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Andersen LW, Isbye D, Kjaergaard 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 Sep 29. pii: 2784625. doi: 10.1001/jama.2021.16628. (Original study)

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.

Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.

Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021.

Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.

Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2).

Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively.

Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Related DynaMed Topics

Discipline Area Score
Emergency Medicine 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Cardiology Coming Soon...
Comments from MORE raters

Cardiology rater

This trial corroborates findings from previous research to suggest that after cardiac arrest, vasopressin and glucocorticoid administration may lead to some improvement in outcomes. In this case, return of spontaneous circulation. Further research is needed to know whether: a) these findings are consistent across all related trials; and b) the benefits described translate into improved clinical outcomes.

Emergency Medicine rater

A well done RCT that highlights a benefit for a non-patient-centered outcome (ROSC) but no benefits in patient-centered outcomes: No survival or favorable neurological outcomes in 30 and 90 days.

Emergency Medicine rater

Nice study with deja vu outcomes - more ROSC but no clear impact on survival. So, the key question now is: What would an SR show that combines all the relevant trials?

Emergency Medicine rater

The RR for the primary outcome has a CI that is very close to 1.0 and there was no difference in the patient-important secondary outcomes.

Emergency Medicine rater

Before it becomes standard of care, further studies on long-term clinically important outcomes are needed.

Internal Medicine rater

Vasopressin plus methylprednisolone given to patients having in-hospital cardiac arrests resulted in greater recovery of spontaneous circulation but had no benefit for 30-day survival or favorable neurologic outcome when added to standard care.

Internal Medicine rater

Interesting results, and given the signal for increased sponteanous return of circulation, I think this will influence my practice.
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