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Epinephrine Plus Vasopressin vs Epinephrine Plus Placebo in Pediatric Intensive Care Unit Cardiopulmonary Resuscitation: A Randomized Double Blind Controlled Clinical Trial

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To compare the efficacy of epinephrine plus vasopressin vs epinephrine plus placebo in the pediatric intensive care unit (PICU) cardiopulmonary resuscitation (CPR).


Randomized, double-blind controlled clinical trial.


PICU in a tertiary care institute from February, 2019 to May, 2020.


Children aged one month to 13 years who required CPR during PICU stay. Patients in whom vascular access was not available or return of spontaneous circulation (ROSC) was achieved by defibrillation without epinephrine were excluded.


Patients were randomized to receive vasopressin 0.1 mL per kg (=0.8 unit per kg) or placebo (0.1 mL per kg normal saline) in addition to epinephrine (1:10000) 0.1 mL per kg. The drugs were given as bolus doses every three minutes until the ROSC or up to a maximum of five doses, whichever was earlier.

Outcome Measure

The primary outcome was the proportion of patients who achieved ROSC. The secondary outcomes were survival rate and functional status (at 24-hour, PICU, hospital, and 90-day post-discharge), need for organ supports, length of stay (PICU and hospital), and adverse effect(s) of the study drugs.


90 patients (epinephrine plus vasopressin group, n=45 and epinephrine plus placebo group, n=45) were analyzed on intention-to-treat basis. There was no significant difference in the primary outcome between epinephrine plus vasopressin (n=25, 55.5%) and epinephrine plus placebo groups (n=24, 53.3%) (Relative risk 1.04, 95% CI 0.71 to 1.52). There was no significant difference in survival rate at 24-hour (n=7, 15.6% vs. n=8, 17.8%), at PICU, hospital, and 90-day post-discharge (n=1, 2.2% vs n=1, 2.2%). There was no difference in other secondary outcomes. No trial drug-related serious adverse events were observed.


A combination of epinephrine plus vasopressin did not improve the rate of return of spontaneous circulation in the pediatric intensive care unit cardiopulmonary resuscitation as compared with epinephrine plus placebo.

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Mrs. S. Raja Deepa B.Com, MCA (JIPMER Campus, Puducherry, India) for blinded data handling, review and editing of the manuscript; Mr. Rakesh Mohindra (Punjab University, Chandigarh, India) and Mrs. Thenmozhi M (M.Sc, Ph.D., Senior Demonstrator, CMC, Vellore, India) for helping with statistical analysis and Mrs. Harpreet Kaur (Punjab University, Chandigarh, India), and Mrs. Neelima Chadha (Tulsi Das Library, PGIMER, Chandigarh, India) for helping with the medical literature search.

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Correspondence to Ramachandran Rameshkumar.

Additional information


The preliminary study data was presented in the 21st National Conference of IAP Intensive Care Chapter (NCPIC 2019), from 5th to 8th December, 2019, Bengaluru.


RR: had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis; RR: Study concept and design; AS, MC, KM, RSK, AJ, RB: acquisition, analysis, or interpretation of data and drafting of the first manuscript; MC, RB, NB, SM: protocol development and revision of the manuscript; RR, SM: critical revision of the manuscript for important intellectual content; RR, NB: study supervision. RR: is the guarantor of the paper. All authors approved the final version of the manuscript. Funding: None

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None stated.

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Sheriff, A., Rameshkumar, R., Chidambaram, M. et al. Epinephrine Plus Vasopressin vs Epinephrine Plus Placebo in Pediatric Intensive Care Unit Cardiopulmonary Resuscitation: A Randomized Double Blind Controlled Clinical Trial. Indian Pediatr 58, 624–630 (2021).

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