Journal of Medical Toxicology

, Volume 15, Issue 1, pp 22–29 | Cite as

Impact of Targeted Temperature Management on ED Patients with Drug Overdose–Related Cardiac Arrest

  • Sharaf KhanEmail author
  • Chad M. Meyers
  • Suzanne Bentley
  • Alex F. Manini
Original Article



Drug overdose is the leading cause of non-traumatic out-of-hospital cardiac arrest (OHCA) among young adults. This study investigates whether targeted temperature management (TTM) improves hospital survival from presumed overdose-related cardiac arrest.


Retrospective chart review of consecutive cardiac arrests presenting to an urban tertiary care hospital ED from 2011 to 2015. ED patients with cardiac arrest were included if < 50 years old, and excluded if there was a non-overdose etiology (e.g., trauma, ST-elevation myocardial infarction, subarachnoid hemorrhage). The main intervention was TTM, carried out with a combination of the Arctic Sun device and refrigerated crystalloid/antipyretics (goal temperature 33–36 °C). The primary outcome was survival to hospital discharge; neurologically intact survival was the secondary outcome.


Of 923 patients with cardiac arrest, 802 (86.9%) met exclusion criteria, leaving 121 patients for final analysis. There were 29 patients in the TTM group (24.0%) vs 92 patients in the non-TTM group (76.0%). Eleven patients (9.1%) survived to hospital discharge. TTM was associated with increased odds of survival to hospital discharge (OR 11.3, 95% CI 2.8–46.3, p < 0.001), which increased substantially when palliative outcomes were excluded from the cohort (OR 117.3, 95% CI 17.0–808.4, p < 0.001). Despite achieving statistical significance (OR 1.1, 95% CI 1.0–1.3), TTM had no clinically significant effect on neurologically intact survival.


TTM was associated with improved survival in ED patients with presumed drug overdose–related cardiac arrest. The impact of TTM on neurologically intact survival among these patients requires further study.


Toxicology Cardiac arrest Targeted temperature management 



We thank Yanoh Jalloh, M.P.H., for her contributions to the institutional approvals process.

Author Contributions

AFM, CMM, and SB conceived the research questions and study design. AFM supervised the conduct of the study and the data collection. SK reviewed charts and performed data abstraction. AFM provided statistical advice on study design and performed statistical analyses on the data. SK drafted the manuscript, and all authors contributed significantly to its revision. AFM takes responsibility for the paper as a whole.


This study received no explicit funding. Dr. Manini receives salary support from grant DA037317 from the NIH. The other authors do not receive any specific grant funding. The manufacturers of the Arctic Sun device had no role in, or knowledge of, the study protocol.

Compliance with Ethical Standards

Conflict of Interest



  1. 1.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135:e146–603.CrossRefGoogle Scholar
  2. 2.
    Katz AZ, Grossestreuer AV, Gaieski DF, Abella BS, Kumar V, Perrone J. Outcomes of patients resuscitated from cardiac arrest in the setting of drug overdose. Resuscitation. 2015;94:23–7.CrossRefGoogle Scholar
  3. 3.
    Koller AC, Salcido DD, Callaway CW, Menegazzi JJ. Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest. Resuscitation. 2014;85:1375–9.CrossRefGoogle Scholar
  4. 4.
    Modisett KL, Walsh SJ, Heffner AC, Pearson DA, Kerns W 2nd. Outcomes in cardiac arrest patients due to toxic exposure treated with therapeutic hypothermia. J Med Toxicol. 2016;12:263–9.CrossRefGoogle Scholar
  5. 5.
    Kim HJ, Kim GW, Oh SH, Park SH, Choi JH, Kim KH, et al. Therapeutic hypothermia after cardiac arrest caused by self-inflicted intoxication: a multicenter retrospective cohort study. Am J Emerg Med. 2014;32:1378–81.CrossRefGoogle Scholar
  6. 6.
    Hedegaard H, Warner M, Minino AM. Drug overdose deaths in the United States, 1999-2015. NCHS Data Brief. 2017:1–8.Google Scholar
  7. 7.
    Deasy C, Bray JE, Smith K, Harriss LR, Bernard SA, Cameron P. Out-of-hospital cardiac arrests in young adults in Melbourne, Australia. Resuscitation. 2011;82:830–4.CrossRefGoogle Scholar
  8. 8.
    Centers for Disease Control and Prevention Opioid overdose - understanding the epidemic. Opioid overdose centers for disease control and Prevention; December 16, 2016.
  9. 9.
    Centers for Disease Control and Prevention Opioid overdose - prescription opioid overdose data. centers for disease control and Prevention; December 16, 2016.
  10. 10.
    Centers for Disease Control and Prevention. HIV and AIDS--United States, 1981-2000. MMWR Morb Mortal Wkly Rep. 2001;50:430–4.Google Scholar
  11. 11.
    Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445–52.CrossRefGoogle Scholar
  12. 12.
    Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.CrossRefGoogle Scholar
  13. 13.
    Vargas M, Servillo G, Sutherasan Y, Rodriguez-Gonzalez R, Brunetti I, Pelosi P. Effects of in-hospital low targeted temperature after out of hospital cardiac arrest: a systematic review with meta-analysis of randomized clinical trials. Resuscitation. 2015;91:8–18.CrossRefGoogle Scholar
  14. 14.
    Anderson KB, Poloyac SM, Kochanek PM, Empey PE. Effect of hypothermia and targeted temperature management on drug disposition and response following cardiac arrest: a comprehensive review of preclinical and clinical investigations. Ther Hypothermia Temp Manag. 2016;6:169–79.CrossRefGoogle Scholar
  15. 15.
    Kontio T, Salo A, Kantola T, Toivonen L, Skrifvars MB. Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication. Ther Hypothermia Temp Manag. 2015;5:104–9.CrossRefGoogle Scholar
  16. 16.
    Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest (supplementary appendix). N Engl J Med. 2013;369:2197–206.CrossRefGoogle Scholar
  17. 17.
    Deasy C, Bray JE, Smith K, Harriss LR, Bernard SA, Cameron P, et al. Out-of-hospital cardiac arrests in the older age groups in Melbourne, Australia. Resuscitation. 2011;82:398–403.CrossRefGoogle Scholar
  18. 18.
    Manini AF, Nelson LS, Stimmel B, Vlahov D, Hoffman RS. Incidence of adverse cardiovascular events in adults following drug overdose. Acad Emerg Med. 2012;19:843–9.CrossRefGoogle Scholar
  19. 19.
    Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369:2197–206.CrossRefGoogle Scholar
  20. 20.
    Kim F, Olsufka M, Longstreth WT Jr, Maynard C, Carlbom D, Deem S, et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation. 2007;115:3064–70.CrossRefGoogle Scholar
  21. 21.
    Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pene F, et al. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011;123:877–86.CrossRefGoogle Scholar
  22. 22.
    Arrich J. European resuscitation council hypothermia after cardiac arrest registry study G. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007;35:1041–7.CrossRefGoogle Scholar
  23. 23.
    Herlitz J, Svensson L, Engdahl J, Gelberg J, Silfverstolpe J, Wisten A, et al. Characteristics of cardiac arrest and resuscitation by age group: an analysis from the Swedish cardiac arrest registry. Am J Emerg Med. 2007;25:1025–31.CrossRefGoogle Scholar
  24. 24.
    Paredes VL, Rea TD, Eisenberg MS, Cobb LA, Copass MK, Cagle A, et al. Out-of-hospital care of critical drug overdoses involving cardiac arrest. Acad Emerg Med. 2004;11:71–4.CrossRefGoogle Scholar
  25. 25.
    Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med. 2007;35:2196–204.CrossRefGoogle Scholar
  26. 26.
    Bjelland TW, Klepstad P, Haugen BO, Nilsen T, Dale O. Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and propofol in intensive care unit patients. Drug Metab Dispos. 2013;41:214–23.CrossRefGoogle Scholar
  27. 27.
    Manini AF, Nelson LS, Olsen D, Vlahov D, Hoffman RS. Medical examiner and medical toxicologist agreement on cause of death. Forensic Sci Int. 2011;206:71–6.CrossRefGoogle Scholar
  28. 28.
    New York City Department of City Planning. Population 2010 Census. Accessed on September 30, 2017 at

Copyright information

© American College of Medical Toxicology 2018

Authors and Affiliations

  1. 1.Department of Emergency MedicineThe Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Department of Emergency MedicineThe Icahn School of Medicine at Mount Sinai, Elmhurst Hospital CenterNew YorkUSA
  3. 3.Division of Medical ToxicologyThe Icahn School of Medicine at Mount Sinai, Elmhurst Hospital CenterNew YorkUSA

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