Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery.

BACKGROUND: Epidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. OBJECTIVES: To assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials via OVID (CENTRAL) (The Cochrane Library, Issue 3, 2004); OVID MEDLINE (1966 to July 2004); and EMBASE (1980 to June 2004). We assessed non-English language reports and contacted researchers in the field. We did not seek unpublished data. SELECTION CRITERIA: We included all randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adult patients who underwent elective open abdominal aortic surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data. MAIN RESULTS: Thirteen studies involving 1224 patients met our inclusion criteria; 597 patients received epidural analgesia and 627 received systemic opioid analgesia. The epidural analgesia group showed significantly lower visual analogue scale for pain on movement (up to postoperative day three), regardless of the site of epidural catheter and epidural formulation. Postoperative duration of tracheal intubation and mechanical ventilation was significantly shorter by about 20% in the epidural analgesia group. The overall incidence of cardiovascular complication; myocardial infarction; acute respiratory failure (defined as an extended need for mechanical ventilation); gastrointestinal complication; and renal insufficiency was significantly lower in the epidural analgesia group, especially in trials that used thoracic epidural analgesia. AUTHORS' CONCLUSIONS: Epidural analgesia provides better pain relief (especially during movement) for up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly 20%. The occurrence of prolonged postoperative mechanical ventilation, overall cardiac complication, myocardial infarction, gastric complication and renal complication was also reduced by epidural analgesia, especially thoracic. However, current evidence does not confirm the beneficial effect of epidural analgesia on postoperative mortality and other types of complications.

Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer.

BACKGROUND: Since the 1970s, when endogenous opioids and opioid receptors were first isolated in the central nervous system, attempts have been made to optimize opioid therapy by delivering the medication centrally rather than systemically. Although the vast majority of cancer patients obtain satisfactory pain relief from individualized systemic treatment, there remain the few whose pain is refractory to systemic treatments. These patients may obtain relief from neuraxial opioid therapy: intracerebroventricular, epidural or subarachnoid. OBJECTIVES: To compare intracerebroventricular therapy with other neuraxial treatments and to determine whether intracerebroventricular (ICV) has anything to offer over epidural (EPI) and subarachnoid (SA) catheters in terms of efficacy, adverse effects, and complications. SEARCH STRATEGY: A number of electronic databases were searched to retrieve information for inclusion in this review. Non-English language reports are awaiting assessment. Unpublished data were not sought. SELECTION CRITERIA: Randomised studies of intracerebroventricular therapy for patients with intractable cancer pain were sought. However, this level of evidence was not available so data from uncontrolled trials, retrospective case series and uncontrolled prospective cohort studies were assessed. DATA COLLECTION AND ANALYSIS: Our search did not retrieve any controlled trials. We therefore used data from uncontrolled studies to compare incidences of analgesic efficacy, adverse effects, and complications. We found 72 uncontrolled trials assessing ICV (13 trials, 337 patients), EPI (31 trials, 1343 patients), and SA (28 trials, 722 patients) in cancer patients. From these we extracted data on analgesic efficacy, common pharmacologic adverse effects, and complications. MAIN RESULTS: Data from uncontrolled studies reported excellent pain relief among 73% of ICV patients compared with 72% EPI and 62% SA. Unsatisfactory pain relief was low in all treatment groups. Persistent nausea, persistent and transient urinary retention, transient pruritus, and constipation occurred more frequently with EPI and SA. Respiratory depression, sedation and confusion were most common with ICV. The incidence of major infection when pumps were used with EPI and SA was zero. There was a lower incidence of other complications with ICV therapy than with EPI or SA. AUTHORS' CONCLUSIONS: Neuraxial opioid therapy is often effective for treating cancer pain that has not been adequately controlled by systemic treatment. However, long-term use of neuraxial therapy can be complicated by problems associated with the catheters. The data from uncontrolled studies suggests that ICV is at least as effective against pain as other neuraxial treatments and may be a successful treatment for patients whose cancer pain is resistant to other treatments.

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

UNLABELLED: We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.33-0.85) and had a weak tendency to reduce the incidence of pulmonary infections (RR 0.53, 95% CI 0.18-1.53) and pulmonary complications overall (RR 0.51, 95% CI 0.20-1.33). Epidural local anesthetics increased PaO2 (difference 4.56 mm Hg, 95% CI 0.058-9.075) and decreased the incidence of pulmonary infections (RR 0.36, 95% CI 0.21-0.65) and pulmonary complications overall (RR 0.58, 95% CI 0.42-0.80) compared with systemic opioids. Intercostal nerve blockade tends to improve pulmonary outcome measures (incidence of atelectasis: RR 0.65, 95% CI 0.27-1.57, incidence of pulmonary complications overall: RR 0.47, 95% CI 0.18-1.22), but these differences did not achieve statistical significance. There were no clinically or statistically significant differences in the surrogate measures of pulmonary function (FEV1, FVC, and PEFR). These analyses support the utility of epidural analgesia for reducing postoperative pulmonary morbidity but do not support the use of surrogate measures of pulmonary outcome as predictors or determinants of pulmonary morbidity in postoperative patients. IMPLICATIONS: When individual trials are unable to produce significant results, it is often because of insufficient patient numbers. It may be impossible for a single institution to study enough patients. Meta-analysis is a useful tool for combining the data from multiple trials to increase the patient numbers. These meta-analyses confirm that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity.

The impact of choice of muscle relaxant on postoperative recovery time: a retrospective study.

UNLABELLED: To test the hypothesis that the use of long-acting muscle relaxants is associated with prolonged postoperative recovery when compared with the use of shorter-acting relaxants, we undertook a retrospective study of 270 patients with induced paralysis recovering from general anesthesia. We calculated the mean recovery time associated with each muscle relaxant used. Regression analyses were performed to control for potential confounding of the results by length and type of surgery, as well as age and sex. Taking these into account, the adjusted difference in mean recovery time between patients receiving short- and intermediate-acting relaxants (mivacurium, atracurium, and vecuronium) versus those receiving long-acting relaxants (d-tubocurarine, pancuronium, and pancuronium and d-tubocurarine combination) was 30 min (95% confidence interval [CI] 8-53). The adjusted difference in mean recovery time between patients receiving vecuronium and those receiving pancuronium (i.e., the single most frequently used drug in each category) was 33 min (95% CI 1-66). Shortened recovery time accounted for an estimated average $37.95 decrease in recovery room charge per patient when vecuronium was used instead of pancuronium, versus a $22.84 increase in drug cost. Our data and analyses support the hypothesis that the use of long-acting muscle relaxants is associated with prolonged recovery after surgery and provide preliminary evidence that restricting the use of the more expensive, shorter-acting muscle relaxants may represent a false economy. IMPLICATIONS: In this retrospective study, the use of old-fashioned, inexpensive, long-acting paralyzing drugs was found to be associated with prolonged postoperative recovery. This has implications when deciding whether, as an economic measure, to restrict the use of the more expensive, shorter-acting paralyzing drugs, because prolonged recovery also has a price.

Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer.

BACKGROUND AND OBJECTIVES: Although rarely used, intracerebroventricular opioid therapy (ICV) is an option for the control of intractable pain due to cancer when systemic treatments have failed. The aim of the present study is to use available data from published trials to compare ICV with the more common epidural (EP) and subarachnoid (SA) opioid treatments in an attempt to establish the utility and safety of ICV. METHODS: Because there are no published controlled trials comparing these routes of administration, the combined data from multiple uncontrolled trials were used, with differences between the treatments analyzed statistically. Trials assessing ICV (13 trials, 268 patients). EPI (29 trials, 909 patients) and SA (21 trials, 410 patients) in cancer patients were identified; data on analgesic efficacy, common pharmacologic side effects, and complications were then extracted and the accumulated incidence data analyzed. RESULTS: The findings (weighted means) indicated ICV to be at least as effective against pain as other neuraxial treatments, with 75% of ICV-treated patients obtaining excellent pain relief as compared with 72% of EPI- and 58% of SA-treated patients (not significant). The failure rate of both spinal treatments tended to be greater than that of ICV and was significantly higher in the case of EPI (P = .045). In general, persistent side effects appeared to be more of a problem with the spinal treatments, while transient symptoms occur more often with ICV. Persistent nausea, urinary retention, and pruritus all were more frequent with the two spinal treatments than with ICV, but transient nausea and respiratory depression occurred more often with ICV. Sedation and confusion appeared to occur more often with ICV than with spinal therapy, while constipation and headache were rarely encountered with ICV. There were no real differences in infectious complication rates among the three treatments (except for a lower rate of infection when an implanted pump was used), but technical problems such as catheter blockage, misplacement, or leakage tended to occur less often with ICV. CONCLUSIONS: Intracerebroventricular therapy appears to be at least as effective against pain as other neuraxial treatments. The ICV technique is the only fixed system that is associated with fewer technical problems than the use of simple percutaneous epidural catheters (difference 9%, standard error of the difference 3.4). The present state of evidence indicates that ICV is a successful treatment for patients with intractable cancer pain and compares well with spinal opioid treatments in terms of efficacy, side effects, and complications.

Postoperative patient-controlled analgesia: meta-analyses of initial randomized control trials.

STUDY OBJECTIVE: To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials. DESIGN: Meta-analyses of 15 randomized control trials. PATIENTS: Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures. INTERVENTIONS: Either PCA or conventional analgesia for postoperative pain control. MEASUREMENTS AND MAIN RESULTS: Data were extracted on analgesic efficacy, analgesic use, patient satisfaction, length of hospital stay, and side effects. Meta-analyses of the data showed the following: (1) greater analgesic efficacy when PCA was used, with a mean additional benefit of 5.6 on a scale of 0 to 100 (SED, 2.2; p = 0.006); (2) a nonsignificant trend toward reduced analgesic use in PCA patients, based on a count of trials finding in one direction or the other (p = 0.092); (3) a 42% difference in the proportion of patients expressing satisfaction over dissatisfaction (SED, 20%; p = 0.02), with PCA being preferred; (4) a nonsignificant trend toward shortening of length of hospital stay with PCA use (mean, 0.15 days, SED, 0.13; p = 0.24); (5) no significant differences in the occurrence of any side effect. CONCLUSIONS: Patient preference strongly favors PCA over conventional analgesia. Patients using PCA also obtain better pain relief than those using conventional analgesia, without an increase in side effects. Favorable effect of PCA upon analgesic usage and length of hospital stay did not in the initial trials attain statistical significance. Nonetheless, the favorable trends in the mean effect sizes for both outcomes argue that further studies of both outcomes should be performed to determine whether the favorable impact of PCA upon either may become statistically significant if larger numbers of patients are enrolled.

Pituitary-adrenal stress response in the absence of brain-pituitary connections.

To examine whether an acute pituitary-adrenal response to stress may occur in vivo in the absence of hypothalamic-pituitary connections, we measured plasma beta-endorphin (beta-EP) and corticosterone (C) in rats after acute thermal injury. beta-EP rose significantly after thermal injury in normal rats and rats bearing pituitary-to-kidney autotransplants but not in animals with pituitary aspiration without reimplantation. Corticosterone responses paralleled beta-EP but were significant only in normal controls. Propranolol pretreatment did not reduce postburn beta-EP and C rises in autotransplanted animals. Therefore, since circulating factors contribute in vivo to pituitary-adrenal responses, the widespread practice of using "stress hormone" responses to quantitate perioperative stress or pain may in some circumstances be flawed.

Practolol and deafness.

Practolol ('Eraldin') is a beta-blocking agent whose prolonged use may result in the appearance of untoward side-effects, notably ocular symptoms, skin rashes and deafness. We report ten cases of deafness due, or thought to be due, to practolol; and in all except three of the cases (8,9 and 10), the deafness became manifest many months after the appearance of lesions in the skin and eyes. Progression of any hearing loss caused by this drug seems to be arrested by its withdrawal. Otologists are urged to report any suspicious cases to the Committee on Safety of Medicines, Finsbury Square House, 33/37A Finsbury Square, London EC2A IPP.