CPR, Epinephrine … Vasopressin and Steroids?

Considering we’re still mighty skeptical regarding the ill effects of epinephrine on coronary and cerebral blood flow during resuscitation, I have to say I’m a little doubtful regarding the addition of a second vasopressor, along with steroids.

But, these authors, building on their prior work, attempt a randomized, placebo-controlled evaluation of epinephrine versus a combination of epinephrine, vasopressin, and methylprednisolone – along with a 7-day course of additional stress-dose steroids vs. placebo if post-ROSC hypotension was observed.  At hospital discharge, there were over twice as many neurologically intact survivors in the combination group as the epinephrine group – 18/130 vs. 7/138 – and thusly the authors conclude:

“Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status.”

Regrettably, with such a concisely worded conclusion, the authors devote barely two sentences to their limitations.  Indeed, for a study with so much to discuss, the authors compose a discussion section that occupies far less than even a full page.

There are a couple glaring problems with this study – not the least of which are the baseline differences between groups.  Despite randomization, the epinephrine group was saddled with quite different causes of cardiac arrest, almost certainly favoring the intervention group.  A randomization of additional patients with hypotension as their primary cause of arrest to the steroid group is almost certainly an allocation of a more favorable cohort, whereas “metabolic” causes of arrest are probably not corticosteroid deficient.  Similarly, the epinephrine group had far more asystole than the combination group – another poor prognostic feature.  Indeed, in their multivariate logistric regression (supplemental appendix), the cause of arrest and initial rhythm had statistically similar association with good outcome as intervention group membership.

The second issue is the problem of multiple interventions.  It is not clear whether the observed effect, if present, is secondary to the vasopressin-epinephrine-methylprednisolone cocktail during resuscitation or the stress-dose hydrocortisone given to nearly all survivors of the intervention group.  55% of the epinephrine group is alive 4 hours after ROSC vs. 66% of the intervention group, which, along with their physiologic data, implies the resuscitation intervention has some treatment effect.  Then, it’s unclear what favorable effect the stress-dose steroids has – particularly considering some of the epinephrine-only group then received open-label stress-dose hydrocortisone.  After resuscitation, different numbers of each group underwent PCI and similar numbers in each group received therapeutic hypothermia – but not all, leading to potential further confounding through selection bias.

Ultimately, it’s a mess – and it’s difficult to generalize these findings from a heterogenous and unbalanced cohort to routine practice.  The authors should be applauded for their ambitious goals, but a larger study, with a more effective randomization protocol, is yet needed.

“Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest”
www.ncbi.nlm.nih.gov/pubmed/23860985‎