Patrick J. Coppler, David J. Gagnon, Katharyn L. Flickinger, Jonathan Elmer, Clifton W. Callaway, Francis X. Guyette, Ankur Doshi, Alexis Steinberg, Cameron Dezfulian, Ari L. Moskowitz, Michael Donnino, Teresa L May, David B Seder, Jon C. Rittenberger
Clin Exp Emerg Med 2024;11(2):205-212. Published online January 29, 2024
Objective We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group.
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Targeted temperature management with mild hypothermia (TTM-hypothermia; 32–34 °C) is a treatment strategy for adult patients who are comatose after cardiac arrest. Robust preclinical data support the beneficial effects of hypothermia beginning within 4 hours of reperfusion and maintained during the several days of postreperfusion brain dysregulation. TTM-hypothermia increased survival and functional recovery after adult cardiac arrest in several trials and in realworld implementation studies. TTM-hypothermia also benefits neonates with hypoxic-ischemic brain injury. However, larger and methodologically more rigorous adult trials do not detect benefit. Reasons for inconsistency of adult trials include the difficulty delivering differential treatment between randomized groups within 4 hours and the use of shorter durations of treatment. Furthermore, adult trials enrolled populations that vary in illness severity and brain injury, with individual trials enriched for higher or lower illness severity. There are interactions between illness severity and treatment effect. Current data indicate that TTM-hypothermia implemented quickly for adult patients after cardiac arrest, may benefit select patients at risk of severe brain injury but not benefit other patients. More data are needed on how to identify treatment-responsive patients and on how to titrate the timing and duration of TTM-hypothermia.
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Patrick J. Coppler, Benjamin S. Abella, Clifton W. Callaway, Minjung Kathy Chae, Seung Pill Choi, Jonathan Elmer, Won Young Kim, Young-Min Kim, Michael Kurz, Joo Suk Oh, Joshua C. Reynolds, Jon C. Rittenberger, Kelly N. Sawyer, Chun Song Youn, Byung Kook Lee, David F. Gaieski, on behalf of the Korean Hypothermia Network Investigators and the National Post-Arrest Research Consortium
Clin Exp Emerg Med 2018;5(2):100-106. Published online April 30, 2018
Objective A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea.
Methods In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey results using descriptive statistics.
Results Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for >75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers.
Conclusion A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies.
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