Is epinephrine safe to use when treating cardiac arrest? This is the question that researchers at the University of Warwick, UK, addressed in a study published in the New England Journal of Medicine. 
This randomised, double-blind trial included 8014 patients with out-of-hospital cardiac arrest. These patients were treated by paramedics who administered either parenteral epinephrine or placebo (saline solution). Patients also received standard care.
The primary outcome was survival at 30 days, but researchers were also interested in survival rates until hospital discharge with favourable neurological outcome (defined as less than grade 3 on the Rankin scale).
At 30 days, 3.2 per cent of patients in the epinephrine group, and 2.4 per cent in the placebo group had survived at 30 days. However, more patients at the time of hospital discharge had severe brain damage in the epinephrine group than in the placebo group (31.0 per cent vs. 17.8 per cent).
Therefore, although there was a slight benefit in terms of 30-day survival in the epinephrine group, this was negated by the higher proportion of those survivors who had severe brain damage (defined as modified Rankin scale grade 4 or 5). 
The reasons for this is unknown. Researchers suggest that epinephrine increases blood flow to the heart, but it also reduces cerebral microvascular blood flow. They also hypothesise that the brain is simply more susceptible to ischaemia and reperfusion injury.
Lead investigator, Professor Gavin D. Perkins, tells Cardiology News that: “Our own work with patients and the public before starting the trial identified survival without brain damage [as] more important […] than survival alone.” 
Therefore, clinicians must weigh the benefits of treating with epinephrine against the risks of neurological damage. As the researchers conclude: “Patients may be less willing to accept burdensome treatments if the chances of recovery are small, or the risk of survival with an impaired neurologic outcome is high.”