• Lars W Andersen, Dan Isbye, Jesper Kjærgaard, Camilla M Kristensen, Søren Darling, Stine T Zwisler, Stine Fisker, Jens Christian Schmidt, Hans Kirkegaard, Anders M Grejs, Jørgen R G Rossau, Jacob M Larsen, Bodil S Rasmussen, Signe Riddersholm, Kasper Iversen, Martin Schultz, Jakob L Nielsen, Bo Løfgren, Kasper G Lauridsen, Christoffer Sølling, Kim Pælestik, Anders G Kjærgaard, Dorte Due-Rasmussen, Fredrik Folke, Mette G Charlot, JepsenRikke Malene H GRMHGDepartment of Anesthesiology, Zealand University Hospital, Køge, Denmark., Sebastian Wiberg, Michael Donnino, Tobias Kurth, Maria Høybye, Birthe Sindberg, Mathias J Holmberg, and Asger Granfeldt.
• Research Center for Emergency Medicine, Department of Clinical Medicine and Emergency Department, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
• JAMA. 2021 Oct 26; 326 (16): 1586-1594.

ImportancePrevious trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.ObjectiveTo determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.Design, Setting, And ParticipantsMulticenter, 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.InterventionPatients 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 MeasuresThe 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).ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT03640949.

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