A systematic review of cooling for neuroprotection in neonates with hypoxic ischemic encephalopathy - are we there yet?

Department of Neonatal Paediatrics, Women's and Children's Health Service, Perth, Australia.
BMC Pediatrics (Impact Factor: 1.93). 09/2007; 7(article 30):30. DOI: 10.1186/1471-2431-7-30
Source: PubMed

ABSTRACT The objective of this study was to systematically review randomized trials assessing therapeutic hypothermia as a treatment for term neonates with hypoxic ischemic encephalopathy.
The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL databases, reference lists of identified studies, and proceedings of the Pediatric Academic Societies were searched in July 2006. Randomized trials assessing the effect of therapeutic hypothermia by either selective head cooling or whole body cooling in term neonates were eligible for inclusion in the meta-analysis. The primary outcome was death or neurodevelopmental disability at >or= 18 months.
Five trials involving 552 neonates were included in the analysis. Cooling techniques and the definition and severity of neurodevelopmental disability differed between studies. Overall, there is evidence of a significant effect of therapeutic hypothermia on the primary composite outcome of death or disability (RR: 0.78, 95% CI: 0.66, 0.92, NNT: 8, 95% CI: 5, 20) as well as on the single outcomes of mortality (RR: 0.75, 95% CI: 0.59, 0.96) and neurodevelopmental disability at 18 to 22 months (RR: 0.72, 95% CI: 0.53, 0.98). Adverse effects include benign sinus bradycardia (RR: 7.42, 95% CI: 2.52, 21.87) and thrombocytopenia (RR: 1.47, 95% CI: 1.07, 2.03, NNH: 8) without deleterious consequences.
In general, therapeutic hypothermia seems to have a beneficial effect on the outcome of term neonates with moderate to severe hypoxic ischemic encephalopathy. Despite the methodological differences between trials, wide confidence intervals, and the lack of follow-up data beyond the second year of life, the consistency of the results is encouraging. Further research is necessary to minimize the uncertainty regarding efficacy and safety of any specific technique of cooling for any specific population.

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Available from: Sven M Schulzke, Sep 25, 2015
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    • "2011 (ICE) 478 638 552 650 1,320 (767) 1,440 (979) 963 1,214 Efficacy Efficacy Safety Efficacy Safety Efficacy Safety Efficacy Efficacy Safety Efficacy Efficacy Table 4. Efficacy Outcomes of Systemic Reviews or Meta-analyses of Cooling for Newborns with Hypoxic Ischemic Encep halopathy RR 95% CI P value NNT (95% CI ) Edwards AD, et al. 2006 Jacobs S, et al. 2007 Schulzke S, et al. 2007 Shah PS, et al. 2007 Edwards AD, et al. 2010 Shah PS. 2010 Jacobs S, et al. 2010 Tagin MA, et al. 2012 0.76 0.76 0.78 0.76 0.81 0.74 0.80 0.76 0.65-0.89 0.65-0.89 "
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    01/2013; 20(1):2. DOI:10.5385/nm.2013.20.1.2
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    • "Although brief transient PCr recovery overshoot has been described in skeletal and cardiac muscle in response to stress (Flaherty et al., 1982; Kida et al., 1991; Kobara et al., 1996; Flogel et al., 2004; Korzeniewski and Zoladz, 2005), this is the first description of a similar phenomenon in brain after transient HI. Therapeutic hypothermia is the first effective and safe therapy for neonatal encephalopathy (Azzopardi and Edwards, 2007; Jacobs et al., 2007; Schulzke et al., 2007). However, not all infants benefited from this therapy (Gluckman et al., 2005): screening for potential treatment responders at an early stage would be of great clinical advantage. "
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