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Sedation Confounds Outcome Prediction in Cardiac Arrest Survivors Treated with Hypothermia

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Therapeutic hypothermia is commonly used in comatose survivors’ post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment.


Post-CPR comatose survivors were prospectively enrolled. Six outcome predictors [pupillary and corneal reflexes, motor response to pain, and somatosensory-evoked potentials (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels <72 h] were systematically recorded. Poor outcome was defined as death or vegetative state at 3 months. Patients were considered “sedated” if they received any sedative drugs ≤12 h prior the 72 h neurological assessment.


Of 85 prospectively enrolled patients, 53 (62%) underwent hypothermia. Furthermore, 53 of the 85 patients (62%) had a poor outcome. Baseline characteristics did not differ between the hypothermia and normothermia groups. Sedative drugs at 72 h were used in 62 (73%) patients overall, and more frequently in hypothermia than in normothermia patients: 83 versus 60% (P = 0.02). Status myoclonus <72 h, absent cortical responses by SSEPs >72 h, and absent pupillary reflexes >72 h predicted poor outcome with a 100% specificity both in hypothermia and normothermia patients. In contrast, absent corneal reflexes >72 h, motor response extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome with 100% specificity only in non-sedated patients, irrespective of prior treatment with hypothermia.


Sedative medications are commonly used in proximity of the 72-h neurological examination in comatose CPR survivors and are an important prognostication confounder. Patients treated with hypothermia are more likely to receive sedation than those who are not treated with hypothermia.

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  1. Booth CM, et al. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291(7):870–9.

    Article  PubMed  CAS  Google Scholar 

  2. Zheng ZJ, et al. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001;104(18):2158–63.

    Article  PubMed  CAS  Google Scholar 

  3. Lloyd-Jones D, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46–e215.

    Google Scholar 

  4. Peberdy MA, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation. 2003;58(3):297–308.

    Article  PubMed  Google Scholar 

  5. Lim C, et al. The neurological and cognitive sequelae of cardiac arrest. Neurology. 2004;63(10):1774–8.

    PubMed  CAS  Google Scholar 

  6. Bates D, et al. A prospective study of nontraumatic coma: methods and results in 310 patients. Ann Neurol. 1977;2(3):211–20.

    Article  PubMed  CAS  Google Scholar 

  7. Bernard SA, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.

    Article  PubMed  Google Scholar 

  8. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.

    Google Scholar 

  9. American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005;112(24 Suppl):IV1–203.

    Google Scholar 

  10. Sunde K, et al. Determination of prognosis after cardiac arrest may be more difficult after introduction of therapeutic hypothermia. Resuscitation. 2006;69(1):29–32.

    Article  PubMed  Google Scholar 

  11. Wijdicks EF, et al. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67(2):203–10.

    Article  PubMed  CAS  Google Scholar 

  12. Wijman CA, et al. Prognostic value of brain diffusion-weighted imaging after cardiac arrest. Ann Neurol. 2009;65(4):394–402.

    Article  PubMed  Google Scholar 

  13. Lowry R. VassarStats: web site for statistical computation [cited 2009 November].

  14. Bouwes A, et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology. 2009;73(18):1457–61.

    Article  PubMed  CAS  Google Scholar 

  15. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet. 1997;32(3):210–58.

    Article  PubMed  CAS  Google Scholar 

  16. 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(9):2196–204.

    Article  PubMed  CAS  Google Scholar 

  17. Arpino PA, Greer DM. Practical pharmacologic aspects of therapeutic hypothermia after cardiac arrest. Pharmacotherapy. 2008;28(1):102–11.

    Article  PubMed  CAS  Google Scholar 

  18. Sessler DI. Complications and treatment of mild hypothermia. Anesthesiology. 2001;95(2):531–43.

    Article  PubMed  CAS  Google Scholar 

  19. Fukuoka N, et al. Biphasic concentration change during continuous midazolam administration in brain-injured patients undergoing therapeutic moderate hypothermia. Resuscitation. 2004;60(2):225–30.

    Article  PubMed  CAS  Google Scholar 

  20. Fritz HG, et al. The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs. Anesth Analg. 2005;100(4):996–1002.

    Article  PubMed  CAS  Google Scholar 

  21. Kress JP, Pohlman AS, Hall JB. Sedation and analgesia in the intensive care unit. Am J Respir Crit Care Med. 2002;166(8):1024–8.

    Article  PubMed  Google Scholar 

  22. Chamorro C, et al. Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: a systematic review. Anesth Analg. 2010;110(5):1328–35.

    Google Scholar 

  23. Zandbergen EG, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66(1):62–8.

    Article  PubMed  CAS  Google Scholar 

  24. Tiainen M, et al. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34(12):2881–6.

    Article  PubMed  CAS  Google Scholar 

  25. Oksanen T, et al. Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation. 2009;80(2):165–70.

    Article  PubMed  Google Scholar 

  26. Rundgren M, et al. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80(7):784–9.

    Article  PubMed  CAS  Google Scholar 

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The authors would like to thank Stephanie Kemp for administrative support for this study and Marion Buckwalter, Chitra Venkatasubramanian, Amie Hsia, Maarten Lansberg, Neil Schwartz, and Gregory Albers for their assistance with patient enrollment. Dr. Wijman has received funding from the following grants for this research: AHA Scientist Development Award, 043275N, and NIH RO1 HL089116-01A2.

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Correspondence to Christine A. C. Wijman.

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The statistical analyses were conducted by Drs. Michael Mlynash and Edgar A. Samaniego.

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Samaniego, E.A., Mlynash, M., Caulfield, A.F. et al. Sedation Confounds Outcome Prediction in Cardiac Arrest Survivors Treated with Hypothermia. Neurocrit Care 15, 113–119 (2011).

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