Search

The bispectral index (BIS) was used to examine the hypnotic efficacy of propofol in 25 smokers (20 cigarettes/day for 2 years) and 24 matched non-smokers (same gender, age, height, weight). BIS was recorded at baseline, at four incremental effect-site concentrations of propofol and at loss of consciousness. Compared with non-smokers, smokers were found to have higher BIS values at baseline (mean (SD)) (97 (1) vs 98 (1)), at 0.7 microg x ml(-1) (95 (3) vs 97 (1)) and at 1.1 microg x ml(-1) (89 (6) vs 94 (4)), p = 0.0099, and they lost consciousness at higher propofol concentrations (2.0 (0.4) vs 2.4 (0.8) microg x ml(-1)), p = 0.03, and at lower BIS values (66 (10) vs 60 (10)), p = 0.04. The hypnotic efficacy of propofol is reduced when used at low effect-site concentrations in smokers. This phenomenon may have some impact on the management of smokers undergoing sedation using target controlled infusion systems.

Two areas of controversy in altitude medicine are briefly reviewed. The first area concerns the prevention of acute mountain sickness (AMS) with acetazolamide. It is argued that for full prevention of AMS symptoms 500-750mg a day is necessary, but that symptom attenuation may be possible with lower doses. The second concerns the study of the relationship between cerebral blood flow and acute mountain sickness. Multiple methodological problems can be identified; some are related to the experimental settings and some to limitations of the technical tools that are used to estimate cerebral blood flow. For the moment it remains unknown whether or not a change in cerebral blood flow is an etiological factor for the development of acute mountain sickness.

The effect of a treatment versus controls may be expressed in relative or absolute terms. For rational decision-making, absolute measures are more meaningful. The number needed to treat, the reciprocal of the absolute risk reduction, is a powerful estimate of the effect of a treatment. It is particularly useful because it takes into account the underlying risk (what would happen without the intervention?). The number needed to treat tells us not only whether a treatment works but how well it works. Thus, it informs health care professionals about the effort needed to achieve a particular outcome. A number needed to treat should be accompanied by information about the experimental intervention, the control intervention against which the experimental intervention has been tested, the length of the observation period, the underlying risk of the study population, and an exact definition of the endpoint. A 95% confidence interval around the point estimate should be calculated. An isolated number needed to treat is rarely appropriate to summarize the usefulness of an intervention; multiple numbers needed to treat for benefit and harm are more helpful. Absolute risk reduction and number needed to treat should become standard summary estimates in randomized controlled trials.

Introduction: : The association between the degree of neurological deficit and cardiopulmonary dysfunction in patients with spontaneous subarachnoid hemorrhage (SAH) is poorly understood., Method: A systematic search (MEDLINE, bibliographies, to 9.2004) was performed for prospective studies (any architecture; > or = 10 patients with SAH), reporting on neurological deficit and cardiopulmonary dysfunction. Neurological deficit was graded according to the Hunt-Hess or Botterell scores as minimal (1 or 2 points), moderate (3), or severe (4 or 5), and tested for an association with cardiopulmonary dysfunction (Chi-square test)., Results: Relevant data came from two randomized trials, four case control studies, and 31 uncontrolled series. In eight studies (386 patients), ECG abnormalities were found in 32% of patients with minimal, 55% with moderate, and 58% with severe neurological deficit (P < 0.0001). In six studies (135), echocardiographic abnormalities were found in 4% of patients with minimal, 30% with moderate, and 52% with severe neurological deficit (P = 0.0001). In two trials (63), creatinine phosphoskinase was increased in 18% of patients with minimal, 71% with moderate, and 100% with severe neurological deficit (P < 0.0001). In three trials (309), troponin-I was increased in 10% of patients with minimal, 20% of patients with moderate, and 46% with severe neurological deficit (P < 0.0001). In five trials (163), pulmonary edema was found in 4% of patients with minimal, 12% with moderate, and 35% with severe neurological deficit (P < 0.0001). Seventeen studies reported on mortality; 26% of the patients died, 80% of deaths were directly related to SAH., Conclusions: In patients with spontaneous SAH, cardiopulmonary dysfunction is more likely to occur with increasing neurological deficit.

Background to the Debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the efficacy and safety of many treatments.

Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.

Significant improvement towards a better control of postoperative nausea and vomiting have been achieved in recent years. Today, we understand better who is likely to vomit or to be nauseous after surgery. Significant amounts of the huge literature on anti-emetic interventions have been systematically reviewed, critically appraised and quantitatively synthesized. Thus, we know what anti-emetic interventions work, and how well they work, and we know their adverse effect profile. We also know which interventions have no worthwhile efficacy. A rational approach to postoperative nausea and vomiting includes three steps: identification of patients at risk, keeping the baseline risk low, and prophylactic administration of anti-emetics in those patients who are most likely to need them. For patients who are identified as high-risk patients, all measurements should be simultaneously initiated (multimodal anti-emesis).

Shivering is a frequent complication in the postoperative period. The relative efficacy of pharmacological interventions to prevent this phenomenon is not well understood. We performed a systematic search for full reports of randomized comparisons of prophylactic, parenteral, single-dose antishivering interventions with inactive control (placebo or no treatment). Variable doses were converted to fixed doses. Dichotomous data on the absence of shivering were analyzed by using relative benefit (RB) and number needed to treat (NNT) with 95% confidence intervals (CI). Data from 27 trials (1348 adults received an antishivering intervention; 931 were controls) were analyzed. The average incidence of shivering in controls was extremely frequent (52%). Clonidine 65-300 microg (1078 patients), meperidine 12.5-35 mg (250 patients), tramadol 35-220 mg (250 patients), and nefopam 6.5-11 mg (204 patients) were tested in at least 3 trials each. All were more effective than control. For clonidine, meperidine, and nefopam, there was some weak evidence of dose responsiveness. For small-dose clonidine (65-110 microg), the RB compared with control was 1.32 (95% CI, 1.16-1.51); for medium-dose clonidine (140-150 microg), the RB was 1.83 (95% CI, 1.47-2.27); and for large-dose clonidine (220-300 microg), the RB was 1.52 (95% CI, 1.30-1.78). For all clonidine regimens combined, the RB was 1.58 (95% CI, 1.43-1.74), with an NNT of 3.7. For all meperidine regimens combined, the RB was 1.67 (95% CI, 1.37-2.03), with an NNT of 3. For all tramadol regimens combined, the RB was 1.93 (95% CI, 1.56-2.39), with an NNT of 2.2. For all nefopam regimens combined, the RB was 2.62 (95% CI, 2.02-3.40), with an NNT of 1.7. Methylphenidate, midazolam, dolasetron, ondansetron, physostigmine, urapidil, and flumazenil were tested in no more than 3 trials each, with a limited number of patients.

There is a controversy as to whether the number of lumens in the central venous catheters may impact the incidence of catheter-related bloodstream infection. We performed a systematic search (MEDLINE, PREMEDLINE, Cochrane Library, EMBASE, BIOSIS Previews, CINAHL, HealthSTAR/Ovid healthstar, bibliographies, any language, to April, 2003) for full reports on randomized comparisons of single-lumen and multi-lumen catheters. Trials had to report on dichotomous data of catheter colonization or bloodstream infection. Meta-analyses were performed using a fixed effect model. Data were expressed as odds ratio (OR) and number-needed-to-treat (NNT) with 95% confidence interval (CI). Five randomized trials (1987-1995) with data on 255 single-lumen and 275 multi-lumen catheters were analyzed. Average insertion times were 8 to 21 days with multi-lumen catheters and 9 to 24 days with single-lumen catheters. In 4 trials, 23 of 176 (13.1%) multi-lumen and 26 of 177 (14.7%) single-lumen catheters were colonized (OR, 0.92; 95% CI, 0.49-1.72). In 5 trials, bloodstream infection occurred with 23 of 275 (8.4%) multi-lumen and with 8 of 255 (3.1%) single-lumen catheters (OR, 2.58; 95% CI, 1.24-5.37; NNT, 19; 95% CI, 11-75). For every 20 single-lumen catheters inserted, one bloodstream infection will be avoided that would have occurred had multi-lumen catheters been used. The risk of catheter colonization is not decreased. Although these conclusions are based on limited data, single-lumen catheters should be used whenever feasible.

In critically ill patients, adequate analgesia and sedation increase comfort, reduce stress response and facilitate diagnostic and therapeutic procedures. Analgesia and sedation may also have a beneficial impact on morbidity, particularly by reducing pulmonary complications such as atelectasis and pneumonia, and delirium or agitation with subsequent accidental extubation. The method and depth of analgesia and sedation should be adapted to the needs of the individual patient. While evaluation of analgesia and sedation is important, technical tools for assessment are generally unreliable. Accordingly, management of these patients is best guided by simple clinical scores, though there is no consensus on how frequently pain and sedation should be evaluated. While there is some degree of consensus on what constitutes an acceptable level of pain relief, the same is not true of sedation, with the attendant risk of over-sedation. Analgesia and sedation are performed chiefly by pharmacological means. The first step includes adequate analgesia, usually with opioids. There is no evidence of a difference in efficacy between opioids as far as clinically relevant outcomes are concerned. However, there is some evidence that more sophisticated methods of opioid administration, such as patient-controlled analgesia, may improve pulmonary outcomes. In Europe, midazolam and propofol are most frequently used for sedation of the critically ill. Regular evaluation of the effect of these drugs and subsequent adaptation of dosage are more important than the choice of specific analgesics and hypnotics. Implementation of guidelines for rational analgesia and sedation would help to reduce patients' length of stay in the intensive care unit.

Cerebral blood flow is thought to increase at high altitude and in subjects suffering from acute mountain sickness (AMS); however, data from the literature are contentious. Blood flow velocity in the middle cerebral artery (MCAv) may be used as a proxy measure of cerebral blood flow. Using transcranial Doppler sonography, MCAv was measured during normo- and hyper-ventilation in subjects who participated in a trial that tested the effect of magnesium supplementation on the prevention of AMS. First, MCAv was recorded at 353 m (baseline). Subjects were then randomized to receive oral magnesium citrate and matching placebo. A second measurement was taken after a 24 +/- 2 h ascent from 1130 m to 4559 m (altitude I), and a third after a 20-24 h stay at 4559 m (altitude II). Using multivariate linear regression, an association was sought between MCAv and magnesium supplementation, subjects' age and gender, altitude itself, a temporary stay at altitude, and the presence of AMS (Lake Louise Score >6 with ataxia, nausea and/or headache). Subjects with AMS had additional Doppler recordings immediately before and after rescue medication (oxygen, dexamethasone and acetazolamide). Forty-seven subjects had measurements at baseline, 39 (21 receiving magnesium and 18 placebo) at altitude I and 26 (13 receiving magnesium and 13 placebo) at altitude II. During hyperventilation, MCAv decreased consistently (for each measurement, P<0.001). Magnesium significantly increased MCAv by 8.4 cm.s(-1) (95% confidence interval, 1.8-15), but did not prevent AMS. No other factors were associated with MCAv. Eleven subjects had severe AMS [median score (range), 11 (8-16)] and, after rescue medication, the median score decreased to 3 (range, 0-5; P=0.001), but MCAv remained unchanged (65 +/- 18 cm.s(-1) before compared with 67 +/- 16 cm.s(-1) after rescue medication; P=0.79). MCAv was increased in subjects who received magnesium, but was not affected by exposure to high altitude or by severe AMS.

Magnesium is a physiological N-methyl-D-aspartate (NMDA) antagonist. The NMDA receptor may be involved in the pathogenesis of acute mountain sickness (AMS). In the present study, healthy subjects were randomized to receive either 400 mg of oral magnesium citrate (16 mmol) or matching placebo every 8 h for 5 days (prevention trial). Subjects then climbed to 4559 m in approx. 24 h and stayed there for 48 h. A Lake Louise Score <3 at any time was defined as the absence of AMS, whereas a score >6 (with ataxia, headache and nausea) was defined as a prevention failure. In a subsequent trial (treatment trial), subjects with a Lake Louise Score >6 (with ataxia, headache and/or nausea) were randomized to receive either 4 g of intravenous magnesium sulphate (16 mmol) or matching placebo. A decrease in the score >50% within 60 min was regarded as a treatment success. Dichotomous data were analysed using relative risk (RR) or odds ratio (OR), and continuous data using Student's t test or Wilcoxon's rank-sum test. In the prevention trial, data from 61 subjects (30 receiving magnesium and 31 placebo) were analysed. With oral magnesium, 20% of subjects had no AMS compared with 16.1% in the placebo group [RR (95% CI), 1.2 (0.4-3.6); where CI is confidence interval]. With magnesium, 40% were prevention failures compared with 35.5% in the placebo group [RR (95% CI), 1.13 (0.59-2.15)]. The mean time to failure and severity of AMS was similar between the two groups. With magnesium, 38.2% had loose stools compared with 11.8% in placebo group [RR (95% CI), 3.25 (1.18-8.97)]. In the treatment trial, 12 subjects received magnesium and 13 received the placebo. With intravenous magnesium, 25% were regarded as treatment successes compared with none in the placebo group [OR (95% CI), 9.71 (0.91-103.4)]. With magnesium, mean (+/- S.D.) scores decreased from 11.6 +/- 1.7 before treatment to 9.0 +/- 3.5 after treatment (P=0.009); scores remained unchanged in the placebo group. With magnesium, 75% of subjects experienced a transient flushing compared with 7.7% in the placebo group [RR (95% CI), 0.05 (0.01-0.25)]. In conclusion, oral magnesium does not prevent AMS. In subjects with established AMS, intravenous magnesium reduces the severity of symptoms to some extent, but this effect is of no clinical importance.

Context: Duplicate publication is publication of an article that overlaps substantially with an article published elsewhere. Patterns of duplication are not well understood., Objective: To investigate duplication patterns and propose a decision tree for classification., Data Sources: We searched a comprehensive list of systematic reviews (1989 through August 15, 2002) in anesthesia and analgesia that is accessible on the Internet. We selected published full articles of duplicates that had been identified in these systematic reviews. Abstracts, letters, or book chapters were excluded., Study Selection and Data Extraction: Authors of 56 (40%) of 141 systematic reviews acknowledged identification of duplicates. Duplication patterns were identified independently by all investigators comparing samples and outcomes of pairs of duplicates and main articles. Information on cross-reference, sponsorship, authorship, and publication characteristics was extracted from the articles., Data Synthesis: The 56 systematic reviews included 1131 main articles (129 337 subjects) and excluded 103 duplicates (12 589 subjects) that originated from 78 main articles. Sixty articles were published twice, 13 three times, 3 four times, and 2 five times. We identified 6 duplication patterns: (1A) identical samples and identical outcomes (21 pairs); (1B) same as 1A but several duplicates assembled (n = 16); (2) identical samples and different outcomes (n = 24); (3A) increasing sample and identical outcomes (n = 11); (3B) decreasing sample and identical outcomes (n = 11); (4) different samples and different outcomes (n = 20). The prevalence of covert duplicate articles (without a cross-reference to the main article) was 5.3% (65/1234). Of the duplicates, 34 (33%) were sponsored by the pharmaceutical industry, and 66 (64%) had authorship that differed partly or completely from the main article. The median journal impact factor was 1.8 (range, 0.1-29.5) for duplicates and 2.0 (range, 0.4-29.5) for main articles (P =.13). The median annual citation rate was 1.7 (range, 0-27) for duplicates and 2.1 (range, 0-31) for main articles (P =.45). The median number of authors was 4 (range, 1-14) for duplicates and 4 (range, 1-15) for corresponding main articles (P =.02). The median delay in publication between main articles and duplicates was 1 year (range, 0-7 years)., Conclusions: Duplication goes beyond simple copying. Six distinct duplication patterns were identified after comparing study samples and outcomes of duplicates and corresponding main articles. Authorship was an unreliable criterion. Duplicates were published in journals with similar impact factors and were cited as frequently as main articles.

Objective: To assess whether respiratory physiotherapy prevents pulmonary complications after cardiac surgery., Data Sources: Searches through Medline, Embase, Cinahl, the Cochrane library, and bibliographies, for randomised trials comparing any type of prophylactic respiratory physiotherapy with another type or no intervention after cardiac surgery, with a follow up of at least two days, and reporting on respiratory outcomes., Review Methods: Investigators assessed trial validity independently. Information on study design, population, interventions, and end points was abstracted by one investigator and checked by the others., Results: 18 trials (1457 patients) were identified. Most were of low quality. They tested physical therapy (13 trials), incentive spirometry (eight), continuous positive airway pressure (five), and intermittent positive pressure breathing (three). The maximum follow up was six days. Four trials only had a no intervention control; none showed any significant benefit of physiotherapy. Across all trials and interventions, average values postoperatively were: incidence of atelectasis, 15-98%; incidence of pneumonia, 0-20%; partial pressure of arterial oxygen per inspired oxygen fraction, 212-329 mm Hg; vital capacity, 37-72% of preoperative values; and forced expiratory volume in one second, 34-72%. No intervention showed superiority for any end point. For the most labour intensive intervention, continuous positive airway pressure, the average cost of labour for each patient day was 27 euro (pound 19; 32 dollars)., Conclusions: The usefulness of respiratory physiotherapy for the prevention of pulmonary complications after cardiac surgery remains unproved. Large randomised trials are needed with no intervention controls, clinically relevant end points, and reasonable follow up periods.

The antiemetic dose response of droperidol when it is added to patient-controlled analgesia with morphine is not well known. We randomly allocated adults who received postoperative morphine patient-controlled analgesia (1-mg bolus, 5-min lockout) to one of four regimens: no droperidol (control) or 5, 15, or 50 micro g of droperidol per milligram of morphine. Efficacy and adverse effects were recorded during 24 h and were analyzed with number needed to treat (NNT) and number needed to harm with 95% confidence intervals. Data from 82 controls, 82 patients receiving droperidol 5 micro g, 82 receiving droperidol 15 micro g, and 83 receiving droperidol 50 micro g were analyzed. Average consumption of droperidol per 24 h was 0.2 mg with the 5- micro g regimen, 0.61 mg with the 15- micro g regimen, and 2.04 mg with the 50- micro g regimen. In controls, the incidence of nausea was 48.8%; with droperidol 5 micro g, it was 42.7% (NNT compared with control, 16 [95% confidence interval, 4.7 to -11]); with 15 micro g, it was 32.9% (NNT, 6.3 [3.3-100]); and with 50 micro g, it was 21.7% (NNT, 3.7 [2.4 to 7.6]). In controls, the incidence of vomiting was 24.4%; with droperidol 5 micro g, it was 23.2% (NNT compared with control, 82 [7 to -8.5]); with 15 micro g, it was 22.0% (NNT, 41 [6.5 to -9.6]); and with 50 micro g, it was 12% (NNT, 8.1 [4.2-142]). In controls, the incidence of pruritus was 12.2%; with droperidol 5 micro g, it was 6.1% (NNT compared with control, 16 [6.7 to -37]); and with 15 and 50 micro g, it was 2.4% (NNT, 10 [5.7-52]). In controls, the incidence of sedation was 2.4%; with droperidol 5 micro g, it was 8.5% (number needed to harm (NNH) compared with control, 16 [7.7 to -123]); with 15 micro g, it was 6.1% (NNH, 27 [10 to -40]); and with 50 micro g, it was 18.1% (NNH, 6.4 [4.1-15]). There were no extrapyramidal symptoms and no cardiac adverse events. There was no difference in patient satisfaction. The optimal antiemetic dose of droperidol is 15-50 micro g/mg of morphine. Larger doses may have more antivomiting efficacy but are likely to be unacceptably sedating.

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).

Background: It has been estimated that about 45% of abstracts that are accepted for presentation at biomedical meetings will subsequently be published in full. The acceptance of abstracts at meetings and their fate after initial rejection are less well understood. We set out to estimate the proportion of abstracts submitted to meetings that are eventually published as full reports, and to explore factors that are associated with meeting acceptance and successful publication., Methods: Studies analysing acceptance of abstracts at biomedical meetings or their subsequent full publication were searched in MEDLINE, OLDMEDLINE, EMBASE, Cochrane Library, CINAHL, BIOSIS, Science Citation Index Expanded, and by hand searching of bibliographies and proceedings. We estimated rates of abstract acceptance and of subsequent full publication, and identified abstract and meeting characteristics associated with acceptance and publication, using logistic regression analysis, survival-type analysis, and meta-analysis., Results: Analysed meetings were held between 1957 and 1999. Of 14945 abstracts that were submitted to 43 meetings, 46% were accepted. The rate of full publication was studied with 19123 abstracts that were presented at 234 meetings. Using survival-type analysis, we estimated that 27% were published after two, 41% after four, and 44% after six years. Of 2412 abstracts that were rejected at 24 meetings, 27% were published despite rejection. Factors associated with both abstract acceptance and subsequent publication were basic science and positive study outcome. Large meetings and those held outside the US were more likely to accept abstracts. Abstracts were more likely to be published subsequently if presented either orally, at small meetings, or at a US meeting. Abstract acceptance itself was strongly associated with full publication., Conclusions: About one third of abstracts submitted to biomedical meetings were published as full reports. Acceptance at meetings and publication were associated with specific characteristics of abstracts and meetings.

Implications: We present evidence-based guidelines developed by an international panel of experts for the management of postoperative nausea and vomiting.

The Cochrane Collaboration is an international non-profit organisation that aims to help clinicians in making well-informed decisions about health care issues. This is done through preparing, maintaining and disseminating systematic reviews on the effects of health care interventions. To facilitate this task, review groups have been established. These groups cover specific health care areas and form the organisational basis of the collaboration. They provide methodological and logistic help to the authors of the systematic reviews. The Cochrane Anaesthesia Review Group (CARG) covers anaesthesia, perioperative medicine, intensive care,pre-hospital medicine, resuscitation, and emergency medicine. Protocols and completed Cochrane reviews are published in a structured format in the electronic Cochrane Library. Beside this Cochrane database of systematic reviews, the Cochrane library contains a database with summaries of non-Cochrane systematic reviews (database of abstracts of reviews of effectiveness), and a comprehensive database with controlled clinical trials (Cochrane central register of controlled trials). Thus the Cochrane library is a useful source of information on health care interventions for anaesthetists.

Unlabelled: 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)., Implications: The evidence for nonsteroidal antiinflammatory drugs to increase the risk of bleeding after tonsillectomy is equivocal, and the risk-benefit ratio is not straightforward. There is some evidence for an increased likelihood of reoperation because of bleeding. The agenda must be one of further research rather than of clinical recommendations.

Unlabelled: Insertion of a peripheral IV cannula is a common, although painful, procedure. We tested the analgesic efficacy, adverse effects, and cost-effectiveness of a needle-free intradermal drug delivery system (Jet) with lidocaine for the insertion of an IV cannula (18-gauge; dorsum of hand). Four-hundred patients were randomly allocated to one of four groups: (a) no treatment, (b) Jet (J-Tip), National Medical Products Inc, CA; $3.0 per device) with 0.5 mL of saline, (3) Jet with 0.5 mL of lidocaine 1%, and (4) Jet with 0.5 mL of lidocaine 2%. Pain was evaluated using a numerical verbal scale (NVS 0-10). A NVS < or =3 was considered as acceptable in this context. Incremental cost-effectiveness ratios were calculated. Without treatment, 42.4% of patients had a NVS < or = 3, 39.3% with saline, 60.7% with 1% lidocaine (relative risk [RR] compared with no treatment, 0.70; 95% confidence interval [CI], 0.53-0.93), and 86.7% with 2% lidocaine (RR, 0.49; 95% CI, 0.38-0.62). Nineteen and one-half percent of patients had a NVS >3 because of Jet treatment, 13.5% had local hyperemia, and 16.9% had minor local bleeding. Of all Jet treatments, 10.5% were technical failures, and there were 17.6% cannula insertion failures (10.1% without treatment [RR, 1.74; 95% CI, 0.92-3.32]). Compared with no treatment, costs to generate one additional patient with a NVS < or =3 were $23 with lidocaine 1% and $10 with lidocaine 2%. On insertion of an IV cannula on the back of the hand, 58% of patients report at least moderate pain. Lidocaine-Jet is analgesic; there is dose-responsiveness. However, Jet treatment is not painless, and costs incurred to achieve one success compared with doing nothing are not negligible., Implications: Insertion of an IV cannula is painful. Four-hundred patients were randomly allocated to test the analgesic efficacy, adverse effects, and cost-effectiveness of the needle-free intradermal drug delivery system (J-Tip); Jet). Jet with lidocaine is effective, but its application is not painless. Costs to achieve one patient with no more than moderate pain (numerical verbal scale < or =3 of 10) on insertion of an IV cannula are $10.

Postoperative shivering consists of muscular tremor and rigidity. It is often associated with body heat loss, although hypothermia alone does not fully explain the occurrence of shivering. Shivering is self-limiting, never becomes chronic, and is rarely associated with major morbidity. However, it affects the comfort of the patients, and may sometimes lead to more serious complications. The efficacy of a great variety of pharmacologic interventions to prevent shivering and to treat established symptoms has been tested in randomized controlled trials. These can be gathered systematically; recommendations on prevention and treatment can then be based on the strongest evidence. Unfortunately all these trials have been performed in adults. Thus, recommendations for the control of postoperative shivering in children have to be extrapolated from adult data. In adults, a systematic review strongly suggests that simple measurements are efficacious for both prevention and treatment. For prevention, extrapolation of these adult data indicates that three children have to receive intravenous clonidine 1.5 micro g/kg during anesthesia for one not to shiver, when they would have done so had they not received clonidine. For this degree of efficacy, the expected incidence of shivering (baseline risk) has to be high (approximately 50%). For treatment, extrapolation from adult data indicates that less than two children need to receive intravenous meperidine (pethidine) 0.35 mg/kg, or clonidine 1.5 micro g/kg for one to stop shivering five minutes after drug administration, when they would not have done so had they not received one of these drugs. Since the treatment of established shivering is efficacious, simple, inexpensive, and relatively safe, and since prevention is only efficacious if the baseline risk is very high, we recommend the 'wait and see' strategy.

Objective: To test the evidence that the risk of infection related to central venous catheters (CVCs) is decreased by anti-infective coating or cuffing., Design: Systematic review of randomized, controlled trials comparing anti-infective with inactive (control) CVCs., Interventions: Average insertion times were taken as a measurement of the length of insertion. Dichotomous data were combined using a fixed effect model and expressed as odds ratio (OR) with 95% confidence interval (CI95)., Results: Two trials on antibiotic coating (343 CVCs) had an average insertion time of 6 days; the risk of BSI decreased from 5.1% with control to 0% with anti-infective catheters. There were no trials with longer average insertion times. In three trials on silver collagen cuffs (422 CVCs), the average insertion time ranged from 5 to 8.2 days (median, 7 days); the risk of BSI was 5.6% with control and 3.2% with anti-infective catheters. In another trial on silver collagen cuffs (101 CVCs), the average insertion time was 38 days; the risk of BSI was 3.7% with control and 4.3% with anti-infective catheters. In five trials on chlorhexidine-silver sulfadiazine coating (1,269 CVCs), the average insertion time ranged from 5.2 to 7.5 days (median, 6 days); the risk of BSI decreased from 4.1% with control to 1.9% with anti-infective catheters. In five additional trials on chlorhexidine-silver sulfadiazine coating (1,544 CVCs), the average insertion time ranged from 7.8 to 20 days (median, 12 days); the risk of BSI was 4.5% with control and 4.2% with anti-infective catheters., Conclusions: Antibiotic and chlorhexidine-silver sulfadiazine coatings are anti-infective for short (approximately 1 week) insertion times. For longer insertion times, there are no data on antibiotic coating, and there is evidence of lack of effect for chlorhexidine-silver sulfadiazine coating. For silver-impregnated collagen cuffs, there is evidence of lack of effect for both short- and long-term insertion.

Magnesium is a physiological antagonist of both calcium and the NMDA receptor. Patients with chronic pain of a limb (>1 month's duration) were treated with two Bier's blocks (250 mmHg, 10 m) in a randomised, double-blind, cross-over design. They received once 20% magnesium sulphate (500 mg) + lignocaine 1% (75 mg), and once physiological saline + lignocaine 1% (75 mg). The volume of both treatments was 10 ml. Efficacy data from 49 treatments (25 magnesium, 24 placebo) could be analysed. With magnesium-lignocaine, the duration of pain relief as reported by the patients was on average 23 days (95% CI 8-38) compared with 6 days (95% CI 2-10) with lignocaine alone (P = 0.043). With magnesium-lignocaine, 54.2% of patients had more than 50% pain relief compared with 25% with lignocaine alone (number-needed-to-treat 3.5, P = 0.075). With magnesium-lignocaine, 20% of patients had a treatment failure (i.e. pain relief <24 h) compared with 50% with lignocaine alone (number needed-to-treat 3.3, 95% CI 1.8-29, P = 0.038). The magnesium-lignocaine treatment was painful in 52% of patients compared with 8% with lignocaine alone (number-needed-to-harm 2.3, 95% CI 1.5-4.5, P =0.0008). For patients with chronic limb pain, the addition of magnesium to a Bier's block with lignocaine improves and prolongs pain relief and reduces the number of treatment failures. The optimal dose of lignocaine to prevent magnesium-induced aching of the treated limb needs to be established. Bier's block with magnesium-lignocaine may provide a possible treatment alternative in these patients., (Copyright 2002 International Association for the Study of Pain)

Data on seizure-like phenomena (SLP) in patients receiving propofol were systematically reviewed. Reports had to provide detailed information on SLP in individual patients who received propofol. Phenomena were classified according to the time point of their occurrence during anesthesia or sedation (induction, maintenance, emergence, delayed [>30 minutes after emergence]) and their clinical presentation (generalized tonic-clonic seizures, focal motor seizures, events presented as increased tone with twitching and rhythmic movements not perceived as generalized tonic-clonic seizures, opisthotonos, involuntary movements). In 70 patients without epilepsy, SLP happened during induction in 24 (34%), during maintenance in two (3%), during emergence in 28 (40%), and was delayed in 16 (23%). Most frequent clinical presentations of SLP were generalized tonic-clonic seizures in 30 patients (43%), events presented as increased tone with twitching and rhythmic movements not perceived as generalized tonic-clonic seizures in 20 (36%), and involuntary movements in 11 (16%). Of 11 patients with epilepsy, seven (64%) had generalized tonic-clonic seizure during emergence. Of all 81 patients, 26 (32%) only had an EEG, and 12 (15%) only a neurologic consultation. SLP may happen in patients with or without epilepsy receiving propofol. The time point of the occurrence of SLP suggests that a change in cerebral concentration of propofol may be causal. To confirm this hypothesis, to estimate the prevalence of propofol-related SLP, and to identify patients at risk, data of higher quality are needed.

Objective: To evaluate fetal and maternal adverse effects of intrathecal opioid analgesia during labour., Data Sources: A systematic search was performed, in Medline, Embase, the Cochrane Library, bibliographies, and personal contact with authors, in any language, up to February 2001., Study: selection Full reports on randomised comparisons of any analgesia with intrathecal opioid (experimental group) with any non-intrathecal opioid regimen (control group) during labour., Data Extraction: Dichotomous data from 24 trials (3513 women)., Results: With intrathecal opioids, there was a significant increase in the risk of fetal bradycardia: odds ratio 1.8 (95% confidence interval 1.0 to 3.1), number-needed-to-harm 28. The risk of caesarean section due to fetal heart rate abnormalities was similar (6.0% versus 7.8%). The incidence of pruritus was significantly higher with intrathecal opioids: relative risk 29.6 (95% CI 13.6 to 64.6), number-needed-to-harm 1.7., Conclusions: Intrathecal opioids for labour increase the risk of fetal bradycardia and maternal pruritus. The risk of subsequent caesarean section is not increased.

Unlabelled: Shivering is a frequent complication in the postoperative period. The relative efficacy of interventions that are used for the treatment of postoperative shivering is not well understood. We performed a systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, all languages, to August, 2000) for full reports of randomized comparisons of any pharmacological antishivering intervention (active) with placebo (control) in the postoperative period. Dichotomous data on absence of further shivering after treatment and adverse effects were extracted from original reports. Relative risk (RR) and number-needed-to-treat (NNT) were calculated with 95% confidence interval (CI) using a fixed effect model. Data from 20 trials (944 adults received an active intervention, 413 were controls) were analyzed. Antishivering efficacy depended on the active regimen and the length of follow-up. Efficacy with meperidine 25 mg, clonidine 150 microg, ketanserin 10 mg, and doxapram 100 mg was reported in at least three trials; all were significantly more effective than control. After 1 min, the NNT of meperidine 25 mg for no further shivering compared with placebo was 2.7 (RR, 6.8; 95% CI, 2.5-18.5). After 5 min, the NNT of meperidine 25 mg was 1.3 (RR, 9.6; 95% CI, 5.7-16), the NNT of clonidine 150 microg was 1.3 (RR, 6.8; 95% CI, 3.3-14.2), the NNT of doxapram 100 mg was 1.7 (RR 4.0; 95% CI, 2.4-6.5), and the NNT of ketanserin 10 mg was 2.3 (RR 3.1; 95% CI, 1.9-5.1). After 10 min, the NNT of meperidine 25 mg was 1.5 (RR 4.0; 95% CI, 2.5-6.2). After 15 min, the NNT of ketanserin 10 mg was 3.3 (RR 1.5; 95% CI, 1.2-1.9). Long-term outcome data were lacking. There were not enough data for alfentanil, fentanyl, morphine, nalbuphine, lidocaine, magnesium, metamizol, methylphenidate, nefopam, pentazocine, and tramadol to draw meaningful conclusions. Reporting of adverse drug reactions was sparse. Fewer than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo., Implications: Less than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo.

Background and Purpose: Transcranial Doppler (TCD) is used for diagnosis of vasospasm in patients with subarachnoid hemorrhage due to a ruptured aneurysm. Our aim was to evaluate both the accuracy of TCD compared with angiography and its usefulness as a screening method in this setting., Methods: A search (MEDLINE, EMBASE, Cochrane Library, bibliographies, hand searching, any language, through January 31, 2001) was performed for studies comparing TCD with angiography. Data were critically appraised using a modified published 10-point score and were combined using a random-effects model., Results: Twenty-six reports compared TCD with angiography. Median validity score was 4.5 (range 1 to 8). Meta-analyses could be performed with data from 7 trials. For the middle cerebral artery (5 trials, 317 tests), sensitivity was 67% (95% CI 48% to 87%), specificity was 99% (98% to 100%), positive predictive value (PPV) was 97% (95% to 98%), and negative predictive value (NPV) was 78% (65% to 91%). For the anterior cerebral artery (3 trials, 171 tests), sensitivity was 42% (11% to 72%), specificity was 76% (53% to 100%), PPV was 56% (27% to 84%), and NPV was 69% (43% to 95%). Three of these 7 studies reported on the same patients, each on another artery, and for 4, data recycling could not be disproved. Other arteries were tested in only 1 trial each., Conclusions: For the middle cerebral artery, TCD is not likely to indicate a spasm when angiography does not show one (high specificity), and TCD may be used to identify patients with a spasm (high PPV). For all other situations and arteries, there is either lack of evidence of accuracy or of any usefulness of TCD. Most of these data are of low methodological quality, bias cannot not be ruled out, and data reporting is often uncritical.

The aim of Evidence-based medicine (EBM) is the unbiased and systematic identification and synthesis of valid scientific data. These best-evidence data may then be used for clinical decision-making. The systematic review is the most important tool of EBM and gives a specific answer to a specific question. More than 200 systematic reviews have been published in perioperative medicine. They treat complications and risks related to anaesthesia, postoperative and labour analgesia, nausea and vomiting, regional anaesthesia, blood transfusion and fluids replacement, and resuscitation. The majority of these systematic reviews are of good quality. In the specific settings of perioperative medicine the number of systematic reviews has become so important that recommendations for evidenced-based strategies of prevention and therapy can be formulated.

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.

Objective: To establish whether cannabis is an effective and safe treatment option in the management of pain., Design: Systematic review of randomised controlled trials., Data Sources: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches., Study Selection: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score., Data Extraction: Independent data extraction; discrepancies resolved by consensus., Data Synthesis: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common., Conclusion: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.

Objective: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy., Design: Systematic review., Data Sources: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000., Studies: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours., Results: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11., Conclusions: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

Background and Objective: Numerous drugs have been used to prevent or to treat opioid-induced pruritus in the surgical setting. Their relative efficacy is not well understood., Methods: The methods employed involved the systematic search (MEDLINE, EMBASE, Cochrane library, bibliographies, without language restriction, up to June 2000) for full reports of randomized comparisons of any intervention which is thought to be anti-pruritic (active) compared with placebo or no treatment (control) in surgical (including labour) patients receiving opioids. The number of patients who had no pruritus were analysed using relative risk and number-needed-to-treat with 95% confidence interval., Results: Twenty-two trials (1477 patients) were analysed. Two trials (66 patients), both with low-dose propofol, were on treatment of established pruritus; propofol had no anti-pruritic effect compared with Intralipid. In prophylaxis trials, the average incidence of pruritus with control was 59% (range, 10% to 100%). Most mu-receptor antagonists were efficacious: intravenous naloxone 0.25-2.4 microg kg-1 h-1, relative risk 2.31 (95% confidence interval, 1.5 to 3.54), number-needed-to-treat to prevent pruritus compared with control 3.5; oral naltrexone 9 mg, relative risk 2.80 (1.35-5.80), number-needed-to-treat 1.7; naltrexone 6 mg was less effective and 3 mg did not work; different intravenous and epidural nalbuphine regimens, relative risk 1.71 (1.12-2.62), number-needed-to-treat 4.2. Intravenous nalmefene 0.5 or 1 mg was not anti-pruritic. Intravenous (but not epidural) droperidol 2.5 mg was efficacious, relative risk, 1.71 (1.28-2.29), number-needed-to-treat 4.9. There was a lack of evidence for any anti-pruritic efficacy with prophylactic propofol, epidural or intrathecal epinephrine, epidural clonidine, epidural prednisone, intravenous ondansetron, or intramuscular hydroxyzine., Conclusion: Naloxone, naltrexone, nalbuphine and droperidol are efficacious in the prevention of opioid-induced pruritus; minimal effective doses remain unknown. There is a lack of valid data on the efficacy of interventions for the treatment of established pruritus.

A systematic search (Medline, Cochrane library, Embase, bibliographies, to 5.2000, no language restriction) was performed for published reports of randomized comparisons of propofol and methohexital for anesthesia during electroconvulsive therapy. We analyzed 15 trials with data on 706 patients. The duration of motor seizure was shorter with propofol (range, 18-39 seconds) than with methohexital (range, 26-48 seconds, weighted mean difference 8.4 seconds [95% CI, 6.6-10.0]). With both propofol and methohexital, there was little evidence of an association between dose and duration of motor seizure (for propofol: r2 = 0.25, P = .08; for methohexital: r2 = 0.11, P = .27). Two small trials investigated clinical outcome; results were inconclusive. Data on adverse effects were sparse. Duration of seizure was not proven to be a useful measure of treatment success in the study of electroconvulsive therapy with propofol or methohexital. The impact of the technique of anesthesia on the underlying disease needs to be established.

Unlabelled: Propofol and midazolam are often used for sedation in the intensive care unit. The aim of this systematic review was to estimate the efficacy and harm of propofol versus midazolam in mechanically ventilated patients. A systematic search (Medline, Cochrane Library, Embase, bibliographies), any language, up to June 1999 was performed for reports of randomized comparisons of propofol with midazolam. Data from 27 trials (1624 adults) were analyzed. The average duration of sedation varied between 4 and 339 h. In 10 trials, the duration of adequate sedation was longer with propofol (weighted mean difference 2.9 h; 95% confidence interval [CI], 0.2-5.6 h). In 13 trials (mostly postoperative), sedation lasted 4 to 35 h; in 9 of those, average weaning time from mechanical ventilation with propofol was 0.8-4.3 h; with midazolam it was 1.5-7.2 h (weighted mean difference 2.2 h [95% CI, 0.8 to 3.7 h]). In 8 trials, sedation lasted 54 to 339 h; there was a lack of evidence for difference in weaning times. Arterial hypotension (relative risk 2.5 [95% CI, 1.3 to 4.5]; number-needed-to-treat, 12), and hypertriglyceridemia (relative risk 12.1 [95%CI, 2.9 to 49.7]; number-needed-to-treat, 6) occurred more often with propofol. The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation <36 h, weaning is faster with propofol., Implications: The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation < 36 h, weaning is faster with propofol.

Unlabelled: Systematic reviews are structured reviews that use scientific strategies to reduce bias in the collection, appraisal, and interpretation of relevant studies. We undertook a systematic review of published systematic reviews in perioperative medicine to summarize the areas currently covered by this type of literature, to evaluate the quality of systematic reviews in this field, and to assess some of the methodologic and reporting issues that are unique to systematic reviews. Computerized bibliographic databases, citation review, and hand searches were performed to identify eligible articles. Quality was assessed using the Overview Quality Assessment Questionnaire. Eight-two systematic reviews were found. Reviews in perioperative medicine tended to evaluate prophylactic or therapeutic interventions. No differences were seen in quality between reviews published in anesthesia and nonanesthesia journals. Nearly half of all systematic reviews had only minor or minimal flaws; however, methods can be improved with expanded search strategies, use of least two reviewers to assess each study, use of validated methods to evaluate quality, and assessment of potential sources of bias., Implications: The quality of systematic reviews relating to perioperative medicine was examined systematically and found to be similar in quality to those in other specialties. Adoption of recently published criteria on writing and methods could further improve this type of literature.

BACKGROUND: The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood. METHODS: Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000) for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. RESULTS: In seven trials (1,267 patients), 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809) had placebo controls. Dolasetron 12.5-100 mg, granisetron 0.1-3 mg, tropisetron 0.5-5 mg, and ondansetron 1-8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%-30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK1 antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. CONCLUSIONS: Of 100 vomiting surgical patients receiving a 5-HT3 receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed.

Background and Aim: The effects of analgesic drugs on sleep are poorly understood. We investigated short- and medium-term effects of tramadol on sleep structure., Methods: Eight healthy volunteers received a placebo (predrug placebo-night), then, in a randomized, double-blind, cross-over fashion a single oral dose of tramadol 50 mg or 100 mg (drug-night), and finally, again a placebo (postdrug placebo-night). Standardized polysomnography (electroencephalogram, electro-oculogram, submental electromyogram) was continuously recorded during placebo- and drug-nights., Results: During drug-nights both doses of tramadol significantly increased the duration of stage 2 sleep, and significantly decreased the duration of slow-wave sleep (stage 4). Tramadol 100 mg but not 50 mg significantly decreased the duration of paradoxical (rapid eye movement) sleep. In the placebo-night after tramadol 100 mg (but not after 50 mg) duration of stage 2 sleep was significantly shorter, and duration of stage 4 sleep was significantly longer compared with the predrug placebo-night., Conclusion: In healthy volunteers, a single dose of tramadol 50 mg disturbs sleep in the night of drug application. With 100 mg, sleep is disturbed in both the night of drug application and in the subsequent night.