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Randomized Controlled Trial
. 2017 Jan 26;376(4):318-329.
doi: 10.1056/NEJMoa1610493. Epub 2017 Jan 24.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Frank W Moler  1 , Faye S Silverstein  1 , Richard Holubkov  1 , Beth S Slomine  1 , James R Christensen  1 , Vinay M Nadkarni  1 , Kathleen L Meert  1 , Brittan Browning  1 , Victoria L Pemberton  1 , Kent Page  1 , Marianne R Gildea  1 , Barnaby R Scholefield  1 , Seetha Shankaran  1 , Jamie S Hutchison  1 , John T Berger  1 , George Ofori-Amanfo  1 , Christopher J L Newth  1 , Alexis Topjian  1 , Kimberly S Bennett  1 , Joshua D Koch  1 , Nga Pham  1 , Nikhil K Chanani  1 , Jose A Pineda  1 , Rick Harrison  1 , Heidi J Dalton  1 , Jeffrey Alten  1 , Charles L Schleien  1 , Denise M Goodman  1 , Jerry J Zimmerman  1 , Utpal S Bhalala  1 , Adam J Schwarz  1 , Melissa B Porter  1 , Samir Shah  1 , Ericka L Fink  1 , Patrick McQuillen  1 , Theodore Wu  1 , Sophie Skellett  1 , Neal J Thomas  1 , Jeffrey E Nowak  1 , Paul B Baines  1 , John Pappachan  1 , Mudit Mathur  1 , Eric Lloyd  1 , Elise W van der Jagt  1 , Emily L Dobyns  1 , Michael T Meyer  1 , Ronald C Sanders Jr  1 , Amy E Clark  1 , J Michael Dean  1 ; THAPCA Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Frank W Moler et al. N Engl J Med. .

Abstract

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 .).

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Figures

Figure 1
Figure 1. (facing page). Enrollment, Randomization, and Treatment
Scores on the Glasgow Coma Scale (GCS) motor-response subscale range from 1 to 6, with lower scores indicating worse function. Scores on the Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scales range from 1 to 6, with lower scores indicating less disability. Scores on the Vineland Adaptive Behavior Scales, second edition (VABS-II), range from 20 to 160, with higher scores indicating better function; the VABS-II has an age-corrected mean score of 100. CNS denotes central nervous system, ECMO extracorporeal membrane oxygenation, ICU intensive care unit, ITT intention to treat, and THAPCA Therapeutic Hypothermia after Pediatric Cardiac Arrest.
Figure 2
Figure 2. Kaplan–Meier Estimates of Survival from 0 to 365 Days after Cardiac Arrest
Shown are Kaplan–Meier estimates of survival from 0 to 365 days after cardiac arrest in the therapeutic hypothermia group and the therapeutic normothermia group (P = 0.45 by log-rank test stratified according to age category).
See this image and copyright information in PMC

Comment in

References

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