VSE in cardiac arrest and modern views on intra-arrest resuscitation

By Paul Trinquero

We came across a lecture from SMACCgold 2014 on the new intra-arrest management by the one and only Scott Weingart. That being said we decided to take a look at a fairly recent article on one new therapy discussed, vasopressin-steroids-epinephrine (VSE) for in-hospital cardiac arrest. Have a look at what's changing and what is on the horizon and review the the literature for yourself below. 

And now onto the study...

Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA: the Journal of the American Medical Association 2013 July 17, 310 (3): 270-9

 There were 209,000 episodes of in-hospital cardiac arrest in the United States last year (according to the AHA). The survival rate (survival to discharge) was 20.9% for adults and 40.2% for children. This study (conducted in 3 Greek tertiary care centers) looked specifically at hospital in-patients who suffered cardiac arrest and required pressors during resuscitation and tried to determine whether a regimen of vasopressin and corticosteroids in addition to CPR and epinephrine would improve short and long-term survival and /or neurological outcomes.

The study:

• Study Design: Multi-center RCT in 3 Greek tertiary care centers
• Population: 300 hospital in-patients suffering cardiac arrest and receiving resuscitation requiring vasopressors
  • Exclusion criteria: (1) Age younger than 18, (2) Terminal illness (life expectancy  <6wks) (3) DNR status (4) Arrest due to exsanguination (ruptured AAA) (5) Cardiac arrest before hospital admission (6) Treatment with IV corticosteroids before cardiac arrest (7) Previous enrollment in or exclusion from study

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• Intervention protocol: Vasopressin-Epinephrine-Corticosteroids + CPR versus Epinephrine + CPR alone 
  • For the first 5 cycles, arginine vasopressin (20IU/cycle) was added to epinephrine (1mg/cycle) in premixed vials and given to the VSE group (normal saline premixed with epi was given to control group). So depending on duration, patients in VSE group received 20-100IU of vasopressin
  • In addition, 40mg of methylprednisolone sodium succinate was administered solely during the first CPR cycle after enrollment (normal saline placebo was given to control group).
  • Finally, in survivors of the VSE group, starting at 4hrs post resuscitation, stress dose hydrocortisone (300mg/d for 7 days followed by taper) was given as continuous infusion (patients with evidence of acute MI received 3 days or less in order to prevent retardation of infarct healing). Control group received infusions of 100ml of normal saline when applicable.
• Primary outcome(s):
  • Alive at hospital discharge with CPC (Cerebral Performance Categories) score of 1 or 2
  • ROSC for 20 minutes or longer (adjusted to Utstein style)
• Secondary outcome(s):
  • (1) Arterial Pressure during and approximately 20 min after CPR (2) Arterial pressure and CVO2 sat during days 1 thru 10 (3) Number of organ failure-free days during days 1 thru 60 (4) Potentially corticosteroid associated complications such as hyperglycemia, infections, bleeding peptic ulcers, paresis
• Results: Combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in post-resuscitation shock, compared with epinephrine-saline placebo, resulted in a higher likelihood of ROSC for >20 min (83.9% in treatment group and 65.9% of control group) and improved survival to hospital discharge with favorable neurologic status (13.8% of treatment group, 5.1% of control group)

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• Interpretation: There have been recent critiques on the decades-old practice of using epinephrine as standard of care during cardiac arrest. Perhaps most notably, an RCT published in Resuscitation in 2011 screened over 4000 cardiac arrests and showed no improvement in survival to discharge in patients treated with epinephrine compared to those treated with a saline placebo. Epinephrine was shown to improve the likelihood of ROSC, but did not effect long-term survival. That being said, epinephrine remains widely utilized across the country and it stands to reason that if we are using epinephrine as standard of care, we should be open to the possibility of adding vasopressin and steroids in an effort to improve neurological outcomes. Secondary outcomes from the VSE trial, especially peri-arrest and 20min physiologic data, provide a potential physiological mechanism for the better outcomes seen in the VSE group. It has been hypothesized that epinephrine aids in ROSC primarily through improved back perfusion of the coronaries. This hypothesis is supported by the fact that epinephrine increased the odds of ROSC even in studies where it did not lead to improved long term outcomes(2). Meanwhile, vasopressin is thought to act to improve cerebral micro-perfusion and steroids are thought to be synergistic. This is evidenced by the higher BP’s and shorter duration of arrest in the VSE group, which could indicate decreased cerebral hypoxia and could account for the better long term neurological outcomes seen in this study. Obviously more work remains before definitive conclusions can be reached. The next step would be to study the VSE regimen against not only epinephrine controls but also against normal saline placebo controls.
• Comments:
  • Strengths: (1) Randomization and blinding was excellent, and post-hoc analysis shows no significant differences between the two groups (2) The follow up was excellent, the flow chart clearly depicts the outcomes of every patient initially selected for the study (3) Well powered study: Study population seems generalizable to other populations of in-patients at academic institutions (4) Results are striking: Outcomes are significantly better in treatment group.
  • Weaknesses: Essentially studied two partially unrelated variables (addition of vasopressin and methylprednisolone to epinephrine during CPR, as well as adding stress dose corticosteroids during post-resuscitation), which makes it harder to draw conclusions about either intervention alone.

Original Article

References:

1. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. Mentzelopoulos SD, Malachias S, Chamos C, et al. JAMA.2013;310(3):270-279. doi:10.1001/jama.2013.7832.
2. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Jacobs, Ian G. et al. Resuscitation , Volume 82 , Issue 9 , 1138 - 1143.