Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest

Abstract

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 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). 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.

Efficacy of combination triple therapy with vasopressin, steroid, and epinephrine in cardiac arrest: a systematic review and meta-analysis of randomized-controlled trials

“…3 a, combination therapy with VSE could not significantly increase the survival ratio (OR: 2.082, 95% CI: 0.638–6.796, P value = 0.225), while the heterogeneity was reported to be high (Cochrane Q test: I 2 = 78.52%, P value = 0.010). Sensitivity analysis showed that Andersen et al study [ 26 ] had an impact on the rate of hospital mortality; however, they did not affect the significance of the results (OR: 2.082, 95% CI: 0.638–6.796, P value = 0.225).

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“…After assessment of full texts of the studies, 17 papers were also excluded from further evaluation, because of irrelevant population and the type of studies. A total of three RCTs were eligible for including in the current systematic review and meta-analysis, carried out on 869 subjects [ 26 – 28 ]. The PRISMA flow diagram for screening inclusion/exclusion criteria in identification of the related papers is illustrated in Fig.…”

“…All of the studies were parallel RCTs and were written in English language. Among three RCTs, two studies were conducted in Greece [ 27 , 28 ] and the other one in Denmark [ 26 ].…”

“…The need for mechanical ventilation may indicate respiratory failure. All three studies (869 participants) reported data on ventilator free days [ 26 – 28 ]. The overall meta-analysis showed that there was no significant effect of VSE therapy on ventilator free days, while there was a high between-study heterogeneity (SMD = 0.201, 95% CI: − 0.677 to 1.079 days; P value = 0.838; Cochrane Q test: I 2 = 95.466%; P value-heterogeneity < 0.001) (Fig.…”

“…Therefore, mechanically, it seems that the combination of these three drugs can be associated with better efficacy in IHCA via improving blood flow to critical organs and stabilization of endothelial glycocalyx barrier. As a result, several clinical trials have been designed to evaluate the effect of pharmacotherapy with the combination of these three drugs of vasopressin, epinephrine and glucocorticoids in CA patients, which have been associated with conflicting results in improving the return of spontaneous circulation during cardiopulmonary resuscitation and patient survival [ 26 – 28 ]. Considering the high mortality rate in CA victims, many attempts have been made to explore some therapeutic strategies to improve survival in CA.…”