Review Article  |   April 2006
Analgesic Treatment after Laparoscopic Cholecystectomy: A Critical Assessment of the Evidence
Author Affiliations & Notes
  • Thue Bisgaard, M.D., D.Sc.
  • * Senior Registrar.
Article Information
Review Article / Ambulatory Anesthesia / Gastrointestinal and Hepatic Systems / Pain Medicine / Pharmacology
Review Article   |   April 2006
Analgesic Treatment after Laparoscopic Cholecystectomy: A Critical Assessment of the Evidence
Anesthesiology 4 2006, Vol.104, 835-846. doi:
Anesthesiology 4 2006, Vol.104, 835-846. doi:
SEVERAL analgesic interventions with varying targets and mechanisms have been investigated for their influence on early pain after laparoscopic cholecystectomy. The current review was undertaken to analyze current literature to propose a procedure-specific, multimodal analgesic strategy after laparoscopic cholecystectomy.
There are numerous arguments for a procedure-specific assessment of the evidence of analgesic treatment after laparoscopic cholecystectomy. Postoperative pain is reduced compared with open traditional cholecystectomy,1 but effective analgesic treatment after laparoscopic cholecystectomy has remained a clinical challange.2 In 17–41% of the patients, pain is the main reason for staying overnight in the hospital on the day of surgery,3–7 and pain is the dominating complaint and the primary reason for prolonged convalescence after laparoscopic cholecystectomy.2,8 Moreover, it has been hypothesized that intense acute pain after laparoscopic cholecystectomy may predict development of chronic pain (e.g.  , postlaparoscopic cholecystectomy syndrome),9 but this has not been studied prospectively.
The validity of postoperative quantitative estimates from non–procedure-specific analyses (number needed to treat) has recently been questioned because data are derived from a variety of procedures, which may potentially hinder the interpretation of the number needed to treat for specific procedures.10 Therefore, it is proposed that analgesic data and optimized analgesic treatment should be specific for the type of surgical procedure.10–12 In addition, growing evidence suggests that treatment of postoperative pain should be multimodal and opioid sparing to accelerate recovery and avoid potential side effects.13,14 
The fact that acute pain after laparoscopic cholecystectomy is complex in nature and does not resemble pain after other laparoscopic procedures2,7,15 suggests that effective analgesic treatment should be multimodal. Therefore, detailed prospective studies in individual laparoscopic procedures such cholecystectomy, gynecologic procedures, hernia repair, and fundoplication have shown procedure-related individual pain patterns requiring procedure-specific analgesic treatment regimens.7,16 In laparoscopic cholecystectomy, overall pain is a conglomerate of three different and clinically separate components: incisional pain (somatic pain), visceral pain (deep intraabdominal pain), and shoulder pain (presumably referred visceral pain).7 Characteristically, overall pain after laparoscopic cholecystectomy carries a high interindividual variability in intensity and duration and is largely unpredictable.7 Pain is most intense on the day of surgery and on the following day and subsequently declines to low levels within 3–4 days. However, pain may remain severe in approximately 13% of patients throughout the first week after laparoscopic cholecystectomy.7 In this review, pain  refers to postoperative pain not defined in detail unless stated otherwise.
In a recent systematic review of postoperative analgesia, the role of timing of treatment for postoperative pain relief was investigated (preemptive analgesia).17 Based on findings from a variety of surgical procedures, the authors concluded preemptive and postoperative analgesic effects were comparable.17 In the current review, timing of intervention refers to analgesic treatment at the start versus  end of surgery. The issue is raised where data allows it and addressed in the sections relevant to each analgesic intervention.
Methodologic Considerations
Clinical randomized trials of analgesia after laparoscopic cholecystectomy were included in the current review. Conclusions were restricted to findings from principal analgesic outcome trials. Trials were identified by literature searches in Medline, Embase, and the Cochrane Library (1985 to June 2005). The search string (free Text Terms and Medical Subject Headings [MeSH]) for pain consisted of postoperative pain  and laparoscopic cholecystectomy  in combination. Additional studies were identified by manually searching references provided by reviews and original articles. The searches were limited to English-language journals. The methodologic quality of the randomized trials was evaluated according to Slim et al.  18 A validated assessment form containing generic questions regarding research methodology in randomized trials was used. The assessment included 11 questions as to whether the trial had a stated aim, an adequate control group and statistics, an account of the selection process, randomization technique, adequate statistics, baseline equivalence, clearly defined study endpoint and unbiased assessment, description of the intervention procedure and operation, and adequate postoperative follow-up. Answers for each question were scored and trials were accordingly categorized into three quality groups: A = ideal quality, B = moderate quality, and C = poor quality. Randomized analgesic trials by the present author19 were evaluated by an independent assessor (see acknowledgments).
Results and Comments
In total, 64 randomized principal analgesic trials were identified, including a total of 5,018 evaluated patients (tables 1 and 2). Table 3summarizes evidence-based grading of analgesic recommendations according to the criteria by the Oxford Center for Evidence based Medicine.120 In the following and for informative reasons, the pharmacologic mechanisms of the individual analgesics are briefly summarized, and the results from the randomized trials are listed and critically commented on.
Table 1. Randomized Trials on the Analgesic Effects of Local Anesthetics after Laparoscopic Cholecystectomy 
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Table 1. Randomized Trials on the Analgesic Effects of Local Anesthetics after Laparoscopic Cholecystectomy 
Table 1. (Continued) 
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Table 1. (Continued) 
Table 2. Randomized Trials on Various Analgesic Techniques after Laparoscopic Cholecystectomy 
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Table 2. Randomized Trials on Various Analgesic Techniques after Laparoscopic Cholecystectomy 
Table 3. Evidence-based Recommendations for Analgesic Treatment after Laparoscopic Cholecystectomy 
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Table 3. Evidence-based Recommendations for Analgesic Treatment after Laparoscopic Cholecystectomy 
NSAIDs/COX-2 Inhibitors
The principal action of nonsteroidal antiinflammatory drugs (NSAIDs) (or cyclooxygenase-2 [COX-2] inhibitors) is modulation of the local inflammatory response by inhibiting cyclooxygenase in the spinal cord and periphery to reduce prostanoid synthesis.21,22 The analgesic effects of acetaminophen are mediated in the central nervous system by inhibiting the synthesis of prostaglandins.23 
Optimally, analgesic therapy should be started in time to be effective at the time of emergence from anesthesia. Laparoscopic cholecystectomy is a short surgical procedure, often less than 1 h. It seems that initiation of treatment of NSAIDs or COX-2 inhibitors and the centrally acting acetaminophen shortly before or during laparoscopic cholecystectomy is optimal.24–26 The analgesic effects of timing have been studied in one high-quality trial demonstrating that preoperative administered intravenous ketoprofen (100 mg) improved postoperative analgesia compared with postoperative administration24 (table 2). Preoperative ketoprofen was shown to significantly improve postoperative analgesia compared with preoperative and postoperative propacetamol.24 Another trial of poor methodologic quality found no analgesic advantage of early treatment versus  late treatment with NSAIDs.27 Data from other minor surgical procedures, such as breast biopsy,28,29 have demonstrated that intravenous tenoxicam (20 mg) administered 30 min before surgery improved postoperative analgesia compared with treatment initiated at induction of anesthesia.
The analgesic efficacy of NSAIDs/COX-2 inhibitors and acetaminophen has been established in 10 trials after laparoscopic cholecystectomy (table 2). In many different surgical procedures, including laparoscopic cholecystectomy (table 2), the optimal benefit of NSAIDs or COX-2 inhibitors and acetaminophen is obtained by continuous prophylactic use by daily oral administration throughout the postdischarge period.26,27,30–37 Evidence from other minor surgical procedures supports clinically relevant analgesic effects in laparoscopic cholecystectomy of acetaminophen alone and with additive effects when used in combination with other NSAIDs.38–40 Acetaminophen has not been compared with placebo after laparoscopic cholecystectomy. The opioid sparing effects of NSAIDs or COX-2 inhibitors and acetaminophen are in the range of 20–30%.25–27,32,33,35,37,41 Recent data from routine use of NSAIDs or COX-2 inhibitors and acetaminophen suggested hastened and higher quality of recovery along with less use of opioids in cholecystectomy and other minor surgical procedures.13,25,26,41,42 Therefore, in laparoscopic cholecystectomy, a single intravenous dose of 40 mg parecoxib (30 min before operation) and 40 mg oral valdecoxib once daily on postoperative days 1–4 reduced pain intensity and opioid requirements.26 Duration of stay in the postoperative anesthetic care unit and vomiting in the first 24 h were also significantly reduced, and patients slept better the first night, returned to normal activity earlier, and expressed greater satisfaction with the analgesic treatment compared with placebo treatment.26,32 There were no differences in side effects or complications between treatment groups.
In summary, NSAIDs or COX-2 inhibitors are recommended for routine use in patients undergoing laparoscopic cholecystectomy (table 3). Treatment should be initiated shortly before or at induction of anesthesia or during surgery and continued for 3–4 days. The literature does not allow definite conclusions on drug dose.
Local Anesthetics
Local anesthetics prevent transmission of nerve signals from the trauma site to the spinal cord and reduce neurogenic local inflammation at the trauma site.43 
Incisional Instillation.
Seven of eight trials favored the use of incisional local anesthetics (table 1). The methodologic quality of the trials was moderate or low. In half of the eight studies, incisional local anesthetics had significant opioid-sparing effects. A quantitative systematic analysis of postoperative visual analog scale pain scores from selected trials2found significant analgesia within 0–6 h,19,44–47 6–12 h,45 and even 12–24 after laparoscopic cholecystectomy compared with controls.44,45,48 These investigations used various doses and application sites, and the study quality was questionable. Conclusions on exact analgesic duration are difficult, but median analgesic duration is at least 2–3 h after the end of surgery.19 Two trials of poor methodologic quality investigated the effect of preemptive analgesic treatment46,48 but failed to show advantages of local anesthetics administered before incision versus  at the end of surgery.
Intraperitoneal Instillation.
The analgesic effects of intraperitoneal local anesthetic blockade after laparoscopic cholecystectomy versus  placebo have been investigated in 24 randomized trials (predominantly of poor or modest methodologic quality) (table 1). Nine trials were negative (1 high- and 8 poor-quality trials), and 15 trials demonstrated significant analgesic benefits (5 high- or moderate- and 10 poor-quality trials). There was no obvious relation between instillation site, dose, timing, and degree of pain relief (table 1). A recent combined systematic quantitative and qualitative review49 (literature search 1966–1999) suggested a statistically significant weighted mean difference of 13 mm in visual analog scale scores in favor of intraperitoneal local anesthetic compared with placebo after laparoscopic cholecystectomy. However, a quantitative analysis of pooled data from these intraperitoneal local anesthetic trials is problematic. The intraperitoneal local anesthetic trials used highly variable study protocols with a variety of doses of different local anesthetics ranging from 50 to 380 mg, and many different protocols were used for application sites of the local anesthetics (table 1). One trial of poor methodologic quality50 suggested that early instillation of intraperitoneal local anesthetics provided better postoperative pain control compared with instillation at the end of surgery but was contradicted by another trial of moderate methodologic quality.51 
Incisional and Intraperitoneal Instillation.
Bisgaard et al.  19 applied a near-maximum dose of local anesthetic or placebo in a randomized trial (table 1). Ropivacaine (or saline) was infiltrated into the port incisions and ropivacaine (or saline) at several sites intraperitoneally (table 1). Both treatment groups were given NSAIDs and acetaminophen in fixed doses and opioids when needed. The local anesthetic regimen significantly reduced incisional pain during the first 3 h postoperatively.19 No analgesic benefits on visceral pain or shoulder pain were found, but overall pain was significantly reduced during the first 2 postoperative hours and opioid requirements were decreased during the first 3 postoperative hours. Nausea was significantly reduced in the ropivacaine group compared with placebo.19 The findings were later replicated in a similar trial by Lee et al.  44 In a trial of low methodologic quality,52 there were no analgesic differences between incisional versus  intraperitoneal local anesthetic regimens (table 1).
In summary, the evidence from two high- and three moderate-quality trials supports routine use of local anesthetics in all trocar incisions to reduce pain after laparoscopic cholecystectomy (table 3). The literature does not provide conclusive information on specific dose and timing of local anesthetic infiltration, but a dose of more than 100 mg bupivacaine (or other long-acting local anesthetics) is recommended. Routine use of intraperitoneal local anesthetics cannot be recommended, because of the low study quality in many trials and conflicting results.
Opioids reduce pain by decreasing local inflammation at the trauma site and in the dorsal horn by activating inhibitory pathways to the descending spinal segments.53,54 
The analgesic effects of different treatment regimens of prophylactic opioids in laparoscopic cholecystectomy were investigated in seven randomized trials (table 2). The only positive trial in favor of prophylactic opioid treatment compared with placebo was of poor methodologic quality.55 In a recent trial of moderate quality,56 peripheral opioid analgesia was investigated. A low dose of opioid was injected at the trocar sites (2 mg morphine in 20 ml saline) alone or in a mixture with incisional bupivacaine. The authors found no significant analgesic differences compared with placebo treatment (table 2). One trial of high methodologic quality found that routine treatment of opioids at the beginning of operation conferred significantly better postoperative pain control than opioids given at the end of surgery.27 
The valuable analgesic properties of opioids in the treatment of acute, intense postoperative pain after major and minor surgery are well accepted.57 However, to hasten recovery and minimize opioid-related side effects (somnolence and sedation, nausea and vomiting, sleep disturbances, urinary retention, and respiratory depression), prophylactic use of opioids in postoperative pain is avoided.14,22,53,58 Other drugs, such as NSAIDs or COX-2 inhibitors, incisional local anesthetics, and steroids have been shown to have valuable opioid-sparing effects (tables 1 and 2; see Multimodal Analgesia section).
In summary, there are no specific data to support prophylactic use of opioids in patients after laparoscopic cholecystectomy (table 3). Based on findings from a variety of surgical procedures, the use of short-acting opioids is the treatment of choice for intense persistent pain and to supplement other analgesics if no surgical reason is found as the cause of the pain after laparoscopic cholecystectomy.
The onset of biologic action is at 1–2 h and the timing of preoperative steroid administration seem to be important to attenuate postoperative inflammatory activation59 but have not been specifically addressed in surgical patients. The analgesic effects of steroids are mainly provided through peripheral inhibition of phospholipase enzyme and hereby decreasing products of cyclooxygenase and lipoxygenase pathways in the inflammatory response.59,60 
A recent review based on available randomized trials (1966 to May 2001) focused on the effects of perioperative single-dose steroid administration.61 The authors concluded that steroids may have analgesic effects in minor surgical procedures such as hemorrhoidectomy, hallux valgus correction, thyroidectomy, and dental surgery.61 A recent randomized trial investigated analgesia using a single dose of dexamethasone (8 mg) intravenously given 90 min before laparoscopic cholecystectomy (table 2).62 Postoperative pain and supplementary opioid requirements were reduced by approximately 50% in the dexamethasone group compared with placebo. Patients in the dexamethasone group reported significantly lower levels of postoperative fatigue, nausea, and vomiting, and resumed normal activities faster compared with placebo.62 However, other studies using a single intravenous dose of 8 mg63 or 5 mg64 or a varying dose of dexamethasone in combination with ondansetron65 failed to show analgesic benefits after laparoscopic cholecystectomy. In these trials, dexamethasone was given immediately before incision, and postoperative nausea and vomiting were the principal outcomes. All trials in laparoscopic cholecystectomy62–65 and in other surgical procedures66 found significant antiemetic effects using prophylactic dexamethasone, and no side effects were observed. In the dexamethasone trials reporting no analgesic effects, postoperative pain was not the principal outcome, and dexamethasone was administered immediately before the operation.63–65 
Obviously, concerns about a possible association between steroids and impaired wound healing, postoperative infection, or other complications are important. In a meta-analysis,67 it was concluded that perioperative administration of high-dose methylprednisolone (30–35 mg/kg), a dose equivalent to 50 times the dose of dexamethasone (8 mg), was not associated with significant side effects. Also, a recent meta-analysis of postoperative nausea and vomiting indicated that a single dose of dexamethasone did not increase infectious or other complications.68 
In summary, the analgesic potential of dexamethasone after laparoscopic cholecystectomy warrants further evaluation before final conclusions can be made (table 3).
Epidural Analgesia
Epidural local anesthetics work by blocking afferent nerve activity at the spinal level.69 
The efficacy of postoperative epidural analgesia in major surgical procedures is well established.70 Poor methodologic quality in trials in laparoscopic cholecystectomy have suggested significant analgesic benefits of epidural analgesia71,72 and intrathecal morphine/local anesthesia73 compared with controls (table 2). However, it may be argued that safety, cost–benefit, and analgesic superiority over noninvasive analgesic regimens must be documented before epidural analgesia is recommended for laparoscopic cholecystectomy in otherwise healthy patients. The effect of timing of analgesia has not been studied in laparoscopic cholecystectomy.
In summary, epidural analgesia and intrathecal local anesthesia/morphine probably provide effective control of pain after laparoscopic cholecystectomy. However, these invasive techniques cannot be recommended as routine in laparoscopic cholecystectomy, because of the potential risks (table 3).
Gabapentin, an antiepileptic drug, works centrally by reducing the release of monoamine neurotransmitters.74 In patients undergoing breast surgery,75,76 in patients undergoing spinal surgery,77 and after abdominal hysterectomy,78 gabapentin (1,200 mg) had clinically important effects on postoperative pain and morphine consumption. In a recent large-scale, double-blind, randomized trial of 459 patients undergoing laparoscopic cholecystectomy (moderate methodologic quality; table 2), the analgesic effects of a very low dose of 300 mg oral gabapentin 2 h before operation was compared with 100 mg oral tramadol or placebo.79 Gabapentin significantly decreased total opioid consumption by 17% versus  tramadol and by 37% versus  placebo. Also, there was a significant decrease in visual analog scale pain scores compared with placebo and tramadol treatment.79 The effect of timing of administration of gabapentin has not been studied in laparoscopic cholecystectomy.
In summary, dose–response studies of the analgesic efficacy of gabapentin are warranted in laparoscopic cholecystectomy before this treatment can be recommended as routine (table 3).
Clonidine, an α2agonist, reduces peripheral sympathetic outflow, inhibits the release of substance P from the dorsal horn, and suppresses noxious activity at the spinal cord level.80 
Two randomized trials81,82 indicated clinically important postoperative analgesic effects using a single 150-μg or 3-μg/kg dose of clonidine before laparoscopic cholecystectomy. Unfortunately, both trials were of very poor methodologic quality, and conclusions about analgesia are not possible (tables 2 and 3). The effect of timing of administration of clonidine has not been studied in laparoscopic cholecystectomy.
In summary, current evidence does not support routine use (table 3).
NMDA Receptor Antagonists
N  -methyl-d-aspartate (NMDA) receptor antagonists (e.g.  , ketamine and dextromethorphan) reduce spinal nociceptive neuron activity, thereby changing spinal nociceptive processing and hyperexcitablility.83 
It remains unclear whether prophylactic treatment with NMDA receptor antagonists has a role in the control of pain after surgery.84,85 In laparoscopic cholecystectomy, the analgesic effects of preemptive NMDA receptor antagonists have been investigated in five randomized trials of predominantly poor or moderate methodologic quality (table 2).86–90 In the only trial of moderate methodologic quality and reporting positive findings, dextromethorphan (40 mg intramuscular) administered 30 min before incision provided significantly better postoperative pain relief than treatment after surgery and control groups.87–89 In a trial of moderate quality, Mathisen et al.  86 found no significant analgesic effects of a racemic ketamine (1 mg/kg intravenous) treatment administered 3–10 min before surgical incision compared with ketamine treatment at skin closure or placebo treatment.
In summary, analgesic efficacy from future high-quality trials with NMDA receptor antagonists in laparoscopic cholecystectomy is essential before this treatment can be recommended (table 3).
Multimodal Analgesia
Results from patients after outpatient hernia repair,91 major upper gastrointestinal surgery,92,93 cesarian delivery,94,95 and abdominal hysterectomy96 have suggested enhanced analgesic efficacy using multimodal analgesic strategies compared with unimodal analgesic treatment as assessed by pain, opioid needs, pulmonary dysfunction, physical activity, mood and sleep disturbances.96 
The complexity of pain after laparoscopic cholecystectomy provides rationale for a multimodal analgesic approach. Michaloliakou et al.  42 investigated the effect of a multimodal analgesic therapy or placebo in a randomized trial in 45 patients undergoing laparoscopic cholecystectomy (table 2). The treatment group received a combination of preoperative intramuscular opioid, ketorolac, and combined incisional–intraperitoneal local anesthetic blockade. The multimodal analgesia almost eliminated reports of postoperative pain and need for supplemental morphine, and recovery, mobilization, and functional activity were significantly enhanced. Although not based on randomized comparison, it is noteworthy that 65–92% of patients receiving a single mode of analgesic treatment may need supplementary opioids on the day of laparoscopic cholecystectomy.7,32 Only 20–29% of patients treated with a multimodal analgesic treatment require supplemental opioids.42,62 However, in studies by Bisgaard et al.  62,97 using a prophylactic multimodal analgesia, pain was not eliminated after the operation. In these trials, the pain treatment consisted of intraoperative opioids, incisional local anesthetics, and NSAIDs in combination with dexamethasone.62 The addition of gabapentin and/or clonidine and/or ketamine, and/or NMDA receptor antagonists may have added additional analgesic control. Two trials in laparoscopic cholecystectomy suggested that preincisional dextromethorphan in combination with and tenoxicam88 or intravenous lidocaine89 provided additional pain relief compared with placebo. However, both trials were of poor methodologic quality, precluding definitive conclusions.
In summary, the complexity of pain after laparoscopic cholecystectomy and previous investigations using multimodal analgesic treatment in a variety of surgical procedures support that pain after laparoscopic cholecystectomy should be managed using a multifaceted opioid-sparing analgesic regimen (table 3). High-qualitytrials are needed in laparoscopic cholecystectomy to provide evidence for the optimal multimodal analgesic regimen.
Six randomized trials in laparoscopic cholecystectomy of various quality with different interventions (propofol-based general anesthesia vs.  desflurane-based anesthesia,98,99 metoclopramide [20 mg]vs.  ondansetron,100 preoperative carbohydrate beverage vs.  placebo,101 and outpatient vs.  inpatient laparoscopic cholecystectomy)102 monitored postoperative pain, but pain was by no means a principal outcome measure, and conclusions about analgesia are not possible.
Interventions to Reduce Incisional, Visceral, and Shoulder Pain
Few analgesic trials have investigated the different components of pain after laparoscopic cholecystectomy (tables 1 and 2). The literature suggests that incisional pain is reduced by incisional local anesthetics and dexamethasone (tables 1 and 2). Visceral pain is reduced by intraperitoneal local anesthetics and dexamethasone, although findings are not uniform (tables 1 and 2). There are no randomized analgesic trials of high or moderate methodologic quality to provide evidence for the treatment of shoulder pain (tables 1 and 2).
Two investigations from the surgical literature, both of moderate methodologic quality, found that carbon dioxide insufflation pressure of 7–9 mmHg compared with a high insufflation pressure (12–14 mmHg) reduced postoperative shoulder pain after laparoscopic cholecystectomy.103,104 In patients with American Society of Anesthesiologists physical status of I or II, the hemodynamic and circulatory effects of a 12- to 14-mmHg pneumoperitoneum are generally not clinically relevant, but in patients with American Society of Anesthesiologists physical status of III or IV, the use of the lowest intraabdominal pressure allowing adequate exposure is recommended.105 Finally, two randomized surgical trials of high and moderate methodologic quality found significantly lower levels of incisional pain scores using a microlaparoscopic cholecystectomy technique (3.5-mm trocar instrument vs.  10- and 5-mm trocar instruments).97,106 
In summary, only a small number of analgesic trials addressed individual pain components after laparoscopic cholecystectomy, and final conclusions are not possible.
Future Directions
The methodologic quality of randomized trials of pain after laparoscopic cholecystectomy is generally low and should be improved in future trials. The large interindividual variation in pain intensity after laparoscopic cholecystectomy should be taken into consideration in the statistical planning.7 
The effects of multimodal analgesic therapy should be investigated against placebo in patients after laparoscopic cholecystectomy. The clinical implications of pain relief and opioid-sparing effects (quality of recovery, nausea and vomiting, general well-being, patient's satisfaction, sleep, dizziness, fatigue, and duration of convalescence) should be further assessed. The analgesic cost effectiveness of gabapentin, clonidine, ketamine, and NMDA receptor antagonists should be investigated in high-quality trials before being implemented.
Slow-release preparations of local anesthetics107,108 with prolonged postoperative pain relief should be studied. Intraperitoneal instillation of local anesthetics is easy, safe, and inexpensive. Therefore, it is hoped that trials of high quality will be performed to provide definitive conclusions on the analgesic effect of intraperitoneal application of local anesthetics.
More information is needed about dose–response aspects of incisional local anesthetics and NSAIDs and COX-2 inhibitors.
The ability for a single-dose steroid therapy (8 mg dexamethasone) to improve analgesic treatment and other clinical outcomes (fatigue, nausea and vomiting, general well-being, etc.) should be tested in a large, multicenter trial of high methodologic quality. The analgesic efficacy of preoperative intravenous dexamethasone 1–2 h before versus  immediately before surgery should be investigated. Self-administration of oral steroids 1–2 h before surgery could be investigated in a randomized trial.
Finally, the hypothesis that severe acute pain after laparoscopic cholecystectomy predicts development of chronic pain (such as post–laparoscopic cholecystectomy syndrome)9 should be investigated in future well-defined, prospective, large-scale studies. Whether optimized perioperative analgesic treatment reduces risk of chronic pain after laparoscopic cholecystectomy is a question that needs to be answered.
The complexity of pain after laparoscopic cholecystectomy suggests that effective treatment of postoperative pain should be multimodal. Based on a critical analysis of current literature, the regimen includes preoperative single dose of dexamethasone, incisional local anesthetics (at the beginning or at the end of operation, depending on preference), and regular use of NSAIDs or COX-2 inhibitors combined during the first 3–4 postoperative days, including the day of surgery. Prophylactic treatment of postoperative opioids is not recommended because of the many potential side effects. Short-acting opioids should be used only on demand when other analgesic techniques fail.
The author thanks Steen Møiniche, M.D. (Department of Anaesthesiology, Glostrup University Hospital, Glostrup, Denmark), for assessing methodologic quality of randomized analgesic trials by Bisgaard et al.  cited in the current review.
Downs SH, Black NA, Devlin HB, Royston CMS, Russell RCG: Systematic review of the effectiveness and safety of laparoscopic cholecystectomy. Ann R Coll Surg Engl 1996; 78:241–323Downs, SH Black, NA Devlin, HB Royston, CMS Russell, RCG
Bisgaard T, Kehlet H, Rosenberg J: Pain and convalescence after laparoscopic cholecystectomy. Ann R Coll Surg Engl 2001; 167:84–96Bisgaard, T Kehlet, H Rosenberg, J
Lau H, Brooks DC: Predictive factors for unanticipated admissions after ambulatory laparoscopic cholecystectomy. Arch Surg 2001; 136:1150–3Lau, H Brooks, DC
Callesen T, Klarskov B, Mogensen T, Kehlet H: Day case laparoscopic cholecystectomy: Feasibility and convalescence. Ugeskr Læger 1998; 160:2095–100Callesen, T Klarskov, B Mogensen, T Kehlet, H
Fiorillo MA, Davidson PG, Fiorillo M, D'Anna JA, Sithian N, Silich RJ: 149 ambulatory laparoscopic cholecystectomies. Surg Endosc 1996; 10:52–6Fiorillo, MA Davidson, PG Fiorillo, M D'Anna, JA Sithian, N Silich, RJ
Tuckey JP, Morris GN, Peden CJ, Tate JJ: Feasibility of day case laparoscopic cholecystectomy in unselected patients. Anaesthesia 1996; 51:965–8Tuckey, JP Morris, GN Peden, CJ Tate, JJ
Bisgaard T, Klarskov B, Rosenberg J, Kehlet H: Characteristics and prediction of early pain after laparoscopic cholecystectomy. Pain 2001; 90:261–9Bisgaard, T Klarskov, B Rosenberg, J Kehlet, H
Bisgaard T, Klarskov B, Rosenberg J, Kehlet H: Factors determining convalescence after uncomplicated laparoscopic cholecystectomy. Arch Surg 2001; 136:917–21Bisgaard, T Klarskov, B Rosenberg, J Kehlet, H
Bisgaard T, Rosenberg J, Kehlet H: From acute to chronic pain after laparoscopic cholecystectomy: A prospective follow-up analysis. Scand J Gastroenterol 2005; 40:1358–64Bisgaard, T Rosenberg, J Kehlet, H
Gray A, Kehlet H, Bonnet F, Rawal N: Predicting postoperative analgesia outcomes: NNT league tables or procedure-specific evidence? Br J Anaesth 2005; 94:710–4Gray, A Kehlet, H Bonnet, F Rawal, N
Kehlet H: Procedure-specific postoperative pain management. Anesthesiol Clin North Am 2005; 23:203–10Kehlet, H
Rosenquist RW, Rosenberg J: Postoperative pain guidelines. Reg Anesth Pain Med 2003; 28:279–88Rosenquist, RW Rosenberg, J
Kehlet H: Postoperative opioid sparing to hasten recovery: What are the issues? Anesthesiology 2005; 102:1083–5Kehlet, H
Marret E, Kurdi O, Zufferey P, Bonnet F: Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: Meta-analysis of randomized controlled trials. Anesthesiology 2005; 102:1249–60Marret, E Kurdi, O Zufferey, P Bonnet, F
Wills VL, Hunt DR: Pain after laparoscopic cholecystectomy. Br J Surg 2000; 87:273–84Wills, VL Hunt, DR
Bisgaard T, Støckel M, Klarskov B, Kehlet H, Rosenberg J: Prospective analysis of convalescence and early pain after uncomplicated laparoscopic fundoplication. Br J Surg 2004; 91:151–8Bisgaard, T Støckel, M Klarskov, B Kehlet, H Rosenberg, J
Møiniche S, Kehlet H, Dahl JB: A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: The role of timing of analgesia. Anesthesiology 2002; 96:725–41Møiniche, S Kehlet, H Dahl, JB
Slim K, Bousquet J, Kwiatkowski F, Pezet D, Chipponi J: Analysis of randomized controlled trials in laparoscopic surgery. Br J Surg 1997; 84:610–4Slim, K Bousquet, J Kwiatkowski, F Pezet, D Chipponi, J
Bisgaard T, Klarskov B, Kristiansen VB, Callesen T, Schulze S, Kehlet H, Rosenberg J: Multi-regional local anesthetic infiltration during laparoscopic cholecystectomy in patients receiving prophylactic multi-modal analgesia: A randomized, double-blinded, placebo-controlled study. Anesth Analg 1999; 89:1017–24Bisgaard, T Klarskov, B Kristiansen, VB Callesen, T Schulze, S Kehlet, H Rosenberg, J
Eccles M, Clarke J, Livingstone M, Freemantle N, Mason J: North of England evidence based guidelines development project: Guideline for the primary care management of dementia. BMJ 1998; 317:802–8Eccles, M Clarke, J Livingstone, M Freemantle, N Mason, J
Carr DB, Goudas LC: Acute pain. Lancet 1999; 353:2051–8Carr, DB Goudas, LC
White PF: The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg 2002; 94:577–85White, PF
Graham GG, Scott KF: Mechanism of action of paracetamol. Am J Ther 2005; 12:46–55Graham, GG Scott, KF
Boccara G, Chaumeron A, Pouzeratte Y, Mann C: The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen. Br J Anaesth 2005; 94:347–51Boccara, G Chaumeron, A Pouzeratte, Y Mann, C
Horattas MC, Evans S, Sloan-Stakleff KD, Lee C, Snoke JW: Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic cholecystectomy? Am J Surg 2004; 188:271–6Horattas, MC Evans, S Sloan-Stakleff, KD Lee, C Snoke, JW
Gan TJ, Joshi GP, Viscusi E, Cheung RY, Dodge W, Fort JG, Chen C: Preoperative parenteral parecoxib and follow-up oral valdecoxib reduce length of stay and improve quality of patient recovery after laparoscopic cholecystectomy surgery. Anesth Analg 2004; 98:1665–73Gan, TJ Joshi, GP Viscusi, E Cheung, RY Dodge, W Fort, JG Chen, C
Lane GE, Lathrop JC, Boysen DA, Lane RC: Effect of intramuscular intraoperative pain medication on narcotic usage after laparoscopic cholecystectomy. Am Surg 1996; 62:907–10Lane, GE Lathrop, JC Boysen, DA Lane, RC
Colbert ST, O'Hanlon DM, McDonnell C, Given FH, Keane PW: Analgesia in day case breast biopsy: The value of pre-emptive tenoxicam. Can J Anaesth 1998; 45:217–22Colbert, ST O'Hanlon, DM McDonnell, C Given, FH Keane, PW
O'Hanlon DM, Thambipillai T, Colbert ST, Keane PW, Given HF: Timing of pre-emptive tenoxicam is important for postoperative analgesia. Can J Anaesth 2001; 48:162–6O'Hanlon, DM Thambipillai, T Colbert, ST Keane, PW Given, HF
Gilron I, Milne B, Hong M: Cyclooxygenase-2 inhibitors in postoperative pain management: Current evidence and future directions. Anesthesiology 2003; 99:1198–208Gilron, I Milne, B Hong, M
Kehlet H, Dahl JB: The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 1993; 77:1048–56Kehlet, H Dahl, JB
Joshi GP, Viscusi ER, Gan TJ, Minkowitz H, Cippolle M, Schuller R, Cheung R, Fort J: Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor. Anesth Analg 2004; 98:336–42Joshi, GP Viscusi, ER Gan, TJ Minkowitz, H Cippolle, M Schuller, R Cheung, R Fort, J
Liu J, Ding Y, White PF, Feinstein R, Shear JM: Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy. Anesth Analg 1993; 76:1061–6Liu, J Ding, Y White, PF Feinstein, R Shear, JM
Wilson YG, Rhodes M, Ahmed R, Daugherty M, Cawthorn SJ, Armstrong CP: Intramuscular diclofenac sodium for postoperative analgesia after laparoscopic cholecystectomy: A randomised, controlled trial. Surg Laparosc Endosc 1994; 4:340–4Wilson, YG Rhodes, M Ahmed, R Daugherty, M Cawthorn, SJ Armstrong, CP
Fredman B, Olsfanger D, Jedeikin R: A comparative study of ketorolac and diclofenac on post-laparoscopic cholecystectomy pain. J Am Coll Surg 1995; 12:501–4Fredman, B Olsfanger, D Jedeikin, R
Forse A, El-Beheiry H, Butler PO, Pace RF: Indomethacin and ketorolac given preoperatively are equally effective in reducing early postoperative pain after laparoscopic cholecystectomy. Can J Surg 1996; 39:26–30Forse, A El-Beheiry, H Butler, PO Pace, RF
Munro FJ, Young SJ, Broome IJ, Robb HM, Wardall GJ: Intravenous tenoxicam for analgesia following laparoscopic cholecystectomy. Anaesth Intensive Care 1998; 26:56–60Munro, FJ Young, SJ Broome, IJ Robb, HM Wardall, GJ
Romsing J, Møiniche S, Dahl JB: Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia. Br J Anaesth 2002; 88:215–26Romsing, J Møiniche, S Dahl, JB
Hyllested M, Jones S, Pedersen JL, Kehlet H: Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: A qualitative review. Br J Anaesth 2002; 88:199–214Hyllested, M Jones, S Pedersen, JL Kehlet, H
Remy C, Marret E, Bonnet F: Effects of acetaminophen on morphine side-effects and consumption after major surgery: Meta-analysis of randomized controlled trials. Br J Anaesth 2005; 94:505–13Remy, C Marret, E Bonnet, F
Fenton C, Keating GM, Wagstaff AJ: Valdecoxib: A review of its use in the management of osteoarthritis, rheumatoid arthritis, dysmenorrhoea and acute pain. Drugs 2004; 64:1231–61Fenton, C Keating, GM Wagstaff, AJ
Michaloliakou C, Chung F, Sharma S: Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy. Anesth Analg 1996; 82:44–51Michaloliakou, C Chung, F Sharma, S
Barnes PJ, Belvisi MG, Rogers DF: Modulation of neurogenic inflammation: Novel approaches to inflammatory disease. Trends Pharmacol Sci 1990; 11:185–9Barnes, PJ Belvisi, MG Rogers, DF
Lee IO, Kim SH, Kong MH, Lee MK, Kim NS, Choi YS, Lim SH: Pain after laparoscopic cholecystectomy: The effect and timing of incisional and intraperitoneal bupivacaine. Can J Anaesth 2001; 48:545–50Lee, IO Kim, SH Kong, MH Lee, MK Kim, NS Choi, YS Lim, SH
Papaziogas B, Argiriadou H, Papagiannopoulou P, Pavlidis T, Georgiou M, Sfyra E, Papaziogas T: Preincisional intravenous low-dose ketamine and local infiltration with ropivacaine reduces postoperative pain after laparoscopic cholecystectomy. Surg Endosc 2001; 15:1030–3Papaziogas, B Argiriadou, H Papagiannopoulou, P Pavlidis, T Georgiou, M Sfyra, E Papaziogas, T
Sarac AM, Aktan AO, Baykan N, Yegen C, Yalin R: The effect and timing of local anesthesia in laparoscopic cholecystectomy. Surg Laparosc Endosc 1996; 6:362–6Sarac, AM Aktan, AO Baykan, N Yegen, C Yalin, R
Ure BM, Troidl H, Spangenberger W, Neugebauer E, Lefering R, Ullmann K, Bende J: Preincisional local anesthesia with bupivacaine and pain after laparoscopic cholecystectomy: A double-blind randomized clinical trial. Surg Endosc 1993; 7:482–8Ure, BM Troidl, H Spangenberger, W Neugebauer, E Lefering, R Ullmann, K Bende, J
Uzunkoy A, Coskun A, Akinci OF: The value of pre-emptive analgesia in the treatment of postoperative pain after laparoscopic cholecystectomy. Eur Surg Res 2000; 33:39–41Uzunkoy, A Coskun, A Akinci, OF
Møiniche S, Jørgensen H, Wetterslev J, Dahl JB: Local anesthetic infiltration for postoperative pain relief after laparoscopy: A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block. Anesth Analg 2000; 90:899–912Møiniche, S Jørgensen, H Wetterslev, J Dahl, JB
Pasqualucci A, de Angelis V, Contardo R, Colo F, Terrosu G, Donini A, Pasetto A, Bresadola F: Preemptive analgesia: Intraperitoneal local anesthetic in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study. Anesthesiology 1996; 85:11–20Pasqualucci, A de Angelis, V Contardo, R Colo, F Terrosu, G Donini, A Pasetto, A Bresadola, F
Paulson J, Mellinger J, Baguley W: The use of intraperitoneal bupivacaine to decrease the length of stay in elective laparoscopic cholecystectomy patients. Am Surg 2003; 69:275–8Paulson, J Mellinger, J Baguley, W
Johnson RC, Hedges AR, Morris R, Stamatakis JD: Ideal pain relief following laparoscopic cholecystectomy. Int J Clin Pract 1999; 53:16–8Johnson, RC Hedges, AR Morris, R Stamatakis, JD
McQuay H: Opioids in pain management. Lancet 1999; 353:2229–32McQuay, H
Stein C: The control of pain in peripheral tissue by opioids. N Engl J Med 1995; 332:1685–90Stein, C
Naguib M, Attia M, Samarkandi AH: Wound closure tramadol administration has a short-lived analgesic effect. Can J Anaesth 2000; 47:815–8Naguib, M Attia, M Samarkandi, AH
Zajaczkowska R, Wnek W, Wordliczek J, Dobrogowski J: Peripheral opioid analgesia in laparoscopic cholecystectomy. Reg Anesth Pain Med 2004; 29:424–9Zajaczkowska, R Wnek, W Wordliczek, J Dobrogowski, J
Practice guidelines for acute pain management in the perioperative setting: An updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2004; 100:1573–81Practice guidelines for acute pain management in the perioperative setting,
Kehlet H, Rung GW, Callesen T: Postoperative opioid analgesia: Time for a reconsideration? J Clin Anesth 1996; 8:441–5Kehlet, H Rung, GW Callesen, T
Sapolsky RM, Romero LM, Munck AU: How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000; 21:55–89Sapolsky, RM Romero, LM Munck, AU
Callery MP: Preoperative steroids for laparoscopic surgery. Ann Surg 2003; 238:661–2Callery, MP
Holte K, Kehlet H: Perioperative single dose glucocorticoid administration: Pathophysiological effects and clinical implications. J Am Coll Surg 2002; 195:694–712Holte, K Kehlet, H
Bisgaard T, Klarskov B, Kehlet H, Rosenberg J: Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: A randomized double-blind placebo-controlled trial. Ann Surg 2003; 238:651–60Bisgaard, T Klarskov, B Kehlet, H Rosenberg, J
Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, Ho CM: Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth 1999; 83:772–5Wang, JJ Ho, ST Liu, YH Lee, SC Liu, YC Liao, YC Ho, CM
Wang JJ, Ho ST, Uen YH, Lin MT, Chen KT, Huang JC, Tzeng JI: Small-dose dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy: A comparison of tropisetron with saline. Anesth Analg 2002; 95:229–32Wang, JJ Ho, ST Uen, YH Lin, MT Chen, KT Huang, JC Tzeng, JI
Elhakim M, Nafie M, Mahmoud K, Atef A: Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy. Can J Anaesth 2002; 49:922–6Elhakim, M Nafie, M Mahmoud, K Atef, A
Brandstatter G, Schinzel S, Wurzer H: Influence of spasmolytic analgesics on motility of sphincter of Oddi. Dig Dis Sci 1996; 41:1814–8Brandstatter, G Schinzel, S Wurzer, H
Sauerland S, Nagelschmidt M, Mallmann P, Neugebauer EA: Risks and benefits of preoperative high dose methylprednisolone in surgical patients: A systematic review. Drug Safety 2000; 23:449–61Sauerland, S Nagelschmidt, M Mallmann, P Neugebauer, EA
Henzi I, Walder B, Tramer MR: Dexamethasone for the prevention of postoperative nausea and vomiting: A quantitative systematic review. Anesth Analg 2000; 90:186–94Henzi, I Walder, B Tramer, MR
Kehlet H: Modification of responses to surgery by neural blockade: Clinical implications, Neural Blockade in Clinical Anesthesia and Management of Pain. Edited by Cousins, MJ, Bridenbaugh PO. Philadelphia, Lippincott–Raven, 1998, pp 129–75Kehlet, H Cousins, MJ, Bridenbaugh PO Philadelphia Lippincott–Raven
Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, Sage D, Futter M, Saville G, Clark T, MacMahon S: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from overview of randomised trials. BMJ 2000; 321:1493–7Rodgers, A Walker, N Schug, S McKee, A Kehlet, H van Zundert, A Sage, D Futter, M Saville, G Clark, T MacMahon, S
Luchetti M, Palomba R, Sica G, Massa G, Tufano R: Effectiveness and safety of combined epidural and general anesthesia for laparoscopic cholecystectomy. Reg Anesth 1996; 21:465–9Luchetti, M Palomba, R Sica, G Massa, G Tufano, R
Fujii Y, Toyooka H, Tanaka H: Efficacy of thoracic epidural analgesia following laparoscopic cholecystectomy. Eur J Anaesthesiol 1998; 15:342–4Fujii, Y Toyooka, H Tanaka, H
Motamed C, Bouaziz H, Franco D, Benhamou D: Analgesic effect of low-dose intrathecal morphine and bupivacaine in laparoscopic cholecystectomy. Anaesthesia 2000; 55:118–24Motamed, C Bouaziz, H Franco, D Benhamou, D
Taylor CP, Gee NS, Su TZ, Kocsis JD, Welty DF, Brown JP, Dooley L, Boden P, Singh L: A summary of mechanistic hypothesis of gabapentin pharmacology. Epilepsy Res 1998; 29:233–49Taylor, CP Gee, NS Su, TZ Kocsis, JD Welty, DF Brown, JP Dooley, L Boden, P Singh, L
Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q: The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Anesth Analg 2002; 95:985–91Fassoulaki, A Patris, K Sarantopoulos, C Hogan, Q
Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger H, Dahl JB: A randomized study of the effects of single-dose gabapentin versus  placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 2004; 97:560–4Dirks, J Fredensborg, BB Christensen, D Fomsgaard, JS Flyger, H Dahl, JB
Turan A, Karamanlioglu B, Memis D, Hamamcioglu MK, Tukenmez B, Pamukcu Z, Kurt I: Analgesic effects of gabapentin after spinal surgery. Anesthesiology 2004; 100:935–8Turan, A Karamanlioglu, B Memis, D Hamamcioglu, MK Tukenmez, B Pamukcu, Z Kurt, I
Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Møiniche S, Romsing J, Dahl JB: Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: A randomized, double-blind trial. Acta Anaesthesiol Scand 2004; 48:322–7Dierking, G Duedahl, TH Rasmussen, ML Fomsgaard, JS Møiniche, S Romsing, J Dahl, JB
Pandey CK, Priye S, Singh S, Singh U, Singh RB, Singh PK: Preemptive use of gabapentin significantly decreases postoperative pain and rescue analgesic requirements in laparoscopic cholecystectomy. Can J Anaesth 2004; 51:358–63Pandey, CK Priye, S Singh, S Singh, U Singh, RB Singh, PK
De Kock M, Crochet B, Morimont C, Scholtes JL: Intravenous or epidural clonidine for intra- and postoperative analgesia. Anesthesiology 1993; 79:525–31De Kock, M Crochet, B Morimont, C Scholtes, JL
Sung CS, Lin SH, Chan KH, Chang WK, Chow LH, Lee TY: Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Sin 2000; 38:23–9Sung, CS Lin, SH Chan, KH Chang, WK Chow, LH Lee, TY
Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L: Clonidine provides opioid-sparing effect, stable hemodynamics, and renal integrity during laparoscopic cholecystectomy. Surg Endosc 2001; 15:1331–5Laisalmi, M Koivusalo, AM Valta, P Tikkanen, I Lindgren, L
Woolf CJ, Mannion RJ: Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet 1999; 353:1959–64Woolf, CJ Mannion, RJ
McCartney CJ, Sinha A, Katz J: A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg 2004; 98:1385–400McCartney, CJ Sinha, A Katz, J
Elia N, Tramer MR: Ketamine and postoperative pain: A quantitative systematic review of randomised trials. Pain 2005; 113:61–70Elia, N Tramer, MR
Mathisen LC, Aasbo V, Raeder J: Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1999; 43:220–4Mathisen, LC Aasbo, V Raeder, J
Wu CT, Yu JC, Yeh CC, Liu ST, Li CY, Ho ST, Wong CS: Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy. Anesth Analg 1999; 88:1331–4Wu, CT Yu, JC Yeh, CC Liu, ST Li, CY Ho, ST Wong, CS
Yeh CC, Wu CT, Lee MS, Yu JC, Yang CP, Lu CH, Wong CS: Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2004; 48:1049–53Yeh, CC Wu, CT Lee, MS Yu, JC Yang, CP Lu, CH Wong, CS
Wu CT, Borel CO, Lee MS, Yu JC, Liou HS, Yi HD, Yang CP: The interaction effect of perioperative cotreatment with dextromethorphan and intravenous lidocaine on pain relief and recovery of bowel function after laparoscopic cholecystectomy. Anesth Analg 2005; 100:448–53Wu, CT Borel, CO Lee, MS Yu, JC Liou, HS Yi, HD Yang, CP
Launo C, Bassi C, Spagnolo L, Badano S, Ricci C, Lizzi A, Molinino M: Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Minerva Anestesiol 2004; 70:727–34Launo, C Bassi, C Spagnolo, L Badano, S Ricci, C Lizzi, A Molinino, M
Pavlin DJ, Horvath KD, Pavlin EG, Sima K: Preincisional treatment to prevent pain after ambulatory hernia surgery. Anesth Analg 2003; 97:1627–32Pavlin, DJ Horvath, KD Pavlin, EG Sima, K
Barratt SM, Smith RC, Kee AJ, Mather LE, Cousins MJ: Multimodal analgesia and intravenous nutrition preserves total body protein following major upper gastrointestinal surgery. Reg Anesth Pain Med 2002; 27:15–22Barratt, SM Smith, RC Kee, AJ Mather, LE Cousins, MJ
Schumann R, Shikora S, Weiss JM, Wurm H, Strassels S, Carr DB: A comparison of multimodal perioperative analgesia to epidural pain management after gastric bypass surgery. Anesth Analg 2003; 96:469–74Schumann, R Shikora, S Weiss, JM Wurm, H Strassels, S Carr, DB
Rosaeg OP, Lui AC, Cicutti NJ, Bragg PR, Crossan ML, Krepski B: Peri-operative multimodal pain therapy for caesarean section: Analgesia and fitness for discharge. Can J Anaesth 1997; 44:803–9Rosaeg, OP Lui, AC Cicutti, NJ Bragg, PR Crossan, ML Krepski, B
Paech MJ, Pavy TJ, Orlikowski CE, Yeo ST, Banks SL, Evans SF, Henderson J: Postcesarean analgesia with spinal morphine, clonidine, or their combination. Anesth Analg 2004; 98:1460–6Paech, MJ Pavy, TJ Orlikowski, CE Yeo, ST Banks, SL Evans, SF Henderson, J
Gilron I, Orr E, Tu D, O'Neill JP, Zamora JE, Bell AC: A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy. Pain 2005; 113:191–200Gilron, I Orr, E Tu, D O'Neill, JP Zamora, JE Bell, AC
Bisgaard T, Klarskov B, Trap R, Kehlet H, Rosenberg J: Microlaparoscopic versus  conventional laparoscopic cholecystectomy. Surg Endosc 2002; 16:458–64Bisgaard, T Klarskov, B Trap, R Kehlet, H Rosenberg, J
Grundmann U, Silomon M, Bach F, Becker S, Bauer M, Larsen B, Kleinschmidt S: Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2001; 45:320–6Grundmann, U Silomon, M Bach, F Becker, S Bauer, M Larsen, B Kleinschmidt, S
Raeder JC, Mjaland O, Aasbo V, Grogaard B, Buanes T: Desflurane versus  propofol maintenance for outpatient laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1998; 42:106–10Raeder, JC Mjaland, O Aasbo, V Grogaard, B Buanes, T
Quaynor H, Raeder JC: Incidence and severity of postoperative nausea and vomiting are similar after metoclopramide 20 mg and ondansetron 8 mg given by the end of laparoscopic cholecystectomies. Acta Anaesthesiol Scand 2002; 46:109–13Quaynor, H Raeder, JC
Bisgaard T, Kristiansen VB, Hjortsø NC, Jacobsen LS, Rosenberg J, Kehlet H: Randomised clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy. Br J Surg 2004; 91:151–8Bisgaard, T Kristiansen, VB Hjortsø, NC Jacobsen, LS Rosenberg, J Kehlet, H
Keulemans Y, Eshuis J, de Haes H, de Wit L, Gouma DJ: Laparoscopic cholecystectomy: Day-care versus  clinical observation. Ann Surg 1998; 228:734–40Keulemans, Y Eshuis, J de Haes, H de Wit, L Gouma, DJ
Sarli L, Costi R, Sansebastiano G, Trivelli M, Roncoroni L: Prospective randomized trial of low-pressure pneumoperitoneum for reduction of shoulder-tip pain following laparoscopy. Br J Surg 2000; 87:1161–5Sarli, L Costi, R Sansebastiano, G Trivelli, M Roncoroni, L
Barczynski M, Herman RM: A prospective randomized trial on comparison of low-pressure (LP) and standard-pressure (SP) pneumoperitoneum for laparoscopic cholecystectomy. Surg Endosc 2003; 17:533–8Barczynski, M Herman, RM
Neudecker J, Sauerland S, Neugebauer E, Bergamaschi R, Bonjer HJ, Cuschieri A, Fuchs KH, Jacobi C, Jansen FW, Koivusalo AM, Lacy A, McMahon MJ, Millat B, Schwenk W: The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surg Endosc 2002; 16:1121–43Neudecker, J Sauerland, S Neugebauer, E Bergamaschi, R Bonjer, HJ Cuschieri, A Fuchs, KH Jacobi, C Jansen, FW Koivusalo, AM Lacy, A McMahon, MJ Millat, B Schwenk, W
Bisgaard T, Klarskov B, Trap R, Kehlet H, Rosenberg J: Pain after microlaparoscopic cholecystectomy: A randomized double-blind controlled study. Surg Endosc 2000; 14:340–4Bisgaard, T Klarskov, B Trap, R Kehlet, H Rosenberg, J
Dyhre H, Wallin R, Bjorkman S, Engstrom S, Renck H: Inclusion of lignocaine base into a polar lipid formulation: In vitro  release, duration of peripheral nerve block and arterial blood concentrations in the rat. Acta Anaesthesiol Scand 2001; 45:583–9Dyhre, H Wallin, R Bjorkman, S Engstrom, S Renck, H
Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C: The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostal blockade (t9 to t11) in healthy volunteers. Anesth Analg 2003; 96:576–82Kopacz, DJ Lacouture, PG Wu, D Nandy, P Swanton, R Landau, C
Alexander DJ, Ngoi SS, Lee L, So J, Mak K, Chan S, Goh PM: Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy. Br J Surg 1996; 83:1223–5Alexander, DJ Ngoi, SS Lee, L So, J Mak, K Chan, S Goh, PM
Dath D, Park AE: Randomized, controlled trial of bupivacaine injection to decrease pain after laparoscopic cholecystectomy. Can J Surg 1999; 42:284–8Dath, D Park, AE
Hasaniya NW, Zayed FF, Faiz H, Severino R: Preinsertion local anesthesia at the trocar site improves perioperative pain and decreases costs of laparoscopic cholecystectomy. Surg Endosc 2001; 15:962–4Hasaniya, NW Zayed, FF Faiz, H Severino, R
Lepner U, Goroshina J, Samarutel J: Postoperative pain relief after laparoscopic cholecystectomy: A randomised prospective double-blind clinical trial. Scand J Surg 2003; 92:121–4Lepner, U Goroshina, J Samarutel, J
Chundrigar T, Hedges AR, Morris R, Stamatakis JD: Intraperitoneal bupivacaine for effective pain relief after laparoscopic cholecystectomy. Ann R Coll Surg Engl 1993; 75:437–9Chundrigar, T Hedges, AR Morris, R Stamatakis, JD
Pasqualucci A, Contardo R, Da BU, Colo F, Terrosu G, Donini A, Sorrentino M, Pasetto A, Bresadola F: The effects of intraperitoneal local anesthetic on analgesic requirements and endocrine response after laparoscopic cholecystectomy: A randomized double-blind controlled study. J Laparoendosc Surg 1994; 4:405–12Pasqualucci, A Contardo, R Da, BU Colo, F Terrosu, G Donini, A Sorrentino, M Pasetto, A Bresadola, F
Berven S, Horvarh K, Brooks DC: The effect of topical intraperitoneal bupivacaine on post-operative pain following laparoscopic cholecystectomy. Minimally Invasive Therapy 1995; 4:67–71Berven, S Horvarh, K Brooks, DC
Szem JW, Hydo L, Barie PS: A double-blinded evaluation of intraperitoneal bupivacaine versus  saline for the reduction of postoperative pain and nausea after laparoscopic cholecystectomy. Surg Endosc 1996; 10:44–8Szem, JW Hydo, L Barie, PS
Mraovic B, Jurisic T, Majeric VK, Sustic A: Intraperitoneal bupivacaine for analgesia after laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1997; 41:193–6Mraovic, B Jurisic, T Majeric, VK Sustic, A
Weber A, Munoz J, Garteiz D, Cueto J: Use of subdiaphragmatic bupivacaine instillation to control postoperative pain after laparoscopic surgery. Surg Laparosc Endosc 1997; 7:6–8Weber, A Munoz, J Garteiz, D Cueto, J
Cunniffe MG, McAnena OJ, Dar MA, Calleary J, Flynn N: A prospective randomized trial of intraoperative bupivacaine irrigation for management of shoulder-tip pain following laparoscopy. Am J Surg 1998; 176:258–61Cunniffe, MG McAnena, OJ Dar, MA Calleary, J Flynn, N
Gharaibeh KI, Al-Jaberi TM: Bupivacaine instillation into gallbladder bed after laparoscopic cholecystectomy: Does it decrease shoulder pain? J Laparoendosc Adv Surg Tech 2000; 10:137–41Gharaibeh, KI Al-Jaberi, TM
Elhakim M, Elkott M, Ali NM, Tahoun HM: Intraperitoneal lidocaine for postoperative pain after laparoscopy. Acta Anaesthesiol Scand 2000; 44:280–4Elhakim, M Elkott, M Ali, NM Tahoun, HM
Gupta A, Thorn SE, Axelsson K, Larsson LG, Agren G, Holmstrom B, Rawal N: Postoperative pain relief using intermittent injections of 0.5% ropivacaine through a catheter after laparoscopic cholecystectomy. Anesth Analg 2002; 95:450–6Gupta, A Thorn, SE Axelsson, K Larsson, LG Agren, G Holmstrom, B Rawal, N
Maestroni U, Sortini D, Devito C, Pour MKB, Anania G, Pavanelli L, Pasqualucci A, Donini A: A new method of preemptive analgesia in laparoscopic cholecystectomy. Surg Endosc 2002; 16:1336–40Maestroni, U Sortini, D Devito, C Pour, MKB Anania, G Pavanelli, L Pasqualucci, A Donini, A
Labaille T, Mazoit JX, Paqueron X, Franco D, Benhamou D: The clinical efficacy and pharmacokinetics of intraperitoneal ropivacaine for laparoscopic cholecystectomy. Anesth Analg 2002; 94:100–5Labaille, T Mazoit, JX Paqueron, X Franco, D Benhamou, D
Ng A, Swami A, Smith G, Robertson G, Lloyd DM: Is intraperitoneal levobupivacaine with epinephrine useful for analgesia following laparoscopic cholecystectomy? A randomized controlled trial. Eur J Anaesthesiol 2004; 21:653–7Ng, A Swami, A Smith, G Robertson, G Lloyd, DM
Rademaker BM, Kalkman CJ, Odoom JA, de Wit L, Ringers J: Intraperitoneal local anaesthetics after laparoscopic cholecystectomy: Effects on postoperative pain, metabolic responses, and lung function. Br J Anaesth 1994; 72:263–6Rademaker, BM Kalkman, CJ Odoom, JA de Wit, L Ringers, J
Joris J, Thiry E, Paris P, Weerts J, Lamy M: Pain after laparoscopic cholecystectomy: Characteristics and effect of intraperitoneal bupivacaine. Anesth Analg 1995; 81:379–84Joris, J Thiry, E Paris, P Weerts, J Lamy, M
Scheinin B, Kellokumpu I, Lindgren L, Haglund C, Rosenberg PH: Effect of intraperitoneal bupivacaine on pain after laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1995; 39:195–8Scheinin, B Kellokumpu, I Lindgren, L Haglund, C Rosenberg, PH
Raetzell M, Maier C, Schroder D, Wulf H: Intraperitoneal application of bupivacaine during laparoscopic cholecystectomy: Risk or benefit? Anesth Analg 1995; 81:967–72Raetzell, M Maier, C Schroder, D Wulf, H
Steinberg HS, Weninger E, Jokisch D, Hofstetter B, Misera A, Lange V, Stein C: Intraperitoneal versus  interpleural morphine or bupivacaine for pain after laparoscopic cholecystectomy. Anesthesiology 1995; 82:634–40Steinberg, HS Weninger, E Jokisch, D Hofstetter, B Misera, A Lange, V Stein, C
Busley R, Blobner M, Jelen-Esselborn S, Feussner H, Kochs E: Intraperitoneal local anaesthetics via  subphrenic catheter following laparoscopic cholecystectomy: Pain relief and pulmonary function. Min Invas Ther and Allied Technol 1999; 8:219–25Busley, R Blobner, M Jelen-Esselborn, S Feussner, H Kochs, E
Elfberg BA, Sjovall-Mjoberg S: Intraperitoneal bupivacaine does not effectively reduce pain after laparoscopic cholecystectomy: A randomized, placebo-controlled and double-blind study. Surg Laparosc Endosc Percutan Tech 2000; 10:357–9Elfberg, BA Sjovall-Mjoberg, S
Zmora O, Stolik-Dollberg O, Bar-Zakai B, Rosin D, Kuriansky J, Shabtai M, Perel A, Ayalon A: Intraperitoneal bupivacaine does not attenuate pain following laparoscopic cholecystectomy. JSLS 2000; 4:301–4Zmora, O Stolik-Dollberg, O Bar-Zakai, B Rosin, D Kuriansky, J Shabtai, M Perel, A Ayalon, A
Jiranantarat V, Rushatamukayanunt W, Lert-akyamanee N, Sirijearanai R, Piromrat I, Suwannanonda P, Muangkasem J: Analgesic effect of intraperitoneal instillation of bupivacaine for postoperative laparoscopic cholecystectomy. J Med Assoc Thai 2002; 85:S897–903Jiranantarat, V Rushatamukayanunt, W Lert-akyamanee, N Sirijearanai, R Piromrat, I Suwannanonda, P Muangkasem, J
Owen H, Plummer JL, Ilsley AH, Tordoff K, Toouli J: Pain control in the week following laparoscopic surgery: A comparison of sustained-release ibuprofen and paracetamol. Min Invas Ther and Allied Technol 1997; 6:235–40Owen, H Plummer, JL Ilsley, AH Tordoff, K Toouli, J
O'Hanlon DM, Colbert S, Ragheb J, McEntee GP, Chambers F, Moriarty DC: Intraperitoneal pethidine versus  intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: Randomized trial. World J Surg 2002; 26:1432–6O'Hanlon, DM Colbert, S Ragheb, J McEntee, GP Chambers, F Moriarty, DC
Munoz HR, Guerrero ME, Brandes V, Cortinez LI: Effect of timing of morphine administration during remifentanil-based anaesthesia on early recovery from anaesthesia and postoperative pain. Br J Anaesth 2002; 88:814–8Munoz, HR Guerrero, ME Brandes, V Cortinez, LI
Naguib M, Seraj M, Attia M, Samarkandi AH, Seet M, Jaroudi R: Perioperative antinociceptive effects of tramadol: A prospective, randomized, double-blind comparison with morphine. Can J Anaesth 1998; 45:1168–75Naguib, M Seraj, M Attia, M Samarkandi, AH Seet, M Jaroudi, R
Chung F, Tong D, Miceli PC, Reiz J, Harsanyi Z, Darke AC, Payne LW: Controlled-release codeine is equivalent to acetaminophen plus codeine for post-cholecystectomy analgesia. Can J Anaesth 2004; 51:216–21Chung, F Tong, D Miceli, PC Reiz, J Harsanyi, Z Darke, AC Payne, LW
Table 1. Randomized Trials on the Analgesic Effects of Local Anesthetics after Laparoscopic Cholecystectomy 
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Table 1. Randomized Trials on the Analgesic Effects of Local Anesthetics after Laparoscopic Cholecystectomy 
Table 1. (Continued) 
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Table 1. (Continued) 
Table 2. Randomized Trials on Various Analgesic Techniques after Laparoscopic Cholecystectomy 
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Table 2. Randomized Trials on Various Analgesic Techniques after Laparoscopic Cholecystectomy 
Table 3. Evidence-based Recommendations for Analgesic Treatment after Laparoscopic Cholecystectomy 
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Table 3. Evidence-based Recommendations for Analgesic Treatment after Laparoscopic Cholecystectomy