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Background The routine use of sedation and analgesia during post-cardiac arrest care and its association with clinical outcomes remain unclear. This study aimed to describe the use of sedatives and analgesics in post-cardiac arrest care, and evaluate associations with good functional outcome, survival, clinical seizures, and late awakening. Methods This was a post hoc analysis of the TTM2-trial, which randomized 1900 out-of-hospital cardiac arrest patients to either normothermia or hypothermia. In both groups, deep sedation (Richmond Agitation and Sedation Scale ≤ -4) was mandatory during the 40-h intervention. Cumulative doses of sedatives and analgesic drugs were recorded within the first 72 h from randomization. Outcomes were functional outcome (modified Rankin Scale) and survival status at 6 months, occurrence of clinical seizures during the intensive care stay, and late awakening (Full outline of unresponsiveness motor score of four 96 h after randomization). Cumulative propofol doses were divided into quartiles (Q1-Q4). Logistic regression models were used to assess associations between sedative doses and functional outcome and survival, clinical seizures, and late awakening, adjusting for the severity of illness and other clinical factors influencing sedation. Results A total of 1861 patients were analyzed. In a multivariable logistic regression model, higher propofol doses (Q3, 100.7–153.6 mg/kg) were associated with good functional outcome (OR 1.62, 95%CI 1.12—2.34) and (Q2 and Q3, 43.9–153.6 mg/kg) with survival (OR 1.49, 95%CI 1.05—2.12 and OR 1.84, 95%CI 1.27—2.65, respectively). Receiving fentanyl and remifentanil were associated with good functional outcome (OR 1.69, 95%CI 1.27—2.26 and OR 1.50, 95%CI 1.11—2.02) and survival (OR 1.80, 95%CI 1.35—2.40 and OR 1.56, 95%CI 1.16—2.10). Receiving fentanyl (OR 0.64, 95%CI 0.48—0.86) and higher propofol doses (Q2-4 (43.9–669.4 mg/kg) were associated with the occurrence of clinical seizures. The highest quartile of propofol dose (153.7–669.4 mg/kg, OR 3.19, 95%CI 1.91—5.42) was associated with late awakening. Conclusions In this study, higher doses of propofol and the use of remifentanil and fentanyl were associated with good functional outcome and survival, occurrence of clinical seizures, and late awakening.

Background Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016.

PurposeApplication of standardised and automated assessments of head computed tomography (CT) for neuroprognostication after out-of-hospital cardiac arrest.MethodsProspective, international, multicentre, observational study within the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial. Routine CTs from adult unconscious patients obtained > 48 h ≤ 7 days post-arrest were assessed qualitatively and quantitatively by seven international raters blinded to clinical information using a pre-published protocol. Grey–white-matter ratio (GWR) was calculated from four (GWR-4) and eight (GWR-8) regions of interest manually placed at the basal ganglia level. Additionally, GWR was obtained using an automated atlas-based approach. Prognostic accuracies for prediction of poor functional outcome (modified Rankin Scale 4–6) for the qualitative assessment and for the pre-defined GWR cutoff < 1.10 were calculated.Results140 unconscious patients were included; median age was 68 years (interquartile range [IQR] 59–76), 76% were male, and 75% had poor outcome. Standardised qualitative assessment and all GWR models predicted poor outcome with 100% specificity (95% confidence interval [CI] 90–100). Sensitivity in median was 37% for the standardised qualitative assessment, 39% for GWR-8, 30% for GWR-4 and 41% for automated GWR. GWR-8 was superior to GWR-4 regarding prognostic accuracies, intra- and interrater agreement. Overall prognostic accuracy for automated GWR (area under the curve [AUC] 0.84, 95% CI 0.77–0.91) did not significantly differ from manually obtained GWR.ConclusionStandardised qualitative and quantitative assessments of CT are reliable and feasible methods to predict poor functional outcome after cardiac arrest. Automated GWR has the potential to make CT quantification for neuroprognostication accessible to all centres treating cardiac arrest patients.

IntroductionAfter resuscitation from out of hospital cardiac arrest (OHCA), mechanical ventilation (MV) and respiratory management are fundamental to support patients in the intensive care unit (ICU) and to minimise secondary brain injury. Best practices for MV and association with clinical outcomes in patients with OHCA remain unclear.Methods and analysisThis protocol describes a pre-planned respiratory-focused series of sub-analyses within the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, an ongoing interventional study evaluating 6-month mortality after randomisation in patients admitted to ICUs following OHCA. The primary aim is to describe real-world ventilator settings and gas-exchange targets during the first 72 hours after ICU admission in patients receiving invasive mechanical ventilation after OHCA. Secondary aims include to estimate the incidence of respiratory complications during ICU stay (eg, ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma); and to explore the association between early ventilator settings/gas-exchange parameters and 6-month outcomes (mortality and neurological status). Exploratory aim is to characterise weaning and extubation practices, including timing and failure rates.Eligible patients will include adult STEPCARE participants receiving invasive MV after return of spontaneous circulation with available respiratory data recorded within the STEPCARE database.Data collected in the STEPCARE trial that will be analysed include patients’ prehospital characteristics; clinical examination at hospital admission and at ICU admission; ventilator settings and arterial blood gases recorded at predefined time points during ICU stay. In particular: MV setting (mode, tidal volume, positive end-expiratory pressure, fraction of inspired oxygen, tidal volume, mechanical power, plateau/driving pressures), gas-exchange values (arterial partial pressure of oxygen and carbon dioxide, pH, arterial saturation of oxygen), timing of measurements and the occurrence/timing of respiratory complications and weaning outcomes.Ethics and disseminationThe STEPCARE study has been approved by the regional ethics committee at Lund University (Dnr 2022-02425-01, Approved IRB on 2022-06-18) and by all ethics boards in the participating countries. No additional ethical approval is required for this predefined secondary analysis, as no further data collection or interventions will be performed. Findings will be disseminated through publication in peer-reviewed journals and, where appropriate, conference abstracts and presentations. Patients and the public were not involved.ClinicalTrials.govNCT05564754.

Background Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest. Methods Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score. Results Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p  = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p  = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p  < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12–0.27], p  < 0.001. Conclusion Copeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure. Trial registration Clinical Trials, NCT01020916 . Registered November 26, 2009.

Background: Targeted temperature management at 33 degrees C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) &gt;= 70 mmHg; (2) moderate-vasopressor support MAP &lt; 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose &lt;= 0.25 mu g/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose &gt; 0.25 mu g/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78-1.39] in the no-, 1.22 [98.3% CI 0.97-1.53] in the moderate-, and 0.97 [98.3% CI 0.68-1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions: In this exploratory analysis, temperature control at 33 degrees C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission.