Clinical paperShorter time to target temperature is associated with poor neurologic outcome in post-arrest patients treated with targeted temperature management☆
Introduction
The implementation targeted temperature management (TTM) has resulted in improved neurologic outcomes and increased survival for patients suffering from post-cardiac arrest syndrome (PCAS).1, 2 The mechanism for such neurologic protection is thought to be multifactorial, including limitation of post-arrest endothelial dysfunction, decreased free radical production, and blunting of the post-reperfusion inflammatory cascade.3 However, significant variation in patient outcomes when treated with TTM raises fundamental questions with regard to enrollment of patients in TTM protocols, neuroprognostication, and accurate identification of those individuals who will return to their pre-arrest neurologic state versus those who will remain neurologically devastated.
In animal models, reducing time from successful resuscitation to arrival at target temperature has shown improved neurologic outcome,4 but evidence to corroborate these findings in human patients is mixed.5, 6, 7, 8 Early initiation of TTM has been the mainstay of post-arrest treatment to maximize neuroprotection.9 In clinical practice, wide variability in the time to initiate TTM exists.6, 7, 8, 10 Despite protocolized management, substantial variability exists in the time from initiation of TTM to arrival at target temperature (“induction time”) (Fig. 1). In contrast to animal studies, which are performed in a highly controlled fashion, clinical investigators have observed that precipitous achievement of target temperature may be associated with poor neurologic outcomes,8 perhaps illustrating the complex relationship between injury, early neurologic damage, and patient thermoregulatory control post-arrest. Given that target temperature is static, and cooling devices are programmed to rapidly cool patients to a pre-specified target temperature, variability in time to target temperature is theorized to be secondary to the heat generation produced by the post-arrest patient.
Significant variability in pre-induction and induction time has been observed in post arrest patients treated with TTM. The primary objectives of this study were to examine the relationship between the length of the pre-induction and induction phases of TTM and neurologic outcome. We hypothesized that: (1) Individuals with shorter pre-induction times will survive with better neurologic outcomes as measured by Cerebral Performance Category (CPC). (2) Individuals who suffer greater neurologic injury during their cardiac arrest may exhibit loss of thermoregulatory control and lack of heat generation, resulting in shorter induction times and poor neurologic outcome as measured by CPC.
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Study design and setting
The Penn Alliance for Therapeutic Hypothermia (PATH) Registry was created in 2010 as a national, on-line repository for patient data from multiple centers performing TTM. Data were utilized from two institutions that utilize the same TTM protocol and supply data to PATH: A large urban, level-1 trauma center, and an academic community affiliate. This study was approved by the University of Pennsylvania Institutional Review Board.
Study subjects and TTM protocols
Patients were considered for inclusion if they were: older than 18
Population, demographics, arrest characteristics
We identified 342 patients from the PATH database who received TTM after cardiac arrest from 5/2005 to 1/2013. Thirteen patients were then excluded as they had TTM initiated but did not arrive at target temperature secondary to re-arrest, withdrawal of care, or physician decision to discontinue therapy. Two patients were excluded as they arrested secondary to trauma and intracranial hemorrhage. Finally, six patients were excluded as they were transferred from outside hospitals, and had
Discussion
This study was a multi-center retrospective study investigating the association between pre-induction time, induction time, and neurologic outcome. We found no association between pre-induction time and neurologic outcome. We found that patients who have a prolonged induction time have a greater likelihood of good neurologic outcome, while more precipitous time to target temperature is associated with worse outcomes. In examining this association we determined that age, initial shockable rhythm
Limitations
There are recognized limitations to this study. Primarily, this was a retrospective analysis that was limited by data that could be extracted from chart review. Cardiac arrest literature is plagued by the difficulty of gathering accurate time data, and therefore, we recognize that chart documentation, especially pertaining to downtime, may not have yielded the most accurate time intervals. We do not report initial temperatures for all patients in this cohort. In review of the data, there was
Conclusion
We found that patients with shorter induction times suffered worse neurologic outcome versus those with more prolonged induction times. No difference in pre-induction time was found in this cohort of post-arrest patients. Further study is needed to determine if induction time may assist in improving upon neurologic prognostication or treatment algorithms in comatose survivors of cardiac arrest who undergo therapeutic hypothermia.
Funding sources
Dr. Perman was supported by an NIH T-32 training grant (5T32 NSO61779-05) for the duration of this research project.
Conflict of interest statement
On behalf of all authors, the corresponding author states that there is no conflict of interest.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.10.018.