Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

BACKGROUND: Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. METHODS: Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. RESULTS: Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. CONCLUSIONS: Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial.

PURPOSE: The efficacy of myocardial conditioning strategies is compromised in patients with advanced age, diabetes, or low ejection fraction. We conducted a single-centre parallel-arm blinded randomized-controlled trial to determine whether propofol provides perioperative myocardial protection. METHODS: Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass (CPB) with blood cardioplegia. The participants were stratified by diabetic status and left ventricular ejection fraction and randomly assigned to receive either an elevated dose of propofol -previously associated with experimental cardioprotection- or an isoflurane preconditioning regime. The primary endpoint was the coronary sinus (CS) concentration of 15-F2t-isoprostane (isoP). Secondary endpoints included in-hospital low cardiac output syndrome (LCOS) and major adverse cardiac events, 12- and 24-hr CS cardiac troponin I (cTnI) release, and myocardial B-cell lymphoma 2 (Bcl-2) protein expression. RESULTS: Data were analyzed from 125 of 137 randomized participants. Participants receiving propofol experienced a greater mean (SD) increase from baseline in CS 15-F2t-isoP levels compared with those receiving isoflurane [26.9 (10.9) pg·mL(-1) vs 12.1 (10.4) pg·mL(-1), respectively; mean difference, 14.8; 95% confidence interval (CI), 11.0 to 18.6; P < 0.001] but a decreased incidence of LCOS (20.9% vs 57.1%, respectively; relative risk [RR],0.37; 95% CI, 0.22 to 0.62; P < 0.001). The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus (DM2) (P = 0.382) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup (17.9% vs 70.3%, respectively; RR, 0.26; 95% CI, 0.13 to 0.52; P < 0.001). Propofol was associated with an increase in myocardial Bcl-2 protein expression (P = 0.005), a lower incidence of a CS cTnI threshold for myocardial infarction (P = 0.014), and fewer heart failure events (P < 0.001). CONCLUSION: Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest. The study is registered at www.clinicaltrials.gov (NCT00734383) and www.controlled-trials.com (ISRCTN70879185).

Perioperative management of patients with obstructive sleep apnea: a survey of Canadian anesthesiologists.

INTRODUCTION: Obstructive sleep apnea (OSA) may increase the incidence of postoperative complications when undiagnosed. The purpose of this study was to evaluate the perspectives of Canadian anesthesiologists regarding the perioperative management of patients with diagnosed or suspected OSA. METHODS: This study was conducted as a survey of Canadian anesthesiologists using a self-administered scenario-based questionnaire. We initially mailed the survey questionnaire and then mailed it again to non-respondents six weeks later. Subsequently, we e-mailed the online version of our survey to active members of the Canadian Anesthesiologists' Society. RESULTS: The response rates were 35% and 26% for the postal and online modes of administration, respectively. About 50% of the respondents relied on clinical suspicion rather than on a systematic screening to identify patients who may have undiagnosed OSA preoperatively. Forty-seven percent of all respondents either did not know of any institutional policy to guide their perioperative management of patients with OSA or reported an absence of an institutional policy. Fifteen percent of the respondents would discharge diagnosed OSA inpatients with compliant use of continuous positive airway pressure (CPAP) to the ward without monitoring. Nevertheless, a more conservative approach was observed for CPAP non-compliant inpatients. We indeed observed that more than 40% of respondents would send an ambulatory OSA patient home, while another 60% would favour hospital admission. CONCLUSIONS: The majority of anesthesiologists continue to rely on clinical suspicion alone to identify OSA. Moreover, the lack of institutional policy is concerning. A concerted effort to develop an evidence-based guideline may be the next step to assist institutions.

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; I = 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; I = 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; I = 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; I = 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; I = 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; I = 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.

A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study.

PURPOSE: Clonidine may help prevent cardiac complications in patients undergoing non-cardiac surgery and receiving chronic beta-blocker therapy. We conducted a multicentre pilot randomized trial to estimate recruitment rates for a full-scale trial and to assess the safety and tolerability of combining clonidine with chronic beta-blockade. METHODS: Patients who were at elevated perioperative cardiac risk, receiving chronic beta-blockade, and scheduled for major non-cardiac surgery were recruited in a blinded (participants, clinicians, outcome assessors) placebo-controlled randomized trial at three Canadian hospitals. Participants were randomized to clonidine (0.2 mg oral tablet one hour before surgery, plus 0.2 mg·day(-1) transdermal patch placed one hour before surgery and removed four days after surgery or hospital discharge, whichever came first) or matching placebo. Feasibility was evaluated based on recruitment rates, with each centre being required to recruit 50 participants within 12-18 months. Additionally, we reviewed study drug withdrawals and safety outcomes, including clinically significant hypotension or bradycardia. RESULTS: Eighty-two of the 168 participants were randomized to receive clonidine and 86 to receive placebo. The average time to recruit 50 participants at each centre was 14.3 months. Six patients (7%) withdrew from clonidine, while four (5%) withdrew from placebo. Based on qualitative review, there were no major safety concerns related to clonidine. There was a moderate overall rate of cardiac morbidity, with 18 participants (11%) suffering postoperative myocardial infarction. CONCLUSION: This pilot randomized trial confirmed the feasibility, safety, and tolerability of a full-scale trial of oral and transdermal clonidine for reducing the risk of cardiac complications during non-cardiac surgery. This trial was registered at www.clinicaltrials.gov: NCT00335582.

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.

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 ß-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.

Glidescope® video-laryngoscopy versus direct laryngoscopy for endotracheal intubation: a systematic review and meta-analysis.

INTRODUCTION: The Glidescope(®) video-laryngoscopy appears to provide better glottic visualization than direct laryngoscopy. However, it remains unclear if it translates into increased success with intubation. METHODS: We systematically searched electronic databases, conference abstracts, and article references. We included trials in humans comparing Glidescope(®) video-laryngoscopy to direct laryngoscopy regarding the glottic view, successful first-attempt intubation, and time to intubation. We generated pooled risk ratios or weighted mean differences across studies. Meta-regression was used to explore heterogeneity based on operator expertise and intubation difficulty. RESULTS: We included 17 trials with a total of 1,998 patients. The pooled relative risk (RR) of grade 1 laryngoscopy (vs ≥ grade 2) for the Glidescope(®) was 2.0 [95% confidence interval (CI) 1.5 to 2.5]. Significant heterogeneity was partially explained by intubation difficulty using meta-regression analysis (P = 0.003). The pooled RR for nondifficult intubations of grade 1 laryngoscopy (vs ≥ grade 2) was 1.5 (95% CI 1.2 to 1.9), and for difficult intubations it was 3.5 (95% CI 2.3 to 5.5). There was no difference between the Glidescope(®) and the direct laryngoscope regarding successful first-attempt intubation or time to intubation, although there was significant heterogeneity in both of these outcomes. In the two studies examining nonexperts, successful first-attempt intubation (RR 1.8, 95% CI 1.4 to 2.4) and time to intubation (weighted mean difference -43 sec, 95% CI -72 to -14 sec) were improved using the Glidescope(®). These benefits were not seen with experts. CONCLUSION: Compared to direct laryngoscopy, Glidescope(®) video-laryngoscopy is associated with improved glottic visualization, particularly in patients with potential or simulated difficult airways.

Persistent hypothermia after intrathecal morphine: case report and literature review.

PURPOSE: To describe a case of persistent hypothermia following spinal anesthesia with intrathecal morphine. CLINICAL FEATURES: Following elective right total knee arthroplasty under spinal anesthesia with isobaric 0.5% bupivacaine 11 mg, fentanyl 15 µg, and preservative-free morphine 150 µg, a 57-yr-old female (93.5 kg, 151 cm) developed postoperative hypothermia with a nadir rectal temperature of 33.6°C four hours after surgery. At times, her temperature could not be measured by tympanic, temporal arterial, oral, axillary, or rectal routes. In spite of the low temperature, the patient complained of feeling hot and was diaphoretic without shivering. With the exception of her temperature, her vital signs were normal postoperatively, and aside from hyperglycemia, complete blood count, electrolytes, thyroid-stimulating hormone, serum cortisol, troponin, and twelve-lead electrocardiogram were normal. Her temperature did not respond to warming efforts with a forced-air warming blanket, infusion of warmed intravenous crystalloid, and hourly bladder irrigation with warm saline through an indwelling urinary catheter. Normothermia returned after she received a small dose of sublingual lorazepam eight hours after surgery. The remainder of her postoperative stay was uneventful. CONCLUSION: Patients undergoing spinal anesthesia with intrathecal morphine may develop postoperative hypothermia that is resistant to warming measures. This complication may be treated successfully with lorazepam.

Risk factors for urinary retention after hip or knee replacement: a cohort study.

INTRODUCTION: In 2006, our provincial government initiated a program to reduce wait times for total hip or knee replacements by referring patients to a single tertiary-care centre. This program provided an opportunity to identify risk factors for perioperative complications as part of a continuing quality improvement project. We report the risk of postoperative urinary retention after hip and knee replacements and the risk factors associated with this complication. METHODS: After local Research Ethics Board approval, data were abstracted from charts of patients who underwent elective primary unilateral total hip or knee replacement surgery. The outcome was urinary retention in the first 24 hr after surgery. Risk factors were identified using multivariable logistic regression, and they were expressed as odds ratios (OR) or 95% confidence intervals (CI). RESULTS: From April 1, 2006 to May 31, 2007, 1,440 patients underwent 1,515 elective total hip replacement or total knee replacement. We abstracted data from 1,031 (71.3%) patients: mean age, 62 yr (interquartile range [IQR] 55-70); 53.7% female; 605 total hip replacements; and 426 total knee replacements. The procedures were performed under spinal (81.8%), general (10.2%), or combined spinal and general (8.0%) anesthesia. Patients spent 100 [IQR 90-114] min in the operating room and 3 [IQR 3-4] days in hospital. The 24-hr incidence of urinary retention was 43.3% (446/1031). Male sex (odds ratio [OR] 3.9; 95% CI 3.0 to 5.2), total hip replacement (OR 1.4; 95% CI 1.1 to 1.9), and intrathecal morphine were risk factors. DISCUSSION: Postoperative urinary retention is a common complication after total hip or total knee replacement, especially amongst men and patients receiving intrathecal morphine.

Ultrasound imaging accurately identifies the lateral femoral cutaneous nerve.

BACKGROUND: Anesthesia of the lateral femoral cutaneous nerve (LFCN) is useful in surgery involving the anterolateral thigh. We investigated the accuracy of ultrasound compared with anatomical landmarks in identifying the LFCN in human cadavers and volunteers. METHODS: Twenty cadavers were examined. A needle was inserted targeting the LFCN with ultrasound guidance and green dye was injected. A second needle was inserted using anatomical landmarks. The LFCN was identified by dissection, and coloring of the LFCN and needle positions were evaluated. A volunteer study with 10 individuals was performed. Transdermal nerve stimulation was used to identify the LFCN bilaterally. Its position was compared with marked positions identified in advance using ultrasound and anatomical landmarks. RESULTS: Sixteen of 19 needles inserted under ultrasound guidance in the cadavers were in contact with the LFCN. The median horizontal distance from the needle tip to the nerve was 0.0 mm (interquartile range [IQR], 0.0-0.0 mm). Only 1 of 19 needles inserted using anatomical landmarks was in contact with the LFCN. The median horizontal distance from the needle tip to the nerve was 18.0 mm (IQR, 11.0-23.0 mm). Sixteen of 20 marked positions made using ultrasound guidance corresponded to the identified LFCN in volunteers. The median horizontal distance from the pen-mark to the LFCN was 0.0 mm (IQR, 0.0-0.0 mm). None of the 20 marked positions made with anatomical landmarks corresponded to the LFCN. The median horizontal distance from the pen-mark to the LFCN was 15.0 mm (IQR, 10.8-20.0 mm). CONCLUSIONS: Identification of the LFCN by ultrasound is technically feasible and more accurate than anatomical landmarks.

Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis.

BACKGROUND: Clinicians should consider the clinical impact of anticoagulant-related bleeding when deciding on the duration of anticoagulant therapy in patients with venous thromboembolism. PURPOSE: To provide reliable estimates of the clinical impact of anticoagulant-related bleeding, defined as the case-fatality rate of major bleeding and the risk for intracranial bleeding. DATA SOURCES: MEDLINE (January 1989 to May 2003), Cochrane Controlled Trial Registry, thromboembolism experts, and reference lists; English-language literature only. STUDY SELECTION: Randomized, controlled trials and prospective cohort studies that investigated patients with venous thromboembolism who received oral anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at least 3 months and that reported major bleeding and death as primary study outcomes. DATA EXTRACTION: Two reviewers independently extracted data on the number of anticoagulant-related major and intracranial bleeding episodes and on whether these events were fatal or nonfatal. DATA SYNTHESIS: The authors analyzed 33 studies involving 4374 patient-years of oral anticoagulant therapy. For all patients, the case-fatality rate of major bleeding was 13.4% (95% CI, 9.4% to 17.4%) and the rate of intracranial bleeding was 1.15 per 100 patient-years (CI, 1.14 to 1.16 per 100 patient-years). For patients who received anticoagulant therapy for more than 3 months, the case-fatality rate of major bleeding was 9.1% (CI, 2.5% to 21.7%), and the rate of intracranial bleeding was 0.65 per 100 patient-years (CI, 0.63 to 0.68 per 100 patient-years) after the initial 3 months of anticoagulation. CONCLUSION: The clinical impact of anticoagulant-related major bleeding in patients with venous thromboembolism is considerable, and clinicians should take this into account when deciding whether to continue long-term oral anticoagulant therapy in an individual patient.

An observational study found that authors of randomized controlled trials frequently use concealment of randomization and blinding, despite the failure to report these methods.

BACKGROUND AND OBJECTIVE: Readers of randomized controlled trials (RCTs) commonly assume that what was not reported did not occur. We undertook an observational study to determine whether concealment of randomization or blinding was used in RCTs that failed to report these bias-reducing strategies. METHODS: We recorded the reporting of concealment of randomization and blinding in 105 RCTs. We subsequently contacted the authors and determined if they had used these methodological safeguards. RESULTS: We successfully obtained data from 98 authors. The authors in the full-text publications of these 98 RCTs failed to report the presence or absence of concealment of randomization in 55%, and the blinding status of participants in 26%, health care providers in 64%, data collectors in 84%, outcome assessors in 83%, and data analysts in 96%. In direct contact, authors frequently reported concealing randomization (96%; 95% confidence interval CI=87-100%), blinding participants (20%; 95% CI=7-41%), blinding health care providers (65%; 95% CI=52-77%), blinding data collectors (65%; 95% CI=53-75%), blinding outcome assessors (79%; 95% CI=69-87%), and blinding data analysts (50%; 95% CI=40-60%), despite not reporting the use of these methodological safeguards in their publications. CONCLUSIONS: Readers should not assume that bias-reducing procedures not reported in an RCT did not occur.

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.

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 > or = 45 years old, had an expected hospital stay > or = 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.