VAM-IHCA Trial

Background:

• Glucocorticoids have the potential to improve outcome in patients with cardiac arrest as they upregulate expression of α receptors on vascular endothelium, thus potentiating the effects of adrenergic agents. Additionally, steroids support adrenal insufficiency and modulate the systemic inflammatory response syndrome that results after ischemia reperfusion.

What was the research question?

• Does the administration of methylprednisolone in addition to vasopressin improve the return of spontaneous circulation in patients with in-hospital cardiac arrest?

How did they do it?

• Multicenter, randomized, double-blind, placebo-controlled trial in ten hospitals in Denmark.

• A total of 512 adult patients with in-hospital cardiac arrest were randomized to receive a combination of vasopressin (20 IU) and methylprednisolone (40 mg) after the first dose of epinephrine (n = 245) or placebo (n = 267). Additional doses of vasopressin were given after each epinephrine for total of 4 doses.

• Primary outcome was return of spontaneous circulation and Secondary outcomes included survival and favorable neurologic outcome at 30 days.

What did they find?

• Return of spontaneous circulation was achieved in 42% of the intervention group compared to 33% in the placebo group (RR, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03).

• 30-day survival rate was 9.7% in the intervention group compared to 12% in the placebo group (P = .48).

• No difference in the favorable neurologic outcome between the two groups (7.6% vs 7,6%, p>0.99).

Any limitation?

• High percentage of patients who were potentially eligible were not included which might affect the generalizability of the study.

• The was a delay in administering the study drug which may affect the study results.

• 30 days may not be long enough to assess long term effect of the intervention.

• Contamination rate is high as 46% of patients who survived in the placebo group receive steroids.

• Not powered for the secondary outcome.

• Not powered to detect difference in effect of study medication in types of cardiac arrest (asystole, PEA, or V-fib/v-tach)

• The average dose of vasopressin was lower than what was used in earlier positive studies.

What does it mean?

• The study shows that the combination of vasopressin and methylprednisolone significantly improves the return of spontaneous circulation in patients with in-hospital cardiac arrest. The study is unable to determine long-term benefits.

• It is unlikely that this study is going to change the recommendations of the ACLS in cardiac arrest.