Published online February 29, 2008
PEDIATRICS Vol. 121 No. 3 March 2008, pp. 649-650 (doi:10.1542/peds.2007-3567)

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LETTER TO THE EDITOR

Hypothermia: An Evolving Treatment for Neonatal Hypoxic Ischemic Encephalopathy: In Reply

Haresh Kirpalani, BM, MSc
Neonatal Medicine
Children's Hospital of Philadelphia
Philadelphia, PA 19104

John Barks, MD
Pediatrics
C. S. Mott Children's Hospital
University of Michigan
Ann Arbor, MI 48109-0253

Kristian Thorlund, MSc
Trials Unit
Copenhagen University Hospital
Copenhagen, Denmark

Gordon Guyatt, MD, MSc
Clinical Epidemiology
McMaster University
Hamilton, Ontario, Canada L8N 3Z5

We thank Gunn et al for their thoughtful comments. They state that we are "concerned" about therapeutic hypothermia being offered on a "compassionate basis." On the contrary, we agree that clinicians who are persuaded of the robustness of the data can reasonably and cautiously offer the therapy to individual parents. Indeed, one of us (Dr Barks) participated in the Cool Cap continued access protocol, in which more infants were cooled on a compassionate-use basis (300) than in all 3 large randomized trials published thus far, and in which all safety data continued to be reported to the US Food and Drug Administration.

Gunn et al seem to agree with our stated position in the commentary that cooling should not be currently considered a standard of care. Nevertheless, despite the absence of new published randomized trials since official statements^1–4 cautioned against acceptance of cooling as "standard of care," there may have been a change of climate. This is suggested because an informal survey has suggested that procedure-specific consent is not being universally obtained from affected families (N. Cook MD, and J. Evans MD, Children's Hospital of Philadelphia, personal communication, 2007); and 1 trial Infant Cooling Evaluation was recently halted due to "lack of equipoise." Cautious clinicians in the larger neonatal community are still left to ask whether the evidence is sufficiently strong to conclude that cooling is a therapy they ought to provide as standard of care?

Addressing this question requires an appropriately conducted and interpreted systematic review and meta-analysis. When there is heterogeneity of results, inferences are weaker, pooled estimates less trustworthy, and appropriate random-effects confidence intervals wider. Results among the currently available trials have been consistent. However, if, as Gunn et al speculate, subsequent trials were to yield no effect, would result in large and potentially puzzling heterogeneity. Were this to occur, inferences regarding the effectiveness of cooling would be seriously in question, particularly if the later trials avoided the methodologic shortcomings of the earlier ones.

We offered our "optimal information size" calculations as a rational way to answer the question, "When can we be confident?" for cooling and its meta-analyses and as a method for answering similar questions for future novel therapies. We do not agree that this is an "arbitrary" approach.

REFERENCES

1. Blackmon LR, Stark AR; American Academy of Pediatrics, Committee on Fetus and Newborn. Hypothermia: a neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy. Pediatrics.2006; 117 (3):942 –948[Free Full Text]
2. Higgins RD, Raju TN, Perlman J, et al. Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. J Pediatr.2006; 148 (2):170 –175[CrossRef][Web of Science][Medline]
3. American Heart Association. 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: pediatric basic life support. Pediatrics.2006; 117 (5):989 –1004[Free Full Text]
4. International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: pediatric basic and advanced life support. Pediatrics.2006; 117 (5):955 –977[Abstract/Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kirpalani, H. Articles by Guyatt, G. Search for Related Content PubMed Articles by Kirpalani, H. Articles by Guyatt, G. Related Collections Premature & Newborn Social Bookmarking                         What's this?