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Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

ABSTRACT: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.We 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.A 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.In 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.).

SUBMITTER: Moler FW

PROVIDER: S-EPMC4470472 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

Moler Frank W FW Silverstein Faye S FS Holubkov Richard R Slomine Beth S BS Christensen James R JR Nadkarni Vinay M VM Meert Kathleen L KL Clark Amy E AE Browning Brittan B Pemberton Victoria L VL Page Kent K Shankaran Seetha S Hutchison Jamie S JS Newth Christopher J L CJ Bennett Kimberly S KS Berger John T JT Topjian Alexis A Pineda Jose A JA Koch Joshua D JD Schleien Charles L CL Dalton Heidi J HJ Ofori-Amanfo George G Goodman Denise M DM Fink Ericka L EL McQuillen Patrick P Zimmerman Jerry J JJ Thomas Neal J NJ van der Jagt Elise W EW Porter Melissa B MB Meyer Michael T MT Harrison Rick R Pham Nga N Schwarz Adam J AJ Nowak Jeffrey E JE Alten Jeffrey J Wheeler Derek S DS Bhalala Utpal S US Lidsky Karen K Lloyd Eric E Mathur Mudit M Shah Samir S Wu Theodore T Theodorou Andreas A AA Sanders Ronald C RC Dean J Michael JM

The New England journal of medicine 20150425 20

<h4>Background</h4>Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.<h4>Methods</h4>We 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 ...[more]

PMID: 25913022

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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 .).

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.

Project description:Therapeutic 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.To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest.In 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.Induction of therapeutic hypothermia.The 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.Overall, 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).Among 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.

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

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

Publications

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

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