F. Camu

A Systematic Review of Randomized Trials Evaluating Regional Techniques for Postthoracotomy Analgesia

BACKGROUND:Thoracotomy induces severe postoperative pain and impairment of pulmonary function, and therefore regional analgesia has been intensively studied in this procedure. Thoracic epidural analgesia is commonly considered the “gold standard” in this setting; however, evaluation of the evidence is needed to assess the comparative benefits of alternative techniques, guide clinical practice and identify areas requiring further research. METHODS:In this systematic review of randomized trials we evaluated thoracic epidural, paravertebral, intrathecal, intercostal, and interpleural analgesic techniques, compared to each other and to systemic opioid analgesia, in adult thoracotomy. Postoperative pain, analgesic use, and complications were analyzed. RESULTS:Continuous paravertebral block was as effective as thoracic epidural analgesia with local anesthetic (LA) but was associated with a reduced incidence of hypotension. Paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia, whereas thoracic epidural analgesia did not. Thoracic epidural analgesia was superior to intrathecal and intercostal techniques, although these were superior to systemic analgesia; interpleural analgesia was inadequate. CONCLUSIONS:Either thoracic epidural analgesia with LA plus opioid or continuous paravertebral block with LA can be recommended. Where these techniques are not possible, or are contraindicated, intrathecal opioid or intercostal nerve block are recommended despite insufficient duration of analgesia, which requires the use of supplementary systemic analgesia. Quantitative meta-analyses were limited by heterogeneity in study design, and subject numbers were small. Further well designed studies are required to investigate the optimum components of the epidural solution and to rigorously evaluate the risks/benefits of continuous infusion paravertebral and intercostal techniques compared with thoracic epidural analgesia.

A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty

The PROSPECT Working Group, a collaboration of anaesthetists and surgeons, conducts systematic reviews of postoperative pain management for different surgical procedures (http://www.postoppain.org). Evidence‐based consensus recommendations for the effective management of postoperative pain are then developed from these systematic reviews, incorporating clinical practice observations, and transferable evidence from other relevant procedures. We present the results of a systematic review of pain and other outcomes following analgesic, anaesthetic and surgical interventions for total knee arthroplasty (TKA). The evidence from this review supports the use of general anaesthesia combined with a femoral nerve block for surgery and postoperative analgesia, or alternatively spinal anaesthesia with local anaesthetic plus spinal morphine. The primary technique, together with cooling and compression techniques, should be supplemented with paracetamol and conventional non‐steroidal anti‐inflammatory drugs or COX‐2‐selective inhibitors, plus intravenous strong opioids (high‐intensity pain) or weak opioids (moderate‐ to low‐intensity pain).

Linearity of Pharmacokinetics and Model Estimation of Sufentanil

Background The pharmacokinetic profiles of sufentanil available in the literature are conflicting because of methodologic differences. Length of sampling and assay sensitivity are key factors involved in accurately estimating the volumes of distribution, clearances, and elimination phase. The unit disposition function of increasing doses of sufentanil were investigated and the influence of dose administered on the linearity of pharmacokinetics was assessed.

Disposition kinetics of propofol during alfentanil anaesthesia.

The pharmacokinetics of a constant rate infusion of propofol were studied in 11 patients who received total intravenous anaesthesia for ENT surgery. Alfentanil was administered as an exponentially decreasing infusion using a computer‐assisted infusion device with a constant target plasma alfentanil concentration of 300 ng/ml. Propofol was infused at a constant rate of 6 mg/kg/hours. Plasma alfentanil concentrations were determined by gas chromatography and whole blood propofol concentrations by high‐performance liquid chromatography in arterial blood samples collected at selected times during and up to 8 hours after infusion. Pharmacokinetic modelling of the blood propofol concentration‐time data indicated that a three‐compartment open model with central elimination was most appropriate. Derived pharmacokinetic parameters were in agreement with previous studies on the pharmacokinetics of propofol. The plasma alfentanil concentrations in 10 patients significantly exceeded the expected values at any time during the infusion. The population mean bias amounted to 20.2% (S D 12.6). Only three data sets were significantly underestimated after the infusion was stopped (mean bias 11.9% (SD 25.5)). The elimination half‐life of alfentanil was approximately 75 minutes (SD 21). We conclude that alfentanil does not interfere with the pharmacokinetic profile of propofol but that propofol induces higher plasma alfentanil concentrations than expected.

A procedure-specific systematic review and consensus recommendations for postoperative analgesia following laparoscopic cholecystectomy

Background:Laparoscopic cholecystectomy has advantages over the open procedure for postoperative pain. However, a systematic review of postoperative pain management in this procedure has not been conducted.Methods:A systematic review was conducted according to the guidelines of the Cochrane Collaboration. Randomized studies examining the effect of medical or surgical interventions on linear pain scores in patients undergoing laparoscopic cholecystectomy were included. Qualitative and quantitative analyses were performed. Recommendations for patient care were derived from review of these data, evidence from other relevant procedures, and clinical practice observations collated by the Delphi method among the authors.Results:Sixty-nine randomized trials were included and 77 reports were excluded. Recommendations are provided for preoperative analgesia, anesthetic and operative techniques, and intraoperative and postoperative analgesia.Conclusions:A step-up approach to the management of postoperative pain following laparoscopic cholecystectomy is recommended. This approach has been designed to provide adequate analgesia while minimizing exposure to adverse events.

Pharmacokinetics of alfentanil in man.

The distribution and elimination kinetics of alfentanil, a new short-acting analgesic, were studied in five surgical patients. Its behavior, following a bolus injection of 120 μg/ml, was compatible with a three-compartment open-model distribution. The disappearance of the drug from plasma was rapid (t½π = 3.5 ± 1.3 minutes, t½α = 16.8 ± 6.4 minutes) with 96.4% of the drug eliminated from plasma in 1 hour, indicating extensive transfer to the remote peripheral compartment. This was followed by a slower elimination phase with a t½β of 94 ± 38 minutes. Total volume of distribution was 1.03 ± 0.50 L/kg. Total plasma clearance was 456 ± 155 ml/min. The short analgesic effect of this drug might be attributed to the rapid displacement of the drug from the central and intermediate compartments to the remote peripheral compartment. Approximately 25% of the injected dose was present in the remote peripheral compartment 30 to 60 minutes after alfentanil administration. As the return of drug from this peripheral to the central compartment is slower than the elimination rate of the drug, it could be the rate-limiting step in the elimination of alfentanil from the body.

Alfentanil infusion for postoperative pain : a comparison of epidural and intravenous routes

The efficacy of intravenous (iv) and epidural infusions of alfentanil for postoperative pain relief was investigated in 24 patients (ASA physical status 1-2) who were scheduled for abdominal hysterectomy. The patients were allocated randomly to receive either epidural or iv alfentanil. In both groups, a loading dose of 15 micrograms.kg-1 was administered, followed by a constant rate infusion of 18 micrograms.kg-1.h-1 alfentanil for 20 h. Both routes provided similar degrees of analgesia; however, analgesia occurred earlier in the intravenously treated group (P less than 0.03). Mean plasma alfentanil concentrations (Cps) varied between 42 and 82 ng.ml-1 in the iv group and 23 and 68 ng.ml-1 in the epidural group, with higher concentrations in the iv group for the first 60 min only (P less than 0.01). Cps increased with infusion time, suggesting accumulation of alfentanil. After infusion ended, pain recurred at the same time in both groups, whereas the alfentanil Cps still were greater than 45 ng/ml. Postoperative epinephrine concentrations decreased after 60 min of infusion (P less than 0.02), whereas, after 6 h, cortisol levels decreased to preoperative values. Norepinephrine concentrations decreased only slightly. The only clinically meaningful effect on vital signs that occurred was an abrupt reduction of respiratory rate after the iv loading dose. PaCO2 increased to the same extent in both groups during the first 15 min only. The incidence of opioid-related side effects was similar in both groups. These results suggest that the iv and epidural routes were equally effective for providing postoperative pain control and controlling the postoperative response to surgical stress.

Cardiovascular safety of the cyclooxygenase-2 selective inhibitors parecoxib and valdecoxib in the postoperative setting: an analysis of integrated data.

BACKGROUND: Studies of parecoxib, the inactive prodrug of the cyclooxygenase-2 selective inhibitor valdecoxib, and valdecoxib for postoperative pain relief in patients undergoing coronary artery bypass graft surgery revealed an increased risk of cardiovascular (CV) adverse events compared with placebo. We conducted this study to address whether parecoxib and valdecoxib increased CV risk in noncardiac surgery patients. METHODS: A pooled post hoc analysis was conducted using 2 large datasets: 17 controlled trials of parecoxib for noncardiac studies and 32 studies, including the 17 noncardiac parecoxib studies plus 15 studies of valdecoxib. The 32-study dataset provided 95% power to detect a twofold increase in the incidence of CV adverse events assuming a placebo group incidence of 1% (estimated from previous study data), and 69% power to detect a twofold increase from a 0.5% incidence. RESULTS: The incidence of total CV events for the 17 parecoxib studies was 0.44% (13 of 2966) in patients who received parecoxib and 0.37% (7 of 1915) in those receiving placebo (P > 0.20). In the analysis of 32 studies, the incidence of total CV events was 0.40% (21 of 5285) in the parecoxib/valdecoxib group compared with 0.50% (16 of 3226) in the placebo group (P > 0.20). No significant differences in the incidence of total or any individual CV event category were observed between the parecoxib or parecoxib/valdecoxib and placebo groups in the two analyses. When patients were stratified by number of baseline CV risk factors, no significant difference in CV events was detected in parecoxib/valdecoxib patients compared with placebo. CONCLUSIONS: In the largest analysis of the CV risk of cyclooxygenase selective inhibitors or nonsteroidal antiinflammatory drugs for perioperative pain management, parecoxib and valdecoxib were not found to increase the risk of CV adverse events after noncardiac surgery.

The safety and effectiveness of remifentanil as an adjunct sedative for regional anesthesia

We assessed the sedative potential of continuous infusions of remifentanil with a validated composite alertness scale in 160 patients (ASA physical status I or II) undergoing hip replacement surgery with spinal block (n 5 61) or hand surgery using brachial plexus block (n 5 93). They were randomized to receive one of the following initial dose regimens in double-blinded fashion: placebo or 0.04, 0.07, or 0.1 mg z kg 21 z min 21 remifentanil subsequently titrated to effect. Additional midazolam IV was allowed for adequate sedation as required. The combined analysis of both surgery groups revealed a dose-related increase in achievement of sedation level

The Role of COX-2 Inhibitors in Pain Modulation

2 within 15 min of the start of the study drug infusion; all remifentanil dose comparisons with placebo reached significance (P , 0.001). The remifentanil 50% effective dose for a composite sedation level