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Updating Evidence for Using Hypothermia in Pediatric Severe Traumatic Brain Injury: Conventional and Bayesian Meta-Analytic Perspectives*

Tasker, Robert C. MD, FRCP; Vonberg, Frederick W. MBBS; Ulano, Elizabeth D. MD; Akhondi-Asl, Alireza PhD

Pediatric Critical Care Medicine: April 2017 - Volume 18 - Issue 4 - p 355–362
doi: 10.1097/PCC.0000000000001098
Neurocritical Care

Objective: To evaluate clinical trials of hypothermia management on outcome in pediatric patients with severe traumatic brain injury using conventional and Bayesian meta-analyses.

Data Sources: Screening of PubMed and other databases to identify randomized controlled trials of hypothermia for pediatric severe traumatic brain injury published before September 2016.

Study Selection: Four investigators assessed and reviewed randomized controlled trial data.

Data Extraction: Details of trial design, patient number, Glasgow Coma Scale score, hypothermia and control normothermia therapy, and outcome of mortality were collated.

Data Synthesis: In conventional meta-analysis, random-effects models were expressed as odds ratio (odds ratio with 95% credible-interval). Bayesian outcome probabilities were calculated as probability of odds ratio greater than or equal to 1. In seven randomized controlled trials (n = 472, patients 0–17 yr old), there was no difference in mortality (hypothermia vs normothermia) with pooled estimate 1.42 (credible-interval, 0.77–2.61; p = 0.26). Duration of hypothermia (24, 48, or 72 hr) did not show difference in mortality. (Similar results were found using poor outcome.) Bayesian analyses of randomized controlled trials ordered by time of study completed recruitment showed, after the seventh trial, chance of relative risk reduction of death by greater than 20% is 1-in-3. An optimistic belief (0.90 probability that relative risk reduction of death > 20% hypothermia vs normothermia) gives a chance of relative risk reduction of death by greater than 20% of 1-in-2.

Conclusions: Conventional meta-analysis shows the null hypothesis—no difference between hypothermia versus normothermia on mortality and poor outcome—cannot be rejected. However, Bayesian meta-analysis shows chance of relative risk reduction of death greater than 20% with hypothermia versus normothermia is 1-in-3, which may be further altered by one’s optimistic or skeptical belief about a patient.

1Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA.

2Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, MA.

*See also p. 388.

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©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies