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Introduction: Post-resuscitation care of cardiac arrest patients may be complicated by systemic inflammation elicited in response to whole-body ischaemia–reperfusion injury. We assessed the association between early WBC with one-year mortality in a large, unselected population of cardiac arrest patients. Methods: We collected a retrospective multicentre cohort of ICU-treated CA patients from the Finnish national ICU registry. We used locally estimated scatterplot smoothing (LOESS) curve to assess the association between the most abnormal WBC of the first 24 h in the ICU with the likelihood of death within a year. Multivariable logistic regression analyses were performed to assess the independent association between WBC and one-year mortality. In nested cohort analysis, we tested the association of delay from collapse to return of spontaneous circulation (ROSC) with WBC in linear regression models. Results: The LOESS curve was U-shaped, with the lowest predicted mortality at 7.5 109/L WBC. Based on this cut-off value, patients were divided into high (≥ 7.5 109/L) and low (< 7.5 109/L) WBC groups. In 4229 patients with high WBC, higher WBC was independently associated with increased one-year mortality (adjusted odds ratio (OR) 1.03 per 109/L, 95 % confidence interval (CI) 1.02–1.04, p

Summary: Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83–1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92–1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94–1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. Funding: None.

Summary: Background: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. Methods: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. Findings: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18–4.90]). No adverse events were reported. Interpretation: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. Trial registration: NCT03237910. Funding: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.