Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials

Barnaby R. Scholefield, Faye S. Silverstein, Russell Telford, Richard Holubkov, Beth S Slomine, Kathleen L. Meert, James R Christensen, Vinay M. Nadkarni, J. Michael Dean, Frank W. Moler

Research output: Contribution to journalArticle

Abstract

Background: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. Methods: Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. Results: 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. Conclusions: Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalResuscitation
Volume133
DOIs
StatePublished - Dec 1 2018

Fingerprint

Induced Hypothermia
Heart Arrest
Hypothermia
Randomized Controlled Trials
Pediatrics
Psychological Adaptation
Survival
Sample Size
Confidence Intervals
Out-of-Hospital Cardiac Arrest
Pediatric Intensive Care Units
Coma
Resuscitation
Canada
Cardiac Arrhythmias
Clinical Trials
Safety
Temperature
Mortality
Incidence

Keywords

  • Paediatric cardiac arrest
  • Randomised controlled trials
  • Targeted temperature management
  • Therapeutic hypothermia
  • Therapeutic normothermia

ASJC Scopus subject areas

  • Emergency Medicine
  • Emergency
  • Cardiology and Cardiovascular Medicine

Cite this

Scholefield, B. R., Silverstein, F. S., Telford, R., Holubkov, R., Slomine, B. S., Meert, K. L., ... Moler, F. W. (2018). Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials. Resuscitation, 133, 101-107. https://doi.org/10.1016/j.resuscitation.2018.09.011

Therapeutic hypothermia after paediatric cardiac arrest : Pooled randomized controlled trials. / Scholefield, Barnaby R.; Silverstein, Faye S.; Telford, Russell; Holubkov, Richard; Slomine, Beth S; Meert, Kathleen L.; Christensen, James R; Nadkarni, Vinay M.; Dean, J. Michael; Moler, Frank W.

In: Resuscitation, Vol. 133, 01.12.2018, p. 101-107.

Research output: Contribution to journalArticle

Scholefield, BR, Silverstein, FS, Telford, R, Holubkov, R, Slomine, BS, Meert, KL, Christensen, JR, Nadkarni, VM, Dean, JM & Moler, FW 2018, 'Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials', Resuscitation, vol. 133, pp. 101-107. https://doi.org/10.1016/j.resuscitation.2018.09.011
Scholefield, Barnaby R. ; Silverstein, Faye S. ; Telford, Russell ; Holubkov, Richard ; Slomine, Beth S ; Meert, Kathleen L. ; Christensen, James R ; Nadkarni, Vinay M. ; Dean, J. Michael ; Moler, Frank W. / Therapeutic hypothermia after paediatric cardiac arrest : Pooled randomized controlled trials. In: Resuscitation. 2018 ; Vol. 133. pp. 101-107.
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abstract = "Background: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. Methods: Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. Results: 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28{\%} [75/271] and 26{\%} [63/246], respectively; relative risk, 1.08; 95{\%} confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22{\%} (hypothermia) and 21{\%} (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44{\%} [138/317] and 38{\%} [113/ 297], respectively; relative risk, 1.15; 95{\%} CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. Conclusions: Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.",
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T1 - Therapeutic hypothermia after paediatric cardiac arrest

T2 - Pooled randomized controlled trials

AU - Scholefield, Barnaby R.

AU - Silverstein, Faye S.

AU - Telford, Russell

AU - Holubkov, Richard

AU - Slomine, Beth S

AU - Meert, Kathleen L.

AU - Christensen, James R

AU - Nadkarni, Vinay M.

AU - Dean, J. Michael

AU - Moler, Frank W.

PY - 2018/12/1

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N2 - Background: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. Methods: Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. Results: 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. Conclusions: Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.

AB - Background: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. Methods: Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. Results: 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. Conclusions: Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.

KW - Paediatric cardiac arrest

KW - Randomised controlled trials

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KW - Therapeutic hypothermia

KW - Therapeutic normothermia

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