52 in 52 – #22: The VAM: ICHA Trial

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Post #22 looks at vasopressin + methylprednisolone for in-hospital cardiac arrest.

Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Effect of Vasopressin and Methylprednisolone vs Placebo on Return
of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest:
A Randomized Clinical Trial

AKA: The VAM: ICHA Trial


Does use of vasopressin + methylprednisolone (VAM) result in improved ROSC in patients with in-hospital cardiac arrest (IHCA)

Design: Multi-center, block randomized, double-blind,  placebo-controlled trial




  • Enrolled patients in 10 hospitals in Denmark
  • Inclusion
    • Age > 10 years
    • Patients with in-hospital cardiac arrest (ER patients were included in this)
    • Must have been given 1 dose of epinephrine
  • Exclusion
    • A valid DNR
    • Was previously enrolled in this trial
    • Invasive circulatory support (ECMO, Impella, etc.)
    • Known/suspected pregnancy


  • 40 mg methylprednisolone + 20 IU vasopressin immediately following the first dose of epinephrine
  • Vasopressin repeated for up to 4 total doses


  • An equal volume of normal saline


  • Primary outcome ROSC
    • 42% in the intervention arm vs 33% in the control arm
    • RR 1.30 (95% CI 1.03-1.63)
    • Fragility index (FI) = 3
  • Secondary outcome: No difference in 30 or 90 day survival or favorable neurologic outcome
  • No significant difference in safety outcomes on hyperglycemia, hypernatremia, GI bleeding.


Take Aways:

  • This trial suggests that patients with IHCA who receive vasopressin and methylprednisolone have improved likelihood of ROSC.
  • However, the rate of survivors with a good neurologic outcome was no different between the groups. When looking at other trials (i.e., PARAMEDIC 2) epinephrine alone demonstrated increased ROSC with increased rates of poor neurologic outcome.
  • Two preceding trials suggest improved survival with good neurologic outcomes in those receiving vasopressin and methylprednisolone in the setting of IHCA.2,3
  • There were several notable limitations to this 2021 study.
    • A significant number of patients were excluded “for other reasons”. 193 patients were excluded because the “team forgot”. 170 patients were excluded due to “physician preference”.
  • This study only included patients in one country (Denmark). This limits external validity.
  • Higher rates of extracorporeal support were noted in the placebo group. This may suggest a failure of randomization as typically sicker patients receive this therapy.
  • Overall there were low rates of TTM (27% in intervention, 26% in control).
  • The study was powered for a ROSC rate of 45%, but they only obtained a ROSC rate of 33%. This can bias the data away from the null.
  • These are fragile data (FI = 3) displaying a benefit of VAM in IHCA. These data add to a contingent of studies suggesting a benefit of VAM in IHCA.

My Take:

These are relatively fragile data supporting the use of VAM in resuscitation in IHCA. At the individual level, I will keep this in my back pocket when it comes to “pulling out all the stops”. Based on current guidelines I will not use this as a routine. However, at the big table, we need to be having discussions about the inclusion of VAM in standard resuscitation of IHCA.


  1. Andersen LW, Isbye D, Kjærgaard J, et al. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.JAMA. 2021;326(16):1586-1594. doi:10.1001/jama.2021.16628
  2. Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial.JAMA. 2013;310(3):270-279. doi:10.1001/jama.2013.7832
  3. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest.Arch Intern Med. 2009;169(1):15-24. doi:10.1001/archinternmed.2008.509


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