Mild therapeutic hypothermia after out-of-hospital cardiac arrest: What does really matter?
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ABSTRACT: Background
Mild therapeutic hypothermia (MTH) is a recommended treatment of comatose patients after out-of-hospital cardiac arrest (OHCA). The aim of the study was to examine determinants of clinical outcome in OHCA survivors treated with MTH and variables associated with MTH induction time.Methods
Presented herein is an analysis of combined results from a retrospective and a prospective observational study which included 90 OHCA survivors treated with MTH from January 2010 to March 2018. Multivariate regression analysis was performed to determine variables associated with poor neurologic outcome (Cerebral Performance Category 3-5), mortality, and prolonged induction time.Results
At hospital discharge, 59 (65.6%) patients were alive, of whom 36 (61%) had a good neurologic outcome. Older patients (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.12) with lower Glasgow Coma Scale (GCS) (OR 0.49, 95% CI 0.30-0.80) were at higher risk of poor neurological outcome. The predictors of in-hospital death included: older age (OR 1.08, 95% CI 1.02-1.13), lower GCS score (OR 0.47, 95% CI 0.25-0.85), presence of cardiogenic shock (OR 3.43, 95% CI 1.11-10.53), and higher doses of adrenaline (OR 1.27, 95% CI 1.04-1.56). Longer induction was associated with shorter cardio-pulmonary resuscitation (CPR) (unstandardized coefficient -3.95, 95% CI -7.09 to -0.81) and lower lactate level (unstandardized coefficient -18.55, 95% CI -36.10 to -1.01).Conclusions
Unfavorable neurologic outcome in OHCA patients treated with MTH is associated with age and lower GCS score. Risk factors for in-hospital mortality include age, high-dose adrenaline administration, lower GCS score and presence of cardiogenic shock. CPR duration and lactate level were predictive of prolonged MTH induction time.
SUBMITTER: Ratajczak J
PROVIDER: S-EPMC8078942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.).
| S-EPMC4470472 | biostudies-literature
Project description:Hypothermia has emerged as a potent neuroprotective modality following resuscitation from cardiac arrest. Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling begun immediately following the return of spontaneous circulation may be more beneficial. Cooling in the field following resuscitation, however, presents new challenges, in that the cooling method has to be portable, safe, and effective. Rapid infusion of intravenous fluid at 4 degrees C, the use of a cooling helmet, and cooling plates have all been proposed as methods for field cooling, and are all in various stages of clinical and animal testing. Whether field cooling will improve survival and neurologic outcome remains an important unanswered clinical question.
| S-EPMC2741140 | biostudies-literature
Project description:Guidelines recommend mild therapeutic hypothermia (MTH) for survivors of out-of-hospital cardiac arrest (OHCA). However, there is little literature demonstrating a survival benefit. We performed a meta-analysis of randomized controlled trials (RCTs) assessing the efficacy of MTH in patients successfully resuscitated from OHCA.Electronic databases were searched for RCT involving MTH in survivors of OHCA, and the results were put through a meta-analysis. The primary endpoint was all-cause mortality, and the secondary endpoint was favorable neurological function. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using the Mantel-Haenszel method. A fixed-effect model was used and, if heterogeneity (I2 ) was >40, effects were analyzed using a random model.Six RCT (n = 1400 patients) were included. Overall survival was 50.7%, and favorable neurological recovery was 45.5%. Pooled data demonstrated no significant all-cause mortality (OR, 0.81; 95% CI 0.55-1.21) or neurological recovery (OR, 0.77; 95% CI 0.47-1.24). No evidence of publication bias was observed.This meta-analysis demonstrated that MTH did not confer benefit on overall survival rate and neurological recovery in patients resuscitated from OHCA.
| S-EPMC4900372 | biostudies-other
Project description:ImportanceDespite evidence that therapeutic hypothermia improves patient outcomes for out-of-hospital cardiac arrest, use of this therapy remains low.ObjectiveTo determine whether the use of therapeutic hypothermia and patient outcomes have changed after publication of the Targeted Temperature Management trial on December 5, 2013, which supported more lenient temperature management for out-of-hospital cardiac arrest.Design, setting, and participantsA retrospective cohort was conducted between January 1, 2013, and December 31, 2016, of 45 935 US patients in the Cardiac Arrest Registry to Enhance Survival who experienced out-of-hospital cardiac arrest and survived to hospital admission.ExposuresCalendar time by quarter year.Main outcomes and measuresUse of therapeutic hypothermia and patient survival to hospital discharge.ResultsAmong 45 935 patients (17 515 women and 28 420 men; mean [SD] age, 59.3 [18.3] years) who experienced out-of-hospital cardiac arrest and survived to admission at 649 US hospitals, overall use of therapeutic hypothermia during the study period was 46.4%. In unadjusted analyses, the use of therapeutic hypothermia dropped from 52.5% in the last quarter of 2013 to 46.0% in the first quarter of 2014 after the December 2013 publication of the Targeted Temperature Management trial. Use of therapeutic hypothermia remained at or below 46.5% through 2016. In segmented hierarchical logistic regression analysis, the risk-adjusted odds of use of therapeutic hypothermia was 18% lower in the first quarter of 2014 compared with the last quarter of 2013 (odds ratio, 0.82; 95% CI, 0.71-0.94; P = .006). Similar point-estimate changes over time were observed in analyses stratified by presenting rhythm of ventricular tachycardia or ventricular fibrillation (odds ratio, 0.89; 95% CI, 0.71-1.13, P = .35) and pulseless electrical activity or asystole (odds ratio, 0.75; 95% CI, 0.63-0.89; P = .001). Overall risk-adjusted patient survival was 36.9% in 2013, 37.5% in 2014, 34.8% in 2015, and 34.3% in 2016 (P < .001 for trend). In mediation analysis, temporal trends in use of hypothermia did not consistently explain trends in patient survival.Conclusions and relevanceIn a US registry of patients who experienced out-of-hospital cardiac arrest, the use of guideline-recommended therapeutic hypothermia decreased after publication of the Targeted Temperature Management trial, which supported more lenient temperature thresholds. Concurrent with this change, survival among patients admitted to the hospital decreased, but was not mediated by use of hypothermia.
| S-EPMC6324404 | biostudies-literature
Project description:BackgroundOut-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI.MethodsIn a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose.ResultsIn patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0-12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p = 0.01).ConclusionsBioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA.Trial registrationClinicalTrials.gov Identifier: NCT02611934.
| S-EPMC8079092 | biostudies-literature
Project description:BACKGROUND:Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS:In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours 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 score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS:The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS:Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).
| S-EPMC5310766 | biostudies-literature
Project description:BACKGROUND:Therapeutic Hypothermia (TH) is a standard of care after out-of-hospital cardiac arrest (OHCA). Previous reports failed to prove a significant benefit for survival or neurological outcomes. We examined whether the proper selection of patients would enhance treatment efficacy. METHOD:We conducted a retrospective cohort study. Data was collected from January 2000 and August 2018. Patients were enrolled after OHCA and classified into two groups, patients treated with TH and patients who were not treated with TH. RESULTS:A total of 92 patients were included in the study. 57 (63%) patients were in the TH Group and 34 (37%) in the Non-TH group. There was no statistical difference in favorable neurological outcomes between the groups. Patients presenting with ventricular fibrillation had a higher 1-year survival rate from TH, while patients with asystole were found to benefit only if they were younger than 65 years (p < .007, p < .02, respectively). CONCLUSION:Therapeutic Hypothermia patients failed to demonstrate a significant benefit in terms of improved neurological outcomes. Patients treated with TH following ventricular fibrillation experienced the most benefit in terms of 1-year survival, while patients who had suffered from asystole experienced a modest benefit only if they were younger than 65 years of age. Guidelines should address age and primary arrhythmia for proper treatment selection.
| S-EPMC6946126 | biostudies-literature
Project description:In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.
| S-EPMC5016592 | biostudies-other
Project description:BackgroundMild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia.ObjectiveTo determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia.MethodsA retrospective observational study of patients treated with therapeutic hypothermia after cardiac arrest from 2007 through 2014. Baseline demographic data and daily delirium assessments throughout the intensive care unit stay were obtained. The association between duration of delirium and various risk factors was assessed.ResultsOf 251 patients, 107 (43%) awoke from coma. Among the 107 survivors, all had at least 1 day of delirium during their intensive care unit stay. Median number of days of delirium was 4.0 (interquartile range, 2.0-7.5). Multivariable analysis revealed that age (odds ratio, 1.72; 95% CI, 1.0-2.95; P = .05), time from cardiopulmonary resuscitation to return of spontaneous circulation (odds ratio 1.52; 95% CI, 1.11-2.07; P = .01), and total dose of prewarming propofol (odds ratio, 0.02; 95% CI, 0.00-0.48; P = .02) were associated with duration of delirium.ConclusionsAll survivors of cardiac arrest treated with mild therapeutic hypothermia had at least 1 day of delirium. Age and time from initiation of cardiopulmonary resuscitation to return of spontaneous circulation were associated with prolonged delirium, whereas exposure to propofol was protective against delirium. These findings are limited to this unique cohort and may not be generalizable to different populations.
| S-EPMC5240926 | biostudies-literature
Project description:ImportanceTherapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not exist, and comparative effectiveness data are limited.ObjectiveTo evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest.Design, setting, and patientsIn this cohort study, within the national Get With the Guidelines-Resuscitation registry, 26 183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015.ExposureInduction of therapeutic hypothermia.Main outcomes and measuresThe primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests.ResultsOverall, 1568 of 26 183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5% male) were matched by propensity score to 3714 non-hypothermia-treated patients (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, -3.6% [95% CI, -6.3% to -0.9%]; P = .01), and this association was similar (interaction P = .74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76 to 0.99]; risk difference, -3.2% [95% CI, -6.2% to -0.3%]) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference, -4.6% [95% CI, -10.9% to 1.7%]). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% [246 of 1443 patients]; non-hypothermia-treated group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk difference, -4.4% [95% CI, -6.8% to -2.0%]; P < .001) and for both rhythm types (interaction P = .88).Conclusions and relevanceAmong patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.
| S-EPMC5486217 | biostudies-literature