Aug 162013
Adding Vasopressin, Steroids to Epinephrine Improved Cardiac Arrest Outcomes

Contrary to what watching TV or even reading the newspaper will lead one to believe, outcomes after in-hospital cardiac arrest are very poor. Only about 1 in 5 survive to leave the hospital after cardiac arrest, and most survivors suffer significant cognitive impairment; up to half suffer severe brain damage or are in a vegetative state. Outcomes after pulseless electrical activity / asystole cardiac arrests are significantly worse than after "shockable" ventricular tachycardia / fibrillation arrests, which are more often due to treatable coronary artery disease.

Although the rate of survival after in hospital cardiac arrest seems to have improved over recent years, the proportion of people leaving the hospital with good neurologic function has not. The gap between caregivers' and families' intuitive understanding of these odds complicates the intensely emotionally charged interaction and imposes costs on all participants in these real-life medical dramas. Both better understanding, and better treatments are needed for cardiac arrest, but research in this area is difficult and progress slow.

There have been few bright spots in improving these sad statistics, but one randomized trial (n=100) showed that adding vasopressin and methylprednisolone to the usual epinephrine given according to ACLS CPR protocol after in-hospital cardiac arrest quintupled survival to hospital discharge (19% vs 4%).

The rationale: a vasopressin-epinephrine combination previously improved outcomes in animal studies of cardiac arrest, and in people, cortisol levels are low during and after cardiac arrest.

That study was not powered adequately to answer questions about neurologic outcome, and was only done at a single center. So Spyros Mentzelopoulos et al tested the effect of adding vasopressin and steroids to epinephrine in a larger number of patients at multiple centers. Their results are in the July 17, 2013 JAMA.

What They Did

Authors randomized 268 consecutive patients suffering in-hospital cardiac arrest at 3 Greek tertiary care centers to receive the usual epinephrine, plus either placebo or vasopressin (20 IU per CPR cycle) for the first 5 CPR cycles (epinephrine alone could continue after that). Patients in the intervention arm also got methylprednisolone (Solu-Medrol), 40 mg once during the first CPR cycle, and if shock persisted after return of spontaneous circulation, 300 mg daily of hydrocortisone for up to 7 days.

The main outcomes measured were return of spontaneous circulation for at least 20 minutes, and survival to hospital discharge with a good neurologic outcome (a cerebral performance category score of 1 or 2, meaning able to function independently in daily life).

Patients who were randomized but had return of circulation before receiving any study drug were excluded from the analysis. This is a modification of intention to treat that could raise eyebrows. However, a roughly equal percentage of randomized patients in each group were excluded in this way.

What They Found

Patients receiving the vasopressin-corticosteroid-epinephrine combination fared better than those receiving epinephrine and placebo:

  • 109 (84%) vs 91 (66%) had return of spontaneous circulation for 20 minutes or longer.
  • 18 (14%) survived to hospital discharge with good cerebral performance, compared to 7 (5%) receiving epinephrine only.
  • Among those who re-experienced shock after resuscitation, those initially treated with vasopressin-steroids-epinephrine survived to discharge with good neurological function 21% of the time (16 patients), compared to 8% (6 patients).

There were similar rates of adverse events in both groups.

What It Means

This study suggests that adding vasopressin and corticosteroids to epinephrine during resuscitation from cardiac arrest, and continuing steroids if shock is present, may markedly improve outcomes -- from abysmal to just very poor.

Epinephrine's utility as a standalone agent for cardiac arrest has been questioned by results of previous studies. In the largest randomized trial to date (n=534), epinephrine did not improve CPR outcomes after out-of-hospital cardiac arrest, and an observational study in JAMA last year also suggested epinephrine is not helpful after out-of-hospital cardiac arrest. Animal data suggest that epinephrine reduces cerebral blood flow during cardiac arrest in animals as compared to either vasopressin, placebo, or epinephrine + placebo.

The American Heart Association, which publishes the standard-of-care-defining Advanced Cardiac Life Support algorithms and treatment protocols, did not comment on this article publicly (that I saw). ACLS protocols currently endorse the use of vasopressin 40 units IV as an alternative to the first or second dose of epinephrine during resuscitation from cardiac arrest with pulseless electrical activity (PEA) or asystole.

Spyros Mentzelopoulos et al. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac ArrestA Randomized Clinical Trial. JAMA 2013;310(3):270-279.

Saket Girotra, et al. Trends in Survival after In-Hospital Cardiac Arrest. N Engl J Med 2012; 367:1912-1920.

Jianmin Tian et al. Outcomes of Critically Ill Patients Who Received Cardiopulmonary Resuscitation, AJRCCM 182;4:501-506.

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Vasopressin, steroids, epinephrine cocktail improved cardiac arrest outcomes