Intraoperative Inspiratory Oxygen Fraction and Myocardial Injury After Noncardiac Surgery: Results From an International Observational Study in Relation to Recent Controlled Trials.

BACKGROUND: Two trials reported that a high inspiratory oxygen fraction (F io2 ) does not promote myocardial infarction or death. Observational studies can provide larger statistical strength, but associations can be due to unobserved confounding. Therefore, we evaluated the association between intraoperative F io2 and cardiovascular complications in a large international cohort study to see if spurious associations were observed. METHODS: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials. RESULTS: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34). CONCLUSIONS: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials.

Management of Acute Respiratory Distress Syndrome and Refractory Hypoxemia. A Multicenter Observational Study.

RATIONALE: Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described. OBJECTIVES: To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS, including refractory hypoxemia. METHODS: This was a prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an FiO2 of 0.50 or greater in 24 intensive care units. RESULTS: We enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm H2O (n = 653); 568 patients (87%) received PEEP less than 15 cm H2O. Treatment adjuncts were common (n = 440, 66%): neuromuscular blockers (n = 276, 42%), pulmonary vasodilators (n = 118, 18%), prone positioning (n = 67, 10%), extracorporeal life support (n = 29, 4%), and high-frequency oscillatory ventilation (n = 29, 4%). Refractory hypoxemia, defined as PaO2 less than 60 mm Hg on FiO2 of 1.0, occurred in 138 (21%) patients. At onset of refractory hypoxemia, mean Vt was 7.1 (SD = 2.0) ml/kg (n = 124); 95 patients (77%) received Vt greater than 6 ml/kg. Mean PEEP was 12.1 (SD = 4.4) cm H2O (n = 133); 99 patients (74%) received PEEP less than 15 cm H2O. Among patients with refractory hypoxemia, 91% received treatment adjuncts (126/138), with increased use of neuromuscular blockers (n = 87, 63%), pulmonary vasodilators (n = 57, 41%), and prone positioning (n = 32, 23%). CONCLUSIONS: Patients with moderate-to-severe ARDS receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g., pulmonary vasodilators) were over-used, whereas those with more evidence (e.g., prone positioning, neuromuscular blockade) were under-used. Patients received higher Vts and lower PEEP than would be suggested by the evidence.

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.

BACKGROUND: Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers. METHODS: We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039. FINDINGS: All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053). INTERPRETATION: Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.