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Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2).

ABSTRACT: BACKGROUND:This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. METHODS:This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24?months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24?months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7?months, using sensitivity and specificity analyses. DISCUSSION:In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03543371 . Registered 1 June 2018.

SUBMITTER: Blennow Nordstrom E

PROVIDER: S-EPMC7542852 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2).

Blennow Nordström Erik E Lilja Gisela G Vestberg Susanna S Ullén Susann S Friberg Hans H Nielsen Niklas N Heimburg Katarina K Evald Lars L Mion Marco M Segerström Magnus M Grejs Anders M AM Keeble Thomas T Kirkegaard Hans H Ljung Hanna H Rose Sofia S Wise Matthew P MP Rylander Christian C Undén Johan J Cronberg Tobias T

BMC cardiovascular disorders 20201007 1

<h4>Background</h4>This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA.<h4>Methods</h4>This longitudinal multi-center clinical study is a sub-study of the TTM2-tr ...[more]

PMID: 33028221

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Project description:AimsThe primary aim of this study is to investigate whether out-of-hospital cardiac arrest (OHCA) survivors have lower levels of self-reported physical activity compared to a non-cardiac arrest (CA) control group who had acute myocardial infarction (MI). Additional aims are to explore potential predictors of physical inactivity (older age, female gender, problems with general physical function, global cognition, mental processing speed/attention, anxiety symptoms, depression symptoms, kinesiophobia, fatigue), and to investigate the relationship between self-reported and objectively measured physical activity among OHCA-survivors.MethodsThe Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial) collects information regarding age, gender, self-reported physical activity, general physical function, global cognition and mental processing speed/attention at 6 months after OHCA. In this TTM2-trial cross-sectional prospective sub-study, participants at selected sites are invited to an additional follow-up meeting within 4 weeks from the main study follow-up. At this meeting, information regarding anxiety symptoms, depression symptoms, kinesiophobia and fatigue is collected. The OHCA-survivors are then provided with an objective measure of physical activity, a hip-placed accelerometer, to wear for one week, together with a training diary. At the end of the week, participants are asked to once again answer two self-reported questions regarding physical activity for that specific week. MI-controls attend a single follow-up meeting and perform the same assessments as the OHCA-survivors, except from wearing the accelerometer. We aim to include 110 OHCA-survivors and 110 MI-controls in Sweden, Denmark and the United Kingdom.ConclusionThe results from this sub-study will provide novel information about physical activity among OHCA-survivors.Trial registrationRegistered at ClinicalTrials.gov: NCT03543332, date of registration June 1, 2018.

Project description:PurposeThe optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes.MethodsPreplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization.ResultsA total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH20, plateau pressure was 20 cmH20 (IQR = 17-23), driving pressure was 12 cmH20 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36-45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003-1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001-1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome.ConclusionsProtective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.

Project description:BackgroundTherapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.MethodsWe conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.ResultsA total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.ConclusionsIn comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Project description:Background: In animal models, early initiation of therapeutic cooling, intra-arrest, or restored circulation has been shown to be neuroprotective shortly after cardiac arrest. We aimed to assess the feasibility and cooling efficacy of transnasal evaporative cooling, initiated as early as possible after hospital arrival in patients randomized to cooling in the TTM2 trial. Methods: This study took the form of a single-center (Södersjukhuset, Stockholm) substudy of the TTM2 trial (NCT02908308) comparing target temperature management (TTM) to 33 °C versus normothermia in OHCA. In patients randomized to TTM33 °C, transnasal evaporative cooling was applied as fast as possible. The primary objectives were the feasibility aspects of initiating cooling in different hospital locations (i.e., in the emergency department, coronary cathlab, intensive care unit (ICU), and during intrahospital transport) and its effectiveness (i.e., time to reach target temperature). Transnasal cooling was continued for two hours or until patients reached a core temperature of <34 °C. Cooling intervals were compared to participants at the same site who were randomized to hypothermia and treated at 33 °C but who for different reasons did not receive transnasal evaporative cooling. Results: From October 2018 to January 2020, 32 patients were recruited, of which 17 were randomized to the TTM33. Among them, 10 patients (8 men, median age 69 years) received transnasal evaporative cooling prior to surface systemic cooling in the ICU. In three patients, cooling was started in the emergency department; in two patients, it was started in the coronary cathlab, and in five patients, it was started in the ICU, of which three patients were subsequently transported to the coronary cathlab or to perform a CT scan. The median time to initiate transnasal cooling from randomization was 9 min (range: 5 to 39 min). The median time from randomization to a core body temperature of 34 °C was 120 min (range 60 to 334) compared to 178 min among those in the TTM33 group that did not receive TNEC and to 33 °C 230 min (range: 152 to 351) vs. 276 min (range: 150 to 546). No feasibility or technical issues were reported. No adverse events occurred besides minor nosebleeds. Conclusions: The early induction of transnasal cooling in out-of-hospital cardiac arrest patients was feasible to initiate in the emergency department, coronary cathlab, ICU, and during intrahospital transport. Time to target temperature was shortened compared to standard cooling.

Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.

Project description:To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome.DesignPost hoc analysis.SettingTen European ICUs.PatientsPatients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months.InterventionsNone.Measurements and main resultsOf 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95-0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13-0.91; p = 0.03) were associated with less rebound hyperthermia, whereas male gender (odds ratio, 3.94; 95% CI, 1.34-11.57; p = 0.01), highest C-reactive protein value (odds ratio, 1.04; 95% CI, 1.01-1.07; p = 0.02), and use of mechanical chest compression during cardiopulmonary resuscitation (odds ratio, 2.00; 95% CI, 1.10-3.67; p = 0.02) were associated with more rebound hyperthermia. Patients with favorable functional outcome spent less time after rewarming over 38.5°C (2.5% vs 6.3%; p = 0.03), 39°C (0.14% vs 2.7%; p < 0.01), and 39.5°C (0.03% vs 0.71%; p < 0.01) when compared with others. Median time to rebound hyperthermia was longer in the unfavorable functional outcome group (33.2 hr; interquartile range, 14.3-53.0 hr vs 6.5 hr; interquartile range, 2.2-34.1; p < 0.01). In a predefined multivariate binary logistic regression model, rebound hyperthermia was associated with decreased odds of favorable functional outcome (odds ratio, 0.42; 95% CI, 0.22-0.79).ConclusionsOne-third of targeted temperature management patients experience rebound hyperthermia, and it is more common in younger male patients with an aggravated inflammatory response and those treated with a mechanical chest compression device. Later onset of rebound hyperthermia and temperatures exceeding 38.5°C associate with unfavorable outcome.

Dataset Information

Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2).

Publications

Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2).

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