Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

Moler, Frank W.; Silverstein, Faye S.; Holubkov, Richard; Slomine, Beth S.; Christensen, James R.; Nadkarni, Vinay; Meert, Kathleen L.; Clark, Amy; Browning, Brittan; Pemberton, Victoria L.; Page, Karen; Shankaran, Seetha; Hutchison, Jamie; Newth, Christopher J L; Bennett, Kimberly Statler; Berger, John; Topjian, Alexis; Pineda, José; Koch, Joshua D.; Schleien, Charles L.; Dalton, Heidi J.; Ofori-Amanfo, George; Goodman, Denise M.; Fink, Ericka L.; McQuillen, Patrick S.; Zimmerman, Jerry J.; Thomas, Neal J.; Jagt, Élise W. van der; Porter, Melissa; Meyer, Michael T.; Harrison, Rick; Pham, Nga; Schwarz, Adam; Nowak, Jeffrey; Alten, Jeffrey A.; Wheeler, Derek S.; Bhalala, Utpal; Lidsky, Karen; Lloyd, Eric; Mathur, Mudit; Shah, Samir; Wu, Theodore; Theodorou, Andreas; Sanders, Ronald C.; Dean, J. Michael

doi:10.1056/nejmoa1411480

Cited by 381 publications

(377 citation statements)

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“…These results have raised questions regarding the benefits of cooling to 33°C. Recently, Moler et al (2015) studied the effect of TH (target temperature of 33°C for 48 h) versus controlled normothermia (36.8°C) in children who suffered an out-of-hospital CA. A trend toward improved outcome (12-month survival with favorable neurological outcome as assessed by the Vineland Adaptive Behavioral Scale) was seen with hypothermia versus normothermia ( p = 0.14) along with mortality ( p = 0.13).…”

Section: Introductionmentioning

confidence: 99%

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Anderson

Poloyac

Kochanek

et al. 2016

Therapeutic Hypothermia and Temperature Management

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Targeted temperature management (TTM) has been shown to reduce mortality and improve neurological outcomes in out-of-hospital cardiac arrest (CA) patients and in neonates with hypoxic-ischemic encephalopathy (HIE). TTM has also been associated with adverse drug events in the critically ill patient due to its effect on drug pharmacokinetics (PKs) and pharmacodynamics (PDs). We aim to evaluate the current literature on the effect of TTM on drug PKs and PDs following CA. MEDLINE/PubMed databases were searched for publications, which include the MeSH terms hypothermia, drug metabolism, drug transport, P450, critical care, cardiac arrest, hypoxic-ischemic encephalopathy, pharmacokinetics, and pharmacodynamics between July 2006 and October 2015. Twenty-three studies were included in this review. The studies demonstrate that hypothermia impacts PK parameters and increases concentrations of cytochrome-P450-metabolized drugs in the cooling and rewarming phase. Furthermore, the current data demonstrate a combined effect of CA and hypothermia on drug PK. Importantly, these effects can last greater than 4-5 days post-treatment. Limited evidence suggests hypothermia-mediated changes in the Phase II metabolism and the Phase III transport of drugs. Hypothermia also has been shown to potentially decrease the effect of specific drugs at the receptor level. Therapeutic hypothermia, as commonly deployed/applied during TTM, alters PK, and elevates concentrations of several commonly used medications. Hypothermia-mediated effects are an important factor when dosing and monitoring patients undergoing TTM treatment.

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Section: Introductionmentioning

confidence: 99%

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Anderson

Poloyac

Kochanek

et al. 2016

Therapeutic Hypothermia and Temperature Management

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“…5,17 The Pediatric Emergency Care Applied Research Network (PECARN) was established to overcome the barriers of conducting research pertaining to acutely ill and injured children during all phases of emergency care and has a history of successful completion of large multicenter clinical trials. [18][19][20][21][22][23][24][25] Due to the promising preclinical and phase II studies for the use of progesterone for adult TBI, PECARN investigators were funded to conduct feasibility planning for a clinical trial of progesterone and other promising agents for TBI in children. 26 In this article we report a prospective observational feasibility study of children with moderate-to-severe TBI presenting to 16 pediatric EDs across the United States.…”

Section: Resultsmentioning

confidence: 99%

Challenges Enrolling Children Into Traumatic Brain Injury Trials: An Observational Study

Stanley

Johnson

Vance

et al. 2017

Academic Emergency Medicine

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Objectives: In preparation for a clinical trial of therapeutic agents for children with moderate-to-severe blunt traumatic brain injuries (TBIs) in emergency departments (EDs), we conducted this feasibility study to (1) determine the number and clinical characteristics of eligible children, (2) determine the timing of patient and guardian arrival to the ED, and (3) describe the heterogeneity of TBIs on computed tomography (CT) scans. Methods:We conducted a prospective observational study at 16 EDs of children ≤ 18 years of age presenting with blunt head trauma and Glasgow Coma Scale scores of 3-12. We documented the number of potentially eligible patients, timing of patient and guardian arrival, patient demographics and clinical characteristics, severity of injuries, and cranial CT findings.

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“…For the critical outcome of neurologic function at 1 year, we identified moderate-quality evidence (downgraded for imprecision) from 1 RCT of pediatric OHCA, 87 involving 260 infants and children, that failed to show a significant difference in the proportion of patients receiving a score higher than 70 at 1 year (27/138 versus 15/122; RR, 1.54; 95% CI, 0.85-2.76), when comparing patients who received TTM to either 33°C or 36.8°C (Vineland Adaptive Behavioral Scale, 2nd edition).…”

Section: Consensus On Sciencementioning

confidence: 99%