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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Circulation. Author manuscript; available in PMC 2017 April 26.
Published in final edited form as:
PMCID: PMC5035132

Response to Letter to the Editor by Dr. Paul Chan Regarding “The Utility of Therapeutic Hypothermia for Post-Cardiac Arrest Syndrome Patients With an Initial Non-Shockable Rhythm” by Perman et al on November 16, 2015

To the Editors of Circulation

Thank you for the opportunity to respond to Dr. Paul Chan’s insightful comments regarding our manuscript “The Utility of Therapeutic Hypothermia for Post-Cardiac Arrest Syndrome Patients With an Initial Non-Shockable Rhythm.”1 In this manuscript, we utilized propensity score matching in a quasi-experimental design to mimic a randomized controlled trial (RCT). Propensity score analyses have been both promoted and criticized in the literature, with a known limitation being the impact of unmeasured variables; however, there have been no published randomized trials of targeted temperature management versus no temperature management for patients with initial non-shockable rhythms due to various barriers. Our analysis, which included 519 patients with an initial non-shockable rhythm from the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000–2013, was an achievable, alternative approach, offering some insights on this important question.

Dr. Chan raises concern that the variables included in our derivation of a propensity score did not reflect patients’ severity of illness and did not account for date (year) of the arrest and hospital location, as cardiac arrest outcomes have improved over time and variability in hospital performance has been observed.2,3 He also suggested that a much larger cohort would have been helpful. In deriving our propensity score we applied the findings of Lindner et al., who determined that age, sex, initial rhythm, witnessed arrest, duration of arrest and location of arrest all contribute to an individual’s propensity to receive therapeutic hypothermia.4 Additionally, in order to perform this quasi-experimental analysis, our untreated cohort included a larger number of patients from the early years of data collection, when hypothermia was under utilized, and patients who were potential candidates for therapy did not receive it. In order to address Dr. Chan’s concerns, we re-calculated our propensity score to include both year of arrest and treating hospital. We determined the odd’s ratios (OR) for good neurologic outcome and for survival to hospital discharge to be 2.36 (95% CI: 1.31–4.27) and 2.23 (95% CI: 1.35–3.71), respectively. In order to further explore the timing phenomenon, we applied the previously described propensity score derivation to the subset of patients who were treated after 2007 and found similar results for good neurologic outcome and survival to hospital discharge (OR 2.66 (95% CI: 1.44–4.91) and 2.40 (95% CI: 1.41–4.06), respectively). Incorporating the two variables suggested by Dr. Chan into a more robust propensity score confirms our published findings and strengthens the results.

In response to Dr. Chan’s comment calling for a repeat study in a larger cohort utilizing a more robust propensity score, we agree and hope that the recommendations from the recent IOM report calling for a national registry on cardiac arrest might allow for such an analysis. In addition, Lascarrou and colleagues recently published the study protocol for HYPERION, a multicenter trial in which 543 patients successfully resuscitated from non-shockable cardiac arrest will be randomized to therapeutic hypothermia versus therapeutic normothermia.5 We eagerly await the results of this ambitious multicenter trial.


1. Perman SM, Grossestreuer AV, Wiebe DJ, Carr BG, Abella BS, Gaieski DF. The Utility of Therapeutic Hypothermia for Post-Cardiac Arrest Syndrome Patients With an Initial Nonshockable Rhythm. Circulation. 2015;132:2146–2151. [PMC free article] [PubMed]
2. Girotra S, Nallamothu BK, Spertus JA, Li Y, Krumholz HM, Chan PS, American Heart Association Get with the Guidelines–Resuscitation Investigators Trends in survival after in-hospital cardiac arrest. N Engl J Med. 2012;367:1912–1920. [PMC free article] [PubMed]
3. Girotra S, Cram P, Spertus JA, Nallamothu BK, Li Y, Jones PG, Chan PS, American Heart Association’s Get With the Guidelines®-Resuscitation Investigators Hospital variation in survival trends for in-hospital cardiac arrest. J Am Heart Assoc. 2014;3:e000871. [PMC free article] [PubMed]
4. Lindner T, Langørgen J, Sunde K, Larsen AI, Kvaløy JT, Heltne JK, Draegni T, Søreide E. Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU. Crit Care Lond Engl. 2013;17:R147. [PMC free article] [PubMed]
5. Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Delahaye A, Hssain AA, Chakarian JC, Pichon N, Desachy A, Bellec F, Thevenin D, Quenot JP, Sirodot M, Labadie F, Plantefeve G, Vivier D, Girardie P, Giraudeau B, Reignier J, Clinical Research in Intensive Care and Sepsis (CRICS) Group and HYPERION Study Group Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial. Scand J Trauma Resusc Emerg Med. 2015;23:26. [PMC free article] [PubMed]