Matthew T. V. Chan

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

BACKGROUNDnAwareness 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.nnnMETHODSnWe 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.nnnFINDINGSnOf 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%).nnnINTERPRETATIONnBIS-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.

Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.

CONTEXTnOf the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days.nnnOBJECTIVEnTo determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality.nnnDESIGN, SETTING, AND PARTICIPANTSnA prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery.nnnMAIN OUTCOME MEASURESnPatients TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients risk of death.nnnRESULTSnA total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001).nnnCONCLUSIONnAmong patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.

BIS-guided anesthesia decreases postoperative delirium and cognitive decline.

Background: Previous clinical trials and animal experiments have suggested that long-lasting neurotoxicity of general anesthetics may lead to postoperative cognitive dysfunction (POCD). Brain function monitoring such as the bispectral index (BIS) facilitates anesthetic titration and has been shown to reduce anesthetic exposure. In a randomized controlled trial, we tested the effect of BIS monitoring on POCD in 921 elderly patients undergoing major noncardiac surgery. Methods: Patients were randomly assigned to receive either BIS-guided anesthesia or routine care. The BIS group had anesthesia adjusted to maintain a BIS value between 40 and 60 during maintenance of anesthesia. Routine care group had BIS measured but not revealed to attending anesthesiologists. Anesthesia was adjusted according to traditional clinical signs and hemodynamic parameters. A neuropsychology battery of tests was administered before and at 1 week and 3 months after surgery. Results were compared with matched control patients who did not have surgery during the same period. Delirium was measured using the confusion assessment method criteria. Results: The median (interquartile range) BIS values during the maintenance period of anesthesia were significantly lower in the control group, 36 (31 to 49), compared with the BIS-guided group, 53 (48 to 57), P<0.001. BIS-guided anesthesia reduced propofol delivery by 21% and that for volatile anesthetics by 30%. There were fewer patients with delirium in the BIS group compared with routine care (15.6% vs. 24.1%, P=0.01). Although cognitive performance was similar between groups at 1 week after surgery, patients in the BIS group had a lower rate of POCD at 3 months compared with routine care (10.2% vs. 14.7%; adjusted odds ratio 0.67; 95% confidence interval, 0.32-0.98; P=0.025). Conclusions: BIS-guided anesthesia reduced anesthetic exposure and decreased the risk of POCD at 3 months after surgery. For every 1000 elderly patients undergoing major surgery, anesthetic delivery titrated to a range of BIS between 40 and 60 would prevent 23 patients from POCD and 83 patients from delirium.

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.

Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis

PurposeThe literature was reviewed to determine the risks or benefits of short-term (less than four weeks) smoking cessation on postoperative complications and to derive the minimum duration of preoperative abstinence from smoking required to reduce such complications in adult surgical patients.SourceWe searched MEDLINE, EMBASE, Cochrane, and other relevant databases for cohort studies and randomized controlled trials that reported postoperative complications (i.e., respiratory, cardiovascular, wound-healing) and mortality in patients who quit smoking within six months of surgery. Using a random effects model, meta-analyses were conducted to compare the relative risks of complications in ex-smokers with varying intervals of smoking cessation vs the risks in current smokers.Principal findingsWe included 25 studies. Compared with current smokers, the risk of respiratory complications was similar in smokers who quit less than two or two to four weeks before surgery (risk ratio [RR] 1.20; 95% confidence interval [CI] 0.96 to 1.50 vs RR 1.14; CI 0.90 to 1.45, respectively). Smokers who quit more than four and more than eight weeks before surgery had lower risks of respiratory complications than current smokers (RR 0.77; 95% CI 0.61 to 0.96 and RR 0.53; 95% CI 0.37 to 0.76, respectively). For wound-healing complications, the risk was less in smokers who quit more than three to four weeks before surgery than in current smokers (RR 0.69; 95% CI 0.56 to 0.84). Few studies reported cardiovascular complications and there were few deaths.ConclusionAt least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation does not appear to increase or reduce the risk of postoperative respiratory complications.RésuméObjectifLa littérature disponible a été passée en revue pour déterminer les risques ou avantages d’un arrêt du tabagisme à court terme (moins de quatre semaines) sur les complications postopératoires et pour en déduire la durée minimum d’abstinence tabagique préopératoire qui permet de diminuer la survenue de ces complications chez des adultes subissant une chirurgie.SourceNotre étude a porté sur les bases de données MEDLINE, EMBASE, Cochrane, et les autres bases de données pertinentes à la recherche d’études de cohortes ou d’études randomisées et contrôlées ayant décrit les complications postopératoires (c’est-à-dire respiratoires, cardiovasculaires, retard de cicatrisation) et la mortalité chez des patients ayant cessé de fumer dans les six mois ayant précédé l’intervention chirurgicale. Des méta-analyses ont été effectuées en utilisant un modèle à effets aléatoires pour comparer les risques relatifs de complications chez les anciens fumeurs, avec des délais variables d’arrêt du tabagisme, aux risques chez des fumeurs actifs.Constatations principalesNous avons inclus 25 études. Comparés aux fumeurs actifs, les risques de complications respiratoires ont été comparables chez les fumeurs ayant cessé de fumer moins de deux semaines, ou entre deux et quatre semaines avant une intervention chirurgicale (rapport de risque [RR]: 1,20; intervalle de confiance [IC] à 95 %: 0,96-1,50, contre, respectivement, RR: 1,14; IC à 95xa0%: 0,90-1,45). Les fumeurs ayant cessé de fumer plus de quatre semaines et plus de huit semaines avant l’intervention chirurgicale avaient des risques de complications respiratoires moins élevés que les fumeurs actifs (RR: 0,77; IC à 95xa0%: 0,61-0,96 et RR: 0,53; IC à 95xa0%: 0,37-0,76, respectivement). Concernant les complications liées à la cicatrisation, le risque a été plus faible chez les fumeurs ayant cessé plus de trois à quatre semaines avant l’intervention que chez les fumeurs actifs (RR: 0,69; IC à 95%: 0,56-0,84). Peu d’études ont décrit des complications cardiovasculaires et il n’y a eu que peu de décès.ConclusionUn minimum de quatre semaines d’abstinence du tabagisme diminue le risque de complications respiratoires et un minimum de trois à quatre semaines réduit le risque de complications liées à la cicatrisation. L’arrêt à court terme (moins de quatre semaines) du tabagisme ne semble pas augmenter ou réduire le risque de complications respiratoires postopératoires.

Posttraumatic stress disorder in aware patients from the B-aware trial.

BACKGROUND: The long-term consequences of an awareness episode vary. Some patients do not have any long-term disability, whereas others develop psychological problems that may be severe and persistent. In this study, we compared the incidence of posttraumatic stress disorder (PTSD) in patients with and without confirmed awareness who were randomized in the B-Aware Trial. METHODS: We used a matched cohort design, aiming to follow up the 13 patients with confirmed awareness. Each surviving awareness patient was matched with 4 controls for age, sex, surgery type, date of surgery, and hospital. A face-to-face interview was conducted with each awareness patient and matched controls using the Clinician Administered Posttraumatic Stress Disorder Scale. RESULTS: Data collection for this study occurred between June 2006 and March 2007, with a median follow-up time of 5.3 yr (range, 4.3–5.7 yr). Six of the 13 confirmed awareness patients had died. Five of the 7 confirmed awareness patients (71%) and 3 of the 25 controls (12%) fulfilled the criteria for PTSD at the time of the interview (adjusted odds ratio = 13.3 [95% confidence interval: 1.4–650]; P = 0.02). The median onset time of symptoms was 14 days (range, 7–243 days) after surgery, and the median duration of symptoms was 4.7 yr (range, 4.4–5.6 yr). CONCLUSIONS: PTSD was common and persistent in the confirmed awareness patients of the B-Aware Trial. Strategies to prevent awareness in patients under general anesthesia are justified.

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study.

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH). Sixty patients with SAH were randomly allocated to receive either MgSO4 80u2009mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded. Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120u2009cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.

The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): A randomised, single-blind trial

BACKGROUNDnNitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk.nnnMETHODSnWe did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989.nnnFINDINGSnOf 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001).nnnINTERPRETATIONnOur findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown.nnnFUNDINGnAustralian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

Chronic postsurgical pain after nitrous oxide anesthesia

Summary Chronic postsurgical pain was common after major surgery in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial. Nitrous oxide administration was associated with a decrease in the risk of chronic wound pain after surgery. ABSTRACT Nitrous oxide is an antagonist at the N‐methyl‐D‐aspartate receptor and may prevent the development of chronic postsurgical pain. We conducted a follow‐up study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial patients to evaluate the preventive analgesic efficacy of nitrous oxide after major surgery. The ENIGMA trial was a randomized controlled trial of nitrous oxide‐based or nitrous oxide‐free general anesthesia in patients presenting for noncardiac surgery lasting more than 2 hours. Using a structured telephone interview, we contacted all ENIGMA trial patients recruited in Hong Kong (n = 640). We recorded the severity of postsurgical pain of at least 3 months’ duration that was not due to disease recurrence or a pre‐existing pain syndrome, using the modified Brief Pain Inventory. The impact of postsurgical pain on quality of life was also measured. Pain intensity, opioid and other analgesic requirements during the first week of surgery, were retrieved from the trial case report form and medical records. A total of 46 (10.9%) patients reported pain that persisted from the index surgery, and 39 (9.2%) patients had severe pain. In addition, patients with chronic pain rated poorly in all attributes of the quality‐of‐life measures compared with those who were pain free. In a multivariate analysis, nitrous oxide decreased the risk of chronic postsurgical pain. In addition, severe pain in the first postoperative week, wound complication, and abdominal incision increased the risk of chronic pain. In conclusion, chronic postsurgical pain was common after major surgery in the ENIGMA trial. Intraoperative nitrous oxide administration was associated with a reduced risk of chronic postsurgical pain.

Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial

BACKGROUND:There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide–based or nitrous oxide–free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. METHODS:The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. RESULTS:The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). CONCLUSIONS:The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial.