• Journal: JAMA

• PMID: 34587236

• Type of study: Randomized, controlled trial

• Hypothesis: Vasopressin and methylprednisolone will improve ROSC for patient with in-hospital cardiac arrest when added to the standard ACLS algorithms as compared to placebo

• Methods

  • Multicenter, double-blinded, superiority trial

  • 10 hospitals in Denmark

  • Inclusion criteria

    • Adult age (>=18 years) patients with in-hospital cardiac arrest who received at least one dose of epinephrine during the arrest

  • Exclusion criteria

    • DNR order

    • Prior enrollment in the trial

    • Patients on ECMO or with existing LVAD

    • Known or suspected pregnancy

  • Treatment: 40mg methylprednisolone and 20U vasopressin

    • Administered during cardiac arrest ASAP after the first dose of epinephrine

    • Additional doses of vasopressin (max 4 doses) administered after each dose of epinephrine

  • Placebo: NaCl packaged in vials identical to treatment

  • Primary outcome

    • Return of spontaneous circulation (spontaneous circulation with no CPR requirement for at least 20 minutes)

  • Key secondary outcomes

    • #1: survival at 30 days

    • #2: survival at 30 days with a favorable neurologic outcome

• Results

  • Subjects in the vasopressin and methylprednisolone group had an increased rate of ROSC versus the placebo group (42% vs. 33%; risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). There was no significant difference in the number of subjects living after 30 days (9.7% in the intervention group versus 12% in the placebo group (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). There was no difference in favorable neurological outcome between the groups.

• Strengths

  • Multicenter

  • RCT

  • Placebo-controlled

  • Size

  • Generalizability

  • Practical outcome (ROSC)

  • Clear outcome (ROSC established vs. not)

  • Clinically significant

  • Well-blinded

  • No major loss to follow up

• Weaknesses

  • Variations in post-resuscitation management

  • Delays in drug administration

  • Generalizable to out-of-hospital cardiac arrest?

  • Large number of patients excluded

• Key Point: The use of vasopressin and methylprednisolone during in-hospital cardiac arrest increases the rate of return of spontaneous circulation as compared to placebo, but does not increase the rate of 30 day survival or favorable neurological outcome.

JAMA. 2021 Oct 26;326(16):1586-1594