Multicenter Study

. 2023 Mar 13;27(1):105.

doi: 10.1186/s13054-023-04399-5.

The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes

Ryan W Morgan¹, Robert A Berg², Ron W Reeder³, Todd C Carpenter⁴, Deborah Franzon⁵, Aisha H Frazier^{6

7}, Kathryn Graham², Kathleen L Meert⁸, Vinay M Nadkarni², Maryam Y Naim², Bradley Tilford⁸, Heather A Wolfe², Andrew R Yates⁹, Robert M Sutton²; ICU-RESUS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigator Groups

Collaborators, Affiliations

Collaborators

ICU-RESUS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigator Groups:
Tageldin Ahmed, Michael J Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph A Carcillo, J Michael Dean, J Wesley Diddle, Myke Federman, Richard Fernandez, Ericka L Fink, Stuart H Friess, Mark Hall, David A Hehir, Christopher M Horvat, Leanna L Huard, Tensing Maa, Arushi Manga, Patrick S McQuillen, Peter M Mourani, Daniel Notterman, Murray M Pollack, Anil Sapru, Carleen Schneiter, Matthew P Sharron, Neeraj Srivastava, Sarah Tabbutt, Shirley Viteri, David Wessel, Andrew R Yates, Athena F Zuppa

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Wood Building - 6104, Philadelphia, PA, 19104, USA. morganR1@chop.edu.
² Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Wood Building - 6104, Philadelphia, PA, 19104, USA.
³ Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁴ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
⁵ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, USA.
⁶ Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
⁷ Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
⁸ Department of Pediatrics, Children's Hospital of Michigan, Central Michigan University, Detroit, MI, USA.
⁹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

PMID: 36915182
PMCID: PMC10012560
DOI: 10.1186/s13054-023-04399-5

Multicenter Study

The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes

Ryan W Morgan et al. Crit Care. 2023.

. 2023 Mar 13;27(1):105.

doi: 10.1186/s13054-023-04399-5.

Authors

Collaborators

ICU-RESUS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigator Groups:
Tageldin Ahmed, Michael J Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph A Carcillo, J Michael Dean, J Wesley Diddle, Myke Federman, Richard Fernandez, Ericka L Fink, Stuart H Friess, Mark Hall, David A Hehir, Christopher M Horvat, Leanna L Huard, Tensing Maa, Arushi Manga, Patrick S McQuillen, Peter M Mourani, Daniel Notterman, Murray M Pollack, Anil Sapru, Carleen Schneiter, Matthew P Sharron, Neeraj Srivastava, Sarah Tabbutt, Shirley Viteri, David Wessel, Andrew R Yates, Athena F Zuppa

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Wood Building - 6104, Philadelphia, PA, 19104, USA. morganR1@chop.edu.
² Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, 3401 Civic Center Boulevard, Wood Building - 6104, Philadelphia, PA, 19104, USA.
³ Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁴ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
⁵ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, USA.
⁶ Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
⁷ Department of Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
⁸ Department of Pediatrics, Children's Hospital of Michigan, Central Michigan University, Detroit, MI, USA.
⁹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

PMID: 36915182
PMCID: PMC10012560
DOI: 10.1186/s13054-023-04399-5

Abstract

Background: Epinephrine is provided during cardiopulmonary resuscitation (CPR) to increase systemic vascular resistance and generate higher diastolic blood pressure (DBP) to improve coronary perfusion and attain return of spontaneous circulation (ROSC). The DBP response to epinephrine during pediatric CPR and its association with outcomes have not been well described. Thus, the objective of this study was to measure the association between change in DBP after epinephrine administration during CPR and ROSC.

Methods: This was a prospective multicenter study of children receiving ≥ 1 min of CPR with ≥ 1 dose of epinephrine and evaluable invasive arterial BP data in the 18 ICUs of the ICU-RESUS trial (NCT02837497). Blood pressure waveforms underwent compression-by-compression quantitative analysis. The mean DBP before first epinephrine dose was compared to mean DBP two minutes post-epinephrine. Patients with ≥ 5 mmHg increase in DBP were characterized as "responders."

Results: Among 147 patients meeting inclusion criteria, 66 (45%) were characterized as responders and 81 (55%) were non-responders. The mean increase in DBP with epinephrine was 4.4 [- 1.9, 11.5] mmHg (responders: 13.6 [7.5, 29.3] mmHg versus non-responders: - 1.5 [- 5.0, 1.5] mmHg; p < 0.001). After controlling for a priori selected covariates, epinephrine response was associated with ROSC (aRR 1.60 [1.21, 2.12]; p = 0.001). Sensitivity analyses identified similar associations between DBP response thresholds of ≥ 10, 15, and 20 mmHg and ROSC; DBP responses of ≥ 10 and ≥ 15 mmHg were associated with higher aRR of survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score of 1-3 or no worsening from baseline).

Conclusions: The change in DBP following epinephrine administration during pediatric in-hospital CPR was associated with return of spontaneous circulation.

Keywords: Adrenaline; Blood pressure; Cardiac arrest; Cardiopulmonary resuscitation; Epinephrine; Pediatrics.

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Conflict of interest statement

Ryan W. Morgan and Robert M. Sutton report funding paid to their institution from the NIH and volunteer leadership roles within the American Heart Association. Robert A. Berg reports funding paid to his institution from the NIH and membership on Data Safety Monitoring Boards. Ron W. Reeder, Todd C. Carpenter, Kathleen L. Meert, Heather A. Wolfe, and Andrew R. Yates report funding paid to their institutions from the NIH. Vinay M. Nadkarni reports funding paid to his institution from the NIH, Zoll Medical, Laerdal Medical/RQI Partners, and Nihon-Kohden and volunteer leadership roles in the Society of Critical Care Medicine, Citizen CPR Foundation, and International Liaison Committee on Resuscitation. Deborah Franzon, Aisha H. Frazier, Kathyrn Graham, Maryam Y. Naim, and Bradley Tilford have no relevant disclosures.

Figures

**Fig. 1**
Timing of blood pressure sampling. Figure depicts timing of blood pressure sampling relative to epinephrine administration. For this theoretical patient who received epinephrine two minutes into CPR, the 30-s data epochs of that minute of CPR (e.g., 90 s through 150 s) are considered the epinephrine administration period and not included in blood pressure analyses. The immediately preceding 30-s epoch (e.g., 60 s through 90 s) is utilized for pre-epinephrine BP determination. If unavailable, the prior is used (e.g., 30 s through 60 s). The mean BP from the four post-epinephrine epochs following the epinephrine administration period (e.g., minutes 2.5 through 4.5) are utilized for post-epinephrine BP determination. The difference between the mean DBP from this 2-min period and the mean DBP from the pre-epinephrine epoch was used to classify patients as epinephrine responders or non-responders

**Fig. 2**
Temporal change in intra-arrest blood pressure relative to epinephrine administration. Average systolic and diastolic blood pressures plotted over time (minutes) relative to the time of first dose of epinephrine (minute 0). A Depicts epinephrine responders versus non-responders and B depicts patients with ROSC (return of spontaneous circulation) versus patients without ROSC. Each data point represents the mean value for 30-s data epochs for each patient and then averaged within each group. Error bars indicate standard error of the mean for each time point

**Fig. 3**
Spline analysis. Spline curve depicting the relationship between change in DBP (diastolic blood pressure) after the first dose of epinephrine and the probability of ROSC (return of spontaneous circulation). Curve based on a logistic regression model controlling for the same a priori covariates as the primary multivariate analysis (initial CPR rhythm (bradycardia and poor perfusion versus pulseless rhythms); illness category (medical cardiac, medical non-cardiac, surgical cardiac, surgical non-cardiac); presence of a vasopressor infusion at the start of CPR; and preexisting pulmonary hypertension). Shaded area represents 95% confidence interval. The optimal cut point for discriminating patients with and without ROSC, based on receiver operating characteristic curve analysis, was an increase in DBP of 4.4 mmHg

See this image and copyright information in PMC

References

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The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes

Collaborators

Affiliations

The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes

Authors

Collaborators

Affiliations

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Conflict of interest statement

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