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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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Abstract

Objective

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

Design

Randomized, double-blind controlled clinical trial.

Setting

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

Participants

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.

Intervention

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.

Results

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.

Conclusion

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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References

  1. Duncan JM, Meaney P, Simpson P, et al. Vasopressin for in-hospital pediatric cardiac arrest: results from the American Heart Association National Registry of Cardiopulmonary Resuscitation. Pediatr Crit Care Med. 2009;10: 191–5.

    Article  Google Scholar 

  2. de Caen AR, Berg MD, Chameides L, et al. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S526–42.

    Article  Google Scholar 

  3. Panchal AR, Berg KM, Hirsch KG, et al. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardio-pulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2019;140:e881–e94.

    PubMed  Google Scholar 

  4. Voelckel WG, Lurie KG, McKnite S, et al. Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation. Crit Care Med. 2002;30:957–62.

    Article  CAS  Google Scholar 

  5. Mann K, Berg RA, Nadkarni V. Beneficial effects of vasopressin in prolonged pediatric cardiac arrest: a case series. Resuscitation. 2002;52:149–56.

    Article  CAS  Google Scholar 

  6. Carroll TG, Dimas VV, Raymond TT. Vasopressin rescue for in-pediatric intensive care unit cardiopulmonary arrest refractory to initial epinephrine dosing: A prospective feasibility pilot trial. Pediatr Crit Care Med. 2012;13: 265–72.

    Article  Google Scholar 

  7. Fiser DH, Long N, Roberson PK, Hefley G, Zolten K, Brodie-Fowler M. Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments. Crit Care Med. 2000;28:2616–20.

    Article  CAS  Google Scholar 

  8. Zaritsky A, Nadkarni V, Hazinski MF, et al. Recommended Guidelines for Uniform Reporting of Pediatric Advanced Life Support: The Pediatric Utstein Style. Ann Emerg Med. 1995;26:487–503.

    Article  CAS  Google Scholar 

  9. Reis AG, Nadkarni V, Perondi MB, Grisi S, Berg RA. A prospective investigation into the epidemiology of inhospital pediatric cardiopulmonary resuscitation using the international Utstein reporting style. Pediatrics. 2002;109: 200–9.

    Article  Google Scholar 

  10. Jacobs I, Nadkarni V, Bahr J, et al. Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update and Simplification of the Utstein Templates for Resuscitation Registries: A Statement for Healthcare Professionals from a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, Inter American Heart Foundation, Resuscitation Councils of Southern Africa). Circulation. 2004;110:3385–97.

    Article  Google Scholar 

  11. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.

    Article  CAS  Google Scholar 

  12. Rathore V, Bansal A, Singhi SC, Singhi P, Muralidharan J. Survival and neurological outcome following in-hospital paediatric cardiopulmonary resuscitation in North India. Paediatr Int Child Health. 2016;36:141–7.

    Article  Google Scholar 

  13. Donoghue AJ, Abella BS, Merchant R, et al. Cardiopulmonary resuscitation for in-hospital events in the emergency department: A comparison of adult and pediatric outcomes and care processes. Resuscitation. 2015;92: 94–100.

    Article  Google Scholar 

  14. Ridgeon EE, Bellomo R, Aberegg SK, et al. Effect sizes in ongoing randomized controlled critical care trials. Crit Care. 2017;21:132.

    Article  Google Scholar 

  15. Skellett S, Biarent D, Nadkarni V. What works in paediatric CPR? Intensive Care Med. 2018;44:223–6.

    Article  Google Scholar 

  16. Agrawal A, Singh VK, Varma A, Sharma R. Therapeutic applications of vasopressin in pediatric patients. Indian Pediatr. 2012;49:297–305.

    Article  Google Scholar 

  17. Finn J, Jacobs I, Williams TA, Gates S, Perkins GD. Adrenaline and vasopressin for cardiac arrest. Cochrane Database Syst Rev. 2019;1:CD003179.

    PubMed  Google Scholar 

  18. Duncan BW, Ibrahim AE, Hraska V, et al. Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest. J Thorac Cardiovasc Surg. 1998;116: 305–11.

    Article  CAS  Google Scholar 

  19. Morris MC, Wernovsky G, Nadkarni VM. Survival outcomes after extracorporeal cardiopulmonary resuscitation instituted during active chest compressions following refractory in-hospital pediatric cardiac arrest. Pediatr Crit Care Med. 2004;5:440–46.

    Article  Google Scholar 

  20. Thourani VH, Kirshbom PM, Kanter KR, et al. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) in pediatric cardiac support. Ann Thorac Surg. 2006;82:138–44; discussion 144–5.

    Article  Google Scholar 

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Division of Pediatric Critical care, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India

    Abraar Sheriff, Ramachandran Rameshkumar, Muthu Chidambaram, Kaushik Maulik, Routhu Santhosh Kumar, Atahar Jamal, Rohit Bhowmick, Niranjan Biswal & Subramanian Mahadevan

Authors
  1. Abraar Sheriff
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  2. Ramachandran Rameshkumar
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  3. Muthu Chidambaram
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  4. Kaushik Maulik
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  5. Routhu Santhosh Kumar
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  6. Atahar Jamal
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  7. Rohit Bhowmick
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  8. Niranjan Biswal
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  9. Subramanian Mahadevan
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Corresponding author

Correspondence to Ramachandran Rameshkumar.

Additional information

Note

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.

Contributors

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

Competing interest

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). https://doi.org/10.1007/s13312-021-2256-9

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  • DOI: https://doi.org/10.1007/s13312-021-2256-9

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