Background: During general anaesthesia for noncardiac surgery, there remain knowledge gaps regarding the effect of goal-directed haemodynamic therapy on patient-centred outcomes. Methods: Included clinical trials investigated goal-directed haemodynamic therapy during general anaesthesia in adults undergoing noncardiac surgery and reported at least one patient-centred postoperative outcome. PubMed and Embase were searched for relevant articles on March 8, 2021. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. The primary outcomes were mortality and hospital length of stay, whereas 15 postoperative complications were included based on availability. From a main pool of comparable trials, meta-analyses were performed on trials with homogenous outcome definitions. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Results: The main pool consisted of 76 trials with intermediate risk of bias for most outcomes. Overall, goal-directed haemodynamic therapy might reduce mortality (odds ratio¼0.84; 95% confidence interval [CI], 0.64 to 1.09) and shorten length of stay (mean difference¼e0.72 days; 95% CI, e1.10 to e0.35) but with low certainty in the evidence. For both outcomes, larger effects favouring goal-directed haemodynamic therapy were seen in abdominal surgery, very high-risk surgery, and using targets based on preload variation by the respiratory cycle. However, formal tests for subgroup differences were not statistically significant. Goal-directed haemodynamic therapy decreased risk of several postoperative outcomes, but only infectious outcomes and anastomotic leakage reached moderate certainty of evidence.

IMPORTANCEIt is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest. OBJECTIVE To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults. DESIGN, SETTING, AND PARTICIPANTSThis double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021. INTERVENTIONSThe intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine. MAIN OUTCOMES AND MEASURESThe primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. RESULTSBased on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, −7.6% [95% CI, −16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, −3.9% [95% CI, −9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, −4.0% [95% CI, −8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia.CONCLUSIONS AND RELEVANCE Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults.

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Background: Controversy exists regarding the effects of a high versus a low intraoperative fraction of inspired oxygen (FiO 2 ) in adults undergoing general anesthesia. This systematic review and meta-analysis investigated the effect of a high versus a low FiO 2 on postoperative outcomes.Methods: PubMed and Embase were searched on March 22, 2022 for randomized clinical trials investigating the effect of different FiO 2 levels in adults undergoing general anesthesia for non-cardiac surgery. Two investigators independently reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and potential effect measure modification was assessed in subgroup analyses and meta-regression. The evidence certainty was evaluated using GRADE.Results: This review included 25 original trials investigating the effect of a high (mostly 80%) versus a low (mostly 30%) FiO 2 . Risk of bias was intermediate for all trials. A high FiO 2 did not result in a significant reduction in surgical site infections (OR: 0.91, 95% CI 0.81-1.02 [p = .10]). No effect was found for all other included outcomes, including mortality (OR = 1.27, 95% CI: 0.90-1.79 [p = .18]) and hospital length of stay (mean difference = 0.03 days, 95% CI À0.25 to 0.30 [p = .84). Results from subgroup analyses and meta-regression did not identify any clear effect modifiers across outcomes. The certainty of evidence (GRADE) was rated as low for most outcomes.Maria Høybye and Peter C. Lind contributed equally.