Epinephrine Post Cardiac Arrest May Not Improve Survival to Hospital Discharge

Following out-of-hospital cardiac arrest, return of spontaneous circulation (ROSC) and survival to hospital admission are improved with standard-dose epinephrine treatment and may be improved even more with high-dose epinephrine treatment, according to findings of a systematic review and meta-analysis published in Chest.

There is mixed evidence supporting the efficacy of epinephrine for resuscitation after out-of-hospital cardiac arrest (OHCA), even though the drug is commonly used for this purpose. Investigators thus sought to determine the comparative efficacy and safety following treatments post out-of-hospital cardiac arrest (OHCA) of: (1) standard dose epinephrine (1 mg or 0.01-0.02 mg/kg); (2) high dose epinephrine (single dose ³5 mg or ³0.1mg/kg); (3) standard dose epinephrine plus vasopressin; and (4) placebo/no treatment. Primary endpoints included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome.

The researchers conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in EMBASE, Web of Science, Cochrane, Scopus, Medline, and PubMed databases, without language restriction, from inception to June 2022. The researchers identified 18 RCTs (n=21,594) assessing epinephrine use during OHCA resuscitation in patients at least 16 years of age with nontraumatic OHCA.

The investigators found ROSC was increased with epinephrine plus vasopressin (odds ratio [OR], 3.54; 95% CI, 2.94-4.26), standard dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and high dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97) compared with placebo/no treatment. Compared with standard dose epinephrine, epinephrine plus vasopressin probably has no effect on ROSC (OR, 0.96; 95% CI, 0.83-1.12, moderate certainty), and high dose epinephrine probably increases the incidence of ROSC (OR, 1.16; 95% CI, 1.04-1.29, moderate certainty).

Survival to hospital admission was increased with epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44), standard dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and high dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20) compared with placebo/no treatment. Compared with standard dose epinephrine, epinephrine plus vasopressin probably has no effect on survival to hospital admission (OR, 0.93; 95% CI, 0.79-1.10, moderate certainty), and high dose epinephrine probably increases survival to hospital admission (OR, 1.18; 95% CI, 1.04-1.34, moderate certainty).

Investigators found no important difference in survival to hospital discharge with standard dose epinephrine (OR, 1.14; 95% CI, 0.90-1.44, low certainty) compared with placebo/no treatment. They noted an uncertain effect of epinephrine plus vasopressin (OR, 1.06; 95% CI, 0.66-1.71) and high dose epinephrine (OR, 1.10; 95% CI, 0.76-1.60) compared with placebo/no treatment (very low certainty) in improving survival to hospital discharge.

Standard dose epinephrine improved survival to discharge among patients with non-shockable rhythm (OR, 2.10; 95% CI, 1.21-3.63) but not those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85) compared with placebo/no treatment.

Investigators found standard dose epinephrine compared with placebo/no treatment may have no effect on survival with good functional outcome, and the effect of high dose epinephrine on survival with good functional outcome compared with placebo/no treatment was uncertain. They noted high dose epinephrine compared with standard dose epinephrine may have no effect on survival with good functional outcome.

Researchers noted that 7 of the included trials had some risk of bias (varying between some concerns and high risk), and 11 trials had low risk.

Significant systematic review and meta-analysis limitations include the nature of review design, heterogeneity of enrolled patients, insufficient data for some meta-analyses and evaluation of longer-term functional status, lack of data on serious adverse events, unaccounted-for improvements in system care across decades of study results, selection bias, and the lack of protocols for vasopressin use in most trials.

“Use of standard dose epinephrine, high dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome,” investigators concluded. They added that “Standard dose epinephrine improved survival to discharge among patients with non-shockable rhythm, but not those with shockable rhythm.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.