Andersen LW, Isbye D, Kjærgaard 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;326(16):1586–1594. doi:10.1001/jama.2021.16628
Introduction: While early recognition, alerting an emergency response, effective CPR and rapid defibrillation remain the cornerstones of survival after cardiac arrest, Advanced Cardiac Life Support (ACLS) also calls for the use of drugs such as adrenaline/epinephrine and amiodarone. The VAM-IHCA trial is a large RCT examining if there is a benefit to vasopressin and methylprednisolone during resuscitation of in-hospital cardiac arrest.
Population: The trial, conducted in Denmark, screened 2362 patients for inclusion. Included patients were over 18 and suffered a cardiac arrest that began inside hospital. 501 patients met all inclusion and no exclusion criteria.
Intervention: The intervention group received 20 IU of vasopressin and 40 mg of methylprednisolone as soon as possible after the first adrenaline dose. Additional doses of vasopressin could be administered with later doses of adrenaline up to a total of 80 IU.
Control: The control group received placebo doses of saline in identical containers to the trial drugs. The trial was double-blinded, with patients and treating clinicians unaware of the allocation of individual patients.
Outcome: The primary outcome was return of spontaneous circulation (ROSC). Additional secondary outcomes included 30-day survival and 30-day survival with a good neurological outcome.
Results: 42% of the patients in the intervention group and 33% of the control group achieved ROSC, corresponding to a statistically significant risk ratio of 1.30 [95% CI 1.03-1.63]. However, at 30 days, 9.7% and 12% of patients in the intervention and control groups respectively were still alive, giving a 95% confidence interval for the risk ratio of 0.50-1.37. Similarly, the rates of survival with a good neurological outcome at 30 days were 7.6% in each group, giving a confidence interval of 0.55-1.83.
Discussion: The study is the largest to date studying vasopressin and glucocorticoids as an adjunct in cardiac arrest. The results of the study show thathigher rates of ROSC are achieved when using the additional drugs, but this does not translate into a significant long-term benefit to the patient. However, the trial is limited by the substantial proportion of potentially eligible patients excluded, which could introduce bias, and the sample size, which was powered to detect differences in ROSC, but not for longer-term survival.
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