Risk factors associated with bleeding during and after percutaneous dilational tracheostomy

We evaluated the effect of pre-operative coagulation status on the incidence of acute and chronic bleeding in 415 consecutive patients undergoing percutaneous dilational tracheostomy. The incidence of acute bleeding was independent of the coagulation variables tested. The risk of chronic bleeding was higher with an activated partial thromboplastin time above 50 s (OR 3.7 (95% CI 1.1-12.7); NNT 18.4 (95% CI 9.0-infinity); p = 0.04), a platelet count below 50 x 10(9) l(-1) (OR 5.0 (95% CI 1.4-17.2); NNT 12.3 (95% CI 6.2-833.3); p = 0.01) and in the presence of two or more abnormal coagulation variables (OR 9.5 (95% CI 2.3-34.7); NNT 6.2 (95% CI 3.2-68); p = 0.002). Low-dose heparin treatment did not significantly increase the risk of chronic bleeding.     

Reassessment of the role of cannabinoids in the management of pain

PURPOSE OF REVIEW: The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans. RECENT FINDINGS: Very few clinical trials looking at the analgesic effects of cannabinoids in the acute pain settings have been performed. Three recent studies have evaluated the oral administration of synthetic cannabinoids in postoperative pain. At low doses cannabinoids are not different from placebo, whereas at high doses they may be associated with adverse effects or even worsening of pain intensity. In chronic pain patients, the safety and analgesic efficacy of a number of cannabinoid compounds have recently been evaluated in several clinical trials in several chronic pain conditions. While the small size of the trials and the relatively short duration of follow-up limits broad generalization, to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS. SUMMARY: The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.     

Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies

BACKGROUND: Preoperative use of coxibs has been claimed to reduce postoperative pain and analgesic consumption, and to affect other postoperative outcomes. METHODS: Systematic review of randomized trials comparing preoperative coxib with preoperative placebo, or active comparator. Searching of PubMed and Cochrane Library to August 2004. A qualitative and a quantitative analysis. RESULTS: Twenty-two included trials with 2246 patients had high reporting quality and validity scores, though treatment group sizes were small, with a median size of 30 patients. Most trials used oral preoperative rofecoxib (mainly 50 mg) or celecoxib (mainly 200 mg). Preoperative coxibs significantly reduced both postoperative pain and analgesic consumption compared with preoperative placebo in 15/20 trials. In one further trial postoperative pain was reduced and in one analgesic consumption. There was no significant difference in the incidence of postoperative nausea and vomiting in 13/17 studies or when data were pooled. Postoperative antiemetic use was significantly reduced in all five trials reporting it; the NNT to prevent one patient using postoperative antiemetic was 10 (5.5 to 66). No trial reported any significant difference in intraoperative blood loss or recovery from anaesthesia. Patient satisfaction was significantly increased with preoperative coxib use. No conclusions could be drawn from the three trials comparing preoperative coxib with preoperative NSAID. One study reported significantly improved cost-efficacy with rofecoxib. CONCLUSIONS: Preoperative coxibs had clear benefits in terms of reduced postoperative pain, analgesic consumption and patient satisfaction compared with placebo. Effects on postoperative nausea and vomiting remain uncertain, as do those on recovery from surgery or economic benefit. Future trials should be larger and more pragmatic in nature.     

Acute and chronic pain: where we are and where we have to go

In recent years, increasing attention has been focused on the treatment of acute and chronic pain with a considerable number of publications about it. Nevertheless all the attention focused on it, the evidence of pain treatments is still unfolding, and occasionally conflicting. Hence it is still necessary that we point out our research efforts in trying to obtain a better understand of pathophysiology of pain and of real efficacy and safety of acute and chronic pain treatments. Our goal with this review is to summarize the latest research trends and the most advanced therapeutic standards for pain syndromes described in the literature, the discussion will be divided in four main topics, as these topics were treated during the SIMPAR (Study In Multidisciplinary PAin Research) meeting, held on December 2010 in Pavia: pathophysiology of pain, acute postoperative pain, opioids and pain, and chronic pain (Failed Back Surgery Syndrome). In the chapter of pathophysiology of pain we analyzed how to obtain a more personalized treatment through the study of the genetic and neurophysiological characteristics of patients and how to select the right local anesthetic according to anatomic and metabolizing patterns of patients. In acute postoperative pain we focalized our attention on the evidence supporting the use of continuous peripheral nerve blocks in the treatment of postoperative pain and in the prevention of chronic persistent post-operative pain, with a special attention in preventing side effects of regional anesthesia. We also reviewed the current evidence about the use of new very interesting modality to control postoperative pain after laparoscopy: pre-emptive nebulization of local anesthetic in abdominal cavity. As opioids are currently widely used to control chronic oncologic and non-oncologic pain, in this review we analyzed the level of evidence for their use, how to manage them better and psychological factors that can affect their success and/or determine addiction. Finally, we summarized the current evidence about Failed Back Surgery Syndrome focalizing our attention both in diagnosing it correctly and treating this syndrome with specific knowledge of the anatomic space that we have to approach and applying the possible treatments depending on pain pathophysiology and patient characteristics. In conclusion, it is important to try to personalize even better the therapy of patients with acute and chronic pain through a more accurate knowledge of anatomy, pathophysiology of pain, pharmacokinetic of pain drugs and of new device/therapies available.     

Evaluation of capsaicin ointment at the Korean hand acupressure point K-D2 for prevention of postoperative nausea and vomiting

The K-D2 point is the Korean hand acupressure point in Koryo Hand Therapy for prevention of postoperative nausea and vomiting. We evaluated the efficacy of capsaicin ointment at the K-D2 point in 186 patients undergoing laparoscopic cholecystectomy in a randomised, prospective, double-blind and placebo-controlled study. Patients were randomised to have either placebo ointment or capsaicin ointment applied to the K-D2 point of both hands 1 h before surgery under standardised anaesthesia. The ointment was removed 8 h later. Postoperative nausea and vomiting was evaluated 6 and 24 h following surgery. The incidence of postoperative nausea and vomiting was lower in the capsaicin group, with an absolute risk reduction (ARR) of 21%, a relative risk reduction (RRR) of 50% and a number-needed-to-treat (NNT) of 5 at 0-6 h (p = 0.001), and an ARR of 11%, a RRR of 85% and a NNT of 9 at 6-24 h (p = 0.003). The need for rescue anti-emetic treatment was also lower at 0-6 h (3 (3%) vs 11 (12%); p = 0.04) and at 6-24 h (5 (5%) vs 0; p = 0.02).     

Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review

A number of drugs have been tested in clinical trials to decrease cardiac complications in patients undergoing noncardiac surgery. To compare the results of these studies, we conducted a quantitative systematic review. Medline, Embase, and Cochrane databases were searched for randomized trials that assessed myocardial ischemia, myocardial infarction, 30-day cardiac mortality, and adverse effects. Data were combined using a fixed-effect model and expressed as Peto odds ratios (OR) with 95% confidence interval (CI) and as numbers-needed-to-treat/harm (NNT/H). Twenty-one trials involving 3646 patients were included: 11 trials using beta-blockers (6 drugs; 866 patients), 6 clonidine or mivazerol (614 patients), 3 diltiazem or verapamil (121 patients), and 1 nitroglycerin (45 patients). All trials had an inactive control; there were no direct comparisons. beta-blockers decreased ischemic episodes during surgery (7.6% versus 20.2% with placebo; OR 0.32 [95% CI, 0.17-0.58]; NNT 8) and after surgery (15.2% versus 27.9% with control; OR 0.46 [95% CI, 0.26-0.81]; NNT 8). alpha(2)-agonists decreased ischemia during surgery only (19.4% versus 32.8%; OR 0.47 [95% CI, 0.33-0.68]; NNT 7). beta-blockers reduced the risk of myocardial infarction (0.9% versus 5.2%; OR 0.19 [95% CI, 0.08-0.48]; NNT 23) but only when 2 trials with high-risk patients were included. The effect of alpha(2)-agonists on myocardial infarction was not significant (6.1% versus 7.3%; OR 0.85 [95% CI, 0.62-1.14]). beta-blockers significantly decreased the risk of cardiac death from 3.9% to 0.8% (OR 0.25 [95% CI, 0.09-0.73], NNT 32). alpha(2)-agonists significantly decreased the risk of cardiac death from 2.3% to 1.1% (OR 0.50 [95% CI, 0.28-0.91], NNT 83). For calcium channel blockers and nitroglycerin, evidence of any benefit was lacking. The most common adverse effect was bradycardia, which occurred in 24.5% of patients receiving a beta adrenergic blocker versus 9.1% of controls (OR 3.76 [95% CI, 2.45-5.77], NNH 6).     

Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials

OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs) - of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months) - all supported by the manufacturer (Hyben-Vital International) - showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.     

Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by neuraxial opioids: a quantitative systematic review

Pruritus is a frequent adverse event observed after neuraxial administration of opioids. Central 5-hydroxytryptamine subtype 3 (5-HT3) receptors may be activated in this process. This systematic review aimed to evaluate the efficacy of prophylactic 5-HT3 receptor antagonists on neuraxial opioid-induced pruritus. We searched Medline, Embase, and Cochrane Collaboration Library databases. Studies were evaluated with the Oxford Validity Scale. Studies with a score of 3 or more and reporting prophylactic administration of 5-HT3 receptor antagonists vs placebo were included. Fifteen randomized double-blind controlled trials (n=1337) were selected. 5-HT3 antagonists (n=775) significantly reduced pruritus [odds ratio (OR) 0.44 (95% confidence interval, 95% CI, 0.29-0.68), P=0.0002, number-needed-to-treat (NNT) 6 (95% CI, 4-14)], the treatment request for pruritus [OR 0.58 (95% CI, 0.43-0.78), P=0.0003, NNT 10 (95% CI, 7-20)], the intensity of pruritus [weighted mean difference (WMD) -0.35 (95% CI, -0.59 to -0.10), P=0.007], the incidence and the intensity of postoperative nausea and vomiting (PONV), and the need of rescue treatment [respectively, Peto odds ratio (Peto OR) 0.43 (95% CI, 0.31-0.58), P<0.00001, NNT 7 (95% CI, 6-10); WMD -0.12 (95% CI, -0.24 to 0.00), P=0.05 and OR 0.42 (95% CI, 0.20-0.86), P=0.02, NNT 8 (95% CI, 5-35)]. However, the funnel plot was asymmetric, suggesting a risk of publication bias. 5-HT3 receptor antagonists may be an effective strategy in preventing neuraxial opioid-induced pruritus and PONV. Further large randomized controlled trials are required to confirm these findings.     

Preoperative gabapentin for postoperative analgesia: a meta-analysis

PURPOSE: Gabapentin's role in the treatment of chronic neuropathic pain is well known. What is less well established is its role for managing postoperative pain. In order to clarify whether gabapentin's utility in acute pain control is more than just theoretical, we conducted a meta-analysis of all randomized trials that addressed gabapentin's role in acute postoperative pain control. We specifically addressed whether gabapentin reduces pain scores, analgesia consumption, and/or analgesia-related side effects in the first 24 hr following surgery. SOURCE: We identified eight placebo-controlled, randomized controlled trials and conducted a meta-analysis using the primary outcomes of pain scores, total analgesia consumption, and side effects over a 24-hr period. PRINCIPLE FINDINGS: Patients who received gabapentin preoperatively reported significantly lower pain scores (-11.9 at rest and -11.0 with movement on a 100-point visual analogue scale) and opioid consumption (-14.7 mg of morphine in 24 hr) with no difference in the incidence of side effects. CONCLUSION: Although gabapentin given preoperatively decreases pain scores and analgesic consumption in the first 24 hr after surgery, the clinical significance of this finding has yet to be determined. This meta-analysis could not demonstrate a significant reduction in the incidence of side effects. Due to the small numbers enrolled in the studies, larger randomized control trials are warranted.     

Patients' global evaluation of analgesia and safety of injected parecoxib for postoperative pain: a quantitative systematic review

Parecoxib is the only parenterally administered cyclooxygenase-2-selective inhibitor available. We performed a systematic review, including full reports of randomized comparisons of parecoxib compared with any other analgesic intervention for prophylaxis or treatment of postoperative pain. Dichotomous data on patients' global evaluation of their analgesic regimen were extracted by means of the fraction of patients who rated their medication as "good" or "excellent." For safety analysis, data on any reported adverse effects were extracted. Relative risk (RR), number needed to treat (NNT), or number-needed-to-harm were calculated with 95% confidence intervals (CI). Data from 9 trials of 50 initially screened were finally analyzed. One thousand thirteen patients were randomized to receive parecoxib, 218 patients were allocated to an active control, and 507 patients received a placebo. With prophylactic administration, the pooled NNT to obtain the desired outcome ("good"/"excellent" rating) with parecoxib 20 and 40 mg compared with placebo was 4.5 (RR, 1.42; 95% CI, 0.91-2.24) and 4.0 (RR, 1.40; 95% CI, 1.10-1.79), respectively. In the treatment trials, the NNT to obtain the outcome of interest with parecoxib 20 mg was 2.1 (RR, 3.44; 95% CI, 1.49-7.96), 5.3 (RR, 1.43; 95% CI, 1.01-2.02), and -8.3 (RR, 0.85; 95% CI, 0.75-0.97) for the comparisons with placebo, morphine, and ketorolac, respectively. The corresponding NNT for treatment with parecoxib 40 mg was 1.7 (RR, 4.65; 95% CI, 2.04-10.61), 3.7 (RR, 1.62; 95% CI, 1.21-2.16), and 50 (RR, 1.03; 95% CI, 0.89-1.18) for the comparisons with placebo, morphine, and ketorolac, respectively. Overall adverse effects for parecoxib 20 and 40 mg were not different from those with placebo, morphine, or ketorolac. These results suggest a favorable profile for parecoxib compared with inactive or active controls. The optimal dose, timing, and frequency of administration need to be determined.     

Nefopam for the prevention of postoperative pain: quantitative systematic review

Nefopam, a centrally acting analgesic, has been used in the surgical setting in many countries since the mid-1970s. However, clinical trials provide contflicting results for its analgesic potency. We performed a systematic search (multiple databases, bibliographies, any language, to January 2008) for randomized, placebo-controlled trials of nefopam for the prevention of postoperative pain. Data were combined using classic methods of meta-analyses and were expressed as weighted mean difference (WMD), relative risk (RR), and number needed to treat/harm (NNT/H) with 95% confidence interval (CI). Nine trials (847 adult patients, 359 received nefopam) were included. Nefopam (cumulative doses, 20-160 mg) was given orally or i.v., as single or multiple doses, or as a continuous infusion. Compared with placebo, cumulative 24 h morphine consumption was decreased with nefopam: WMD -13 mg (95% CI -17.9 to -8.15). Pain intensity at 24 h was also decreased: on a 100 mm visual analogue scale, WMD -11.5 mm (95% CI -15.1 to -7.85). The incidence of tachycardia was increased with nefopam (RR 3.12, 95% CI 1.11-8.79; NNH 7), as was the incidence of sweating (RR 4.92, 95% CI 2.0-12.1; NNH 13). There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients. The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs. However, dose responsiveness and adverse effect profile remain unclear, and the role of nefopam as part of multimodal analgesia needs to be established. Data in children are lacking.     

腹壁切口疝修补术后慢性疼痛发生状况及危险因素分析

目的探讨腹壁切口疝修补术后慢性疼痛的发生状况及相关因素,以期降低术后慢性疼痛的发生率,提高患者生活质量。 方法选取2015年1月至2019年12月陕西省人民医院收治的213例腹壁切口疝患者作为研究对象。随访观察患者行腹壁切口疝修补术后1年内发生慢性疼痛的情况,将其分为发生疼痛组和未发生疼痛组,筛选出术后慢性疼痛的危险因素。 结果共有27例患者发生慢性疼痛,发生率为12.68%。单因素分析结果显示,两组性别、体质指数（BMI）、复发疝、术后切口并发症比较,差异均有统计学意义（P<0.05）。进一步行多因素Logistic回归分析显示,女性（β=1.82,OR=6.17,95% CI：1.34~28.46,P=0.020）、BMI≥24 kg/m²（β=1.04,OR=2.82,95% CI：1.09~7.32,P=0.034）、复发疝（β=1.73,OR=5.65,95% CI：1.88~17.02,P=0.002）、术后切口并发症（β=1.43,OR=4.16,95% CI：1.53~11.33,P=0.005）是术后发生慢性疼痛的独立危险因素。 结论女性、BMI≥24 kg/m²、复发疝、术后切口并发症是腹壁切口疝患者术后发生慢性疼痛的独立危险因素,因此在行切口疝修补术时要充分评估,做好预防措施,降低术后慢性疼痛的发生率。     

Preoperative predictors of moderate to intense acute postoperative pain in patients undergoing abdominal surgery

BACKGROUND: Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio-cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain. METHODS: A prospective cohort study was performed with 346 inpatients undergoing abdominal elective surgery (ASA physical status I-III, age range 18-60 years). The measuring instruments were Pain Visual Analog Scale, the State-Trait Anxiety Inventory, and the Montgomery-Asberg Depression Rating Scale. Multivariate conditional regression modeling was used to determine independent predictors for moderate to intense acute postoperative pain. RESULTS: Moderate to intense acute postoperative pain was associated with status ASA III (odds ratio (OR) = 1.99), age (OR = 4.72), preoperative moderate to intense pain (OR = 2.96), chronic pain (OR = 1.75), high trait-anxiety and depressive mood moderate to intense (OR = 1.74 and OR = 2.00, respectively). Patients undergoing surgery to treat cancer presented lower risk for reporting moderate to intense pain OR = 0.39, as well as those that received the epidural analgesia and multimodal analgesia with systemic opioid (OR = 0.09 and OR = 0.16, respectively). CONCLUSIONS: The identification of predictive factors for intense acute postoperative pain may be useful for designing specific preventive interventions to relieve patient suffering. Especially because few of these variables are accessible for medical intervention, which would improve the clinical outcomes and quality of life of patients at risk of moderate to intense acute postoperative pain.     

The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis

BACKGROUND AND OBJECTIVES: Gabapentin is an anticonvulsant that has been shown to be effective in the treatment of neuropathic and inflammatory pain in animal and human studies. The analgesic effect of its perioperative use has not been fully elucidated. METHODS: This systematic review (meta-analysis) included 12 randomized controlled trials of 896 patients undergoing a variety of surgical procedures that investigated the impact of perioperative administration of gabapentin on postoperative outcome. RESULTS: The pooled visual analog scores for pain at 4 hours and 24 hours were significantly less in those patients who received gabapentin (weighted mean difference [WMD] = -1.57; 95% confidence interval [CI], -2.14 to -0.99 and WMD = -0.74; CI, -1.03 to -0.45, respectively). A concomitant decrease in opioid usage by those patients who received gabapentin was also noted (odds ratio [OR] = -17.84; CI, -23.50 to -12.18). Gabapentin administration was associated with sedation and anxiolysis (OR = 3.28; CI, 1.21-8.87) but not associated with a difference in lightheadedness, dizziness, nausea, or vomiting. CONCLUSIONS: Based on this systematic review, perioperative oral gabapentin is a useful adjunct for the management of postoperative pain that provides analgesia through a different mechanism than opioids and other analgesic agents and would make a reasonable addition to a multimodal analgesic treatment plan.     

Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials

Postoperative pain management remains a significant challenge for all healthcare providers. The objective of this systematic review was to quantitatively evaluate the efficacy of acupuncture and related techniques as adjunct analgesics for acute postoperative pain management. We searched the databases of Medline (1966-2007), CINAHL, The Cochrane Central Register of Controlled Trials (2006), and Scopus for randomized controlled trials (RCTs) using acupuncture for postoperative pain management. We extracted data about postoperative opioid consumption, postoperative pain intensity, and opioid-related side-effects. Combined data were analysed using a random effects model. Fifteen RCTs comparing acupuncture with sham control in the management of acute postoperative pain were included. Weighted mean difference for cumulative opioid analgesic consumption was -3.14 mg (95% confidence interval, CI: -5.15, -1.14), -8.33 mg (95% CI: -11.06, -5.61), and -9.14 mg (95% CI: -16.07, -2.22) at 8, 24, and 72 h, respectively. Postoperative pain intensity (visual analogue scale, 0-100 mm) was also significantly decreased in the acupuncture group at 8 and 72 h compared with the control group. The acupuncture treatment group was associated with a lower incidence of opioid-related side-effects such as nausea (relative risk, RR: 0.67; 95% CI: 0.53, 0.86), dizziness (RR: 0.65; 95% CI: 0.52, 0.81), sedation (RR: 0.78; 95% CI: 0.61, 0.99), pruritus (RR: 0.75; 95% CI: 0.59, 0.96), and urinary retention (RR: 0.29; 95% CI: 0.12, 0.74). Perioperative acupuncture may be a useful adjunct for acute postoperative pain management.     

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

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

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 degrees 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.     

A genetic association study of the functional A118G polymorphism of the human mu-opioid receptor gene in patients with acute and chronic pain

In this prospective, observational study we explored whether A118G single nucleotide polymorphism in the human mu-opioid receptor (MOR) gene could explain the inter-individual differences in opioid analgesic requirements in patients with acute postoperative pain and chronic pain. The frequency of the wild-type A118 MOR (major) and variant G118 MOR (minor) alleles in the subjects with chronic, noncancer pain (n = 121) and opioid-na?ve subjects with acute postoperative pain (n = 101), serving as the control group, were examined. The relationships among the A118G MOR genotype, opioid requirements, and the numerical pain score were analyzed in both groups. The frequency of the minor allele was significantly lower in the subjects with chronic pain when compared with the group with acute postoperative pain (0.079 versus 0.158; P = 0.009 by chi2 test). No statistically significant association was observed between the presence of A118G MOR polymorphism and the average postoperative pain score or the doses of morphine used in the immediate postoperative period. In the high-quartile, opioid utilization, chronic pain patients, the homozygotic carriers of the major allele required significantly higher opioid dose than did the carriers of the minor allele. The results indicate that although the presence of the minor allele does not appear to affect opioid analgesic use in acute postoperative pain, the minor allele is less common in chronic pain patients, especially in those requiring higher doses of opioid analgesics.     

The analgesic effect of gabapentin and mexiletine after breast surgery for cancer

We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients. They were randomized to receive, in a double-blinded manner, mexiletine 600 mg/d, gabapentin 1200 mg/d, or placebo for 10 days. Anesthesia was standardized, and all patients had access to routine postoperative analgesics on demand. The visual analog scale score assessed pain at rest and after movement. Three months later, all patients were interviewed to identify intensity of chronic pain and analgesic requirements. Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50% (P = 0.029; P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons, respectively). Total paracetamol consumption was also reduced during the same time (P = 0.0085; P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control, respectively). Pain at rest and after movement was reduced by both drugs on the third postoperative day. Pain after movement also was reduced by gabapentin between the second and fifth postoperative day. Three months later, the incidence of chronic pain, its intensity, and need for analgesics were not affected by either treatment. However, burning pain was more frequent in the control group (P = 0.033). IMPLICATIONS: Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.     

Prevention or treatment of postoperative vomiting using ondansetron? A mathematical assessment.

STUDY OBJECTIVES: To assess the effectiveness of ondansetron versus placebo when used as prophylaxis of postoperative vomiting compared to its use for the treatment of established postoperative vomiting. DATA SOURCES: All prospectively randomized controlled trials, identified using the MEDLINE database and which had been included in two previously published meta-analyses. MEASUREMENTS AND MAIN RESULTS: The effectiveness of ondansetron (1, 4, and 8 mg) used for prevention (28 studies) or treatment (two studies) of postoperative vomiting was compared using odds ratios and number needed to treat (NNT) scores. NNT values were extrapolated to a similar incidence of vomiting in the placebo groups. The effectiveness equivalence between both meta-analyses was compared by assessing the degree of coincidence between the respective 95% confidence intervals (CI). The 1-mg dose was superior in treatment than in prophylaxis, odds ratios (95% CI): 2.73 (1.81-4.11) versus 1.34 (1.04-1.74), respectively (p < 0.05), although this difference did not reach statistical significance when the NNT values were compared. For the 4-mg dose, a near congruence was observed in the odds ratios; 3.34 (2.22-5.03) versus 2.61 (2.24-3.05) as well as in the NNT values: 3.90 (2.97-5.78) versus 3.40 (2.93-4.07). For the 8-mg dose, there were equivalent NNT values: 4.10 (3.08-6.23) versus 4.08 (3.28-5.43), and with respect to the odds ratios: 3.18 (2.11-4.81) versus 2.42 (1.95-2.99). The differences were not statistically significant. CONCLUSIONS: For the usual doses recommended for postoperative emesis, there was equivalent effectiveness of ondansetron whether administered as prophylaxis or as a treatment of established vomiting.