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Multicenter Study
. 2024 Sep 1;52(9):1344-1355.
doi: 10.1097/CCM.0000000000006334. Epub 2024 Jun 4.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study

Martha F Kienzle  1 , Ryan W Morgan  1 , Ron W Reeder  2 , Tageldin Ahmed  3 , Robert A Berg  1 , Robert Bishop  4 , Matthew Bochkoris  5 , Joseph A Carcillo  5 , Todd C Carpenter  4 , Kellimarie K Cooper  1 , J Wesley Diddle  1 , Myke Federman  6 , Richard Fernandez  7 , Deborah Franzon  8 , Aisha H Frazier  9 , Stuart H Friess  10 , Meg Frizzola  9 , Kathryn Graham  1 , Mark Hall  7 , Christopher Horvat  5 , Leanna L Huard  6 , Tensing Maa  7 , Arushi Manga  10 , Patrick S McQuillen  8 , Kathleen L Meert  3 , Peter M Mourani  4 , Vinay M Nadkarni  1 , Maryam Y Naim  1 , Murray M Pollack  11 , Anil Sapru  6 , Carleen Schneiter  4 , Matthew P Sharron  11 , Sarah Tabbutt  8 , Shirley Viteri  9 , Heather A Wolfe  1 , Robert M Sutton  1 ; Oxy-PICU Investigators of the Pediatric Critical Care Society Study Group
Collaborators, Affiliations
Multicenter Study

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study

Martha F Kienzle et al. Crit Care Med. .

Erratum in

Abstract

Objectives: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes.

Design: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing.

Setting: Eighteen PICUs and pediatric cardiac ICUs in the United States.

Patients: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded.

Interventions: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes.

Measurements and main results: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01).

Conclusions: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

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Conflict of interest statement

Drs. Kienzle, Berg, Morgan, Reeder, Carcillo, Carpenter, Hall, Horvat, Franzon, Frazier, Friess, Maa, Manga, McQuillen, Meert, Mourani, Naim, Pollack, Sapru, Schnieter, Wolfe, and Sutton received National Institutes of Health (NIH) grant funding to their institution related to this project. Dr. Kienzle disclosed the study was supported by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; U01HD049934, UG1HD049981, UG1HD049983, UG1HD050096, UG1HD063108, UG1HD083166, UG1HD083170, and UG1HD083171) and National Heart, Lung, and Blood Institute (NHLBI; R01HL131544 and K23HL148541) and by the Children’s Hospital of Philadelphia Research Institute Resuscitation Science Center. Dr. Berg reports membership on Data Safety Monitoring Boards. Dr. Carcillo received funding from the NICHD and the National Institute of General Medical Sciences. Dr. Diddle received funding from Mallinckrodt Pharmaceuticals. Dr. Friess received funding for expert testimony. Drs. Berg’s and Maa’s institutions received funding from the NHLBI. Drs. Berg, Carpenter, Horvat, and McQuillen institutions received funding from the NICHD. Drs. Morgan and Sutton report volunteer leadership roles with the American Heart Association. Dr. Morgan’s institution received funding from the NHLBI (K23HL148541). Dr. Hall received funding from the American Board of Pediatrics, AbbVie, Kiadis, Partner Therapeutics, and Sobi. Dr. Nadkarni receives unrestricted research grants to his institution from the NIH, Agency for Healthcare Research and Quality, Department of Defense, Zoll Medical, Nihon Kohden, Resuscitation Quality Improvement Partners, American Heart Association, and Laerdal Foundation. He serves as the president of the Society of Critical Care Medicine (SCCM). The views expressed are his, and not intended to represent the views of the SCCM. Dr. Wolfe received funding for speaking fees. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1:
Figure 1:. Exploring the relationship between documented and estimated epinephrine dosing intervals.
In patients with documented epinephrine dosing times after the first dose (n=103), times were used to create an event-level average dosing interval or “documented dosing interval.” The estimated dosing interval was calculated by the following equation: (CPR duration after the first dose of epinephrine) / (total doses of epinephrine–1). The relationship between estimated and documented dosing intervals was explored visually with a scatterplot of estimated versus documented dosing interval and with Spearman correlation. The average absolute difference between estimated and documented dosing interval was 0.90 minutes; the median absolute difference was 0.67 (minimum difference zero minutes, maximum difference five minutes). Spearman correlation = 0.74.
Figure 2:
Figure 2:
CONSORT Diagram. ECPR indicates extracorporeal cardiopulmonary resuscitation; ICU-RESUS, The ICU-RESUScitation Project; ROC, return of circulation.
See this image and copyright information in PMC

References

    1. Holmberg MJ, Ross CE, Fitzmaurice GM, et al. : Annual incidence of adult and pediatric in-hospital cardiac arrest in the United States. Circ Cardiovasc Qual Outcomes 2019; 12(7):1–8. - PMC - PubMed
    1. Morgan RW, Kirschen MP, Kilbaugh TJ, et al. : Pediatric In-Hospital Cardiac Arrest and Cardiopulmonary Resuscitation in the United States: A Review. JAMA Pediatr 2021; 175(3):293–302. - PMC - PubMed
    1. Holmberg MJ, Wiberg S, Ross CE, et al. : Trends in Survival after Pediatric In-Hospital Cardiac Arrest in the United States. Circulation 2019; 140(17):1398–1408. - PMC - PubMed
    1. Berg RA, Nadkarni VM, Clark AE, et al. : Incidence and Outcomes of Cardiopulmonary Resuscitation in PICUs. Crit Care Med 2016; 44(4):798–808. - PMC - PubMed
    1. Girotra S, Spertus JA, Li Y, et al. : Survival Trends in Pediatric In-Hospital Cardiac Arrests: An Analysis from Get with the Guidelines-Resuscitation. Circ Cardiovasc Qual Outcomes 2013; 6(1):42–49. - PMC - PubMed

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