Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

F. W. Moler, F. S. Silverstein, R. Holubkov, B. S. Slomine, J. R. Christensen, V. M. Nadkarni, K. L. Meert, B. Browning, V. L. Pemberton, K. Page, M. R. Gildea, B. R. Scholefield, S. Shankaran, J. S. Hutchison, J. T. Berger, G. Ofori-Amanfo, C. J L Newth, A. Topjian, K. S. Bennett, J. D. Koch & 30 others N. Pham, N. K. Chanani, J. A. Pineda, R. Harrison, H. J. Dalton, J. Alten, C. L. Schleien, D. M. Goodman, J. J. Zimmerman, U. S. Bhalala, A. J. Schwarz, M. B. Porter, S. Shah, E. L. Fink, P. McQuillen, T. Wu, S. Skellett, N. J. Thomas, J. E. Nowak, P. B. Baines, J. Pappachan, M. Mathur, E. Lloyd, E. W. Van Der Jagt, E. L. Dobyns, M. T. Meyer, R. C. Sanders, A. E. Clark, J. M. Dean,

Research output: Contribution to journalArticle

Abstract

BACKGROUND Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital 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.

Original languageEnglish (US)
Pages (from-to)318-329
Number of pages12
JournalNew England Journal of Medicine
Volume376
Issue number4
DOIs
StatePublished - Jan 26 2017

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Induced Hypothermia
Heart Arrest
Temperature
Coma
Hypothermia
Confidence Intervals
Medical Futility
Out-of-Hospital Cardiac Arrest
Psychological Adaptation
Random Allocation
Survival Rate
Mortality
Incidence
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Moler, F. W., Silverstein, F. S., Holubkov, R., Slomine, B. S., Christensen, J. R., Nadkarni, V. M., ... THAPCA Trial Investigators (2017). Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. New England Journal of Medicine, 376(4), 318-329. DOI: 10.1056/NEJMoa1610493

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. / Moler, F. W.; Silverstein, F. S.; Holubkov, R.; Slomine, B. S.; Christensen, J. R.; Nadkarni, V. M.; Meert, K. L.; Browning, B.; Pemberton, V. L.; Page, K.; Gildea, M. R.; Scholefield, B. R.; Shankaran, S.; Hutchison, J. S.; Berger, J. T.; Ofori-Amanfo, G.; Newth, C. J L; Topjian, A.; Bennett, K. S.; Koch, J. D.; Pham, N.; Chanani, N. K.; Pineda, J. A.; Harrison, R.; Dalton, H. J.; Alten, J.; Schleien, C. L.; Goodman, D. M.; Zimmerman, J. J.; Bhalala, U. S.; Schwarz, A. J.; Porter, M. B.; Shah, S.; Fink, E. L.; McQuillen, P.; Wu, T.; Skellett, S.; Thomas, N. J.; Nowak, J. E.; Baines, P. B.; Pappachan, J.; Mathur, M.; Lloyd, E.; Van Der Jagt, E. W.; Dobyns, E. L.; Meyer, M. T.; Sanders, R. C.; Clark, A. E.; Dean, J. M.; THAPCA Trial Investigators.

In: New England Journal of Medicine, Vol. 376, No. 4, 26.01.2017, p. 318-329.

Research output: Contribution to journalArticle

Moler, FW, Silverstein, FS, Holubkov, R, Slomine, BS, Christensen, JR, Nadkarni, VM, Meert, KL, Browning, B, Pemberton, VL, Page, K, Gildea, MR, Scholefield, BR, Shankaran, S, Hutchison, JS, Berger, JT, Ofori-Amanfo, G, Newth, CJL, Topjian, A, Bennett, KS, Koch, JD, Pham, N, Chanani, NK, Pineda, JA, Harrison, R, Dalton, HJ, Alten, J, Schleien, CL, Goodman, DM, Zimmerman, JJ, Bhalala, US, Schwarz, AJ, Porter, MB, Shah, S, Fink, EL, McQuillen, P, Wu, T, Skellett, S, Thomas, NJ, Nowak, JE, Baines, PB, Pappachan, J, Mathur, M, Lloyd, E, Van Der Jagt, EW, Dobyns, EL, Meyer, MT, Sanders, RC, Clark, AE, Dean, JM & THAPCA Trial Investigators 2017, 'Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children' New England Journal of Medicine, vol 376, no. 4, pp. 318-329. DOI: 10.1056/NEJMoa1610493
Moler FW, Silverstein FS, Holubkov R, Slomine BS, Christensen JR, Nadkarni VM et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. New England Journal of Medicine. 2017 Jan 26;376(4):318-329. Available from, DOI: 10.1056/NEJMoa1610493

Moler, F. W.; Silverstein, F. S.; Holubkov, R.; Slomine, B. S.; Christensen, J. R.; Nadkarni, V. M.; Meert, K. L.; Browning, B.; Pemberton, V. L.; Page, K.; Gildea, M. R.; Scholefield, B. R.; Shankaran, S.; Hutchison, J. S.; Berger, J. T.; Ofori-Amanfo, G.; Newth, C. J L; Topjian, A.; Bennett, K. S.; Koch, J. D.; Pham, N.; Chanani, N. K.; Pineda, J. A.; Harrison, R.; Dalton, H. J.; Alten, J.; Schleien, C. L.; Goodman, D. M.; Zimmerman, J. J.; Bhalala, U. S.; Schwarz, A. J.; Porter, M. B.; Shah, S.; Fink, E. L.; McQuillen, P.; Wu, T.; Skellett, S.; Thomas, N. J.; Nowak, J. E.; Baines, P. B.; Pappachan, J.; Mathur, M.; Lloyd, E.; Van Der Jagt, E. W.; Dobyns, E. L.; Meyer, M. T.; Sanders, R. C.; Clark, A. E.; Dean, J. M.; THAPCA Trial Investigators / Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

In: New England Journal of Medicine, Vol. 376, No. 4, 26.01.2017, p. 318-329.

Research output: Contribution to journalArticle

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title = "Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children",
abstract = "BACKGROUND Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital 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.",
author = "Moler, {F. W.} and Silverstein, {F. S.} and R. Holubkov and Slomine, {B. S.} and Christensen, {J. R.} and Nadkarni, {V. M.} and Meert, {K. L.} and B. Browning and Pemberton, {V. L.} and K. Page and Gildea, {M. R.} and Scholefield, {B. R.} and S. Shankaran and Hutchison, {J. S.} and Berger, {J. T.} and G. Ofori-Amanfo and Newth, {C. J L} and A. Topjian and Bennett, {K. S.} and Koch, {J. D.} and N. Pham and Chanani, {N. K.} and Pineda, {J. A.} and R. Harrison and Dalton, {H. J.} and J. Alten and Schleien, {C. L.} and Goodman, {D. M.} and Zimmerman, {J. J.} and Bhalala, {U. S.} and Schwarz, {A. J.} and Porter, {M. B.} and S. Shah and Fink, {E. L.} and P. McQuillen and T. Wu and S. Skellett and Thomas, {N. J.} and Nowak, {J. E.} and Baines, {P. B.} and J. Pappachan and M. Mathur and E. Lloyd and {Van Der Jagt}, {E. W.} and Dobyns, {E. L.} and Meyer, {M. T.} and Sanders, {R. C.} and Clark, {A. E.} and Dean, {J. M.} and {THAPCA Trial Investigators}",
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TY - JOUR

T1 - Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

AU - Moler,F. W.

AU - Silverstein,F. S.

AU - Holubkov,R.

AU - Slomine,B. S.

AU - Christensen,J. R.

AU - Nadkarni,V. M.

AU - Meert,K. L.

AU - Browning,B.

AU - Pemberton,V. L.

AU - Page,K.

AU - Gildea,M. R.

AU - Scholefield,B. R.

AU - Shankaran,S.

AU - Hutchison,J. S.

AU - Berger,J. T.

AU - Ofori-Amanfo,G.

AU - Newth,C. J L

AU - Topjian,A.

AU - Bennett,K. S.

AU - Koch,J. D.

AU - Pham,N.

AU - Chanani,N. K.

AU - Pineda,J. A.

AU - Harrison,R.

AU - Dalton,H. J.

AU - Alten,J.

AU - Schleien,C. L.

AU - Goodman,D. M.

AU - Zimmerman,J. J.

AU - Bhalala,U. S.

AU - Schwarz,A. J.

AU - Porter,M. B.

AU - Shah,S.

AU - Fink,E. L.

AU - McQuillen,P.

AU - Wu,T.

AU - Skellett,S.

AU - Thomas,N. J.

AU - Nowak,J. E.

AU - Baines,P. B.

AU - Pappachan,J.

AU - Mathur,M.

AU - Lloyd,E.

AU - Van Der Jagt,E. W.

AU - Dobyns,E. L.

AU - Meyer,M. T.

AU - Sanders,R. C.

AU - Clark,A. E.

AU - Dean,J. M.

AU - THAPCA Trial Investigators

PY - 2017/1/26

Y1 - 2017/1/26

N2 - BACKGROUND Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital 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.

AB - BACKGROUND Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital 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.

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