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Background: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine., Methods: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 μg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively., Results: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%])., Conclusions: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Background: It remains unclear to what extent intravenous lidocaine prevents cough and whether there is dose-responsiveness and risk of harm., Methods: We searched electronic databases to January 1, 2017 for randomized trials comparing intravenous lidocaine with placebo for the prevention of cough in surgical patients. Primary outcome was the incidence of cough. Data were analyzed using a random-effects model and were expressed as risk ratio (RR) and number needed to treat (NNT) with 95% confidence interval., Results: In 20 trials in adults (n = 3062) and 5 trials in children (n = 445), intravenous lidocaine 0.5-2 mg·kg was tested for the prevention of intubation-, extubation-, or opioid-induced cough. Twenty-two trials included only American Society of Anesthesiologists I or II patients; 3 trials (n = 99) also included American Society of Anesthesiologists III patients. Lidocaine was associated with a lower incidence of cough compared to placebo in adults and children, irrespective of dosage and cough etiology. Data from adults suggested dose-responsiveness; with 0.5 mg·kg, RR was 0.66 (0.50-0.88) and NNT was 8 (5.4-14.3); with 1 mg·kg, RR was 0.58 (0.49-0.69) and NNT was 7 (4.6-8.9); with 1.5 mg·kg, RR was 0.44 (0.33-0.58) and NNT was 5 (3.3-5.2); and with 2 mg·kg, RR was 0.39 (0.24-0.62) and NNT was 3 (2.0-3.4). Adverse effect reporting was sparse., Conclusions: Within a range of 0.5-2 mg·kg, intravenous lidocaine dose dependently prevents intubation-, extubation-, and opioid-induced cough in adults and children with NNTs ranging from 8 to 3. The risk of harm in high-risk patients remains unknown.

Background: Sedation with propofol is frequently used to facilitate diagnostic and therapeutic procedures. Propofol can be administrated by the patient (patient-controlled sedation [PCS]) or by a clinician (clinician-controlled sedation [CCS]). We aimed to compare these 2 techniques., Methods: PubMed, Embase, CENTRAL, and trial registries were searched up to October 2017 for randomized controlled trials comparing PCS with CCS with propofol. The primary end points were the risks of presenting at least 1 episode of oxygen desaturation, arterial hypotension, and bradycardia, and the risk of requiring a rescue intervention (pharmacologic therapies or physical maneuvers) for sedation-related adverse events. Secondary end points were the dose of propofol administrated, operator and patient satisfaction, and the risk of oversedation. A random-effects model and an α level of .02 to adjust for multiple analyses were used throughout. Trial sequential analyses were performed for primary outcomes. Quality of evidence was assessed according to the Grades of Recommendation, Assessment, Development, and Evaluation system., Results: Thirteen trials (1103 patients; median age, 47 years; American Society of Anesthesiologists physical status I-III) describing various diagnostic and therapeutic procedures with propofol sedation were included. PCS had no impact on the risk of oxygen desaturation (11 trials, 31/448 patients [6.9%] with PCS versus 46/481 [9.6%] with CCS; risk ratio, 0.74 [98% confidence interval, 0.35-1.56]) but decreased the risk of requiring a rescue intervention for adverse events (11 trials, 29/449 patients [6.5%] with PCS versus 74/482 [15.4%] with CCS; risk ratio, 0.45 [98% confidence interval, 0.25-0.81]). For both outcomes, Trial sequential analyses suggested that further trials were unlikely to change the results, although the quality of evidence was graded very low for all primary outcomes. For the risk of arterial hypotension and bradycardia, the required sample size for a definitive conclusion had not been reached. Analysis of secondary outcomes suggested that PCS decreased the risk of oversedation and had no impact on propofol dose administrated, or on operator or patient satisfaction., Conclusions: PCS with propofol, compared with CCS with propofol, had no impact on the risk of oxygen desaturation, but significantly decreased the risk of rescue interventions for sedation-related adverse events. Further high-quality trials are required to assess the risks and benefits of PCS.

Background: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia., Methods: We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression, or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%-50%, depending on the end point considered. Alpha levels were adjusted (1%) for multiple outcome testing., Results: We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9-174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic, femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes; 99% CI, 37-91), analgesia (WMD 34 minutes; 99% CI, 6-62), and the time to 2 segments regression (WMD 20 minutes; 99% CI, 11-28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS, 11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32-100])., Conclusions: Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain.

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

The present guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel critically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. In brief, these guidelines identify risk factors for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic monotherapy and combination therapy regimens for PONV prophylaxis; recommend approaches for treatment of PONV when it occurs; and provide an algorithm for the management of individuals at increased risk for PONV.

Background: Randomized trials have reached different conclusions as to whether magnesium is a useful adjuvant to postoperative analgesia., Methods: We performed a comprehensive search (electronic databases, bibliographies, all languages, to 4.2006) for randomized comparisons of magnesium and placebo in the surgical setting. Information on postoperative pain intensity and analgesic requirements was extracted from the trials and compared qualitatively. Dichotomous data on adverse effects were combined using classic methods of meta-analysis., Results: Fourteen randomized trials (778 patients, 404 received magnesium) tested magnesium laevulinate, gluconate or sulfate. With magnesium, postoperative pain intensity was significantly decreased in four (29%) trials, was no different from placebo in seven (50%), and was increased in one (7%); two trials (14%) did not report on pain intensity. With magnesium, postoperative analgesic requirements were significantly reduced in eight (57%) trials, were no different from placebo in five (36%), and were increased in one (7%). Magnesium-treated patients had less postoperative shivering (relative risk 0.38, 95% confidence interval 0.17-0.88, number-needed-to-treat 14). Seven trials reported on magnesium serum levels. In all, serum levels were increased in patients who received magnesium; in six, serum levels were decreased in those who received placebo., Conclusions: These trials do not provide convincing evidence that perioperative magnesium may have favorable effects on postoperative pain intensity and analgesic requirements. Perioperative magnesium supplementation prevents postoperative hypomagnesemia and decreases the incidence of postoperative shivering. It may be worthwhile to further study the role of magnesium as a supplement to postoperative analgesia, since this relatively harmless molecule is inexpensive, and the biological basis for its potential antinociceptive effect is promising.

Background: Previous studies have suggested that magnesium may be a useful adjuvant to postoperative analgesia., Methods: We randomized adults undergoing ambulatory ilioinguinal hernia repair or varicose vein operation under general anesthesia (propofol, fentanyl, isoflurane-N2O) to receive magnesium sulfate 4 g IV or physiological saline after induction. All patients preoperatively received diclofenac 100 mg rectally and those undergoing hernia repair had a postoperative ilioinguinal-iliohypogastric nerve block done. Pain, analgesic consumption, and adverse effects were recorded in the recovery room and, using a questionnaire, up to 3 days postoperatively., Results: We randomized 200 patients (101 magnesium, 99 placebo). There were no differences in hemodynamic variables before and immediately after study drug injection. Pain intensity at rest and on movement after 1, 2, and 4 h, time to first rescue analgesic, and cumulative numbers of non-opioid and opioid analgesics were similar among groups. There was no difference in the incidence of postoperative nausea and vomiting, dizziness, headache, or fainting. The incidence of postoperative shivering was significantly lower in the magnesium group (4% vs 13.1%, P = 0.0232). Adequately completed questionnaires were returned by 84 placebo and 82 magnesium patients. There was no difference between groups for any of the analyzed outcomes during the first three postoperative days, neither for patients undergoing inguinal hernia repair nor for those undergoing varicose vein stripping., Conclusions: In patients undergoing ambulatory ilioinguinal hernia repair or varicose vein operations under general anesthesia supplemented with other analgesic adjuvants, pretreatment with IV magnesium sulfate 4 g has no impact on postoperative pain and analgesic consumption.

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.

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).

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

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.

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.

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.

Unlabelled: The best intervention to prevent pain on injection with propofol is unknown. We conducted a systematic literature search (Medline, Embase, Cochrane Library, bibliographies, hand searching, any language, up to September 1999) for full reports of randomized comparisons of analgesic interventions with placebo to prevent that pain. We analyzed data from 6264 patients (mostly adults) of 56 reports. On average, 70% of the patients reported pain on injection. Fifteen drugs, 12 physical measurements, and combinations were tested. With IV lidocaine 40 mg, given with a tourniquet 30 to 120 s before the injection of propofol, the number of patients needed to be treated (NNT) to prevent pain in one who would have had pain had they received placebo was 1.6. The closest to this came meperidine 40 mg with tourniquet (NNT 1.9) and metoclopramide 10 mg with tourniquet (NNT 2.2). With lidocaine mixed with propofol, the best NNT was 2.4; with IV alfentanil or fentanyl, it was 3 to 4. IV lidocaine before the injection of propofol was less analgesic. Temperature had no significant effect. There was a lack of data for all other interventions to allow meaningful conclusions. The diameter of venous catheters and speed of injection had no impact on pain., Implications: IV lidocaine (0.5 mg/kg) should be given with a rubber tourniquet on the forearm, 30 to 120 s before the injection of propofol; lidocaine will prevent pain in approximately 60% of the patients treated in this manner.

Unlabelled: The role of dexamethasone in the prevention of postoperative nausea and vomiting (PONV) is unclear. We reviewed efficacy and safety data of dexamethasone for prevention of PONV. A systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, bibliographies, all languages, up to April 1999) was done for full reports of randomized comparisons of dexamethasone with other antiemetics or placebo in surgical patients. Relevant end points were prevention of early PONV (0 to 6 h postoperatively), late PONV (0 to 24 h), and adverse effects. Data from 1,946 patients from 17 trials were analyzed: 598 received dexamethasone; 582 received ondansetron, granisetron, droperidol, metoclopramide, or perphenazine; 423 received a placebo; and 343 received a combination of dexamethasone with ondansetron or granisetron. With placebo, the incidence of early and late PONV was 35% and 50%, respectively. Sixteen different regimens of dexamethasone were tested, most frequently, 8 or 10 mg IV in adults, and 1 or 1.5 mg/kg IV in children. With these doses, the number needed to treat to prevent early and late vomiting compared with placebo in adults and children was 7.1 (95% CI 4.5 to 18), and 3.8 (2.9 to 5), respectively. In adults, the number needed to treat to prevent late nausea was 4.3 (2.3 to 26). The combination of dexamethasone with ondansetron or granisetron further decreased the risk of PONV; the number needed to treat to prevent late nausea and vomiting with the combined regimen compared with the 5-HT3 receptor antagonists alone was 7.7 (4.8 to 19) and 7.8 (4.1 to 66), respectively. There was a lack of data from comparisons with other antiemetics for sensible conclusions. There were no reports on dexamethasone-related adverse effects., Implications: When there is a high risk of postoperative nausea and vomiting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo, without evidence of any clinically relevant toxicity in otherwise healthy patients. Late efficacy seems to be most pronounced. It is very likely that the best prophylaxis of postoperative nausea and vomiting currently available is achieved by combining dexamethasone with a 5-HT3 receptor antagonist. Optimal doses of this combination need to be identified.

Unlabelled: Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids. To identify the optimal prophylactic antiemetic intervention in this setting, we performed a systematic search for randomized trials (MEDLINE, EMBASE, Cochrane library, reference lists, hand-searching, no language restriction) published up to May 1998 that compared prophylactic antiemetic interventions with placebo or no treatment in the postoperative PCA-setting with opioids. Fourteen placebo-controlled trials (1117 patients) with different regimens of droperidol, ondansetron, hyoscine TTS, tropisetron, metoclopramide, propofol, and promethazine were analyzed. One PCA was with tramadol, all others were with morphine. At 24 h, the cumulative incidence of nausea and vomiting without antiemetics was approximately 50%. Droperidol 0.017-0.17 mg/mg of morphine (0.5-11 mg/d droperidol) was statistically significantly more effective than placebo without evidence of dose-responsiveness; the number needed to treat to prevent nausea compared with placebo was 2.7 (95% confidence interval 1.8-5.2), and that to prevent vomiting was 3.1 (2.3-4.8). Compared with placebo, the incidence of minor adverse effects with droperidol was increased with doses >4 mg/d., Implications: Of 100 patients treated with droperidol added in a patient-controlled analgesia pump with morphine, 30 who would have vomited or been nauseated had they not received droperidol will not suffer these effects. There is no evidence of dose-responsiveness for efficacy with droperidol, but the risk of adverse effects is dose-dependent. There is a lack of evidence for other antiemetics.