Use of Epinephrine for Cardiac Arrest Prior to Hospital Arrival

Abstract

To the Editor: Dr Hagihara and colleagues analyzed the use of prehospital epinephrine in patients with out-of-hospital cardiac arrest. We have several concerns about the study. The cohort of patients receiving epinephrine comprised a fraction of the overall population (15 030 of 417 188; 4%) for reasons not addressed by the authors and that could represent selection bias. Given that epinephrine was part of the treatment algorithm, insight into reasons for this would allow for better interpretation of the data. The authors reported the algorithm for epinephrine administration: “ . . . after checking the initial rhythm and using defibrillation when appropriate, along with CPR [cardiopulmonary resuscitation], emergency lifesaving technicians perform tracheal intubation and/or insert an intravenous line with approval from an online emergency physician. Then, after verifying the absence of impulse in the carotid artery, the emergency lifesaving technicians administer epinephrine with the approval of the emergency physician.” This algorithm provides 2 potential causes of bias. First, those with early defibrillation and return of spontaneous circulation (ROSC) would never receive epinephrine but clearly have a survival advantage. Second, the time of administration of epinephrine dictated by this protocol may be too late to allow for adequate survival. For example, airway placement is prioritized above epinephrine with only 1 clinician able to perform both duties, and a telephone call for permission to provide epinephrine would lead to further delay. This concern is supported by an investigation in 1 of the prefectures in Japan, in which the average time to defibrillation was a mean (SD) of 9 (3) minutes, whereas the time to epinephrine was a mean (SD) of 21.3 (6.9) minutes despite the predominate rhythm being nonshockable. Thus, timing and selection bias driven by the protocol may have led to worse outcomes, as opposed to the intrinsic properties of the medication. Theauthorsacknowledgeduncontrolleddifferences inemergency department care as a weakness of the study and tried to account for this by evaluating a subgroup of patients who achieved ROSC in the field. They reported a marked difference in 1-month mortality between the epinephrine (18%) and no epinephrine (46.8%) groups to argue against emergency department epinephrine as a confounder. We are concerned that such a marked difference in 30-day mortality from only 1 mg of epinephrine may reflect an unrecognized intrinsic difference in the patient population rather than an adverse effect of this relatively low total dosage. In addition, the acknowledgment that induced hypothermia was not routinely performed might further explain the lack of 30-day benefit despite increased ROSC.