Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, −0.02 [95% CI, −0.67 to 0.63]; SDMT: mean difference, −0.09 [95% CI, −0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, −2.00 to −1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, −0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. ClinicalTrials.gov Identifier: NCT02908308

Importance:Guidelines for temperature control following out-of-hospital cardiac arrest (OHCA) are based on trials with end points of 180 days or fewer. Objectives:To investigate if targeted hypothermia, compared with targeted normothermia with early treatment of fever, affects functional outcome focusing on societal participation or cognitive functioning at 24 months in initially comatose OHCA survivors. An additional objective was to explore recovery trajectories up to 24 months post arrest. Design, Setting, and Participants:The randomized clinical Targeted Hypothermia vs Targeted Normothermia After OHCA (TTM2) trial (November 2017-2020) included blinded follow-up at 1, 6, and 24 months post randomization (December 2017-June 2022), with analyses performed in 2024. TTM2 was an international, multicenter study conducted at 61 hospitals in 14 countries. The study included 1861 adults with OHCA of presumed cardiac or unknown cause who were initially comatose. There were 992 survivors at 1 month, 943 at 6 months, and 835 at 24 months. Nonparticipation rates at follow-up were 44 (4%), 107 (11%), and 165 (20%), respectively. Intervention:Participants were randomized 1:1 to undergo temperature control via targeted hypothermia (33 °C) or targeted normothermia and early treatment of fever (≥37.8 °C). Main Outcomes and Measures:The functional outcome, including societal participation, was assessed using the Glasgow Outcome Scale-Extended (GOSE). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities Test (SDMT). Results:Of the participants who were followed up, 84% were male, with a mean (SD) age of 60 (14) years, and clinical variables were similar between the hypothermia and normothermia temperature groups. No significant differences were found between temperature groups regarding societal participation (GOSE: odds ratio, 0.97 [95% CI, 0.72-1.30]) or cognitive function (MoCA: mean difference, -0.02 [95% CI, -0.67 to 0.63]; SDMT: mean difference, -0.09 [95% CI, -0.33 to 0.16]) at 24 months. Improvement for GOSE was significant within the first 6 months (1 to 6 months: n = 1707 [95% CI, -2.00 to -1.50]; P < .001; 6 to 24 months: n = 1606 [95% CI, -0.50 to <0.001]; P = .10). Intraindividual improvement and decline corresponding to thresholds for minimal important differences were observed for societal participation and cognitive function up to 24 months. Conclusions and Relevance:Targeted hypothermia, compared with targeted normothermia, did not affect societal participation or cognitive function at 24 months, suggesting no longer-term effect of hypothermia for the explored outcomes. The intraindividual changes observed indicate variability in recovery. Trial Registration:ClinicalTrials.gov Identifier: NCT02908308.

Introduction After 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 analysis This 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 dissemination The 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.gov NCT05564754.

BACKGROUND:Prognostication of recovery in patients who are unconscious following cardiac arrest can be guided by concentrations of brain injury biomarkers in the blood. The optimal biomarker and cutoff concentrations for the prediction of outcome remain unknown. In this study, we aimed to evaluate which biomarker of brain injury is most accurate for predicting functional outcome after cardiac arrest, and to evaluate cutoff levels for the prediction of good and poor outcome. METHODS:This study was a prospective, international, observational biomarker study within the international Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial including adults aged 18 years or older with a presumed cardiac cause or unknown cause of arrest. Patients were recruited from 24 European hospitals. Serum samples were collected at 0, 24, 48, and 72 h after admission to intensive care units. Concentrations of neuron-specific enolase, S100, neurofilament light, and glial fibrillary acidic protein were analysed with Elecsys electrochemiluminescence immunoassays. The primary outcome was 6-month good (modified Rankin Scale 0-3) or poor (modified Rankin Scale 4-6) functional outcome. Prognostic accuracy was evaluated by the area under the receiver operating characteristic curve (AUROC). The biomarker with the highest AUROC at each timepoint was compared with that of the second highest marker using DeLong's test. As pre-specified, to account for multiple comparisons using Bonferroni correction, a p value of less than 0·0125 was considered statistically significant. FINDINGS:Between April, 2018, and January, 2020, 113 (12%) of 932 eligible patients were excluded due to death, missed sampling, or missing outcome data. 661 (81%) of 819 included patients were male and 158 (19%) were female, the mean age was 64 years (SD 13), and 418 (51%) had a poor outcome. In patients who were unconscious, neurofilament light predicted functional outcome with AUROCs at 0, 24, 48, and 72 h of 0·77 (95% CI 0·73-0·80), 0·92 (0·90-0·94), 0·93 (0·91-0·95), and 0·93 (0·91-0·95), respectively. Glial fibrillary acidic protein achieved an AUROC of 0·74 (95% CI 0·70-0·77) at 0 h, 0·87 (0·84-0·90) at 24 h, 0·87 (0·84-0·90) at 48 h, and 0·87 (0·84-0·91) at 72 h. Neuron-specific enolase predicted functional outcome with an AUROC of 0·61 (95% CI 0·56-0·65) at 0 h, 0·78 (0·75-0·82) at 24 h, 0·85 (0·81-0·88) at 48 h, and 0·86 (0·82-0·89) at 72 h. S100 achieved an AUROC of 0·74 (95% CI 0·71-0·78) at 0 h, 0·84 (0·81-0·87) at 24 h, 0·79 (0·75-0·82) at 48 h, and 0·78 (0·74-0·82) at 72 h. Neurofilament light had a statistically significantly higher AUROC than the second highest marker, glial fibrillary acidic protein, at 24, 48, and 72 h (p<0·0001), but not at 0 h (p=0·27). INTERPRETATION:Neurofilament light is a highly accurate predictor of long-term outcome after cardiac arrest and superior to other relevant biomarkers evaluated in this study. FUNDING:The Swedish Research Council (Vetenskapsrådet), the Swedish Heart-Lung Foundation, the Stig and Ragna Gorthon Foundation, the Knutsson Foundation, the Laerdal Foundation, the Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, the Bundy Academy at Lund University, Regional Research Support in Skåne, the Swedish Government, and Roche Diagnostics International.

INTRODUCTION:Qualitative assessment of hypoxic ischaemic encephalopathy on computed tomography (CT) after cardiac arrest is limited by interrater agreement. We explored how qualitative assessment can be improved. METHODS:In-depth analysis of radiological items evaluated in a prospective sub-study within the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial examining unconscious patients with CT > 48 h ≤ 7 days. Prognostic performance to diagnose poor outcome (modified Rankin Scale 4-6 at six months) and interrater agreement were evaluated for: "loss of grey-white matter distinction" and "sulcal effacement" at different anatomical levels, "the Pseudo Subarachnoid Haemorrhage Sign", "the White Cerebellum Sign", and "the Reversal Sign". RESULTS:We included 140 patients examined with CT at median 84 h (IQR 66-109) post-arrest. Median age was 68 years (IQR 59-76), 106 (76%) were male and 105 (75%) had a poor functional outcome. "Loss of grey-white matter distinction" predicted poor functional outcome with 100% specificity and 45-50% sensitivity. The specificity for "sulcal effacement" was 93-99% and the sensitivity 29-49%. "The Pseudo Subarachnoid Haemorrhage Sign", "the Reversal Sign", and the "White Cerebellum Sign" predicted poor functional outcome with 99-100% specificity and 8-11% sensitivity. The highest interrater agreement was "moderate" (κ = 0.74) for the loss of grey-white matter distinction at high convexity level. CONCLUSION:Extensive and bilateral loss of grey-white matter distinction on CT is associated with poor functional outcome after cardiac arrest and yielded the highest interrater agreement. Signs of sulcal effacement were less reliable and should thus be used with caution in neuroprognostication. The TTM2 CT substudy is registered at clinicaltrials.gov (NCT03913065).

BACKGROUND:The international multi-center randomized controlled STEPCARE-trial will investigate optimal management of sedation, temperature, and mean arterial pressure (MAP) during intensive care in out-of-hospital cardiac arrest (OHCA) patients due to various etiologies. The primary outcome is mortality at 6 months. This protocol describes an extended follow-up sub-study of the STEPCARE-trial with the main objective to provide detailed long-term outcomes for survivors and caregivers. It will focus on potential neuroprotection and improved recovery for different targets of sedation, temperature, and MAP management at 6 and 12 months post-OHCA. METHODS:All survivors and one caregiver per survivor at selected STEPCARE sites will be invited to participate. Randomization is stratified by site. This sub-study extends the main STEPCARE follow-up at 6 months by undertaking detailed assessments, face-to-face meetings, inclusion of a caregiver, and repeating the assessments at 12 months. Our main outcome for survivors is cognitive function measured by the Montreal Cognitive Assessment, and for caregivers, the caregiver burden measured by the Zarit Burden Interview. Additional outcomes include symptoms of anxiety, depression, post-traumatic stress disorder, fatigue, physical function, life satisfaction, and life impact (disability), assessed by psychometrically robust measures. The estimated sample size is 600. Efforts to improve interrater reliability and decrease missing data are integral to the study design. CONCLUSION:These detailed long-term outcomes will explore the possible benefits or risks of fever, sedation, and blood pressure management in post-OHCA survivors. Additionally, this study will explore survivorship after cardiac arrest from various perspectives, including different causes of arrest. CLINICALTRIALS:gov: NCT0207942.

Background: Out-of-hospital cardiac arrest (OHCA) survivors and their relatives may face challenges following hospital discharge, relating to mood, cognition, and returning to normal day-to-day activities. Identified research gaps include a lack of knowledge around what type of intervention is needed to best navigate recovery. In this study, we investigate the feasibility and patient acceptability of a new virtual psychoeducational group intervention for OHCA survivors and their relatives and compare it to a control group receiving a digital information booklet. Methods: V-CARE is a comparative, single-blind randomized pilot trial including participants at selected sites of the STEPCARE trial, in the United Kingdom and Sweden. Inclusion criteria are a modified Rankin Scale (mRS) ≤ 3 at 30-day follow-up; no diagnosis of dementia; and not experiencing an acute psychiatric episode. One caregiver per patient is invited to participate optionally. The intervention group in V-CARE receives four semi-structured, one-hour-long, psychoeducational sessions delivered remotely via video call by a trained clinician once a week, 2-3 months after hospital discharge. The sessions cover understanding cardiac arrest; coping with fatigue and memory problems; managing low mood and anxiety; and returning to daily life. The control group receives an information booklet focused on fatigue, memory/cognitive problems, mental health, and practical coping strategies. Results: Primary: feasibility (number of patients consented) and acceptability (retention rate); secondary: satisfaction with care (Client Satisfaction Questionnaire 8 item), self-management skills (Self-Management Assessment Scale) and, where available, health-related outcomes assessed in the STEPCARE Extended Follow-up sub-study including cognition, fatigue, mood, quality of life, and return to work. Conclusions: If preliminary insights from the V-CARE trial suggest the intervention to be feasible and acceptable, the results will be used to design a larger trial aimed at informing future interventions to support OHCA recovery.

To compare the performance of targeted temperature management (TTM) at 33 °C using intravascular (IC) vs. surface-cooling (SFC) devices after out-of-hospital cardiac arrest (OHCA). A post hoc analysis including OHCA patients randomized to hypothermia in the TTM2-trial (NCT02908308) comparing hypothermia with normothermia. The main outcome was cooling performance, defined as the proportion of patients reaching target temperature < 33.5 °C within 4 h, time outside temperature ranges during maintenance, rewarming rate and post-TTM fever. Exploratory outcomes included survival and good functional outcome, defined as modified Rankin Scale (mRS) scores of 0–3 at 6 months, analyzed using Inverse Probability Treatment Weighting (IPTW). Among 930 patients randomized to hypothermia, 876 were treated with a cooling device and included in this study. Of those, 27.3

PURPOSE:To explore modifications of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guideline algorithm for neuroprognostication after cardiac arrest to improve its prognostic accuracy. METHODS:Post-hoc analysis of four prospective multicentre studies (TTM, TTM2, KORHN and ProNeCA). We raised the Glasgow Coma Scale motor (GCS-M) inclusion threshold at 72 h after cardiac arrest from the current GCS-M < 4 to GCS-M < 6 (all unconscious patients). Secondly, we included good outcome predictors (GCS-M 4-5, neuron-specific enolase < 17 µg/L, benign electroencephalography patterns ≤ 72 h post-arrest and normal magnetic resonance imaging at 72-168 h post-arrest) in the algorithm. Functional outcome was assessed dichotomously at six months, including modified Rankin Scale 0-3, Cerebral Performance Category 1-2 or Glasgow Outcome Scale 4-5 (no symptoms to moderate disability) as good outcome. RESULTS:We analysed 3,388 patients, of whom 2,079 had GCS-M < 4 at ≥ 72 h. Of the 874 patients identified by the 2021 ERC/ESICM poor outcome criteria, 870 had poor functional outcome (specificity: 99.6% [95%CI 99.0-99.9]). Using the GCS-M < 6 threshold, 366 more patients entered the algorithm (N = 2,445). Seven more patients with poor outcomes were identified, with close to identical specificity. Good outcome predictors thereafter identified 673 patients with potential recovery, of whom 411 (61%) had a good functional outcome at six months. With the updated algorithm, the number of prognosticated patients with an indeterminate prognosis decreased from 1,205/2,079 (58%) to 891/2,445 (36%). CONCLUSION:Raising the GCS-M inclusion threshold and adding favourable predictors to the 2021 ERC/ESICM prognostication algorithm reduced prognostic uncertainty without increasing falsely pessimistic predictions.

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. 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. 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

Background and Objectives Postanoxic electrographic status epilepticus (PSE) affects up to a third of all comatose patients after cardiac arrest (CA) and is associated with high mortality. Late PSE onset (>24 hours), from a restored continuous background pattern, and absence of established indicators of poor outcome at multimodal prognostication are described in survivors. We aimed to determine the increase in probability of good long-term outcome after PSE in patients presenting with this favorable PSE profile compared with all patients with PSE. Methods This is a prospective observational substudy of the international Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest trial (TTM2-trial, 2017-2020) including adult comatose patients resuscitated from CA with continuous EEG (cEEG) monitoring. EEG background pattern and type of PSE were determined using standardized EEG terminology of the American Clinical Neurophysiology Society, blinded to clinical data. On day 4, multimodal prognostication was performed according to the European postresuscitation guidelines. Good outcome was defined as a modified Rankin Scale score of 0-3 at 6 months. Detailed follow-up was performed at 6 and 24 months. Results A total of 191 patients were monitored with cEEG, of whom 52 (27%) developed possible or definite PSE at a median of 42 hours [IQR 32-46] after CA. The median age was 70 (IQR 63-77) years, and 35% were female. Favorable PSE profile was present in 20 patients (38%), of whom 12 patients (60%) survived until 6 months and 8 (40%) had good outcome; thus, the probability of good outcome increased 2.7 times. All patients lacking a favorable PSE profile had poor outcome. All patients with good outcome obeyed commands within the first 7 days. At 24 months, all 12 survivors were still alive and 7 had good functional outcome. Detailed follow-up at 24 months showed that most had only mild cognitive impairment and overall life satisfaction was similar to the general population. Discussion PSE is compatible with good outcome when onset is late and from a continuous background and no established indicators of poor outcome are present. One-third of patients with PSE had favorable PSE profile, of whom well over a third eventually had good outcome and showed improved level of consciousness within the first week.

Aims:Our aim was to investigate the psychometric properties of the health assessment instrument EQ-5D-5L in OHCA survivors. Methods:We included survivors from the Targeted Hypothermia versus Targeted Normothermia after OHCA (TTM2) trial, who completed EQ-5D-5L at 6 months. Confirmatory factor analysis was used to evaluate the hypothesised unidimensional latent structure of EQ level sum score (EQ LSS), summarizing scores across Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression. Differential item functioning was evaluated for age. We examined internal consistency and precision for the EQ LSS. We evaluated construct validity of EQ LSS, EQ value and EQ VAS, using the modified Rankin Scale and Montreal Cognitive Assessment, representing functional outcome and cognitive function-two common health challenges experienced by OHCA survivors. Results:783 of 939 (84%) eligible survivors were included. Confirmatory factor analysis showed good model fit and strong factor loadings for all dimensions (0.61-0.90). We observed a significant but negligible effect of age on Mobility (β = 0.29, p < 0.001, ΔR2 = 0.019). Internal consistency was 0.88. The floor effect was 35%. Survivors with more functional dependency and/or cognitive problems reported significantly worse health by EQ LSS, EQ value, and EQ VAS (all, p < 0.001). Conclusion:The psychometric properties of EQ LSS support its use to measure health status in OHCA research. The strong association between health and functional dependency indicate robust and comparable construct validity for EQ LSS, EQ value, and EQ VAS in this sample.

OBJECTIVE:Previously proposed "synchronous EEG patterns" predict poor outcome within 24 h after cardiac arrest (CA). We investigate the prognostic performance of these early EEG predictors in addition to the late EEG predictors (>24 h) recommended in the European post-resuscitation guidelines. METHODS:Observational substudy of the TTM2-trial including consecutive comatose resuscitated patients. Continuous EEG-monitoring (cEEG) was blindly assessed using the American Clinical Neurophysiology Societýs standardised EEG terminology and categorised into early EEG predictors (burst-suppression with identical or highly epileptiform bursts, or suppression with generalised periodic discharges) and late EEG predictors (heterogenous burst-suppression or suppression). Poor outcome was defined as modified Rankin Scale 4-6 at six months. RESULTS:Of 191 included patients, 53 % had poor outcome. Early EEG predictors had 100 %[CI 96-100] specificity at all time-points and maximal sensitivity 30 %[CI 21-40] before 24 h. Late EEG predictors had 100 %[CI 96-100] specificity beyond 24 h with maximal sensitivity 32 %[CI 21-43]. Using both early and late EEG predictors, and gradually adding cEEG-information from consecutive time-epochs, sensitivity increased to 49 %[CI 39-59] up to 36 h after CA (p = 0.001). A continuous background within 12 h predicted good outcome (sensitivity 61 %[CI 50-71]; specificity 87 %[CI 79-93]). CONCLUSION:Searching for both early EEG predictors (e.g. identical burst-suppression) and late EEG predictors (e.g. heterogenous burst-suppression > 24 h) significantly improved sensitivity of poor outcome prediction without false positive survivors in this cohort. A self-fulfilling prophecy may have affected our results. cEEG during the first two days after CA identified half of the patients with a long-term poor outcome and half of the patients with a good outcome.

Background: Neuroimaging with magnetic resonance imaging (MRI) may assist clinicians in evaluating brain injury and optimising care in comatose adults resuscitated after out-of-hospital cardiac arrest (OHCA). However, contemporary international data on its use are lacking. Aim: The primary aim was to compare the patient characteristics, early postresuscitation care, and neurological outcomes of patients according to MRI use. Methods: We performed a posthoc analysis of the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial, a multinational randomised trial comparing targeted mild hypercapnia or normocapnia in comatose adults after OHCA. Results: After exclusions, 1639 patients enrolled in the TAME trial were analysed. Of these, 149 (9%) had an MRI. Compared to non-MRI patients, MRI patients were younger (58.9 versus 61.7 years, p: 0.02), had a longer median time from OHCA to return of spontaneous circulation (30 versus 25 min, p < 0.0001), and had a higher average arterial lactate level (8.78 versus 6.74 mmol/L, p < 0.0001) on admission to hospital. MRI patients were more likely to receive additional advanced diagnostic assessments during intensive care unit admission (p < 0.0001). At 6 months, 23 of 140 patients (16.4%) in the MRI group had a favourable neurological outcome, compared with 659 of 1399 patients (47.1%) in the no-MRI group (p < 0.001). On multivariable modelling, country of enrolment was the dominating predictor in the likelihood of an MRI being performed. Conclusions: In the TAME trial, 9% of patients had an MRI during their intensive care unit admission. Among these patients, only 16% had a favourable neurological outcome at 6 months. (c) 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PURPOSE:To assess the risk of self-fulfilling prophecy from withdrawal of life-sustaining therapy (WLST) in comatose cardiac arrest patients undergoing neuroprognostication. METHODS:Post-hoc multicentre study matching adults resuscitated from out-of-hospital cardiac arrests, in WLST-permitting cohorts (TTM and TTM2), and non-WLST-permitting cohorts (KORHN and ProNeCA). We matched patients in a 1:1 ratio based on a propensity score, assessing the risk of WLST due to a presumed poor neurological prognosis and criteria predictive of poor neurological outcome, as outlined in the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guidelines. Functional outcome was compared at six months. RESULTS:We included 1717 patients, of whom 497 (29 %) had WLST due to neurological criteria at a median of 143 h (IQR 108-177). 303 (61 %) patients with WLST retrospectively fulfilled ≥ 2 ERC/ESICM criteria predictive of poor outcome. No patients with ≥ 2 ERC/ESICM criteria had good functional outcome at six months, neither in the WLST cohort nor among the matched controls. One patient (0.3 %) with an indeterminate prognosis (≤1 ERC/ESICM criteria) had a good functional outcome in the WLST cohort versus 18-26 % of the matched controls. In exploratory weighted estimates, up to 18 % of patients with indeterminate prognosis may have survived with a good functional outcome, if WLST had not occurred. CONCLUSION:In patients with at least 2 ERC/ESICM criteria predictive of poor outcome, the risk of self-fulfilling prophecy from WLST was negligible. However, in patients with an indeterminate prognosis, the practice of WLST was associated with a lower likelihood of good functional outcome.

BACKGROUND Acute kidney injury (AKI) is a serious complication of out-of-hospital cardiac arrest (OHCA). Post-resuscitation cardiogenic shock (CS) is a key contributing factor. Targeting a higher arterial carbon dioxide tension may affect AKI after OHCA in patients with or without CS. METHODS Pre-planned exploratory study of a multi-national randomised trial comparing targeted mild hypercapnia or targeted normocapnia. The primary outcome was AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria with modifications. Secondary outcomes included use of renal replacement therapy (RRT) and favourable neurological outcome (Glasgow Outcome Scale Extended, score 5-8) at six-months according to AKI. Exploratory objectives included evaluation of secondary outcomes in patients with both CS and AKI. RESULTS We studied 1668 of 1700 TAME patients. AKI occurred in 1203 patients (72.1%) with 596 (49.6%) in the targeted mild hypercapnia group and 607 (50.4%) in the targeted normocapnia group. Stage 3 AKI occurred in 193 patients (23.3%) and 196 patients (23.4%), respectively and RRT in 82 (9.9%) vs 75 patients (8.9%), respectively. At six-months, 237 of 429 no-AKI patients (55.2%) had a favourable neurological outcome compared to 445 of 1111 AKI patients (40.1%) (p <0.0001). AKI occurred more frequently (P<0.001) in patients with CS, affecting 936 patients (77.8%). For CS and AKI patients, there were no significant differences any secondary outcome. CONCLUSIONS AKI occurred in approximately two-thirds and RRT in approximately one in ten TAME patients without differences according to treatment allocation. CS significantly increased the prevalence of AKI but this effect was not modified by carbon dioxide allocation.

PURPOSE:Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear. METHODS:The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6. RESULTS:A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods. CONCLUSIONS:Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

AIMS:To describe the level of physical activity 6 months after an out-of-hospital cardiac arrest (OHCA) and to explore potential risk factors of a low level of physical activity. METHODS:Post-hoc analyses of the international multicentre Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac arrest (TTM2) trial. At 6 months, survivors at 61 sites in Europe, Australia and New Zeeland were invited to a follow-up. The participants answered two questions on self-reported physical activity. Answers were categorized as a low, moderate, or high level of physical activity and further dichotomized into a low versus moderate/high level of physical activity. Potential risk factors for a low level of physical activity were collected and investigated by univariable and multivariable logistic regression. RESULTS:At 6 months, 807 of 939 (86%) OHCA survivors answered the two questions of physical activity; 34% reported a low, 44% moderate and 22% high level of physical activity. Obesity (OR = 1.75, 95% CI 1.10-2.77, p = 0.018), mobility problems by EuroQol 5 dimensions 5 levels (OR = 1.73, 95% CI 1.06-2.84, p = 0.029), and cognitive impairment by Symbol Digit Modalities Test (OR = 1.78, 95% CI 1.13-2.82, p = 0.013) were significantly associated with a low level of physical activity in the multivariable analysis. CONCLUSION:One third of the OHCA survivors reported a low level of physical activity. Obesity, mobility problems, and cognitive impairment were associated with a low level of physical activity. CLINICALTRIALS: GOV IDENTIFIER:NCT02908308.