Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

Cardiac troponins and volatile anaesthetics in coronary artery bypass graft surgery: A systematic review, meta-analysis and trial sequential analysis.

BACKGROUND: Reports from animal studies indicate that volatile anaesthetics protect the myocardium against the effects of acute ischaemia-reperfusion injury by reducing infarct size. This cardioprotective effect in the clinical setting of coronary artery bypass graft (CABG) surgery, where the heart is subjected to global ischaemia-reperfusion injury, remains controversial. OBJECTIVE: The objective was to demonstrate that clinical studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in CABG are no longer warranted. We also investigated the effect of volatile anaesthetics on cardiac enzymes in off-pump cardiac surgery. DESIGN: Systematic review of randomised clinical trials, meta-analyses and trial sequential analysis (TSA). DATA SOURCES: Trials between January 1985 and March 2015 were obtained from electronic databases (Medline, Excerpta Medica Database (EMBASE), Cochrane Controlled Trial Register, abstracts from major anaesthesiology and cardiology journals and reference lists of relevant randomised trials and review articles. ELIGIBILITY CRITERIA: Relevant randomised clinical trials were included. We investigated the effect of volatile anaesthetics in both off-pump and on-pump CABG surgery with respect to troponin release [peak postoperative cardiac troponin I (cTnI) and cardiac troponin T (cTnT), cTnI/cTnT] and performed two separate meta-analyses. TSA was used to overcome the weakness of a type-1 error associated with repeated meta-analyses. RESULTS: From 30 studies, 2578 patients were pooled for the meta-analysis. The outcome significantly favours the use of peroperative volatile over non-volatile anaesthetics during on-pump CABG surgery with regard to peak postoperative cTnI (0.995 mg l; standard mean difference, 95% confidence interval, -1.316 to -0.673; P < 0.001). Meta-analysis of 11 off-pump studies showed no difference in peak postoperative cTnI (0.385 mg l; standard mean difference, 95% confidence interval, -0.857 to 0.087; P = 0.11). TSA indicated that the required information size for on-pump surgery was 1072 patients, and for off-pump surgery it was 1442; this latter figure has not yet been reached. CONCLUSION: Studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in on-pump CABG surgery are no longer warranted. This is not yet the case for off-pump surgery.