Steen Møiniche

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

THE concept of preemptive analgesia to reduce the magnitude and duration of postoperative pain was paved in 1983 by Woolf, who showed evidence for a central component of postinjury pain hypersensitivity in experimental studies. Subsequently, an overwhelming amount of experimental data demonstrated that various antinociceptive techniques applied before injury were more effective in reducing the postinjury central sensitization phenomena as compared with administration after injury. Finally, these promising experimental findings were taken into clinical testing of the hypothesis. Although early reviews of clinical findings were mostly negative, there is still a widespread belief of the efficacy of preemptive analgesia among clinicians. The definition of preemptive analgesia has varied, thereby causing confusion and misunderstanding of the concept. Because the original observations in experimental studies suggested that timing of analgesic treatment was important to obtain efficient reduction of postinjury pain hypersensitivity phenomena, we performed an updated review of studies to compare the role of timing of analgesia i.e., preoperative versus intraoperative or postoperative initiation of analgesia. In this review we are not considering studies designed to compare preemptive analgesia versus no treatment. We have only included double-blind, randomized, controlled trials of identical or very similar analgesic regimens, where the only difference between study groups was timing of analgesia.

Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review.

The use of nonsteroidal antiinflammatory drugs (NSAIDs) for analgesia after tonsillectomy is controversial because NSAIDS, through platelet inhibition, may increase the risk of perioperative bleeding. We systematically searched for randomized, controlled trials that reported on the incidence of perioperative bleeding attributable to the use of NSAIDs in patients undergoing tonsillectomy. As secondary outcome measures, we analyzed the quality of pain relief and the incidence of postoperative nausea and vomiting. Twenty-five studies with data from 970 patients receiving a NSAID and 883 receiving a non-NSAID treatment or a placebo were analyzed. Data were combined using a fixed-effect model. Of four bleeding end points (intraoperative blood loss, postoperative bleeding, hospital admission, and reoperation because of bleeding), only reoperation happened significantly more often with NSAIDs: Peto-odds ratio, 2.33 (95% confidence interval [CI], 1.12–4.83) and number-needed-to-treat, 60 (95% CI, 34–277). Compared with opioids, NSAIDs were equianalgesic, and the risk of emesis was significantly decreased (relative risk, 0.73; 95% CI, 0.63–0.85; numbers-needed-to-treat, 9; 95% CI, 5–19).

Intraoperative and Postoperative Analgesic Efficacy and Adverse Effects of Intrathecal Opioids in Patients Undergoing Cesarean Section with Spinal Anesthesia A Qualitative and Quantitative Systematic Review of Randomized Controlled Trials

SPINAL anesthesia is commonly used for cesarean section, and it has become a popular practice to add opioids to spinal solutions to enhance and prolong intraoperative and postoperative analgesia. Morphine and fentanyl are the opioids most often used for this purpose, but there is not a general consensus about the benefits of the various regimens, and the incidence of side effects with different opioids and doses is controversial. Recently, a number of systematic reviews have been published in the field of pain and perioperative medicine. The aim of a systematic review is to summarize available information from controlled clinical trials to produce evidence-based estimates of the true clinical effect of an intervention. The purpose of this systematic review was to investigate the effect of intrathecal opioids added to spinal anesthesia on intraoperative and postoperative pain and to evaluate adverse effects in patients scheduled for cesarean section, using evidence from all relevant randomized controlled and blinded trials.

A systematic review of intra-articular local anesthesia for postoperative pain relief after arthroscopic knee surgery

BACKGROUND AND OBJECTIVES In a systematic review, we have evaluated double-blind, randomized, controlled trials of intra-articular local anesthesia compared with placebo or no treatment in the control of postoperative pain after arthroscopic knee surgery. METHODS Outcome measures were pain scores, supplementary analgesics, and time to first analgesic request. Efficacy was estimated by significant difference (P < .05) as reported in the original reports and by calculation of the weighted mean difference of pain scores between treatment groups. RESULTS Twenty studies with data from 895 patients were considered appropriate for analysis. Twelve of these 20 studies showed improved pain relief after intra-articular local anesthesia in at least one of the considered pain parameters, whereas the eight other studies were without such improvements. In ten of the positive studies, pain scores were significantly lower in the treatment groups compared with the control groups with visual analog scale (VAS) score reductions of between 10 and 35 mm early (1-4 hours) postoperatively. Quantitative analysis with calculation of the weighted mean difference in VAS confirmed a statistically significant but minor clinically important effect on postoperative pain scores. In nine studies, the consumption of supplementary analgesics was reduced 10-50% during observation periods of up to 4 hours; however, in most cases, the analgesic requirements were small to moderate. Only in two of six studies, where time to first analgesic request was evaluated, a significant prolongation of pain relief was observed as lasting between 30 and 50 minutes. CONCLUSIONS There is a weak evidence for a reduction of postoperative pain after intra-articular local anesthesia in patients undergoing arthroscopic knee surgery, which although being sinall to moderate and of short duration, may be of clinical significance in day-case surgery.

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

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

Mechanisms of postoperative pain: Clinical indications for a contribution of central neuronal sensitization

Background The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions. Methods In a randomized, controlled, double-blind trial, we assessed mechanical hyperalgesia in skin bordering the surgical wound, and an area of experimentally heat-induced secondary hyperalgesia on the thigh, in 12 patients who underwent abdominal hysterectomy within 5 days prior to the investigation. Observations were made before and during a drug challenge with remifentanil, which has been demonstrated to reduce the area of heat-induced secondary hyperalgesia in volunteers. Results The area of skin with surgically-induced mechanical hyperalgesia, the area of heat-induced secondary hyperalgesia, and pain during cough, were significantly reduced during remifentanil infusion compared with placebo (P = 0.008, P = 0.006, and P = 0.002, respectively). The relative reduction (% of baseline) of the area of skin with surgically-induced hyperalgesia and heat-induced secondary hyperalgesia during infusion of remifentanil was significantly associated (R2 = 0.72, P = 0.001). Conclusions Although remifentanil is not a highly targeted “antihyperalgesic,” these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.

Quantitative sensory examination of epidural anaesthesia and analgesia in man: Effects of pre- and post-traumatic morphine on hyperalgesia

&NA; The objectives of the study were:(1) comparison of hypoalgesic effects of pre‐ and post‐traumatic epidural morphine (EM) on primary and secondary hyperalgesia, and(2) comparison of EM hypoalgesia in normal and injured skin. Burn injuries (25 × 50 mm rectangular thermode, 47°C, 7 min) were produced on the calves of healthy volunteers, at 2 different days at least 1 week apart. In randomized order, the subjects received 4 mg of EM administered via the L2–L3 intervertebral space on one day and no treatment on the other day. One calf was injured 30 min prior to and the other calf 2.5 h after administration of morphine. Hence, the calf injured prior to morphine administration was a model of postinjury treatment, and the calf injured after morphine administration, a model of pretraumatic treatment. The timing of injuries was identical on the morphine treatment and control days. The injuries induced decrease in heat pain detection and tolerance thresholds within the area of injury (area of primary hyperalgesia) as well as reduction of areas of allodynia for brush and pinprick surrounding the injury (area of secondary hyperalgesia). Both pre‐ and post‐traumatic administration of EM increased heat pain detection and tolerance thresholds, and decreased by approximately 50% the areas of secondary hyperalgesia 2.5 h postinjury. The effects of morphine were naloxone (NAL)‐reversible (0.1 mg/kg, i.V.). There was no significant difference between pre‐ and post‐traumatic administration of morphine on the effect of either primary or secondary hyperalgesia. EM increased the heat pain detection threshold more within the injury than at a corresponding non‐injured site. There was no significant difference in the effect of morphine on heat pain tolerance in injured and non‐injured skin. Following NAL, the areas of secondary hyperalgesia expanded beyond control size. It is suggested that the major effect of EM on secondary hyperalgesia is inhibition of C fibre‐mediated activity which maintains the altered response properties of central neurones responsible for secondary hyperalgesia. Possible mechanisms of action of NAL in enhancement of hyperalgesia are discussed.

Susceptibility to fraud in systematic reviews: lessons from the Reuben case.

Background:Dr. Scott Reuben allegedly fabricated data. The authors of the current article examined the impact of Reuben reports on conclusions of systematic reviews. Methods:The authors searched in ISI Web of Knowledge systematic reviews citing Reuben reports. Systematic reviews were grouped into one of three categories: I, only cited but did not include Reuben reports; II, retrieved and considered, but eventually excluded Reuben reports; III, included Reuben reports. For quantitative systematic reviews (i.e., meta-analyses), a relevant difference was defined as a significant result becoming nonsignificant (or vice versa) by excluding Reuben reports. For qualitative systematic reviews, each author decided independently whether noninclusion of Reuben reports would have changed conclusions. Results:Twenty-five systematic reviews (5 category I, 6 category II, 14 category III) cited 27 Reuben reports (published 1994–2007). Most tested analgesics in surgical patients. One of 6 quantitative category III reviews would have reached different conclusions without Reuben reports. In all 6 (30 subgroup analyses involving Reuben reports), exclusion of Reuben reports never made any difference when the number of patients from Reuben reports was less than 30% of all patients included in the analysis. Of 8 qualitative category III reviews, all authors agreed that one would certainly have reached different conclusions without Reuben reports. For another 4, the authors’ judgment was not unanimous. Conclusions:Carefully performed systematic reviews proved robust against the impact of Reuben reports. Quantitative systematic reviews were vulnerable if the fraudulent data were more than 30% of the total. Qualitative systematic reviews seemed at greater risk than quantitative.