Jørgen B. Dahl

The value of "multimodal" or "balanced analgesia" in postoperative pain treatment.

reatment of postoperative pain is provided for humanitarian reasons and to alleviate nocicepT tion-induced responses, such as the endocrine metabolic response to surgery, autonomic reflexes with adverse effects on organ function, reflexes leading to muscle spasm, and other undesirable results (1). During the last decade there has been a virtual explosion in our knowledge of basic pain physiology (2,3), but the implications for clinical practice have been less substantial. The explanation for the discrepancy between the fast progress in basic pain pathophysiology and the rather slow advances in providing optimal postoperative pain treatment may be several, but one important factor may be that more than 95% of the literature on postoperative pain treatment has considered unimodal treatment. We have emphasized previously that total or optimal pain relief allowing normal function can not be achieved by a single drug or method without major strain on equipment and surveillance systems or without significant side effects (4). Therefore, we have recommended combined analgesic regimens (balanced analgesia) or a multimodal approach to the treatment of postoperative pain (4). The rationale for this strategy is achievement of sufficient analgesia due to additive or synergistic effects between different analgesics, with concomitant reduction of side effects, due to resulting lower doses of analgesics and differences in side-effect profiles. We summarize here the existing knowledge concerning the efficacy of analgesic combination therapy from postoperative pain studies. The effects on postoperative outcome are not included, because of lack of sufficient studies. We also exclude obstetric and pediatric pain, which may represent special pain entities and solutions for treatment, although they obviously share many of the problems of general postoperative pain. Primary emphasis will be placed on moderate and severe pain and the use of and need for

Anaesthesia, surgery, and challenges in postoperative recovery

Surgical injury can be followed by pain, nausea, vomiting and ileus, stress-induced catabolism, impaired pulmonary function, increased cardiac demands, and risk of thromboembolism. These problems can lead to complications, need for treatment in hospital, postoperative fatigue, and delayed convalescence. Development of safe and short-acting anaesthetics, improved pain relief by early intervention with multimodal analgesia, and stress reduction by regional anaesthetic techniques, beta-blockade, or glucocorticoids have provided important possibilities for enhanced recovery. When these techniques are combined with a change in perioperative care a pronounced enhancement of recovery and decrease in hospital stay can be achieved, even in major operations. The anaesthetist has an important role in facilitating early postoperative recovery by provision of minimally-invasive anaesthesia and pain relief, and by collaborating with surgeons, surgical nurses, and physiotherapists to reduce risk and pain.

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.

A Randomized Study of the Effects of Single-dose Gabapentin versus Placebo on Postoperative Pain and Morphine Consumption after Mastectomy

BACKGROUND The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.

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.

Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery.

In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough. Evaluation of postoperative analgesic regimens should include assessment of pain during various activities as different analgesics may have differential effects on pain at rest and during mobilization.

Gabapentin Suppresses Cutaneous Hyperalgesia following Heat-Capsaicin Sensitization

Background The anticonvulsant gabapentin, proven effective for neuropathic pain in two large, placebo-controlled clinical trials, is widely used for treatment of chronic pain. Preclinical studies have demonstrated analgesic and antiallodynic effects in models involving neuronal sensitization and nerve injury, without affecting acute pain transmission. The aim of the present study was to link data from animal models and clinical trials for chronic pain by investigating the effect of gabapentin on acute nociception and experimentally induced cutaneous hyperalgesia in healthy volunteers. Methods The human experimental hyperalgesia model, the heat-capsaicin sensitization model, was induced in 25 healthy male volunteers. Subjects received oral gabapentin (1,200 mg) or placebo after heat-capsaicin sensitization was established on the forearm. The primary outcome measures were the sizes of the areas of secondary hyperalgesia to von Frey hair and brush stimulation on the forearm. Secondary outcome measures were as follows: (1) size of secondary hyperalgesia area in response to brief thermal sensitization procedure on the thigh; (2) heat pain detection thresholds in normal and sensitized skin; and (3) painfulness of 1 min of 45°C stimulation in normal skin. Results Oral gabapentin profoundly suppressed established cutaneous sensitization on the forearm and prevented development of cutaneous sensitization on the thigh. Thermal nociception in normal skin was unchanged. Side effects were modest. Conclusion The results link preclinical findings with results from clinical trials of neuropathic pain. The results further suggest that gabapentin may prove effective in acute pain disorders involving neuronal sensitization, such as postoperative pain and acute herpetic pain, and could prove effective in prevention of chronic pain.

Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty: a randomized, double-blind study.

Background and Objectives Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps muscle strength as compared with FNB (primary end point) in patients after TKA. Secondary end points were effects on morphine consumption, pain, adductor muscle strength, morphine-related complications, and mobilization ability. Methods We performed a double-blind, randomized, controlled study of patients scheduled for TKA with spinal anesthesia. The patients were randomized to receive either a continuous ACB or an FNB via a catheter (30-mL 0.5% ropivacaine given initially, followed by a continuous infusion of 0.2% ropivacaine, 8 mL/h for 24 hours). Muscle strength was assessed with a handheld dynamometer, and we used the percentile change from baseline for comparisons. The trial was registered at clinicaltrials.gov (Identifier: NCT01470391). Results We enrolled 54 patients, of which 48 were analyzed. Quadriceps strength as a percentage of baseline was significantly higher in the ACB group compared with the FNB group: (median [range]) 52% [31–71] versus 18% [4–48], (95% confidence interval, 8–41; P = 0.004). There was no difference between the groups regarding morphine consumption (P = 0.94), pain at rest (P = 0.21), pain during flexion of the knee (P = 0.16), or adductor muscle strength (P = 0.39); neither was there a difference in morphine-related adverse effects or mobilization ability (P > 0.05). Conclusions Adductor canal block preserved quadriceps muscle strength better than FNB, without a significant difference in postoperative pain.

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.