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Post-ROSC Targeted Temperature Management (TTM)

Question Type:
Intervention
Full Question:
Among infants and children who are experiencing ROSC after cardiac arrest in any setting (P), does does the use of TTM (eg, therapeutic hypothermia) (I), compared with compared with the use of normothermia (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ICU length of stay, survival to hospital discharge (O)?
Consensus on Science:
For the critical outcome of neurologic function at 1 year, we identified moderate-quality evidence (downgraded for imprecision) from 1 RCT of pediatric OHCA,(Moler 2015, 1898-1908) involving 260 infants and children, that failed to show a significant difference when comparing patients who received TTM to either 33°C or 36.8°C (Vineland Adaptive Behavioral Scale, 2nd edition) higher than 70 at 1 year (27/138 versus 15/122; RR, 1.54; 95% CI, 0.85–2.76). For the critical outcome of survival to 6 months with good neurologic outcome, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 pediatric observational multicenter study of IHCA and OHCA(Doherty 2009, 1492-1500) involving 79 patients that failed to show a significant difference in functional outcome with the use of TTM (specifically Pediatric Cerebral Performance Category [PCPC], 4–6; aOR, 2.00; 95% CI, 0.45–9.01).For the critical outcome of survival to hospital discharge with good neurologic outcome, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 pediatric observational study of asphyxial IHCA and OHCA(Lin 2013, 285-290) of 24 patients, that failed to show significantly improved outcomes (PCPC, 1–2) with the use of TTM (RR, 1.77; 95% CI, 0.92–3.40).For the critical outcome of survival to 6 months, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 pediatric observational multicenter study of IHCA and OHCA(Doherty 2009, 1492-1500) involving 79 patients that failed to show a significant difference in outcome (aOR, 1.99; 95% CI, 0.45–8.85).For the critical outcome of survival to 30 days, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 pediatric observational multicenter study of IHCA and OHCA(Doherty 2009, 1492-1500) involving 79 patients that failed to show a significant difference in outcome (aOR, 2.50; 0.55–11.49).For the critical outcome of survival to hospital discharge, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 2 pediatric observational studies, 1 with both in-hospital and out-of-hospital asphyxial cardiac arrest(Lin 2013, 285-290) of 42 patients, that showed improved outcomes with the use of TTM (RR, 1.69; 95% CI, 1.04–2.74) and a single-center observational study of pediatric OHCA,(Scholefield 2015, 19-25) involving 73 children over a 6-year period, that did not show a difference in survival at discharge from hospital, (13/38 TTM versus 8/35 standard temperature management [STM]; P=0.28).For the important outcome of survival to 1 year, we identified moderate-quality evidence (downgraded for imprecision) from 1 RCT of pediatric OHCA,(Moler 2015, 1898-1908) involving 287 patients, that failed to show a difference when comparing patients who received TTM to either 33°C or 36.8°C (57/151, 33°C group; 39/136, 36.8°C group; RR, 1.29; 95% CI, 0.93–1.79). For the important outcome of PICU LOS, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 3 pediatric observational studies of IHCA and OHCA(Doherty 2009, 1492-1500; Fink 2010, 66-74; Scholefield 2015, 19-25) involving 79, 181, and 73 patients, respectively. Two of these studies failed to show any difference in PICU LOS (Doherty: TTM median LOS was 16 [IQR, 4–30.5] days compared with 9 [IQR 5–22.5] days; P=0.411; Fink: mean PICU LOS was TTM 20±47.7 days versus normothermia 20.1±35.9 days; P=0.5). One study(Scholefield 2015, 19-25) found that the LOS was longer for those treated with TTM than with STM (ie, median duration of 4.1 [IQR, 3.0–6.8] days as compared with 1.3 [IQR, 0.5–6.7] days; P
Treatment Recommendation:
We suggest that for infants and children with OHCA, TTM be used in the post–cardiac arrest period. While the ideal target temperature range and duration are unknown, it is reasonable to use either hypothermia (32°C–34°C) or normothermia (36°C–37.5°C) (weak recommendation, moderate-quality evidence). For pediatric survivors of IHCA, the confidence in effect estimates for the use of TTM is so low that the task force decided that a recommendation was too speculative.Values, Preferences, and Task Force InsightsIn making this recommendation, the task force preferred the use of a targeted temperature of 32°C to 34°C as opposed to the normothermic range, based on the fact that while the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) study did not show success for the primary outcome (neurologic status at 1 year), it was underpowered to show a significant difference for survival, for which the lower 95% CI approached 1, with the Kaplan-Meier survival curves showing a tendency toward better outcomes at the lower temperature ranges. Furthermore, the task force noted that hyperthermia occurs frequently in the postarrest period, and that this is potentially harmful and should be avoided. There were insufficient data on IHCA patients, who may represent a different population. The provision of TTM to an individual patient can be resource intensive. These resources, the associated expertise necessary to deliver and maintain TTM, and the presence of appropriate systems of critical care are required to provide optimal post-ROSC care. The task force noted that the application of TTM may require sedation, analgesia, and neuromuscular blockade that will modify neurologic assessment.
CoSTR Attachments:
Final CoSTR statement on targeted temperature management post TF Dallas 2015_n.docx    
Final Evidence table for targeted temperature management PEDS 387 Dallas 2015_n.docx    
Final Recommendations for targeted temperature management PEDS 387 LANGUAGE COSTR STYLE_n.docx    
Final Summary of Bias Assessments PEDS 387 Targeted temperature Dallas 2015_n.xlsx    

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