Peter T. Choi

Examining the evidence in anesthesia literature : A critical appraisal of systematic reviews

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.

Neuraxial anesthesia for the prevention of postoperative mortality and major morbidity: an overview of cochrane systematic reviews.

BACKGROUND:This analysis summarized Cochrane reviews that assess the effects of neuraxial anesthesia on perioperative rates of death, chest infections, and myocardial infarction. METHODS:A search was performed in the Cochrane Database of Systematic Reviews on July 13, 2012. We have included all Cochrane systematic reviews that examined subjects of any age undergoing any type of surgical (open or endoscopic) procedure, compared neuraxial anesthesia to general anesthesia alone for the surgical anesthesia, or neuraxial anesthesia plus general anesthesia to general anesthesia alone for the surgical anesthesia, and included death, chest infections, myocardial infarction, and/or serious adverse events as outcomes. Studies included in these reviews were selected on the same criteria. RESULTS:Nine Cochrane reviews were selected for this overview. Their scores on the Overview Quality Assessment Questionnaire varied from 4 to 6 of a maximal possible score of 7. Compared with general anesthesia, neuraxial anesthesia reduced the 0- to-30-day mortality (risk ratio [RR] 0.71; 95% confidence interval [CI], 0.53–0.94; I2 = 0%) based on 20 studies that included 3006 participants. Neuraxial anesthesia also decreased the risk of pneumonia (RR 0.45; 95% CI, 0.26–0.79; I2 = 0%) based on 5 studies that included 400 participants. No difference was detected in the risk of myocardial infarction between the 2 techniques (RR 1.17; 95% CI, 0.57–2.37; I2 = 0%) based on 6 studies with 849 participants. Compared with general anesthesia alone, adding neuraxial anesthesia to general anesthesia did not affect the 0- to-30-day mortality (RR 1.07; 95% CI, 0.76–1.51; I2 = 0%) based on 18 studies with 3228 participants. No difference was detected in the risk of myocardial infarction between combined neuraxial anesthesia–general anesthesia and general anesthesia alone (RR 0.69; 95% CI, 0.44–1.09; I2 = 0%) based on 8 studies that included 1580 participants. Adding a neuraxial anesthesia to general anesthesia reduced the risk of pneumonia (RR 0.69; 95% CI, 0.49–0.98; I2 = 9%) after adjustment for publication bias and based on 9 studies that included 2433 participants. The quality of the evidence was judged as moderate for all 6 comparisons. The quality of the reporting score of complications related to neuraxial blocks was 9 (4 to 12 [median {range}]) for a possible maximum score of 14. CONCLUSIONS:Compared with general anesthesia, neuraxial anesthesia may reduce the 0-to-30-day mortality for patients undergoing a surgery with an intermediate-to-high cardiac risk (level of evidence moderate). Large randomized controlled trials on the difference in death and major outcomes between regional and general anesthesia are required.

Neuraxial block, death and serious cardiovascular morbidity in the POISE trial

BACKGROUND This post hoc analysis aimed to determine whether neuraxial block was associated with a composite of cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal cardiac arrest within 30 days of randomization in POISE trial patients. METHODS A total of 8351 non-cardiac surgical patients at high risk of cardiovascular complications were randomized to β-blocker or placebo. Neuraxial block was defined as spinal, lumbar or thoracic epidural anaesthesia. Logistic regression, with weighting using estimated propensity scores, was used to determine the association between neuraxial block and primary and secondary outcomes. RESULTS Neuraxial block was associated with an increased risk of the primary outcome [287 (7.3%) vs 229 (5.7%); odds ratio (OR), 1.24; 95% confidence interval (CI), 1.02-1.49; P=0.03] and MI [230 (5.9%) vs 177 (4.4%); OR, 1.32; 95% CI, 1.07-1.64; P=0.009] but not stroke [23 (0.6%) vs 32 (0.8%); OR, 0.76; 95% CI, 0.44-1.33; P=0.34], death [96 (2.5%) vs 111 (2.8%); OR, 0.87; 95% CI, 0.65-1.17; P=0.37] or clinically significant hypotension [522 (13.4%) vs 484 (12.1%); OR, 1.13; 95% CI, 0.99-1.30; P=0.08]. Thoracic epidural with general anaesthesia was associated with a worse primary outcome than general anaesthesia alone [86 (12.1%) vs 119 (5.4%); OR, 2.95; 95% CI, 2.00-4.35; P<0.001]. CONCLUSIONS In patients at high risk of cardiovascular morbidity, neuraxial block was associated with an increased risk of adverse cardiovascular outcomes, which could be causal or because of residual confounding.

Nitrous Oxide and Serious Morbidity and Mortality in the POISE Trial

BACKGROUND:In this post hoc subanalysis of the Perioperative Ischemic Evaluation (POISE) trial, we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal cardiac arrest within 30 days of randomization. METHODS:The POISE trial of perioperative &bgr;-blockade was undertaken in 8351 patients. Nitrous oxide anesthesia was defined as the coadministration of nitrous oxide in patients receiving general anesthesia, with or without additional neuraxial blockade or peripheral nerve blockade. Logistic regression, with inverse probability weighting using estimated propensity scores, was used to determine the association of nitrous oxide with the primary outcome, MI, stroke, death, and clinically significant hypotension. RESULTS:Nitrous oxide was administered to 1489 (29%) of the 5133 patients included in this analysis. Nitrous oxide had no significant effect on the risk of the primary outcome (112 [7.5%] vs 248 [6.9%]; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.82–1.44; 99% CI, 0.75–1.57; P = 0.58), MI (89 [6.0] vs 204 [5.6]; OR, 0.99; 95% CI, 0.75–1.31; 99% CI, 0.69–1.42; P = 0.94), stroke (6 [0.4%] vs 28 [0.8%]; OR, 0.85; 95% CI, 0.26–2.82; 99% CI, 0.17–4.11; P = 0.79), death (40 [2.7%] vs 100 [2.8%]; OR, 1.04; 95% CI, 0.6–1.81; 99% CI, 0.51–2.15; P = 0.88) or clinically significant hypotension (219 [14.7%] vs 544 [15.0%]; OR, 0.92; 95% CI, 0.74–1.15; 99% CI, 0.70–1.23; P = 0.48). CONCLUSIONS:In this post hoc subanalysis, nitrous oxide was not associated with an increased risk of adverse outcomes in the POISE trial patients. This analysis was limited by the observational nature of the data and the lack of information on the concentration and duration of nitrous oxide administration. Further randomized controlled trial evidence is required.

Effects of Neuraxial Blockade May Be Difficult To Study Using Large Randomized Controlled Trials: The PeriOperative Epidural Trial (POET) Pilot Study

Background Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada. Methodology/Principal Findings After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were ≥45 years old, had an expected hospital stay ≥48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group) and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group) and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5±0.3 (mean±SEM) subjects per week per centre; 112/494 (22.7%) eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5%) of 49 subjects in the epidural group crossed over to the IV group; seven (14.3%) were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8%) of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0%) of 101 subjects were successfully followed up until 30 days after their surgery. Conclusion/Significance Of the criteria we defined for the feasibility of a full-scale trial, only the follow-up target was met. The other feasibility outcomes did not meet our preset criteria for success. The results suggest that a large multicentre trial may not be a feasible design to study the perioperative effects of neuraxial blockade. Trial Registration ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817

An evaluation of an expert system for detecting critical events during anesthesia in a human patient simulator: a prospective randomized controlled study.

BACKGROUND: Perioperative monitoring systems produce a large amount of uninterpreted data, use threshold alarms prone to artifacts, and rely on the clinician to continuously visually track changes in physiological data. To address these deficiencies, we developed an expert system that provides real-time clinical decisions for the identification of critical events. We evaluated the efficacy of the expert system for enhancing critical event detection in a simulated environment. We hypothesized that anesthesiologists would identify critical ventilatory events more rapidly and accurately with the expert system. METHODS: We used a high-fidelity human patient simulator to simulate an operating room environment. Participants managed 4 scenarios (Anesthetic Vapor Overdose, Tension Pneumothorax, Anaphylaxis, and Endotracheal Tube Cuff Leak) in random order. In 2 of their 4 scenarios, participants were randomly assigned to the expert system, which provided trend-based alerts and potential differential diagnoses. Time to detection and time to treatment were measured. Workload questionnaires and structured debriefings were completed after each scenario, and a usability questionnaire at the conclusion of the session. Data were analyzed using a mixed-effects linear regression model; Fisher exact test was used for workload scores. RESULTS: Twenty anesthesiology trainees and 15 staff anesthesiologists with a combined median (range) of 36 (29–66) years of age and 6 (1–38) years of anesthesia experience participated. For the Endotracheal Tube Cuff Leak, the expert system caused mean reductions of 128 (99% confidence interval [CI], 54–202) seconds in time to detection and 140 (99% CI, 79–200) seconds in time to treatment. In the other 3 scenarios, a best-case decrease of 97 seconds (lower 99% CI) in time to diagnosis for Anaphylaxis and a worst-case increase of 63 seconds (upper 99% CI) in time to treatment for Anesthetic Vapor Overdose were found. Participants were highly satisfied with the expert system (median score, 2 on a scale of 1–7). Based on participant debriefings, we identified avoidance of task fixation, reassurance to initiate invasive treatment, and confirmation of a suspected diagnosis as 3 safety-critical areas. CONCLUSION: When using the expert system, clinically important and statistically significant decreases in time to detection and time to treatment were observed for the Endotracheal Tube Cuff Leak scenario. The observed differences in the other 3 scenarios were much smaller and not statistically significant. Further evaluation is required to confirm the clinical utility of real-time expert systems for anesthesia.

The science of opinion: survey methods in research.

Editor’s note We receive many submissions reporting results of sample surveys. We recognize and appreciate that wellconducted survey-based research can yield important information that may be relevant to our readership. Regrettably, many articles do not advance to publication as authors often fail to ensure adequate rigour in their task to pose an unambiguous research question, develop a robust and validated survey instrument, and conduct a survey with appropriate analysis and interpretation. As a guide to those who undertake surveybased research, and to interested readers of survey reports, the following editorial highlights several of the key principles of successful sample surveys. Donald R. Miller, M.D., Editor-in-Chief

Infratentorial neurosurgery is an independent risk factor for respiratory failure and death in patients undergoing intracranial tumor resection.

Background: Respiratory failure and death are devastating outcomes in the postoperative period. Patients undergoing neurosurgical procedures experience a greater frequency of respiratory failure compared with other surgical specialties. Resection of infratentorial mass lesions may be associated with an even higher risk because of several unique factors. Our objectives were: (1) to determine the incidence of postoperative respiratory failure and death in the neurosurgical population; and (2) to determine whether infratentorial procedures are associated with a higher risk compared with supratentorial procedures. Methods: We retrospectively analyzed the American College of Surgeons National Surgical Quality Improvement Program database to identify patients undergoing intracranial tumor resection. The primary outcome was a composite of reintubation within 30 days, failure to wean from mechanical ventilation within 48 hours, and death within 30 days after surgery. We examined the association between the surgical site and the outcomes using multivariate logistic regression. Results: A total of 1699 patients met inclusion criteria (79% supratentorial and 21% infratentorial). The primary outcome occurred in 3.8% of supratentorial procedures and 6.6% of infratentorial procedures (P=0.02). Infratentorial tumor resection was independently associated with the composite outcome in the final model (odds ratio, 1.75; 95% confidence interval, 1.03-2.99; P=0.04) with the strongest association seen between infratentorial site and death (odds ratio, 2.44; 95% confidence interval, 1.23-4.87; P=0.01). Conclusions: Infratentorial neurosurgery is an independent risk factor for respiratory failure and death in patients undergoing intracranial tumor resection. Mortality is an important contributor to this risk and should be a focus for future research.

Rationale, design and baseline characteristics of the PRO-TECT II study: PROpofol CardioproTECTion for Type II diabetics A randomized, controlled trial of high-dose propofol versus isoflurane preconditioning in patients undergoing on-pump coronary artery bypass graft surgery

Diabetes mellitus is a leading cause of death globally and results in significant morbidity and mortality following surgery. After cardiac surgery, diabetic patients are especially at risk for low cardiac output syndrome, which can quadruple the risk for postoperative death. Attempts to prevent low cardiac output syndrome have focused on increasing myocardial tolerance to ischemia (preconditioning), which involves the myocardial mitochondrial ATP-regulated K(ATP) channel, G-protein initiation, nitric oxide synthase, and protein kinase C. Unfortunately, the signal transduction pathways required for preconditioning are corrupted in diabetes. Effective antioxidant intervention during ischemia-reperfusion appears important for preserving myocardial function; thus, alleviating oxidant-mediated post-ischemic injury by increasing antioxidant defenses (cardioprotection) is an alternative to preconditioning. Our previous work suggests that propofol (2,6-diisopropylphenol), an intravenous anesthetic with antioxidant potential, may confer cardioprotection. In this paper, we describe the rationale and methodology of the Pro-TECT II Study, a Phase II randomized controlled trial designed to explore the relationships of biomarkers of oxidative or nitrosative stress in diabetes, to determine the effect of propofol cardioprotection to counteract these effects in patients undergoing elective primary coronary bypass graft surgery with cardiopulmonary bypass, and to provide feasibility and sample size data needed to conduct Phase III trials.

Defining rules for the identification of critical ventilatory events

Purpose: The automated recognition of critical clinical events by physiological monitors is a challenging task exacerbated by a lack of standardized and clinically relevant threshold criteria. The objective of this investigation was to develop consensus for such criteria regarding the identification of three ventilatory events: disconnection or significant leak in the anesthesia circuit, decreased lung compliance or increased resistance, and anesthetic overdose from inhaled anesthetics.Methods: We individually administered a structured interview to five expert anesthesiologists to gain insight into the cognitive processes used by clinicians to diagnose ventilatory events and to determine the common heuristics (rules of thumb) used in clinical practice. We then used common themes, identified from analysis of the structured interviews, to generate questions for a series of web-based questionnaires. Using a modified Delphi technique, iterative questionnaire administration facilitated rapid consensus development on the thresholds for the specific rules used to identify ventilatory events.Results: A threshold for 75% agreement was described for each scenario in a healthy ventilated adult. A disconnection or significant leak in the anesthesia circuit is diagnosed with peak airway pressure (<5 cm H2O or change of 15 cm H2O), ETCO2 (0 mmHg, 40% drop, or value below 10 mmHg for a duration of 20 sec), and inspired-expired volume difference (300 mL). Increased resistance or decreased lung compliance is diagnosed with high peak airway pressure (40 cm H2O or a 20 cm H2O change), asymmetry of capnogram, and changes in measured compliance or resistance. Anesthetic overdose from inhaled anesthetics is diagnosed with high end-tidal anesthetic agent concentration (2 MAC in a patient less than 60 yr of age or 1.75 MAC in a patient over 60 yr of age), low systolic blood pressure (below 60 mmHg), and low modified electroencephalogram (bispectral index or entropy).Conclusion: This investigation has provided a set of consensus-based criteria for developing rules for the identification of three critical ventilatory events and has presented insight into the decision heuristics used by clinicians.RésuméObjectif: La reconnaissance automatisée des événements cliniques critiques par des moniteurs physiologiques constitue un défi rendu difficile par le manque de critères de seuils standardisés et pertinents d’un point de vue clinique. L’objectif de cette étude était de parvenir à un consensus par rapport aux critères nécessaires à l’identification de trois événements respiratoires : une déconnexion ou une fuite considérable du circuit anesthésique, une compliance pulmonaire diminuée ou une résistance accrue, et une overdose anesthésique résultant des anesthésiques inhalés.Méthode: Nous avons individuellement mené des entretiens structurés de cinq anesthésiologistes experts afin d’avoir un aperçu des processus cognitifs utilisés par les cliniciens pour dépister les événements respiratoires et de déterminer les connaissances heuristiques communes (règle empirique) utilisées dans la pratique clinique. Ensuite, nous nous sommes servis des thèmes communs identifiés par l’analyse des entretiens structurés afin de générer des questions pour une série de questionnaires en ligne. À l’aide d’une méthode de Delphi modifiée, l’administration itérative des questionnaires a permis le développement rapide d’un consensus concernant les seuils pour les règles spécifiques utilisées dans l’identification des événements respiratoires.Résultats: Pour chaque scénario chez un adulte sain ventilé, un seuil de concordance de 75 % a été décrit. Une déconnexion ou fuite considérable du circuit anesthésique est diagnostiquée lors d’une pression maximale du conduit aérien (< 5 cm H2O ou changement de 15 cm H2O), ETCO2 (0 mmHg, chute de 40 %, ou valeur en dessous de 10 mmHg pour une durée de 20 sec), et d’une différence de volume inspiré-expiré (300 mL). Une résistance accrue ou une compliance pulmonaire réduite est diagnostiquée lors d’une pression maximale du conduit aérien élevée (40 cm H2O ou un changement de 20 cm H2O), un capnogramme asymétrique, et de changements dans la compliance ou la résistance mesurées. Une overdose anesthésique provoquée par les anesthésiques inhalés est diagnostiquée lors d’une concentration d’anesthésique télo-expira-toire élevée (2 MAC chez un patient de moins de 60 ans ou 1,75 MAC chez un patient de plus de 60 ans), de pression systolique basse (inférieure à 60 mmHg) et d’électroencéphalogramme modifié bas (index bispectral ou moniteur entropy).Conclusion: Cette étude a permis de déterminer un ensemble de critères basés sur un consensus pour le développement de règles permettant l’identification de trois événements respiratoires critiques et a donné un aperçu des connaissances heuristiques utilisés par les cliniciens pour prendre des décisions cliniques.