Safety of a Restrictive versus Liberal Approach to Red Blood Cell Transfusion on the Outcome of AKI in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk. METHODS: In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin<7.5 g/dl, intraoperatively and postoperatively) with a liberal threshold (transfuse if hemoglobin<9.5 g/dl in the operating room or intensive care unit, or if hemoglobin<8.5 g/dl on the nonintensive care ward). We studied 4531 patients undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high risk of perioperative death. The substudy's primary outcome was AKI, defined as a postoperative increase in serum creatinine of ≥0.3 mg/dl within 48 hours of surgery, or ≥50% within 7 days of surgery. RESULTS: Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted-threshold group compared with the liberal-threshold group; P<0.001). AKI occurred in 27.7% of patients in the restrictive-threshold group (624 of 2251) and in 27.9% of patients in the liberal-threshold group (636 of 2280). Similarly, among patients with preoperative CKD, AKI occurred in 33.6% of patients in the restrictive-threshold group (258 of 767) and in 32.5% of patients in the liberal-threshold group (252 of 775). CONCLUSIONS: Among patients undergoing cardiac surgery, a restrictive transfusion approach resulted in fewer red blood cell transfusions without increasing the risk of AKI.

The Potential Dangers of Recruitment Maneuvers During One Lung Ventilation Surgery.

BACKGROUND: Existing evidence regarding lung-protective ventilation (LPV) during one-lung ventilation (OLV) focuses on surrogate outcomes. Our objective was to assess whether an LPV protocol during OLV surgery is associated with reduced respiratory complications. MATERIALS AND METHODS: This was a matched control retrospective cohort study of patients undergoing pulmonary resection at a tertiary Canadian hospital. The experimental group (n = 50) was derived from primary data of two crossover RCTs, which utilized protocolized LPV strategies with varying levels of positive end-expiratory pressure and recruitment maneuvers. The control group was drawn from a prospectively maintained database; these patients received conventional nonprotocolized ventilation (2000-2010). Each experimental group patient was matched 1:1 with a control group patient with respect to clinically relevant variables (age, sex, diagnosis, smoking status, cardiovascular disease status, comorbidity, BMI, preoperative forced expiratory volume in 1 s, surgery type). Major respiratory complications were defined as composite of acute respiratory distress syndrome, need for new positive-pressure ventilation, and atelectasis requiring bronchoscopy. Paired and unpaired statistical tests were used. RESULTS: Patients appeared well matched. Major respiratory complications occurred in 8% (n = 4) and 2% (n = 1) of patients in experimental and control groups, respectively (P = 0.50). There was a trend toward increased mortality (4 versus 0, P = 0.06) with protocolized LPV. The patients who died had respiratory complications; one had acute respiratory distress syndrome and two had profound hypoxemia. CONCLUSIONS: There was a nonsignificant trend toward increased mortality with LPV during OLV. Although limited by a small sample size, our findings identify a potential danger to excessive recruitment maneuvers. Larger studies, with clinically important outcomes are needed to better define the risk/benefit trade-offs for LPV during OLV.

Identifying Obstructive Sleep Apnea in Administrative Data: A Study of Diagnostic Accuracy.

BACKGROUND: Health administrative (HA) databases are increasingly used to identify surgical patients with obstructive sleep apnea (OSA) for research purposes, primarily using diagnostic codes. Such means to identify patients with OSA are not validated. The authors determined the accuracy of case-ascertainment algorithms for identifying patients with OSA with the use of HA data. METHODS: Clinical data derived from an academic health sciences network within a universal health insurance plan were used as the reference standard. The authors linked patients to HA data and retrieved all claims in the 2 yr before surgery to determine the presence of any diagnostic codes, diagnostic procedures, or therapeutic interventions consistent with OSA. RESULTS: The authors identified 4,965 patients (2003 to 2012) who underwent preoperative polysomnogram. Of these, 4,353 patients were linked to HA data; 2,427 of these (56%) had OSA based on diagnosis by a sleep physician or the apnea hypopnea index. A claim for a polysomnogram and receipt of a positive airway pressure device had a sensitivity, specificity, and positive likelihood ratio (+LR) for OSA of 19, 98, and 10.9%, respectively. An International Classification of Diseases, Tenth Revision, code for sleep apnea in hospitalization abstracts was 9% sensitive and 98% specific (+LR, 4.5). A physician billing claim for OSA (International Classification of Diseases, Ninth Revision, 780.5) was 58% sensitive and 38% specific (+LR, 0.9). A polysomnogram and a positive airway pressure device or any code for OSA was 70% sensitive and 36% specific (+LR, 1.1). CONCLUSIONS: No code or combination of codes provided a +LR high enough to adequately identify patients with OSA. Existing studies using administrative codes to identify OSA should be interpreted with caution.

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.

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.

Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial: rationale and design.

BACKGROUND: Globally there are >200 million major surgical procedures undertaken annually, and about 20% of these involve patients who have coronary artery disease. Many receive nitrous oxide, which impairs methionine synthase, thus inhibiting folate synthesis and increasing postoperative homocysteine levels. Nitrous oxide anesthesia leads to postoperative endothelial dysfunction, and there is some evidence that it increases myocardial ischemia and, possibly, myocardial infarction. We have initiated the Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial to test the hypothesis that in inpatients undergoing anesthesia for major noncardiac surgery, avoidance of nitrous oxide will reduce the incidence of death and major cardiovascular events. METHODS: ENIGMA-II is a 7,000-patient, international randomized trial involving patients at risk of coronary artery disease undergoing noncardiac surgery. The patients, health care providers (except for the anesthesiologists), data collectors, and outcome adjudicators are blinded to whether patients receive nitrous oxide-containing or nitrous oxide-free anesthetic. The primary outcome is a composite of death and major nonfatal events (ie, myocardial infarction, cardiac arrest, pulmonary embolism, and stroke) at 30 days after surgery. RESULTS: At present, ENIGMA-II has randomized >1,000 patients in 22 hospitals in 5 countries. To date, patients' mean age is 70 years, 66% are men, 38% have a history of coronary artery disease, 19% have a history of cerebrovascular disease, and 84% have a history of hypertension. Most patients have undergone intra-abdominal 28%, vascular 32%, and orthopedic 16% surgery. CONCLUSIONS: The ENIGMA-II Trial will be the largest study yet conducted to ascertain the benefits and risks of removing nitrous oxide from the gas mixture in anesthesia. The results of this large international trial will guide the clinical care of the hundreds of millions of adults undergoing noncardiac surgery annually.

Use of lung-protective strategies during one-lung ventilation surgery: a multi-institutional survey.

BACKGROUND: Limited evidence suggests that intraoperative lung-protective ventilation (LPV) during one-lung ventilation (OLV) may reduce respiratory complications after thoracic surgery. Little is known about LPV practices during OLV. Our purpose was to assess the state of practice/perspectives of anesthesiologists regarding LPV during elective OLV. METHODS: We conducted a multi-institutional cross-sectional survey of anesthesiologists performing OLV at high-volume Canadian tertiary/university centers. The survey was designed, refined and distributed by a multi-disciplinary team using the Dillman method. Univariable and multivariable analyses were used. RESULTS: Seventy-five (63%) of 120 eligible respondents completed the survey. Although the critical care literature focuses on minimizing tidal volume (TV) as the central strategy of LPV, most respondents (89%, n=50/56) focused on minimizing peak airway pressure (PAP) as their primary strategy of intraoperative LPV. Only 64% (n=37/58) reported actively trying to minimize TV. While 32% (n=17/54) were unsure about the current evidence regarding LPV, 67% (n=36/54) believed that the evidence favoured their use during OLV. Perceived clinical and institutional barriers were the only predictors of reduced attempts to minimize TV on univariate analyses. In multivariable/adjusted analyses, perceived institutional barriers were the only predictors of reduced attempts to minimize TV with adjusted odds ratio of 0.1 (95% CI: 0.03-0.6). CONCLUSIONS: Most anesthesiologists defined low PAP as the primary strategy of LPV during OLV and attempted to minimize it. This study is the first to assess the practice/perspectives of anesthesiologists regarding LPV during OLV and also the first to explore predictors of LPV use. Randomized trials are currently ongoing. However, this study suggests that institutional barriers may subvert future knowledge translation and need to be addressed.

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

OBJECTIVE: To determine the effect of perioperative beta 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 beta 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 beta 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 beta 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 beta blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.

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

Objective To determine the effect of perioperative 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 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 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 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 blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn...