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Individualized Treatment Effects of Therapeutic Hypothermia in Children Postcardiac Arrest: A Reanalysis of Two
Daniel R Balcarcel1, Garrett P Keim1, Sanjiv D Mehta1
1Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.
Insights
This study explored individualized treatment effects of hypothermia versus normothermia in pediatric cardiac arrest survivors. Findings suggest that temperature management strategies may need personalization for optimal outcomes.
Area of Science:
- Pediatric critical care medicine
- Machine learning in clinical research
- Cardiovascular resuscitation
Background:
- Post-cardiac arrest care in children requires optimized temperature management.
- Previous trials established general hypothermia guidelines, but individualized effects remain unclear.
Purpose of the Study:
- To estimate individualized treatment effects (ITE) of hypothermia versus normothermia in pediatric cardiac arrest survivors.
- To identify patient characteristics influencing treatment response to temperature management.
Main Methods:
- Secondary analysis of two large pediatric randomized controlled trials (THAPCA-OH and THAPCA-IH).
- Utilized a causal forest machine learning model to estimate ITEs.
- Analyzed patient data including baseline characteristics and 1-year outcomes (survival with favorable function).
Main Results:
- Estimated ITEs for hypothermia versus normothermia varied across patients in both trials.
- Subgroups with the greatest estimated benefit from hypothermia showed significant observed absolute risk differences.
- One subgroup demonstrated a potential benefit from normothermia.
Conclusions:
- Heterogeneity in treatment effects for temperature management after pediatric cardiac arrest is suggested.
- These findings highlight the potential need for personalized approaches to post-cardiac arrest temperature management.
- Further research is warranted to confirm and refine individualized treatment strategies.
Objectives:
To use patient characteristics to estimate individualized treatment effects (ITE) of hypothermia vs. normothermia after pediatric cardiac arrest.
Design:
Secondary, exploratory analysis of two pediatric randomized controlled trials (RCTs), Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH; NCT00878644) and Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital In-Hospital (THAPCA-IH; NCT00880087), using a causal forest machine learning model to estimate ITEs within each trial.
Setting:
THAPCA-OH was conducted at 38 children's hospitals across the United States and Canada. THAPCA-IH was conducted at 37 children's hospitals across the United States, Canada, and the United Kingdom.
Patients:
Pediatric patients aged 48 hours to 18 years who remained comatose within 6 hours after return of circulation following cardiac arrest and were randomized in THAPCA-OH and THAPCA-IH to normothermia or therapeutic hypothermia for 48 hours. Patients with a baseline Vineland Adaptive Behavior Scales, Second Edition (VABS-II) score less than 70 were excluded.
Interventions:
None.
Measurements And Main Results:
The final cohorts included 260 patients in THAPCA-OH and 257 in THAPCA-IH. The primary outcome was survival at 1 year with VABS-II greater than or equal to 70 (favorable outcome). In THAPCA-OH, estimated ITEs (calculated as the individualized absolute risk difference [iARD] between hypothermia and normothermia, positive favoring hypothermia) ranged from -0.01 to 0.16. Patients were grouped into tertiles of estimated ITE within each trial. In THAPCA-OH, the tertile with the greatest estimated benefit from hypothermia had an observed absolute risk difference (ARD; hypothermia minus normothermia) of 0.18 (95% CI, 0.02-0.34). In THAPCA-IH, estimated ITEs ranged from -0.17 to 0.13. The tertile estimated to benefit most from hypothermia had an ARD of 0.27 (95% CI, 0.07-0.48), whereas the tertile estimated to benefit from normothermia had an ARD of -0.20 (95% CI, -0.40 to -0.01).
Conclusions:
These analyses suggest heterogeneity of treatment effect may exist in postcardiac arrest temperature management warranting further study.
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