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Predicting Neurologic Outcome After Targeted Temperature Management for Cardiac Arrest: Systematic Review and Meta-Analysis*

Golan, Eyal MD, PhDc1,2; Barrett, Kali MD1; Alali, Aziz S. MD2; Duggal, Abhijit MD3; Jichici, Draga MD4; Pinto, Ruxandra PhD5; Morrison, Laurie MD, MSc2,6,7,8; Scales, Damon C. MD, PhD1,2,9,10

doi: 10.1097/CCM.0000000000000335
Review Article

Objectives: Targeted temperature management improves survival and neurologic outcomes for adult out-of-hospital cardiac arrest survivors but may alter the accuracy of tests for predicting neurologic outcome after cardiac arrest.

Data Sources: We systematically searched Medline, Embase, CINAHL, and CENTRAL from database inception to September 2012.

Study Selection: Citations were screened for studies that examined diagnostic tests to predict poor neurologic outcome or death following targeted temperature management in adult cardiac arrest survivors.

Data Extraction: Data on study outcomes and quality were abstracted in duplicate. We constructed contingency tables for each diagnostic test and calculated sensitivity, specificity, and positive and negative likelihood ratios.

Data Synthesis: Of 2,737 citations, 20 studies (n = 1,845) met inclusion criteria. Meta-analysis showed that three tests accurately predicted poor neurologic outcome with low false-positive rates: bilateral absence of pupillary reflexes more than 24 hours after a return of spontaneous circulation (false-positive rate, 0.02; 95% CI, 0.01–0.06; summary positive likelihood ratio, 10.45; 95% CI, 3.37–32.43), bilateral absence of corneal reflexes more than 24 hours (false-positive rate, 0.04; 95% CI, 0.01–0.09; positive likelihood ratio, 6.8; 95% CI, 2.52–18.38), and bilateral absence of somatosensory-evoked potentials between days 1 and 7 (false-positive rate, 0.03; 95% CI, 0.01–0.07; positive likelihood ratio, 12.79; 95% CI, 5.35–30.62). False-positive rates were higher for a Glasgow Coma Scale motor score showing extensor posturing or worse (false-positive rate, 0.09; 95% CI, 0.06–0.13; positive likelihood ratio, 7.11; 95% CI, 5.01–10.08), unfavorable electroencephalogram patterns (false-positive rate, 0.07; 95% CI, 0.04–0.12; positive likelihood ratio, 8.85; 95% CI, 4.87–16.08), myoclonic status epilepticus (false-positive rate, 0.05; 95% CI, 0.02–0.11; positive likelihood ratio, 5.58; 95% CI, 2.56–12.16), and elevated neuron-specific enolase (false-positive rate, 0.12; 95% CI, 0.06–0.23; positive likelihood ratio, 4.14; 95% CI, 1.82–9.42). The specificity of available tests improved when these were performed beyond 72 hours. Data on neuroimaging, biomarkers, or combination testing were limited and inconclusive.

Conclusion: Simple bedside tests and somatosensory-evoked potentials predict poor neurologic outcome for survivors of cardiac arrest treated with targeted temperature management, and specificity improves when performed beyond 72 hours. Clinicians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling.

Supplemental Digital Content is available in the text.

1Interdepartmental Division of Critical Care and Department of Medicine, University of Toronto, Toronto, ON, Canada.

2Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

3Medical Intensive Care Unit, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH.

4Division of Critical Care and Neurology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

5Trauma, Emergency, and Critical Care Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

6Department of Emergency Medicine, St. Michael’s Hospital, Toronto, ON, Canada.

7Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada.

8Rescu, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, ON, Canada.

9Department of Critical Care Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

10Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

* See also p. 1959.

This study was performed at Interdepartmental Division of Critical Care and Department of Medicine, University of Toronto, Toronto, ON, Canada.

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. Morrison received grant support from the National Institutes of Health (NIH), Canadian Institutes of Health Research, American Heart Association, Ministry of Health and Long Term Care, Heart Stroke Foundation of Canada, Laerdal, and Defence Research and Development Canada and received support for article research from the NIH. Her institution received grant support from the NIH. She receives salary support from the U.S. NIH as the principal investigator for the Toronto Regional Coordinating Centre of the Resuscitation Outcomes Consortium, a prehospital clinical trial network in cardiac arrest and life-threatening trauma. Dr. Scales received grant support from the Physicians’ Services Incorporated Foundation (Fellowship in Translational Health Research) and is supported by a New Investigator Award from the Canadian Institutes for Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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