Kate Leslie

Bispectral index monitoring to prevent awareness during anaesthesia: The b-aware randomised controlled trial

BACKGROUND Awareness is an uncommon complication of anaesthesia, affecting 0.1-0.2% of all surgical patients. Bispectral index (BIS) monitoring measures the depth of anaesthesia and facilitates anaesthetic titration. In this trial we determined whether BIS-guided anaesthesia reduced the incidence of awareness during surgery in adults. METHODS We did a prospective, randomised, double-blind, multicentre trial. Adult patients at high risk of awareness were randomly allocated to BIS-guided anaesthesia or routine care. Patients were assessed by a blinded observer for awareness at 2-6 h, 24-36 h, and 30 days after surgery. An independent committee, blinded to group identity, assessed every report of awareness. The primary outcome measure was confirmed awareness under anaesthesia at any time. FINDINGS Of 2463 eligible and consenting patients, 1225 were assigned to the BIS group and 1238 to the routine care group. There were two reports of awareness in the BIS-guided group and 11 reports in the routine care group (p=0.022). BIS-guided anaesthesia reduced the risk of awareness by 82% (95% CI 17-98%). INTERPRETATION BIS-guided anaesthesia reduces the risk of awareness in at-risk adult surgical patients undergoing relaxant general anaesthesia. With a cost of routine BIS monitoring at US16 dollars per use in Australia and a number needed to treat of 138, the cost of preventing one case of awareness in high-risk patients is about 2200 dollars.

Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk

THIS IS THE FIRST OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. In this article, we review the magnitude of the problem, the pathophysiology of these events, approaches to risk assessment and communication of risk. The number of patients undergoing noncardiac surgery worldwide is growing, and annually 500 000 to 900 000 of these patients experience perioperative cardiac death, nonfatal myocardial infarction (MI) or nonfatal cardiac arrest. Although the evidence is limited, a substantial proportion of fatal perioperative MIs may not share the same pathophysiology as nonoperative MIs. A clearer understanding of the pathophysiology is needed to direct future research evaluating prophylactic, acute and long-term interventions. Researchers have developed tools to facilitate the estimation of perioperative cardiac risk. Studies suggest that the Lee index is the most accurate generic perioperative cardiac risk index. The limitations of the studies evaluating the ability of noninvasive cardiac tests to predict perioperative cardiac risk reveals considerable uncertainty as to the role of these popular tests. Similarly, there is uncertainty as to the predictive accuracy of the American College of Cardiology / American Heart Association algorithm for cardiac risk assessment. Patients are likely to benefit from improved estimation and communication of cardiac risk because the majority of noncardiac surgeries are elective and accurate risk estimation is important to allow informed patient and physician decision-making.

How strong is the evidence for the use of perioperative β blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials

Abstract Objective To determine the effect of perioperative β blocker treatment in patients having non-cardiac surgery. Design Systematic review and meta-analysis. Data sources Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals. Study selection and outcomes We included randomised controlled trials that evaluated β blocker treatment in patients having non-cardiac surgery. Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm. Results Twenty two trials that randomised a total of 2437 patients met the eligibility criteria. Perioperative β blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative β blockers showed a relative risk for bradycardia needing treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27 (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66). Conclusion The evidence that perioperative β blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.

Aspirin in patients undergoing noncardiac surgery

BACKGROUND There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Characteristics and Short-Term Prognosis of Perioperative Myocardial Infarction in Patients Undergoing Noncardiac Surgery: A Cohort Study

BACKGROUND Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery. OBJECTIVE To examine the characteristics and short-term outcome of perioperative MI. DESIGN Cohort study. (ClinicalTrials.gov registration number: NCT00182039) SETTING 190 centers in 23 countries. PATIENTS 8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial. MEASUREMENTS Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI. RESULTS Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms. LIMITATION Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed. CONCLUSION Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.

Mild Hypothermia Alters Propofol Pharmacokinetics and Increases the Duration of Action of Atracurium

Mild intraoperative hypothermia is common.We therefore studied the effects of mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atracurium duration of action in healthy volunteers. Six young volunteers were studied on two randomly assigned days, at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental, 3 mg/kg, and maintained with 70% N2 O and 0.6% isoflurane. Core hypothermia was induced by conductive and convective cooling. On the other study day, normothermia was maintained by a Bair Hugger Registered Trademark (Augustine Medical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lean body mass (LBM), then was given, followed by a 4-h infusion at 5 mg centered dot kg-1 centered dot h-1. After 2 h, atracurium 0.5 mg/kg was administered as an intravenous bolus. Indocyanine green was administered for estimation of hepatic blood flow. Arterial blood was assayed for propofol and indocyanine green concentration. Pharmacokinetic analysis was performed using NONMEM. Results are reported as means +/- SEM. Propofol blood concentrations averaged approximate equals 28% more at 34 degrees C than at 37 degrees C (P < 0.05). Hepatic blood flow decreased 23% +/- 11% in normothermic volunteers during the propofol infusion, and 33% +/- 11% in hypothermic volunteers (P = not significant). A three-compartment mamillary model fitted the data best. Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit. The intercompartmental clearances were decreased in the presence of hypothermia. Core hypothermia prolonged the time to recovery of the first twitch in the train-of-four to 10% of its control value (T1 = 10%) after atracurium administration by approximate equals 60% (P < 0.05), from 44 +/- 4 min to 68 +/- 7 min. In contrast, T1 = 25%-75% remained unchanged. We conclude that 3 degrees C of core hypothermia increased propofol blood concentrations and prolonged atracurium duration of action. Hepatic blood flow was decreased during propofol administration, and this change was a significant predictor of propofol clearance, indicating that the effect of propofol on hepatic blood flow impairs the clearance of propofol itself. (Anesth Analg 1995;80:1007-14)

Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial.

Background: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear. Methods: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide–free (80% oxygen, 20% nitrogen) or nitrous oxide–based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery. Results: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide–free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56–0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31–0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide–free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05–1.73; P = 0.02). Conclusions: Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.

Surveillance and prevention of major perioperative ischemic cardiac events in patients undergoing noncardiac surgery: a review

THIS IS THE SECOND OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. Unrecognized myocardial infarctions (MIs) are common, and up to 50% of perioperative MIs may go unrecognized if physicians rely only on clinical signs or symptoms. In this article, we summarize the evidence regarding monitoring strategies for perioperative MI in patients undergoing noncardiac surgery. Perioperative troponin measurements and 12-lead electrocardiograms can detect clinically silent MIs and provide independent prognostic information. Currently, there are no standard diagnostic criteria for perioperative MIs in patients undergoing noncardiac surgery. We propose diagnostic criteria that reflect the unique features of perioperative MIs. Finally, we review the evidence for perioperative prophylactic cardiac interventions. There is encouraging evidence that some perioperative interventions (e.g., β-blockers, α2-adrenergic agonists, statins) may prevent major cardiac ischemic events, but firm conclusions await the results of large definitive trials. The best evidence does not support a management strategy of preoperative coronary revascularization before noncardiac surgery.

Propofol blood concentration and the bispectral index predict suppression of learning during propofol/epidural anesthesia in volunteers

Propofol is often used for sedation during regional anesthesia.We tested the hypothesis that propofol blood concentration, the Bispectral Index and the 95% spectral edge frequency predict suppression of learning during propofol/epidural anesthesia in volunteers. In addition, we tested the hypothesis that the Bispectral Index is linearly related to propofol blood concentration. Fourteen healthy, male volunteers were studied on three randomly ordered days: no propofol, target propofol blood concentration 1 micro gram/mL, and target propofol blood concentration 2 micro gram/mL. Each day, epidural anesthesia (approximate equals T11 level) was induced using 2% 2-chloroprocaine. Propofol was infused by a computer-controlled pump, and propofol concentration measured in central venous blood. We administered a Trivial Pursuit Registered Trademark-type question task on all 3 days. The electroen-cephalogram was monitored continuously (Fp1, Fp2; reference, Cz; ground, mastoid). Propofol caused concentration-related impairment of learning. The propofol blood concentration suppressing learning by 50% was 0.66 +/- 0.1 micro gram/mL. The Bispectral Index value when learning was suppressed by 50% was 91 +/- 1. In contrast, the 95% spectral edge frequency did not correlate well with learning. The Bispectral Index decreased linearly as propofol blood concentration increased (Bispectral Index = -7.4 centered dot [propofol] + 90; r2 = 0.47, n = 278). There was no significant correlation between the 95% spectral edge frequency and propofol concentration. In order to suppress learning, propofol blood concentrations reported to produce amnesia may be targeted. Alternatively, the Bispectral Index may be used to predict anesthetic effect during propofol sedation. (Anesth Analg 1995;81:1269-74)

The Effect of Bispectral Index Monitoring on Long-Term Survival in the B-Aware Trial

BACKGROUND: When anesthesia is titrated using bispectral index (BIS) monitoring, patients generally receive lower doses of hypnotic drugs. Intraoperative hypotension and organ toxicity might be avoided if lower doses of anesthetics are administered, but whether this translates into a reduction in serious morbidity or mortality remains controversial. The B-Aware Trial randomly allocated 2463 patients at high risk of awareness to BIS-guided anesthesia or routine care. We tested the hypothesis that the risks of death, myocardial infarction (MI), and stroke would be lower in patients allocated to BIS-guided management than in those allocated to routine care. METHODS: The medical records of all patients who had not died within 30 days of surgery were reviewed. The date and cause of death and occurrence of MI or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary end point of the study was survival. RESULTS: The median follow-up time was 4.1 (range: 0–6.5) years. Five hundred forty-eight patients (22.2%) had died since the index surgery, 220 patients (8.9%) had an MI, and 115 patients (4.7%) had a stroke. The risk of death in BIS patients was not significantly different than in routine care patients (hazard ratio = 0.86 [95% confidence interval {CI}: 0.72–1.01]; P = 0.07). However, propensity score analysis indicated that the hazard ratio for death in patients who recorded BIS values <40 for >5 min compared with other BIS-monitored patients was 1.41 (95% CI: 1.02–1.95; P = 0.039). In addition, the odds ratios for MI in patients who recorded BIS values <40 for >5 min compared with other BIS-monitored patients was 1.94 (95% CI: 1.12–3.35; P = 0.02) and the odds ratio for stroke was 3.23 (95% CI: 1.29–8.07; P = 0.01). CONCLUSIONS: Monitoring with BIS and absence of BIS values <40 for >5 min were associated with improved survival and reduced morbidity in patients enrolled in the B-Aware Trial.