52 in 52 – #22: The VAM: ICHA Trial

Question:

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

PICO

Population:

• 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

Intervention:

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

Comparator:

• An equal volume of normal saline

Outcome:

• 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.