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.

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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.

BACKGROUND: The optimal ventilation strategy during general anesthesia is unclear. This systematic review investigated the relationship between ventilation targets or strategies (eg, positive end-expiratory pressure [PEEP], tidal volume, and recruitment maneuvers) and postoperative outcomes. METHODS: PubMed and Embase were searched on March 8, 2021, for randomized trials investigating the effect of different respiratory targets or strategies on adults undergoing noncardiac surgery. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and several subgroup analyses were conducted. The certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This review included 63 trials with 65 comparisons. Risk of bias was intermediate for all trials. In the meta-analyses, lung-protective ventilation (ie, low tidal volume with PEEP) reduced the risk of combined pulmonary complications (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.28–0.49; 9 trials; 1106 patients), atelectasis (OR, 0.39; 95% CI, 0.25–0.60; 8 trials; 895 patients), and need for postoperative mechanical ventilation (OR, 0.36; 95% CI, 0.13–1.00; 5 trials; 636 patients). Recruitment maneuvers reduced the risk of atelectasis (OR, 0.44; 95% CI, 0.21–0.92; 5 trials; 328 patients). We found no clear effect of tidal volume, higher versus lower PEEP, or recruitment maneuvers on postoperative pulmonary complications when evaluated individually. For all comparisons across targets, no effect was found on mortality or hospital length of stay. No effect measure modifiers were found in subgroup analyses. The certainty of evidence was rated as very low, low, or moderate depending on the intervention and outcome. CONCLUSIONS: Although lung-protective ventilation results in a decrease in pulmonary complications, randomized clinical trials provide only limited evidence to guide specific ventilation strategies during general anesthesia for adults undergoing noncardiac surgery.

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Background Systematic reviews have disclosed a lack of clinically relevant cardiac arrest animal models. The aim of this study was to develop a cardiac arrest model in pigs encompassing relevant cardiac arrest characteristics and clinically relevant post‐resuscitation care. Methods and Results We used 2 methods of myocardial infarction in conjunction with cardiac arrest. One group (n=7) had a continuous coronary occlusion, while another group (n=11) underwent balloon‐deflation during arrest and resuscitation with re‐inflation after return of spontaneous circulation. A sham group was included (n=6). All groups underwent 48 hours of intensive care including 24 hours of targeted temperature management. Pigs underwent invasive hemodynamic monitoring. Left ventricular function was assessed by pressure‐volume measurements. The proportion of pigs with return of spontaneous circulation was 43% in the continuous infarction group and 64% in the deflation‐reinflation group. In the continuous infarction group 29% survived the entire protocol while 55% survived in the deflation‐reinflation group. Both cardiac arrest groups needed vasopressor and inotropic support and pressure‐volume measurements showed cardiac dysfunction. During rewarming, systemic vascular resistance decreased in both cardiac arrest groups. Median [25%;75%] troponin‐I 48 hours after return of spontaneous circulation, was 88 973 ng/L [53 124;99 740] in the continuous infarction group, 19 661 ng/L [10 871;23 209] in the deflation‐reinflation group, and 1973 ng/L [1117;1995] in the sham group. Conclusions This article describes a cardiac arrest pig model with myocardial infarction, targeted temperature management, and clinically relevant post‐cardiac arrest care. We demonstrate 2 methods of inducing myocardial ischemia with cardiac arrest resulting in post‐cardiac arrest organ injury including cardiac dysfunction and cerebral injury.

Background Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting. Methods The aim of this study was to investigate temporal changes in measures of cerebral injury and metabolism in a cardiac arrest pig model with clinically relevant post-cardiac arrest intensive care. A cardiac arrest group (n = 11) underwent 7 min of no-flow and was compared with a sham group (n = 6). Pigs underwent intensive care with 24 h of hypothermia at 33 °C. Blood markers of cerebral injury, cerebral microdialysis, and intracranial pressure (ICP) were measured. After 48 h, pigs underwent a cerebral MRI scan. Data are presented as median [25th; 75th percentiles]. Results Return of spontaneous circulation was achieved in 7/11 pigs. Time to ROSC was 4.4 min [4.2; 10.9]. Both NSE and NfL increased over time (p < 0.001), and were higher in the cardiac arrest group at 48 h (NSE 4.2 µg/L [2.4; 6.1] vs 0.9 [0.7; 0.9], p < 0.001; NfL 63 ng/L [35; 232] vs 29 [21; 34], p = 0.02). There was no difference in ICP at 48 h (17 mmHg [14; 24] vs 18 [13; 20], p = 0.44). The cerebral lactate/pyruvate ratio had secondary surges in 3/7 cardiac arrest pigs after successful resuscitation. Apparent diffusion coefficient was lower in the cardiac arrest group in white matter cortex (689 × 10–6 mm2/s [524; 765] vs 800 [799; 815], p = 0.04) and hippocampus (854 [834; 910] vs 1049 [964; 1180], p = 0.03). N-Acetylaspartate was lower on MR spectroscopy in the cardiac arrest group (− 17.2 log [− 17.4; − 17.0] vs − 16.9 [− 16.9; − 16.9], p = 0.03). Conclusions We have developed a clinically relevant cardiac arrest pig model that displays cerebral injury as marked by NSE and NfL elevations, signs of cerebral oedema, and reduced neuron viability. Overall, the burden of elevated ICP was low in the cardiac arrest group. A subset of pigs undergoing cardiac arrest had persisting metabolic disturbances after successful resuscitation.

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron‐specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron‐specific enolase was similar between groups, with 81.5 μg/L per hour (SD, 20.4) in the thiamine group and 80.5 μg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, −57.8 to 59.8; P =0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, −38 to 42]; P =0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, −0.5 to 2.7]; P =0.16). Conclusions In this randomized, blinded, placebo‐controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron‐specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.