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Pediatric Targeted Temperature Management Post Cardiac Arrest (PLS): Systematic Review

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Pediatric Targeted Temperature Management Post Cardiac Arrest

CoSTR Citation:

Aickin RP, de Caen AR, Atkins DL, Bingham R, Couto TB, Guerguerian Anne-Marie, Hazinski MF, Lavonas E, Meaney PA, Nadkarni VM, Ng KC, Nuthall GA, Ohshimo S, Ong GYK, Reis AG, Schexnayder SM, Scholefield Barney, Shimizu NS, Tijssen JA, Van de Voorde P, Buick JE, Welsford M, Maconochie I on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Pediatric targeted temperature management post cardiac arrest [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Life Support Task Force, February 2, 2019. Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence process for the production of Consensus of Science and Treatment Recommendations (CoSTR) started with a systematic review regarding pediatric targeted temperature management post cardiac arrest (Welsford M, 2018, PROSPERO CRD42018108441 https://www.crd.york.ac.uk/pro...) conducted by Dr. Michelle Welsford (et al), McMaster University, Canada with involvement of clinical content experts. Evidence for pediatric literature was sought and considered by the Pediatric Life Support Task Force. These data were taken into account when formulating the Treatment Recommendations.

Systematic Review:

Buick JE, Wallner C, Aickin R, Meaney R, de Caen A, Maconochie IK, Skifars M, Welsford M on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Pediatric targeted temperature management post cardiac arrest: a systematic review with meta-analysis. Journal TBA. Accepted TBA.

Pediatric Targeted Temperature Management Post Cardiac Arrest PICOST

PICOST = Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame

Population: Pediatric patients (>24 hours to 18 years of age) who achieved return of sustained circulation (ROSC) after out-of-hospital or in-hospital cardiac arrest

Intervention: Targeted temperature management (TTM) with a target temperature of 32-36⁰C

Comparators: No TTM or TTM at an alternative target temperature range

Outcomes:

Primary Outcome:

  • Good neurobehavioral survival long-term

Secondary Outcomes:

  • Good neurobehavioral survival short-term and intermediate-term
  • Survival short-term, intermediate-term, and long-term
  • Neurobehavioral score changes from pre-arrest, intermediate-term and long-term
  • Health-related quality of life (HRQoL) score intermediate-term, and long-term
  • HRQoL score change from pre-arrest intermediate-term and long-term

Additional In-hospital Adverse Outcomes:

  • Infection (culture proven)
  • Recurrent cardiac arrest (not leading to death)
  • Serious bleeding (red blood cell transfusion)
  • Arrhythmias (any)

Note:

Long-term defined as 1-3 years, intermediate term defined as 3-6 months, short-term defined as 28-30 days (or hospital discharge).

Study Designs: Randomized controlled trials (RCT), quasi-randomized controlled trials (qRCT), and non-randomized cohort studies were eligible to be included. Excluded animal studies, unpublished studies (e.g., conference abstracts), case series.

Timeframe: All years to December 13, 2018

Languages: All languages are included (if English abstract available).

A priori subgroups to be examined: location of cardiac arrest (in-hospital and out-of-hospital), age groups, presumed etiology of cardiac arrest (cardiac, asphyxia, other), and use of extracorporeal membrane oxygenation (ECMO).

PROSPERO Registration: CRD42018108441

Consensus on Science:

1. Main Analysis

Main Analysis Good Neurobehavioral Survival:

For the critical outcome of long-term good neurobehavioral survival (1 year) the evidence of low certainty (downgraded for risk of inconsistency and imprecision) from 2 RCTs (OHCA: Moler 2015 1898, IHCA: Moler 2017 318) with 517 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.15, 95% CI 0.69-1.93, p=0.60; absolute risk reduction [ARR]=3.8% or 38 more patients/1000 had good neurobehavioral survival with the intervention, 95% CI 79 fewer patients/1000 to 238 more patients/1000).

For the critical outcome of intermediate-term good neurobehavioral survival (6 months) the evidence of very low certainty (downgraded for risk of bias) from 1 adjusted observational cohort study (Doherty 2009 1492) with 79 children who achieved ROSC showed no statistical benefit or harm of TTM <35⁰C compared to no TTM (aOR=0.50, 95% CI 0.11-2.22).

For the critical outcome of short-term good neurobehavioral survival (at hospital discharge) the evidence of very low certainty (downgraded for risk of bias) from 1 adjusted observational cohort study (Chang 2016 8) with 663 children who achieved ROSC showed no statistical benefit or harm of TTM 32-34⁰C compared to no TTM (aOR=1.22, 95% CI 0.59-2.51).

There was insufficient information available to provide specific information on neurobehavioral score change, health-related quality of life (HRQoL) scores or HRQoL score change.

Main Analysis Survival:

For the critical outcome of long-term survival (1 year), the evidence of very low certainty (downgraded for inconsistency and imprecision) from 2 RCTs (OHCA: Moler 2015 1898, IHCA: Moler 2017 318) with 614 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.14, 95% CI 0.93-1.39, p=0.20; ARR=5.3% or 53 more patients/1000, 95% CI 27 fewer to 148 more).

For the critical outcome of intermediate-term survival (6 months), the evidence of very low certainty (downgraded for risk of bias) from 1 adjusted observational cohort study (Doherty 2009 1492) with 79 children who achieved ROSC showed no statistical benefit or harm of TTM <35⁰C compared to no TTM (aOR=0.50 95% CI 0.11-2.22).

For the critical outcome of short-term survival (to hospital discharge), the evidence of very low certainty (downgraded for inconsistency and imprecision) from 2 RCTs (OHCA: Moler 2015 1898, IHCA: Moler 2017 318) with 613 children who achieved ROSC showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.14, 95% CI 0.96-1.36, p=0.14; ARR=6.6% or 66 more patients/1000, 95% CI 19 fewer to 169 more).

For the critical outcome of short-term survival (30 days or hospital discharge), the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 3 adjusted observational cohort studies (Doherty 2009 1492, Fink 2010 66, Chang 2016 8) with 341 children who achieved ROSC showed no statistical benefit or harm of TTM 32-36C compared to TTM 36-37.5⁰C or no TTM (aOR=1.08, 95% CI 0.53-2.17, p=0.84).

The overall quality of evidence was rated as very low for all outcomes in the observational cohort studies primarily due to a very serious risk of bias. The individual observational studies were all at a critical risk of bias owing to confounding. Because of this and a high degree of heterogeneity, no meta-analyses could be performed on the unadjusted outcomes from the observational studies, and individual studies are difficult to interpret.

Main Analysis Serious Bleeding:

For the important outcome serious bleeding (red blood cell transfusion), low certainty (downgraded for inconsistency and imprecision) from 2 RCTs (Moler 2015 1898, Moler 2017 318) with 311 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=0.97, 95% CI 0.88-1.07, p=0.49; ARR= -1.9% or 19 fewer patients/1000, 95% CI 78 fewer to 45 more).

For the important outcome serious bleeding (red blood cell transfusion), very low certainty (downgraded for risk of bias, inconsistency, indirectness, and imprecision) from 2 unadjusted observational cohort studies (Doherty 2009 1492, Fink 2010 66) with 260 children who achieved ROSC could not be pooled, but none showed statistical benefit or harm of TTM 32-36C compared to TTM 36-37.5⁰C or no TTM.

2. Subgroup Location of Cardiac Arrest

Out-of-Hospital Cardiac Arrest (OHCA) Good Neurobehavioral Survival:

For the OHCA sub-group, critical outcome of long-term good neurobehavioral survival (1 year) the evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2015 1898) with 260 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.59, 95% CI 0.89-2.85; ARR=7.3% or 73 more patients/1000, 95% CI 14 fewer to 227 more).

For the OHCA sub-group, critical outcome of intermediate-term good neurobehavioral survival (6 months) the evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational cohort study (Lin 2018 180) with 64 children who achieved ROSC showed statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=10.92, 95% CI 1.43-83.50; ARR=25.4% or 254 more patients/1000, 95% CI 11 more to 1000 more).

For the OHCA sub-group, critical outcome of short-term good neurobehavioral survival (6 months) the evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational cohort study (Chang 2016 8) with 663 children who achieved ROSC showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5 or no TTM (RR=1.19, 95% CI 0.76-1.84; ARR=3.6% or 36 more patients/1000, 95% CI 45 fewer to 157 more).

Out-of-Hospital Cardiac Arrest (OHCA) Survival:

For the OHCA sub-group, critical outcome of long-term survival (1 year) the evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2015 1898) with 287 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.32, 95% CI 0.94-1.84; ARR=9.2% or 92 more patients/1000, 95% CI 17 fewer to 241 more).

For the OHCA sub-group, critical outcome of intermediate-term survival (6 months) the evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational cohort study (Lin 2018 180) with 64 children who achieved ROSC showed statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=2.18, 95% CI 1.15-4.13; ARR=30.3% or 303 more patients/1000, 95% CI 38 more to 803 more patients).

For the OHCA sub-group, critical outcome of short-term survival (at discharge) the evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2015 1898) with 292 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.30, 95% CI 0.97-1.76; ARR=9.9% or 99 more patients/1000, 95% CI 10 fewer to 252 more).

For the OHCA sub-group, critical outcome of short-term survival (30 days or hospital discharge) the evidence of very low certainty (downgraded for risk of bias, inconsistency, and indirectness) from 3 unadjusted observational cohort studies (Scholefield 2015 19, Chang 2016 8, Lin 2018 180) with 800 children who achieved ROSC could not be pooled, but two of the individual studies showed no statistical benefit or harm and the third (Lin 2018 180) showed statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C or no TTM (RR=1.95, 95% CI 1.10-3.45; ARR= 29.2% or 292 more patients/1000, 95% CI 31 more to 754 more).

In-Hospital Cardiac Arrest (IHCA) Good Neurobehavioral Survival:

For the IHCA sub-group, the critical outcome of long-term good neurobehavioral survival (1 year) evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2017 318) with 257 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=0.93, 95% CI 0.68-1.28; ARR= -2.7% or 27 fewer patients/1000, 95% CI 124 fewer to 108 more).

For the IHCA sub-group, critical outcome of intermediate-term good neurobehavioral survival (3-6 months) the evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational cohort study (Doherty 2009 1492) with 79 children who achieved ROSC showed statistical harm of TTM 32-36C compared to TTM 36-37.5⁰C or no TTM (RR=0.54, 95% CI 0.30-0.97; ARR=26.7% or 267 more patients/1000, 95% CI 406 fewer to 17 fewer).

In-Hospital Cardiac Arrest (IHCA) Survival:

For the IHCA sub-group, critical outcome of long-term survival (1 year) the evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2017 318) with 327 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.06, 95% CI 0.84-1.33; ARR=2.8% or 28 more patients/1000, 95% CI 74 fewer to 152 more).

For the IHCA sub-group, critical outcome of intermediate-term survival (3-6 months) the evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational cohort study (Doherty 2009 1492) with 79 children who achieved ROSC showed statistical harm of TTM 32-36C compared to TTM 36-37.5⁰C or no TTM (RR=0.50, 95% CI 0.28-0.90; ARR= -31%; or 310 fewer patients/1000 survived, 95% CI 446 fewer to 62 fewer).

For the IHCA sub-group, critical outcome of short-term survival (at discharge) the evidence of moderate certainty (downgraded for imprecision) from 1 RCT (Moler 2017 318) with 321 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.08, 95% CI 0.91-1.28; ARR=4.7% or 47 more patients/1000, 95% CI, 53 fewer to 165 more).

For the IHCA sub-group, critical outcome of short-term survival (30 days or hospital discharge) the evidence of very low certainty (downgraded for risk of bias and inconsistency) from 3 unadjusted observational cohort studies (Doherty 2009 1492, Cheng 2018 83, Torres Andres 2018 451) with 800 children who achieved ROSC could not be pooled, but none of the individual studies showed a statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C or no TTM.

3. Subgroup Presumed Etiology of Cardiac Arrest

Presumed Cardiac Cause of Arrest Survival:

For the presumed cardiac cause sub-group, the critical outcome of short-term survival (1 year) evidence of very low certainty (downgraded for risk of bias, inconsistency and indirectness) from 2 unadjusted observational studies (Cheng 2018 83, Torres Andres 2018 451) with 139 children who achieved ROSC could not be pooled due to significant clinical heterogeneity, but the individual studies showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C.

Presumed Asphyxial Cause of Arrest Good Neurobehavioral Survival (GNS):

For the presumed asphyxial cause sub-group, the critical outcome of intermediate-term good neurobehavioral survival (6 months) evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational study (Lin 2018 180) with 64 children who achieved ROSC showed statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C or no TTM (RR=10.92, 95% CI 1.43-83.50; ARR=25.4% or 254 more patients/1000, 95% CI 11 more to 1000 more).

For the presumed asphyxial cause sub-group, the critical outcome of short-term good neurobehavioral survival (at hospital discharge) evidence of very low certainty (downgraded for risk of bias, and imprecision) from 1 unadjusted observational study (Lin 2013 285) with 24 children who achieved ROSC showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.77, 95% CI 0.93-3.40; ARR=35.5% or 355 more patients/1000, 95% CI 32 fewer to 1000 more).

Presumed Asphyxial Cause of Arrest Survival:

For the presumed asphyxial cause sub-group, the critical outcome of intermediate-term survival (6 months) evidence of very low certainty (downgraded for risk of bias and imprecision) from 1 unadjusted observational study (Lin 2018 180) with 64 children who achieved ROSC showed a statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=2.18, 95% CI 1.15-4.13; ARR=30.3% or 303 more patients/1000, 95% CI 38 more to 803 more).

For the presumed asphyxial cause sub-group, the critical outcome of short-term survival (30 days or hospital discharge) evidence of very low certainty (downgraded for risk of bias, inconsistency, and indirectness) from 3 unadjusted observational studies (Fink 2010 66, Scholefield 2015 19, Lin 2018 180) with 318 children who achieved ROSC could not be pooled, but two of the individual studies showed no statistical benefit or harm and the third (Lin 2018 180) showed statistical benefit of TTM 32-34⁰C compared to TTM 36-37.5⁰C or no TTM (RR=1.95, 95% CI 1.10-3.45; ARR= 29.2% or 292 more patients/1000, 95% CI 31 more to 754 more).

Presumed Drowning Cause of Arrest Good Neurobehavioral Survival:

For the presumed drowning cause sub-group, the critical outcome of long-term good neurobehavioral survival (1 year) evidence of low certainty (downgraded for risk of bias and imprecision) from 1 RCT (non-randomized subgroup) (Moler 2016 712) with 65 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.76, 95% CI 0.64-4.84; ARR=12.7% or 127 more patients/1000, 95% CI 60 fewer to 640 more).

Presumed Drowning Cause of Arrest Survival:

For the presumed drowning cause sub-group, the critical outcome of long-term survival (1 year) evidence of low certainty (downgraded for risk of bias and imprecision) from 1 RCT (non-randomized subgroup) (Moler 2016 712) with 69 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.15, 95% CI 0.67-1.99; ARR=6.3% or 63 more patients/1000, 95% CI 140 fewer to 419 more).

For the presumed drowning cause sub-group, the critical outcome of short-term survival (to hospital discharge) evidence of low certainty (downgraded for risk of bias and imprecision) from 1 RCT (non-randomized subgroup) (Moler 2016 712) with 74 children who achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5, showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C (RR=1.04 95% CI 0.66-1.66; ARR=2.0%;or 20 more patients/1000, 95% CI 170 fewer to 330 more).

4. Subgroup Extracorporeal Membrane Oxygenation (ECMO)

ECMO Good Neurobehavioral Survival:

For the ECMO co-intervention sub-group, the critical outcome of long-term good neurobehavioral survival (at 1 year) showed evidence of low certainty (downgraded for risk of bias and imprecison) from 1 RCT (Supplemental material THAPCA IHCA RCT, Moler 2017 318) with 133 children reported no statistical benefit or harm on long-term good neurobehavioral survival (at 1 year) for TTM at 32-34°C compared to TTM at 36-37.5⁰C (RR: 0.80, 95% CI: 0.48-1.32; ARR= -6.3% or 63 fewer patients/1000, 95% CI 165 fewer to 101 more).

ECMO Survival:

For the ECMO co-intervention sub-group, the critical outcome of short-term survival (to hospital discharge) evidence of very low certainty (downgraded for risk of bias, indirectness, and imprecision) from 1 unadjusted observational cohort study (Torres Andres 2018, 451) with 58 children who achieved ROSC showed no statistical benefit or harm of TTM 32-34⁰C compared to TTM 36-37.5⁰C or no TTM (RR=1.19 95% CI 0.82-1.73; ARR=11.4% or 114 more patients/1000, 95% CI 108 fewer to 438 more).

Notes regarding methods of included studies:

  • The two RCTs were conducted by the same research group and designed to have the same methodology except for the 2 different settings (in-hospital cardiac arrest and out-of-hospital cardiac arrest). The inclusion and exclusion criteria were extensive and included those patients that achieved return of circulation but remained comatose with a Glasgow Coma Scale Motor Score of < 5.
  • The observational studies (mostly retrospective cohort studies), had varying methods as evidenced by different inclusions and exclusions, different comparison groups (some were actively maintained normothermia TTM (preventing fever) and others were no TTM), different length of TTM, and different definitions for some of the harm outcomes.

Treatment Recommendations

We suggest using TTM 32-34⁰C or TTM 36-37.5⁰C for comatose pediatric patients (> 24 hours to 18 years of age) who achieved ROSC after OHCA (weak recommendation, very low certainty of evidence).

We suggest using TTM 32-34⁰C or TTM 36-37.5⁰C for comatose pediatric patients (> 24 hours to 18 years of age) who achieved ROSC after IHCA (weak recommendation, very low certainty of evidence).

Justification and Evidence to Decision Framework Highlights

The Pediatric TF recognises that the causes, pathophysiology and outcomes for pediatric cardiac arrests are significantly different to cardiac arrests in adults and in newborns. The TF places a higher value on pediatric study data and believes that it is not appropriate to extrapolate from studies in other age groups given that 2 pediatric RCTs have now been published.

The available pediatric data includes 2 controlled trials of comatose survivors of cardiac arrest. Both of these studies used a comparison of TTM 32-34⁰C vs TTM 36-37.5⁰C. Temperature was measured centrally. The THAPCA randomized trials compared a duration of TTM 32-34⁰C for 2 days followed by TTM of 36-37.5⁰C for 3 days with a TTM of 36-37.5⁰C for 5 days. The reader is referred to the original publications for details of the protocol. Because these trials did not evaluate the effects of other durations of TTM, the Task Force agreed that a recommendation regarding the duration of TTM would be too speculative at this point.

All of the other pediatric studies included in this review were observational cohort studies which used a variety of TTM temperature range definitions. The TF believes that it is appropriate to base our recommendations on the protocols described in the 2 controlled studies given the variability and uncertainty in approaches described in the cohort studies.
The TF debated whether the temperature range of TTM of 36-37.5⁰C would be comparable to the group of no TTM and took the pragmatic view that the best evidence of the two randomised control trials provided the best guidance.

There is registry evidence of neurological harm resulting from fever in the post resuscitation period (Bembea 2010 723). We feel that avoiding and aggressively treating fever is an important part of post resuscitation care. Targeted Temperature Management protocols may reduce the risk of fever. Active targeted temperature management protocols may also include multiple interventions other than temperature monitoring which could influence neurological outcomes.

This CoSTR compared different temperature ranges, but not techniques of temperature control, rewarming or other aspects of post resuscitation care. As a result, we can make no recommendation on these aspects of TTM which may nonetheless have important effects.

Knowledge Gaps:

  • Duration of TTM and rewarming
  • Temperature ranges other than those studied in the THAPCA trials
  • Methods of cooling and rewarming
  • Influence Co-interventions/bundle of care
  • Impact of ECMO and role of TTM during ECMO

Attachments

EtD: Should Targeted temperature management (TTM) with a target temperature of 32-36°C vs. No TTM or TTM at an alternative target temperature range be used for Post Pediatric Cardiac Arrest?

Acknowledgement

The PLS Task Force would like to acknowledge the work undertaken by CEE and by AHA staff, in particular the assistance given by Dr. Matt Buchanan.

REFERENCES

Bembea MM, Nadkarni VM, Diener-West M, et al. Temperature patterns in the early postresuscitation period after pediatric inhospital cardiac arrest. Pediatr Crit Care Med. 2010;11(6):723-730.

Chang I, Kwak YH, Shin SD, et al. Therapeutic hypothermia and outcomes in paediatric out-of-hospital cardiac arrest: A nationwide observational study. Resuscitation. 2016;105:8-15.

Cheng HH, Rajagopal SK, Sansevere AJ, et al. Post-arrest therapeutic hypothermia in pediatric patients with congenital heart disease. Resuscitation. 2018 May;126:83–9.

Doherty DR, Parshuram CS, Gaboury I, et al. Hypothermia therapy after pediatric cardiac arrest. Circulation. 2009;119(11):1492-1500.

Fink EL, Clark RS, Kochanek PM, Bell MJ, Watson RS. A tertiary care center's experience with therapeutic hypothermia after pediatric cardiac arrest. Pediatr Crit Care Med. 2010;11(1):66-74.

Lin JJ, Lin CY, Hsia SH, et al. 72-h therapeutic hypothermia improves neurological outcomes in paediatric asphyxial out-of-hospital cardiac arrest-An exploratory investigation. Resuscitation. 2018 Dec; 133:180-186.

Lin JJ, Hsia SH, Wang HS, et al. Therapeutic hypothermia associated with increased survival after resuscitation in children. Pediatric Neurology. 2013 Apr;48(4):285–90.

Moler FW, Silverstein FS, Holubkov R, et al. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in children. N Engl J Med. 2015;372(20):1898-1908.

Moler FW, Silverstein FS, Holubkov R, et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med. 2017;376(4):318-329.

Moler FW, Hutchison JS, Nadkarni VM, Silverstein FS, Meert KL, Holubkov R, et al. Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications. Pediatr Crit Care Med. 2016 Aug;17(8): 712–20.

Scholefield BR, Morris KP, Duncan HP, et al. Evolution, safety and efficacy of targeted temperature management after pediatric cardiac arrest. Resuscitation. 2015 Jul;92:19–25.

Torres-Andres F, Fink EL, Bell MJ, Sharma MS, Yablonsky EJ, Sanchez-de-Toledo J. Survival and Long-Term Functional Outcomes for Children With Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation. Pediatr Crit Care Med. 2018;19(5):451-458.


Discussion

profile avatar
ILCOR staff
As many providers will read only the"treatment recomendation section" , I think is important to add to that section that it is related to "central" temperature. I mean it can be dangerous to interpret 37,5C as peripheral temperature, wich means fever "centrally".
Reply
profile avatar
ILCOR staff
The point is that if there is no current evidence that hypothermia is better than normothermia, perhaps normothermia should be recommended, because is less aggressive, easier to perform and with fewer side effects. Hypothermia should be restricted to clinical trials.
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