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Cumulative Epinephrine Dose during Cardiopulmonary Resuscitation and Neurologic Outcome

Wilhelm Behringer, MD; Harald Kittler, MD; Fritz Sterz, MD; Hans Domanovits, MD; Waltraud Schoerkhuber, MD; Michael Holzer, MD; Marcus Mullner, MD; and Anton N. Laggner, MD
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From University of Vienna Medical School, Vienna, Austria Grant Support: Dr. Behringer is supported by the Ministry of Science, Transport and the Arts (BMWVK), Austria (GZ 5.550/12 −Pr/4/95). Dr. Schoerkhuber is supported by the Fonds zur Foerderung der wissenschaftlichen Forschung (Austrian Science Foundation; P11405-MED). Dr. Holzer is supported by BIOMED2 European Commission, DG XII for Science Research and Development, Directorate Life Science and Technologies, Biomedical and Health Research Division (BMH4-CT96-0667). Requests for Reprints: Fritz Sterz, MD, Vienna General Hospital, University Clinics, Department of Emergency Medicine, Waehringerguertel 18-20/6/D, 1090 Vienna, Austria. Current Author Addresses: Drs. Behringer, Kittler, Sterz, Domanovits, Schoerkhuber, Holzer, Mullner, and Laggner: Vienna General Hospital, Waehringerguertel 18-20, 1090 Vienna, Austria.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;129(6):450-456. doi:10.7326/0003-4819-129-6-199809150-00004
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Background: Epinephrine is the drug of choice in advanced cardiac life support, but it can have deleterious side effects after restoration of spontaneous circulation.

Objective: To investigate the association between the cumulative epinephrine dose used in advanced cardiac life support and neurologic outcome after cardiac arrest.

Design: Retrospective cohort study.

Setting: University hospital.

Patients: Adults admitted to the emergency department with witnessed, nontraumatic, normothermic ventricular fibrillation cardiac arrest and unsuccessful initial defibrillation.

Measurements: Functional neurologic outcome was regularly assessed by cerebral performance category (CPC) within 6 months after cardiac arrest. A CPC of 1 or 2 was defined as favorable recovery.

Results: Among 178 enrolled patients, the median cumulative epinephrine dose administered was 4 mg (range, 0 to 50 mg). In 151 patients (84%), spontaneous circulation was restored; 63 of these 151 patients (42%) had favorable neurologic recovery. Patients with an unfavorable CPC received a significantly higher cumulative dose of epinephrine than did patients with a favorable CPC (4 mg compared with 1 mg; P < 0.001). This finding persisted after stratification by duration of resuscitation. After possible cofounders were controlled for, the cumulative epinephrine dose remained an independent predictor of unfavorable neurologic outcome.

Conclusions: The results indicate that an increasing cumulative dose of epinephrine administered during resuscitation is independently associated with unfavorable neurologic outcome after ventricular fibrillation cardiac arrest.


Grahic Jump Location
Figure 1.
Patients who achieved restoration of spontaneous circulation (striped bars) after administration of epinephrine.

White bars represent patients who did not achieve restoration of spontaneous circulation. CPR = cardiopulmonary resuscitation.

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Grahic Jump Location
Figure 2.
Patients who achieved good neurologic outcome after administration of epinephrine (striped bars).

White bars represent patients who did not achieve good neurologic outcome. CPR = cardiopulmonary resuscitation.

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Grahic Jump Location
Figure 3.
Frequencies of favorable and unfavorable neurologic recovery after simultaneous stratification by no-flow duration, low-flow duration, and cumulative epinephrine dose.
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