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Therapeutic Hypothermia and the Risk of Infection: A Systematic Review and Meta-Analysis*

Geurts, Marjolein MD1; Macleod, Malcolm R. FRCP, PhD2; Kollmar, Rainer MD, PhD3; Kremer, Philip H. C. MD1; van der Worp, H. Bart MD, PhD1

doi: 10.1097/CCM.0b013e3182a276e8
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Objective: Observational studies suggest that infections are a common complication of therapeutic hypothermia. We performed a systematic review and meta-analysis of randomized trials to examine the risk of infections in patients treated with hypothermia.

Data Sources: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible studies up to October 1, 2012.

Study Selection: We included randomized controlled clinical trials of therapeutic hypothermia induced in adults for any indication, which reported the prevalence of infection in each treatment group.

Data Extraction: For each study, we collected information about the baseline characteristics of patients, cooling strategy, and infections.

Data Synthesis: Twenty-three studies were identified, which included 2,820 patients, of whom 1,398 (49.6%) were randomized to hypothermia. Data from another 31 randomized trials, involving 4,004 patients, could not be included because the occurrence of infection was not reported with sufficient detail or not at all. The risk of bias in the included studies was high because information on the method of randomization and definitions of infections lacked in most cases, and assessment of infections was not blinded. In patients treated with hypothermia, the prevalence of all infections was not increased (rate ratio, 1.21 [95% CI, 0.95–1.54]), but there was an increased risk of pneumonia and sepsis (risk ratios, 1.44 [95% CI, 1.10–1.90]; 1.80 [95% CI, 1.04–3.10], respectively).

Conclusion: The available evidence, subject to its limitations, strongly suggests an association between therapeutic hypothermia and the risk of pneumonia and sepsis, whereas no increase in the overall risk of infection was observed. All future randomized trials of hypothermia should report on this important complication.

Supplemental Digital Content is available in the text.

1Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.

2Center for Clinical Brain Sciences, Department of Clinical Neurosciences, University of Edinburgh, Scotland, UK.

3Klinik für Neurologie und Neurogeriatrie, Klinikum Darmstadt, Darmstadt, Germany.

* See also p. 445.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Dr. Geurts is supported by grant (2010B239) from the Dutch Heart Foundation. Dr. Macleod received grant support from FP7 for EuroHYP-1 and is employed by the University of Edinburgh. Dr. Kollmar consulted for Zoll and received support for travel from Zoll, Bard, and Elvido. Dr. van der Worp received grant support from the Dutch Heart Foundation (2010T075 and 2010B239) and 7th Framework Programme European Union. Drs. Geurts and van der Worp are the coordinator and principal investigator, respectively, of the ongoing randomized phase II cooling trial COOLIST (NTR 2616), and Drs. Macleod, Kollmar, and van der Worp are coprincipal investigators of the randomized phase III cooling trial EuroHYP-1. Dr. Kremer has disclosed that he does not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins