 mg, was given to all patients in the recovery room and an additional 20 mg on the same day was given as requested by each patient. Pulmonary function studies and arterial blood gas analysis were performed 1 h prior to the operation and at the postoperative 8th and 24th hours. All patients underwent Lichtenstein's tension-free hernioplasty. Postoperative pain and fatigue were registered 8 h and 24 h after the operation. A questionnaire was filled out by the patients, and they were asked to give grades for the general comfort of the anesthesia and the surgical procedure (1 = worst, 10 = best). Postoperative pulmonary function tests were significantly poorer in the GA group both on 8th- and 24th-hour measurements (P < 0.05). Patients who underwent LA had significantly lower PCO2 and higher PO2 at the postoperative 8th hour (P<0.05). Mean postoperative pain and fatigue scores revealed a significant difference in favor of local anesthesia at only the 8th hour (P<0.05). There were two complications, one in each group (a hematoma in LA and a urinary retention in GA). Patient satisfaction grades were not different in the two groups. We conclude that LA in inguinal hernia repair does not adversely affect pulmonary functions, patients feel less pain, and patient satisfaction is comparable to that with GA.

Malazgirt et al 2000

Comparison of Stoppa and Lichtenstein techniques in the repair of bilateral inguinal hernias.

Malazgirt Z, Ozkan K, Dervisoglu A, Kaya E.

Hernia 2000;4(4):264-267.

The feasibility of tension-free repairs in bilateral inguinal hernias has not been well documented. In this prospective randomized study patients' characteristics, intra- and postoperative parameters including pain, return to daily activity and work, were assessed in patients undergoing bilateral hernia repair by means of either the Stoppa or the Lichtenstein techniques. A total of 45 patients having bilateral inguinal hernia repairs were randomly assigned to one of the two treatment groups. Patients in Group I had operations with the simultaneous Lichtenstein technique (n23) and were further randomized to either spinal (n11) or local anesthesia (n12) subgroups. Those in Group II underwent a Stoppa hernioplasty (n22). Complications and recurrences were sought for two years postoperatively. Patients with bilateral Lichtenstein repairs under local anesthesia had lower pain scores at rest and leg-raising test, and returned to pain-free normal daily activity and work on the 15th and 30th days, respectively. Although smaller than those of other groups, none of these parameters were statistically significant. The only prominent difference was seen in the operating time. The Stoppa repair took significantly less time than the Lichtenstein repairs (51 vs. 65 min, p < 0.01). In this study we were unable to demonstrate the superiority of either technique or type of anesthesia used in the repair of bilateral hernias. Both techniques were capable of producing favorable postoperative results, and were well accepted by most of the patients.

Kingsnorth et al 2002a

Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine.

Kingsnorth AN, Cummings CG, Bennett DH.

Eur J Surg 2002a;168(7):391–396.

OBJECTIVE: To assess the use of infiltration with local anaesthetics levobupivacaine and bupivacaine, during inguinal hernia repair. DESIGN: Double-blind, randomised study. SETTING: Postgraduate medical school, United Kingdom. SUBJECTS: 69 male patients aged 18 years or older. INTERVENTIONS: Wound infiltration with 0.25% levobupivacaine and 0.25% racemic bupivacaine. MAIN OUTCOME MEASURES: Area under the curve (AUC) of visual analogue scale (VAS) scores for postoperative pain at rest in the supine position, rising from the supine to the sitting position, and walking, against time for both treatment groups. RESULTS: There were no significant differences between treatment groups for the AUC of VAS scores for postoperative pain, global verbal pain rating or time to first dose of analgesic medication. CONCLUSIONS: Levobupivacaine exerts a similar anaesthetic and analgesic effect to racemic bupivacaine when infiltrated both intraoperatively and during the early postoperative period for elective inguinal hernia repair.

Kingsnorth et al 1979

Evaluation of dextran with local anaesthesia for short-stay inguinal herniorraphy.

Kingsnorth AN, Wijesinha SS, Grixti CJ.

Ann R Coll Surg Engl 1979;61(6):456–458.

A prospective randomised study of 40 patients undergoing unilateral inguinal herniorrhaphy under local anaesthesia was undertaken. Half the patients received the local anaesthetic (0.25% bupivacaine) mixed with dextran 40 solution. Subjective and objective assessments were made of the postoperative pain experienced in the first 48 h after operation. The use of 0.25% bupivacaine local inguinal block results in a postoperative pain-free period of approximately 10 h. Simple oral analgesics are adequate for postoperative pain relief in 87.5% of patients and are required relatively infrequently. The addition of dextran 40 to the local anaesthetic has no significant effect on its duration of action.

Aida et al 1999

The effectiveness of preemptive analgesia varies according to the type of surgery: a randomized, double-blind study.

Aida S, Baba H, Yamakura T, Taga K, Fukuda S, Shimoji K.

Anesth Analg 1999;89(3):711–716.

The reliability of preemptive analgesia is controversial. Its effectiveness may vary among anatomical areas or surgical types. We evaluated preemptive analgesia by epidural morphine in six surgery types in a randomized, double-blind manner. Pain intensity was rated using a visual analog scale, a verbal report, and a measurement of postsurgical morphine consumption. Preemptive analgesia was effective in limb surgery and mastectomy, but ineffective for gastrectomy, hysterectomy, herniorrhaphy, and appendectomy. Relief of postsurgical pain in hemiorrhaphy was more rapid than that in the other surgery types. Preemptive analgesia was effective in limb surgery and mastectomy, but not in surgeries involving laparotomy, regardless of whether the surgery was major (gastrectomy and hysterectomy) or minor (herniorrhaphy and appendectomy). These results suggest that viscero-peritoneal nociception is involved in postsurgical pain. The abdominal viscera and peritoneum are innervated both heterosegmentally (in duplicate or triplicate by the vagus and/or phrenic nerves) and segmentally (by the spinal nerves). Therefore, supraspinal and/or cervical spinal neurons might be sensitized, despite the blockade of the segmental nerves with epidural morphine. The rapid retreat of the pain after hemiorrhaphy suggests that central sensitization remits soon after minor surgery, but that in appendicitis, it may be protracted by additional noxious stimuli, such as infection. IMPLICATIONS: Epidural preemptive analgesia was reliably effective in limb and breast surgeries but ineffective in abdominal surgery, suggesting involvement of

Günal et al 2002

Clinical assessment of spinal and epidural anesthesia in inguinal hernia repair.

Günal O, Arikan Y, Celikel N.

J Anesth 2002;16(2):119–122.

Purpose. The current study was done to compare the effect of spinal and epidural anesthesia on surgical outcome measures of inguinal herniorrhaphy. Methods. Ninety-eight male patients undergoing inguinal hernia repair were randomized to either spinal (SA; n = 39) or epidural (EA; n = 59) anesthesia groups anesthetized with either glycosylated bupivacaine (20 mg) or 0.5% bupivacaine (100 mg). Anesthesia onset time (AOT), postoperative stand-up time (SUT), first pain sensation time (FPT), operation time (OT), analgesic requirement (AR), hospital stay (HS), visual analogue scores of pain (VAS), per- and postoperative complications, and postanesthesia complications were recorded and compared with each other. Results. FPT was 6.6 +/- 0.6h and 3.1 +/- 0.4h and OT was 40 +/- 2 min and 33.1 +/- 1 min in the EA and SA groups, respectively (p < 0.05). SUT was also longer in EA group. VAS scores at 12 and 24h were significantly higher in the EA group (28 +/- 4 mm and 24 +/- 5 mm in EA and 16 +/- 4 and 5 +/- 1 mm in SA; P <0.05). No statistically significant difference was found between the SA and EA groups with respect to the other outcome measures that were considered. Conclusion. Spinal and epidural anesthesia show some differences from each other with respect to outcome measures such as OT, SUT, FPT, and 12- and 24-h VAS scores.

Tverskoy et al 1990

Postoperative pain after inguinal herniorrhaphy with different types of anesthesia.

Tverskoy M, Cozacov C, Ayache M, Bradley EL, Jr., Kissin I.

Anesth Analg 1990;70(1):29–35.

In a randomized, double-blind study, postoperative pain was assessed in 36 patients undergoing inguinal herniorrhaphy with three types of anesthesia: general (thiopental-nitrous oxide-halothane); general with the addition of local (infiltration of the abdominal wall with 0.25% bupivacaine along the line of the proposed incision); and spinal (0.5% bupivacaine). The severity of constant incisional pain, movement-associated incisional pain, and pain upon pressure applied to the surgical wound using an algometer was assessed with a visual analogue self-rating method at 24 h, 48 h, and 10 days after surgery. The addition of local anesthesia significantly decreased the intensity of all types of postoperative pain. This effect was especially evident with constant incisional pain that disappeared almost completely 24 h after surgery. With pain caused by pressure on the site of the surgical incision, the pain score difference between general and general plus local anesthesia was obvious even 10 days after the surgery (with 0.4-kg/cm2 pressure, the pain scores were 16 +/- 3 vs 2 +/- 1, P less than 0.01). The difference in postoperative pain scores between spinal and general anesthesia groups indicated that spinal anesthesia also decreases the pain intensity. However, this decrease is less pronounced than that seen with the addition of local anesthesia: movement-associated pain scores 24 h after surgery were 72 +/- 5 in the general anesthesia group, 40 +/- 6 in the spinal anesthesia group, and 16 +/- 3 in the general plus local anesthesia group (with P less than 0.002 between the groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Gupta et al 2003

Low-dose bupivacaine plus fentanyl for spinal anesthesia during ambulatory inguinal herniorrhaphy: a comparison between 6 mg and 7. 5 mg of bupivacaine. see comment.

Gupta A, Axelsson K, Thorn SE, Matthiessen P, Larsson LG, Holmstrom B, Wattwil M.

Acta Anaesthesiol Scand 2003;47(1):13–19.

BACKGROUND: Inguinal herniorrhaphy is commonly performed as an outpatient procedure. Spinal anesthesia offers some advantages over general anesthesia in this setting. METHODS: Forty patients were randomly divided into two groups according to a double-blind protocol: Group L had spinal anesthesia with bupivacaine 6.0 mg and Group H with bupivacaine 7.5 mg; in both groups, fentanyl 25 micro g was added to the spinal anesthetic. The sensory block was measured by 'pin-prick' and the motor block was evaluated by a modified Bromage scale. RESULTS: No differences were seen in the spread, duration and regression of sensory block between the groups on the operated side. A greater number of patients required analgesics during the operation in Group L (6) compared with Group H (1) (P<0.05). The return of the modified Bromage scale to grade 0 was earlier in Group L than in Group H (P<0.05) but the time to mobilization and discharge was similar. Seven patients (17%) needed to be catheterized and two had the catheter retained overnight. Times to home discharge (median) were 350 and 445 min, respectively, in Groups L and H. Postoperatively and during the first week, visual analog pain scores, analgesic requirements and side-effects were similar between the groups. In Group H, 95% of the patients and in Group L 85% would have the same anesthetic again if operated upon for a similar procedure. CONCLUSIONS: Spinal anesthesia with bupivacaine 7.5 mg and fentanyl offers an alternative to general or local anesthesia for ambulatory inguinal herniorrhaphy. However, the long discharge times and risk for urinary retention restrict its routine use in all patients.

Dobrydnjov et al 2003

Clonidine combined with small-dose bupivacaine during spinal anesthesia for inguinal herniorrhaphy: a randomized double-blinded study.

Dobrydnjov I, Axelsson K, Thorn SE, Matthiesen P, Klockhoff H, Holmstrom B, Gupta A.

Anesth Analg 2003;96(5):1496–1503, table of contents.

The aim of this randomized double-blinded study was to see whether the addition of small-dose clonidine to small-dose bupivacaine for spinal anesthesia prolonged the duration of postoperative analgesia and also provided a sufficient block duration that would be adequate for inguinal herniorrhaphy. We randomized 45 patients to 3 groups receiving intrathecal hyperbaric bupivacaine 6 mg combined with saline (Group B), clonidine 15 micro g (Group BC15), or clonidine 30 micro g (Group BC30); all solutions were diluted with saline to 3 mL. The sensory block level was insufficient for surgery in five patients in Group B, and these patients were given general anesthesia. Patients in Groups BC15 and BC30 had a significantly higher spread of analgesia (two to four dermatomes) than those in Group B. Two-segment regression, return of S1 sensation, and regression of motor block were significantly longer in Group BC30 than in Group B. The addition of clonidine 15 and 30 micro g to bupivacaine prolonged time to first analgesic request and decreased postoperative pain with minimal risk of hypotension. We conclude that clonidine 15 micro g with bupivacaine 6 mg produced an effective spinal anesthesia and recommend this dose for inguinal herniorrhaphy, because it did not prolong the motor block. IMPLICATIONS: The addition of clonidine 15 micro g to 6 mg of hyperbaric bupivacaine increases the spread of analgesia, prolongs the time to first analgesic request, and decreases postoperative pain, compared with bupivacaine alone, during inguinal herniorrhaphy under spinal anesthesia.

Tan et al 2000

Efficacy of intrathecal neostigmine for the relief of postinguinal hemiorrhaphy pain.

Tan PH, Kuo JH, Liu K, Hung CC, Tsai TC, Deng TY.

Acta Anaesthesiol Scand 2000;44(9):1056–1060.

BACKGROUND: Intrathecal administration of various doses of neostigmine has been reported to produce analgesia without neurotoxicity in both animal and human studies. The present study was undertaken to evaluate the efficacy and safety of intrathecal neostigmine for the relief of pain for patients having undergone inguinal herniorrhaphy surgery. METHODS: Sixty men scheduled for elective inguinal herniorrhaphy with spinal anaesthesia were randomly allocated to three groups: group I (n=20) received intrathecal (IT) tetracaine 15 mg, group II (n=20) received IT tetracaine 15 mg+ neostigmine 50 microg, and group III (n=20) received IT tetracaine 15 mg+neostigmine 100 microg. The onset of anaesthesia, duration of analgesia, time to use of first rescue analgesics, the overall 24 h VAS pain scores and the incidence of adverse effects were recorded for 24 h postdrug administration. RESULTS: Onset of anaesthesia (time to T6 sensory block) was significantly faster for group II and III patients compared with group I patients. Motor block (time to lift leg) was greatly prolonged for group III patients, with an average of 6.4 h, compared with 4.1 h for group II patients. Group III patients also showed a later onset of postsurgical pain, lower overall 24-h VAS pain score and prolonged time to first rescue analgesics than did group II patients. There was a significantly greater incidence of adverse effects associated with IT neostigmine, especially nausea and vomiting. CONCLUSION: Our study showed that intrathecal neostigmine at 50 pg or 100 microg enhanced the onset of tetracaine anaesthesia and provided analgesia lasting for 6-9 h, although increased incidences of prolonged motor blockade and nausea or vomiting were noted.

Berndsen et al 2002

Postoperative convalescence after inguinal hernia surgery: prospective randomized multicenter study of laparoscopic versus shouldice inguinal hernia repair in 1042 patients.

Berndsen F, Arvidsson D, Enander LK, Leijonmarck CE, Wingren U, Rudberg C, Smedberg S, Wickbom G, Montgomery A

Hernia 2002;6(2):56–61.

Interest in inguinal hernia surgery has increased significantly with the introduction of new operating techniques during the past decade. This multicenter study compared short-term results in patients treated by the laparoscopic transabdominal preperitoneal patch technique (TAPP; n = 518) and the Shouldice technique (n = 524). We evaluated demographics, operative data, complications, hospital stay, postoperative pain, use of cs, functional status, sick leave, and complaints up to 3 months postoperatively. The median operating time was shorter in the Shouldice group (55 vs. 65 min), but there were no significant differences in complication rates, and major complications were rare. The hospital stay was 1 day or less in over 98% of cases in both groups, but more operations were performed on outpatient basis in the Shouldice group. In the TAPP group postoperative pain and analgesic consumption were less, postoperative functional status was better, and sick leave was shorter (10 vs. 14 days). These results show that the two methods are equally safe and have few major complications. The TAPP operation is associated with less postoperative pain, better postoperative functional status, and shorter sick leave, but at the price of a longer operating time.

Tanphiphat et al 1998

Laparoscopic vs open inguinal hernia repair. A randomized, controlled trial.

Tanphiphat C, Tanprayoon T, Sangsubhan C, Chatamra K.

Surg Endosc 1998;12(6):846–851.

BACKGROUND: The role of laparoscopic inguinal hernia repair is controversial. The aim of this study was to find out whether it is justified to switch from the predominantly modified Bassini repair which the authors had been using to laparoscopic repair. METHODS: Randomized controlled trial in 120 eligible patients admitted for elective hernia repair in a university hospital. RESULTS: Sixty patients underwent laparoscopic transabdominal preperitoneal mesh repair; the other 60 patients had an open repair, mostly with the modified Bassini technique. Operative time for laparoscopic repair was significantly longer, mean (s.d.) 95 (28) min vs 67 (27) min (p < 0.001). The mean analogue pain score during the first 24 h after surgery was 36.2 (20.2) in the laparoscopic group and 49.3 (24.9) in the open group (p = 0.006). The requirement for narcotic injections and postoperative disability in walking 10 m and getting out of bed were also significantly less following laparoscopic repair. The postoperative hospital stay was not significantly different, mean 2.6 (1.2) days for laparoscopic repair and 3.0 (1.5) days for open repair (p = 0.1). Patients were able to perform light activities without pain or discomfort sooner after laparoscopic repair, median interquartile range 8 (5-14) days vs 14 (8-19) days (p = 0.013). Patients also resumed heavy activities sooner, but not significantly, after laparoscopic repair, median 28 (17-60) days vs 35 (20-56) days (p = 0.25). The return to work was not significantly different, median 14 (8-25) days after laparoscopic repair and 15 (11-21) days after open repair (p = 0.14). After a mean follow-up of 32 months one patient developed a recurrent hernia 3 months after a laparoscopic repair. Laparoscopic repair was more costly than open repair by approximately $400. CONCLUSIONS: Laparoscopic inguinal hernia repair was associated with less early postoperative pain and disability and earlier return to full activities than open repair, but there were no benefits regarding postoperative hospital stay and return to work; laparoscopic repair was also more costly.

Schrenk et al 1996b

Prospective randomized trial comparing postoperative pain and return to physical activity after transabdominal preperitoneal, total preperitoneal or Shouldice technique for inguinal hernia repair.

Schrenk P, Woisetschlager R, Rieger R, Wayand W.

Br J Surg 1996b;83(11):1563–1566.

In a prospective randomized study postoperative pain, analgesic consumption, return to physical activity and work, cosmetic result and experience with the type of operation were assessed in 86 patients undergoing inguinal hernia repair by means of either the Shouldice technique (n = 34), the laparoscopic transabdominal preperitoneal (TAPP) (n = 28) or total preperitoneal (TPP) (n = 24) repair. Patients having TAPP repair had decreased visual analogue scale scores for pain on the day of operation compared with those undergoing TPP and Shouldice repair (4.8 versus 6.5 and 6.2 respectively, P = 0.02) and on the first postoperative day compared with TPP (4.0 versus 6.0, P = 0.01). There was no difference between the three groups for days 2, 3, 4, 5 and 30 after operation. Patient satisfaction with the operation, analgesic consumption, return to physical activity such as walking, driving, climbing stairs, running, bicycling and sexual intercourse, as well as return to work, was comparable in the three groups. There was a better cosmetic result after TAPP and TPP repair. This study failed to demonstrate significant benefits from laparoscopic hernia repair over the Shouldice technique.

Heikkinen et al 1997

Total costs of laparoscopic and lichtenstein inguinal hernia repairs: a randomized prospective study.

Heikkinen T, Haukipuro K, Leppala J, Hulkko A.

Surg Laparosc Endosc 1997;7(1):1–5.

In a prospective, randomized study, laparoscopic (n = 20) and Lichtenstein (n = 18) inguinal hernia repairs were compared in relation to operative time, operative costs, hospital stay, postoperative pain, return to work, patient satisfaction, complications, and total costs. All the operations were performed with the patient under general anesthesia. The median operative times in the laparoscopic and Lichtenstein groups were 71.5 (range, 43-140) and 45 (16-83) min, respectively (p < 0.001). Postoperative pain and use of analgesics was less in the laparoscopic group. The median time to return to work was 14 (8-26) days in the laparoscopic group and 19 (5-40) days in the Lichtenstein group. More complications occurred in the Lichtenstein group. The median of the operative costs, in U.S. dollars, was $1,395 and $878, respectively, and the median total costs (including community expenses resulting from lost workdays) were $4,796 in the laparoscopic and $5,320 in the Lichtenstein groups.

Filipi et al 1996

An assessment of pain and return to normal activity. Laparoscopic herniorrhaphy vs open tension-free Lichtenstein repair.

Filipi CJ, Gaston-Johansson F, McBride PJ, Murayama K, Gerhardt J, Cornet DA, Lund RJ, Hirai D, Graham R, Patil K, Fitzgibbons R, Jr., Gaines RD.

Surg Endosc 1996;10(10):983–986.

BACKGROUND: Laparoscopic herniorrhaphy is controversial and deserves critical evaluation. METHODS: In a randomized prospective study transabdominal preperitoneal laparoscopic herniorrhaphy (n = 24) was compared in patients to the tension-free Lichtenstein repair (n = 29) utilizing validated and reliable pain and activity assessment tools. The Sickness Impact Profile (SIP) was used to compare preoperative normal activity to postoperative activity. A Pain-O-Meter (visual analogue scale plus affective and sensory pain descriptors) assessed intensity of pain. The total pain assessment score and SIP were compared across time (postoperative day 1-42). Analgesic medication was used as a covariate. RESULTS: The total pain score was less for laparoscopic herniorrhaphy but this did not reach statistical significance. Similarly, the SIP showed modest improvement for laparoscopic herniorrhaphy. No differences between groups were noted for morphine equivalents of administered analgesics or length of hospitalization. CONCLUSION: Further investigation of laparoscopic herniorrhaphy is warranted.

Barth et al 1998

Short-term outcome after mesh or shouldice herniorrhaphy: a randomized, prospective study.

Barth RJ, Jr., Burchard KW, Tosteson A, Sutton JE, Jr., Colacchio TA, Henriques HF, Howard R, Steadman S.

Surgery 1998;123(2):121–126.

BACKGROUND: Retrospective analyses have shown that long-term recurrence rates after Lichtenstein mesh and Shouldice herniorrhaphies are low. Therefore differences in short-term outcome may be important determinants of one's choice of repair. Although proponents of the mesh repair claim that their methods is less morbid, to our knowledge no prospective comparative studies of short-term morbidity have been reported. METHODS: One hundred five adult patients were randomized to undergo either a mesh or Shouldice inguinal hernia repair. Postoperative pain, narcotic use, and time to resumption of usual activities and employment were recorded. Patients were blinded to the type of repair received until all data were collected. RESULTS: There was no difference between the herniorrhaphy methods with respect to postoperative pain, duration of narcotic use, and time to resumption of usual activity and employment. Recovery was rapid for both groups of patients. By 3 days after operation, 50% of patients rated their pain as very mild or less and no longer required narcotic analgesics. Patients in both groups returned to usual activity and work by a median of 9 days after operation. CONCLUSION: Both of these well-established methods can be used to repair inguinal hernias with local anesthetics in an outpatient setting with minimal morbidity. Despite the "tension-free" design of the mesh repair, short-term outcomes of mesh and Shouldice repairs of inguinal hernias do not differ.

Grant 2002

Open mesh versus non-mesh repair of groin hernia: meta-analysis of randomised trials based on individual patient data [corrected].

Grant AM.

Hernia 2002;6(3):130–136.

BACKGROUND: The EU Hernia Trialists Collaboration was established to provide reliable evaluation of newer methods of groin hernia repair. It involved 70 investigators in 20 countries. MATERIALS AND METHODS: Twenty eligible trials (5016 participants) of open mesh vs. non-mesh groin hernia repair were identified. Meta-analysis was performed using raw individual patient data where possible. RESULTS: Fewer hernia recurrences were reported after mesh repair. There were no clear differences between mesh and non-mesh groups in complications. Overall, those in the mesh groups had a shorter hospital stay, quicker return to usual activities and less frequent persisting pain, but individual trial results varied. CONCLUSIONS: The review provides strong evidence that open mesh repair is associated with a reduction in the risk of recurrence of between 50% and 75%. There is also some evidence of quicker recovery and of lower rates of persisting pain following open mesh repair.

Kingsnorth et al 2002b

Prolene Hernia System compared with Lichtenstein patch: a randomised double blind study of short-term and medium-term outcomes in primary inguinal hernia repair.

Kingsnorth AN, Wright D, Porter CS, Robertson G.

Hernia 2002b;6(3):113–119.

BACKGROUND: Refinements in the configuration of mesh may ease handling and placement and reduce postoperative discomfort. MATERIAL AND METHODS: A total of 206 patients were randomly and blindly allocated to receive the Prolene Hernia System (PHS) or Lichtenstein patch. Collected data included: surgical incision size, procedure time, pain scores, analgesic medication, complications, return to activity and work, and quality of life as measured by Short-Form 36 on days 3 and 14. RESULTS: Immediate post-operative pain was significantly lower with PHS than with the patch. The proportion of PHS patients taking longer than 3 days to return to normal activity was 15.5%, compared to 28.4% of patch patients. Operating time was significantly shorter with PHS (34.1 vs. 38.3 min). There was no treatment effect on any of the quality of life scales as measured by Short-Form 36. There were two recurrences in the patch group. CONCLUSIONS: The study indicates a reduction in operating time (4 min) and postoperative recovery with the PHS compared with patch.

Abu-Own A et al 2000

Primary inguinal hernia repair utilizing the mesh 'plug' technique.

Abu-Own A, Onwudike M, Haque KA, Barker SG.

Ambulatory Surgery 2000;8(1):31–35.

'Tension-free' mesh repairs, as popularised by Lichtenstein, are being used increasingly in the management of primary inguinal hernia. Introduced more recently, the mesh 'plug' technique may enhance further the benefits of such repairs. Twenty six males attending for unilateral, primary, inguinal hernia repair were randomised to have either a Lichtenstein 'patch' repair or to undergo a mesh 'plug' repair. Ease of technique and operating time were recorded. Patients were given a visual analogue pain-scoring sheet and were asked to record the number of analgesic tablets taken each post-operative day. Patients were reviewed in clinic at 1 and 6 weeks post-operatively, when they were asked their time to return to 'normal' activity and time to return to work. Any post-operative complications were noted. The tension-free mesh 'plug' repair requires minimal tissue dissection, no herniotomy and is technically straightforward. Patients experienced less post-operative discomfort and returned to 'normality' more quickly. The results suggest that the mesh 'plug' technique has advantages over the Lichtenstein 'patch' repair. A larger trial of this technique should now be undertaken to confirm the results of our pilot study and to assess long term recurrence rates

Langenbach et al 2003

Comparison of biomaterials in the early postoperative period: Polypropylene meshes in laparoscopic inguinal hernia repair.

Langenbach MR, Schmidt J, Zirngibl H.

Surg Endosc 2003;17(7):1105–1109.

Post et al 2004

Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair.

Post S, Weiss B, Willer M, Neufang T, Lorenz D.

Br J Surg 2004;91(1):44–48.

BACKGROUND: Almost half the patients who undergo hernia repair with mesh report a feeling of stiffness and a foreign body in the groin. This study evaluated whether patients noticed any difference between lightweight and standard polypropylene mesh for the repair of inguinal hernia. METHODS: Patients scheduled for elective repair of unilateral or bilateral, primary or recurrent inguinal hernia by the Lichtenstein technique were randomized to receive either a conventional densely woven polypropylene mesh (100-110 g/m(2)) or a lightweight composite multifilament mesh (polypropylene 27-30 g/m(2)). Quality of life was assessed using Short Form 36 before operation and 6 months after surgery. Pain was assessed by means of a visual analogue scale 2 days and 6 months after surgery. The primary outcome measure was the feeling of a foreign body in the groin at 6 months. RESULTS: Some 122 hernias were randomized; 117 were included in the analysis of perioperative data, and 106 were re-examined after 6 months. There were no differences between the treatment groups with respect to early and late surgical complications. Use of lightweight mesh was associated with significantly less pain on exercise after 6 months (P = 0.042). In addition, fewer patients reported the feeling of a foreign body after repair with lightweight mesh (17.2 versus 43.8 per cent with conventional mesh; P = 0.003). Quality of life was improved significantly at 6 months compared with the preoperative assessment, and there were no differences between the treatment groups. CONCLUSION: Lightweight polypropylene mesh may be preferable for Lichtenstein repair of inguinal hernia. Larger cohorts with longer follow-up are needed before it can be recommended for routine use.

Leibl et al 2002

Are postoperative complaints and complications influenced by different techniques in fashioning and fixing the mesh in transperitoneal laparoscopic hernioplasty? Results of a prospective randomized tr

Leibl BJ, Kraft B, Redecke JD, Schmedt CG, Ulrich M, Kraft K, Bittner R.

World J Surg 2002;26(12):1481–1484.

It is unknown at present what the best method is among mesh implantation, central incision, reconstructing the deep inguinal ring, or a non-incised mesh implant in laparoscopic hernia surgery. Further, it is unproven to what extent a circular enclosure of the cremasteric structures by an incised mesh implant could cause postoperative complications and complaints. To evaluate the possible effects of different configurations and fixation techniques of mesh implants in transperitoneal repair of inguinal hernias, a randomized trial (phase IIIa study) was conducted to compare incised versus non-incised mesh and clip fixation versus suturing the mesh. A total of 360 male patients with unilateral primary hernias were randomized to 3 groups. Postoperative complaints were documented by means of a visual analog scale. These values showed no significant differences between study arms. At the first postoperative control, on day 3, patients after repair of Nyhus type II hernias had significantly fewer complaints than those after Nyhus type IIIa and IIIb repair. To gain additional facts, a duplex flow examination of testicular vessels was performed pre- and postoperatively. Testicular perfusion was not influenced by mesh configurations in the trial. There were no statistical differences in postoperative complications and recurrence rates between groups. In conclusion no influence on postoperative complaints and complications could be demonstrated by different mesh fashioning and fixation alternatives studied in this trial.

Callesen et al 1999

Combined epidural-spinal opioid-free anaesthesia and analgesia for hysterectomy.

Callesen T, Schouenborg L, Nielsen D, Guldager H, Kehlet H.

Br J Anaesth 1999;82(6):881.

Postoperative nausea and vomiting (PONV) are major problems after gynaecological surgery. We studied 40 patients undergoing total abdominal hysterectomy, allocated randomly to receive opioid-free epidural-spinal anaesthesia or general anaesthesia with continuous epidural bupivacaine 15 mg h-1 or continuous bupivacaine 10 mg h-1 with epidural morphine 0.2 mg h-1, respectively, for postoperative analgesia. Nausea, vomiting, pain and bowel function were scored on 4-point scales for 3 days. Patients undergoing general anaesthesia had significantly higher nausea and vomiting scores (P < 0.01) but significantly lower pain scores during rest (P < 0.05) and mobilization (P < 0.01). More patients undergoing general anaesthesia received antiemetics (13 vs five; P < 0.05), but fewer received supplementary opioids on the ward (eight vs 16; P < 0.05). We conclude that opioid-free epidural-spinal anaesthesia for hysterectomy caused less PONV, but with less effective analgesia compared with general anaesthesia with postoperative continuous epidural morphine and bupivacaine.

Thapar et al 2000

Shouldice's herniorrhaphy versus Moloney's darn herniorrhaphy in young patients (a prospective randomised study).

Thapar V, Rao P, Deshpande A, Sanghavi B, Supe AN.

J Postgrad Med 2000;46(1):9–12.

AIMS: Shouldice's repair (SR) and Moloney's darn repair (DR) are commonly practised repairs for hernias in the young age group with acceptably low recurrence rates. The SR is considered technically challenging and difficult, while the DR is gaining popularity in recent years. Therefore, there is a need to compare these repairs. MATERIAL AND METHODS: To compare these techniques a total of 50 cases (age group 18-40 years) were randomised to two groups (SR 25, DR 25). These were well matched for age, the side and the type of hernia. Both groups were studied with respect to operative time; postoperative pain at 6,12 and 24 hours (evaluated by pain scale 1-10) need for analgesia, ambulation (evaluated by a four-point scale), complications and return to work. RESULTS: The SR required a longer time (average 81 minutes) compared to DR (average 43 minutes). Patients undergoing SR complained of pain of a higher scale at 6, 12 and 24 hours post surgery and had a significant higher need for analgesia on day 1 and 2 (p < 0.05). Ambulation grades were significantly better in the DR group on the first postoperative day (p < 0.05). There was no significant difference in the two groups with respect to postoperative complications, return to work, and recurrences rate (2-year follow-up). CONCLUSION: The SR and DR are comparable for young patients having a primary hernia. However, DR is superior in terms of the time taken, post-operative pain, need for analgesia and early ambulation.

Picchio et al 2004

Randomized controlled trial of preservation or elective division of ilioinguinal nerve on open inguinal hernia repair with polypropylene mesh.

Picchio M, Palimento D, Attanasio U, Matarazzo PF, Bambini C, Caliendo A.

Arch Surg 2004;139(7):755–758; discussion 759.

HYPOTHESIS: Our study aimed to evaluate the effect of preservation or elective division of the ilioinguinal nerve on pain and postoperative symptoms after open inguinal hernia repair with mesh. DESIGN: Double-blind, randomized trial. SETTING: Four public, government-financed hospitals in Italy. PATIENTS: From January 1, 1997, to June 30, 2002, 813 patients with primary inguinal hernia were randomly allocated to undergo inguinal hernia repair either with ilioinguinal nerve preservation (408 patients, group A) or elective transection (405 patients, group B). INTERVENTION: Hernia repair with sutureless apposition of a polypropylene mesh. MAIN OUTCOME MEASURES: The primary outcome was the evaluation of chronic pain 1 year after operation. Secondary outcomes were postoperative symptoms assessment at 1 week and 1, 6, and 12 months after operation. Telephone interview was performed 35.5 months (range, 12-59 months) after operation to assess the presence of chronic pain. RESULTS: Of the 302 group A and 291 group B patients who made an office visit 1 year postoperatively, pain was absent in 231 (76.5%) and 213 (73%) (difference, 3.30%; 95% confidence interval, -3.68% to 10.28%), mild in 55 (18%) and 60 (21%), moderate in 11 (4%) and 9 (3%), and severe in 5 (2%) and 9 (3%), respectively (P =.55; Pearson chi2(3) test). At 1-month and 6-month follow-up visits, no difference was found between the 2 groups with respect to pain, but loss of pain or touch sensation were significantly greater when the ilioinguinal nerve was divided. One year after operation, the 2 groups were also comparable with respect to loss of pain sensation, but touch sensation remained decreased in group B. At telephone interview, the presence of chronic pain was similar in both groups. CONCLUSIONS: Pain after open hernia repair with polypropylene mesh is not affected by elective division of the ilioinguinal nerve; sensory disturbances in the area of distribution of the transected nerve are significantly increased.

Khiroya et al 1986

Cryoanalgesia for pain after herniorrhaphy.

Khiroya RC, Davenport HT, Jones JG.

Anaesthesia 1986;41(1):73–76.

The effect of freezing the ilioinguinal nerve on postoperative pain relief was examined in a double blind study in 36 patients undergoing herniorrhaphy, randomly allocated into two groups. Patients in the experimental group had their ilioinguinal nerves frozen during surgery and were compared with the patients in the control group who did not have cryoanalgesia. Pain relief was assessed over a 48-hour period in three ways, namely the linear analogue pain scale, peak expiratory flow rates and the amount of analgesic drugs required by patients in the two groups. We conclude that cryoanalgesia of the ilioinguinal nerve alone does not produce significant early post herniorrhaphy pain relief.

Cashman et al 1985

Comparison of infusions of morphine and lysine acetyl salicylate for the relief of pain after surgery.

Cashman JN, Jones RM, Foster JM, Adams AP.

Br J Anaesth 1985;57(3):255–258.

The effect of a constant i.v. infusion of lysine acetyl salicylate (LAS) on pain after operation was compared with that of a constant infusion of morphine in 30 patients undergoing unilateral inguinal herniorrhaphy. LAS provided analgesia equivalent to that provided by morphine and was associated with significantly less drowsiness, nausea and vomiting. No patient in either group was noted to suffer from respiratory depression. No untoward side effects were noted during or following the administration of LAS.

de los Santos et al 1998

Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following inguinal hernioplasty.

de los Santos AR, Di Girolamo G, Marti ML.

Int J Tissue React 1998;20(2):71–81.

In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double-blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients with pain following inguinal hernioplasty. Patients were treated with one 125 mg tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h after the first intake of day 1 and day 2. Each control included assessment of pain at rest, when coughing, sitting and upon moderate pressure. Both treatment groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients) were comparable in terms of demographic and baseline pain intensities. Spontaneous pain was reduced significantly in both treatment groups from the 1st-h control. The following values were recorded in the lysine clonixinate group during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/- 1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2 were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h: 0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day 1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h: 2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h: 0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing, sitting and pressure showed similar behavior patterns. No significant differences between both treatment groups were encountered in terms of analgesic efficacy. Incidence of adverse effects was significantly higher in the paracetamol/codeine group (X2: p < 0.05): 11 out of 74 patients; three patients had to discontinue treatment. In the lysine clonixinate group four out of 77 patients showed side effects but these did not require treatment discontinuation.

Fenton-Lee et al 1994

The use of a local anaesthetic wound perfusion device versus oral analgesia. A comparison in day case inguinal herniorrhaphy.

Fenton-Lee D, Riach E, Cooke T.

British Journal of Intensive Care 1994;4(5).

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.

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.

Hyllested et al 2002

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review.

Hyllested M, Jones S, Pedersen JL, Kehlet H

Br J Anaesth 2002;88(2):199–214.

BACKGROUND: Quantitative reviews of postoperative pain management have demonstrated that the number of patients needed to treat for one patient to achieve at least 50% pain relief (NNT) is 2.7 for ibuprofen (400 mg) and 4.6 for paracetamol (1000 mg), both compared with placebo. However, direct comparisons between paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been extensively reviewed. The aims of this review are (i) to compare the analgesic and adverse effects of paracetamol with those of other NSAIDs in postoperative pain, (ii) to compare the effects of combined paracetamol and NSAID with those of either drug alone, and (iii) to discuss whether the adverse effects of NSAIDs in short-term use are justified by their analgesic effects, compared with paracetamol. METHODS: Medline (1966 to January 2001) and the Cochrane Library (January 2001) were used to perform a systematic, qualitative review of postoperative pain studies comparing paracetamol (minimum 1000 mg) with NSAID in a double-blind, randomized manner. A quantitative review was not performed as too many studies of high scientific standard (27 out of 41 valid studies, including all major surgery studies) would have been excluded. RESULTS: NSAIDs were clearly more effective in dental surgery, whereas the efficacy of NSAIDs and paracetamol seemed without substantial differences in major and orthopaedic surgery, although firm conclusions could not be made because the number of studies was limited. The addition of an NSAID to paracetamol may confer additional analgesic efficacy compared with paracetamol alone, and the limited data available also suggest that paracetamol may enhance analgesia when added to an NSAID, compared with NSAIDs alone. CONCLUSION: Paracetamol is a viable alternative to the NSAIDs, especially because of the low incidence of adverse effects, and should be the preferred choice in high-risk patients. It may be appropriate to combine paracetamol with NSAIDs, but future studies are required, especially after major surgery, with specific focus on a potential increase in side-effects from their combined use.

Lau et al 2003

Randomized clinical trial of postoperative subfascial infusion with bupivacaine following ambulatory open mesh repair of inguinal hernia.

Lau H, Patil NG, Lee F.

Dig Surg 2003;20(4):285–289.

BACKGROUND: Wound pain remains the commonest problem after ambulatory open repair of inguinal hernia. Postoperative subfascial infusion of the wound with bupivacaine extends local analgesia at home and may achieve superior analgesia compared with oral analgesics alone. The objective of the present trial was to evaluate the efficacy of postoperative subfascial infusion of the wound with 0.5% bupicavaine at 2 ml per hour for 48 h after operation. METHODS: Forty-four patients who underwent ambulatory open tension-free mesh hernioplasties were randomized to two arms of treatment. The pump group had an infusion pump containing 100 ml 0.5% bupivacaine being placed between the external oblique aponeurosis and the Prolene mesh, whereas the nonpump group was treated with oral analgesics alone. Assuming that an observed difference of 2.0 existed between the mean pain scores of the two groups, the estimated sample size would be at least 20 patients in each group. RESULTS: Postoperative pain scores at rest and on coughing were significantly lower in the pump group than in the nonpump group on days 0 and 1 after surgery (p < 0.01). Before being discharged, none of the pump group patients requested analgesics, but 6 patients of the nonpump group required analgesic supplement (p = 0.025). Ten patients (50%) of the pump group experienced no pain during the period of bupivacaine infusion. Recovery variables, including time taken to resume ambulation and micturition, were comparable between the two groups. The pump and nonpump group patients returned to their normal activities after a median of 3 and 4 days, respectively (p = 0.217). The postoperative morbidity rates of the two groups were similar. CONCLUSION: Postoperative subfascial infusion of the wound with 0.5% bupivacaine achieved superior analgesia compared with oral analgesics alone. Portable infusion pump is a safe technique to continue local analgesia at home after ambulatory open repair of inguinal hernia. The drawbacks of the ON-Q Pain Management System included its high cost and frequent seepage of blood-stained anesthetic fluid into the wound dressing.

Oakley et al 1998

Randomized placebo-controlled trial of local anaesthetic infusion in day-case inguinal hernia repair.

Oakley MJ, Smith JS, Anderson JR, Fenton-Lee D.

Br J Surg 1998;85(6):797–799.

BACKGROUND: This study investigated the efficacy of local anaesthetic wound perfusion following day-case inguinal hernia repair. METHODS: Seventy-two patients entered a randomized controlled trial with three patient groups: group 1, pump containing bupivacaine; group 2, pump containing normal saline; and group 3, control group without a pump. All patients had a Lichtenstein hernia repair together with ilioinguinal and iliohypogastric nerve blocks and were prescribed oral analgesia. Postoperative pain was assessed over 5 days using a visual analogue scale. RESULTS: Patients who had a local anaesthetic infusion had significantly less pain than either the placebo or control groups. This was greatest during the first 48 h (day 1, P = 0.028 and 0.011 respectively; day 2, P = 0.012 and 0.037 respectively). CONCLUSION: A portable infusion pump for the delivery of local anaesthetic reduced pain after day-case inguinal hernia repair.

Cameron et al 1985

Pain and mobility after inguinal herniorrhaphy: ineffectiveness of subcutaneous bupivacaine.

Cameron AE, Cross FW.

Br J Surg 1985;72(1):68–69.

We studied pain and mobility in 101 men undergoing elective unilateral inguinal herniorrhaphy. Subcutaneous infusion of 0.5 per cent bupivacaine via a fine catheter was used as an adjunct to conventional analgesia in half of the patients. This had no effect on the perception of pain measured at 8 and 24 h by visual linear analogue, nor on the analgesics requested by the patients. The walking ability of all patients was significantly impaired 24 h postoperatively, but again bupivacaine conferred no benefit. Organisms were cultured from 12.5 per cent of the catheters.

Zieren et al 1999

Repeated boluses of local anaesthetic for pain relief after inguinal hernia repair.

Zieren J, Zieren HU, Jacobi CA, Muller JM.

Eur J Surg 1999;165(5):460–4.

OBJECTIVE: To compare the effect of repeated boluses of local anaesthetics with an oral analgesic for pain management after tension-free inguinal hernia repair. DESIGN: Prospective randomised study. SETTING: University hospital, Germany. SUBJECTS: 104 patients undergoing elective hernia repair. INTERVENTIONS: 52 patients were given boluses of 0.5% bupivacaine 10 ml through a subcutaneous catheter and 52 dipyrone 500 mg orally 6, 12 and 24 hours after operation. MAIN OUTCOME MEASURES: Postoperative pain measured on a visual analogue scale, complications, systemic side effects, supplementary analgesics, costs, and time taken to give the analgesics. RESULTS: There were no significant differences between the groups in absolute pain scores, course of pain, and the effects of analgesics. Thirteen patients [5 in the bupivacaine group and 8 in the dipyrone group] required additional dipyrone [mean (range) 2000 mg (500-5000) and 2500 mg (500-4000) respectively]. There were no systemic side effects of either treatment. There were 5 wound haematomas in the bupivacaine group (10%), and 2 wound haematomas and 1 superficial wound infection in the dipyrone group (6%). Mean costs of material and time taken to give the analgesics were pound sterling 104.70 and 47 minutes in the bupivacaine group compared with pound sterling 3.40 and 6 minutes in the dipyrone group. The median (range) hospital stay was 2 (1-3) days in both groups. CONCLUSIONS: Repeated boluses of local anaesthetic did not result in better or cheaper pain control than oral analgesics after tension-free inguinal hernia repair.

Vintar et al 2002

Incisional self-administration of bupivacaine or ropivacaine provides effective analgesia after inguinal hernia repair.

Vintar N, Pozlep G, Rawal N, Godec M, Rakovec S.

Can J Anaesth 2002;49(5):481–486.

PURPOSE: To evaluate the safety and applicability of two local anesthetic (LA) solutions self-administered for pain treatment after inguinal hernia repair (IHR) by balloon-pumps via catheters placed in the surgical wound. Effectiveness of analgesia was also compared. METHODS: Two groups of patients for IHR were included in the randomized, double-blind study. An epidural catheter was placed in the surgical wound, tunneled subcutaneously and connected to a balloon-pump containing either 0.25% bupivacaine (B) or 0.25% ropivacaine (R). Postoperatively, the patient self-administered the LA into the wound. Administration could be repeated after 20 min. If moderate to severe pain still persisted, rescue medication (piritramid) was given intravenously. The variables recorded in both groups were: visual analogue scale (VAS), pain scores at rest and with movement, number of applications, wound healing, patients' satisfaction. RESULTS: During the first 24 hr, median number of LA applications in 26 B patients was 4 (range 1-6) and in 25 R patients 3 (range 1-5). Both groups showed low VAS pain scores: less than 2 at rest, less than 4 with movement. Eighty percent of patients of each group would choose this type of analgesia again. Two patients from B Group and three from R Group needed rescue medication. No wound infection was observed. There were no statistically significant differences between the groups. CONCLUSION: Self-administration of the LA solution via a catheter in the surgical wound is an effective method of pain relief after IHR with little side-effects.

Yndgaard et al 1994

Subcutaneously versus subfascially administered lidocaine in pain treatment after inguinal herniotomy.

Yndgaard S, Holst P, Bjerre-Jepsen K, Thomsen CB, Struckmann J, Mogensen T.

Anesth Analg 1994;79(2):324–327.

We conducted a randomized, prospective, double-blind trial to compare the efficacy of subfascial (SF) versus subcutaneous (SC) lidocaine (10 mL 1%) given in the wound postoperatively through a catheter placed in the respective layer intraoperatively. The initial pain scores were similar in the two groups before injection of lidocaine. In the SC group, there was a reduction in pain scores during rest from 4 to 3 (P > 0.05), during cough from 6 to 5 (P > 0.05), and during mobilization from 7 to 5.5 (P > 0.05) at 15 min. In the SF group, the reductions in pain scores were from 4 to 2 (P < 0.05), from 6 to 3 (P < 0.05), and from 7 to 3 (P < 0.05), respectively. Supplemental analgesics after the lidocaine administration were needed earlier in the SC group than in the SF group (P < 0.01). We conclude that postoperative pain treatment with local lidocaine application after herniotomy has a better effect when applied in the SF, rather than the SC, layer.

Gilbert et al 1986

Controlled trial of transcutaneous electrical nerve stimulation (TENS) for postoperative pain relief following inguinal herniorrhaphy.

Gilbert JM, Gledhill T, Law N, George C.

Anaesthesia 2001;56(5):414–417.

There is little evidence that local anaesthetics produce pre-emptive analgesia and one reason may be the short duration of action of the drugs studied. We examined the pre-emptive analgesic effect of a bupivacaine field block on postoperative pain in 40 patients following herniorrhaphy in a double-blind, randomised trial. Patients received the block either after induction but before surgery, or after surgery but before the end of anaesthesia. There was no difference in pain scores or analgesic consumption up to 7 days after surgery between the two groups. We have demonstrated that bupivacaine does not appear to provide significant pre-emptive analgesia following a field block for herniorrhaphy. This study does not support the hypothesis that pre-emptive analgesia with local anaesthetic depends upon the duration of action of the drug.