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Abstract Objective Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent. Methods Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO2) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO2, maximum PaO2 difference, and gradually increasing PaO2 levels (13.3–53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO2 and a biomarker of brain injury, peak serum Tau levels. Results Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO2 exposure or maximum PaO2 difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p = 0.146–0.847). We were not able to define a PaO2 level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO2. Conclusion Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC.

Abstract Background The European Resuscitation Council 2021 guidelines for haemodynamic monitoring and management during post-resuscitation care from cardiac arrest call for an individualised approach to therapeutic interventions. Combining the cardiac function and venous return curves with the inclusion of the mean systemic filling pressure enables a physiological illustration of intravascular volume, vasoconstriction and inotropy. An analogue mean systemic filling pressure (Pmsa) may be calculated once cardiac output, mean arterial and central venous pressure are known. The NEUROPROTECT trial compared targeting a mean arterial pressure of 65 mmHg (standard) versus an early goal directed haemodynamic optimisation targeting 85 mmHg (high) in ICU for 36 h after cardiac arrest. The trial data were used in this study to calculate post hoc Pmsa and its expanded variables to comprehensively describe venous return physiology during post-cardiac arrest management. A general estimating equation model was used to analyse continuous variables split by standard and high mean arterial pressure groups. Results Data from 52 patients in each group were analysed. The driving pressure for venous return, and thus cardiac output, was higher in the high MAP group (p

Abstract Background The optimal level of positive end-expiratory pressure (PEEP) during mechanical ventilation for COVID-19 pneumonia remains debated and should ideally be guided by responses in both lung volume and perfusion. Capnodynamic monitoring allows both end-expiratory lung volume ( $${\text{EELV}}_{{{\text{CO}}_{2} }}$$ EELV CO 2 ) and effective pulmonary blood flow (EPBF) to be determined at the bedside with ongoing ventilation. Methods Patients with COVID-19-related moderate to severe respiratory failure underwent capnodynamic monitoring of $${\text{EELV}}_{{{\text{CO}}_{2} }}$$ EELV CO 2 and EPBF during a step increase in PEEP by 50% above the baseline (PEEPlow to PEEPhigh). The primary outcome was a > 20 mm Hg increase in arterial oxygen tension to inspired fraction of oxygen (P/F) ratio to define responders versus non-responders. Secondary outcomes included changes in physiological dead space and correlations with independently determined recruited lung volume and the recruitment-to-inflation ratio at an instantaneous, single breath decrease in PEEP. Mixed factor ANOVA for group mean differences and correlations by Pearson’s correlation coefficient are reported including their 95% confidence intervals. Results Of 27 patients studied, 15 responders increased the P/F ratio by 55 [24–86] mm Hg compared to 12 non-responders (p

Abstract Background Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. Methods Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). Results In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%. Conclusions The posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

Abstract Background Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. Methods A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. Results In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p

Abstract Background Clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of patients, an acute episode of delirium is also common, but its relationship to frailty and increased risk of mortality has not been extensively explored. Therefore, the aim of this study was to explore the relationship between clinical frailty, delirium and hospital mortality of older adults admitted to intensive care. Methods This study is part of a Delirium in Intensive Care (Deli) Study. During the initial 6-month baseline period, clinical frailty status on admission to intensive care, among adults aged 50 years or more; acute episodes of delirium; and the outcomes of intensive care and hospital stay were explored. Results During the 6-month baseline period, 997 patients, aged 50 years or more, were included in this study. The average age was 71 years (IQR, 63–79); 55% were male (n = 537). Among these patients, 39.2% (95% CI 36.1–42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% (n = 127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted rate ratio (adjRR) = 1.71, 95% confidence interval (CI) 1.20–2.43, p = 0.003), had a longer hospital stay (2.6 days, 95% CI 1–7 days, p = 0.009) and had a higher risk of hospital mortality (19% versus 7%, adjRR = 2.54, 95% CI 1.72–3.75, p

Abstract Background Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined. Methods This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3–5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0–7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated. Results Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13–0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (P interaction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC). Conclusions Dyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.

Abstract Background We aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100. Methods This is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 months was assessed using the Cerebral Performance Categories Scale (CPC 1–2 = good outcome, CPC 3–5 = poor outcome). Results We included 687 patients from 29 sites in Europe. Median S100 values were higher in patients with a poor outcome at 24, 48, and 72 h: 0.19 (IQR 0.10–0.49) versus 0.08 (IQR 0.06–0.11) μg/ml, 0.16 (IQR 0.10–0.44) versus 0.07 (IQR 0.06–0.11) μg/L, and 0.13 (IQR 0.08–0.26) versus 0.06 (IQR 0.05–0.09) μg/L (p

Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .