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

Journal

Critical care medicine

ISSN: 1530-0293

Titre abrégé: Crit Care Med

Pays: United States

ID NLM: 0355501

Informations de publication

Date de publication:
04 Jun 2024

Historique:

medline: 4 6 2024

pubmed: 4 6 2024

entrez: 4 6 2024

Statut: aheadofprint

Résumé

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. 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. Eighteen PICUs and pediatric cardiac ICUs in the United States. 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. The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. 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). 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.

Identifiants

DOI: 10.1097/CCM.0000000000006334 PMID: 38833560

pubmed: 38833560

doi: 10.1097/CCM.0000000000006334

pii: 00003246-990000000-00340

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

Déclaration de conflit d'intérêts

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.

Références

Holmberg MJ, Ross CE, Fitzmaurice GM, et al.; American Heart Association’s Get With The Guidelines–Resuscitation Investigators: Annual incidence of adult and pediatric in-hospital cardiac arrest in the United States. Circ Cardiovasc Qual Outcomes 2019; 12:e005580

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; 175:293–302

Holmberg MJ, Wiberg S, Ross CE, et al.: Trends in survival after pediatric in-hospital cardiac arrest in the United States. Circulation 2019; 140:1398–1408

Berg RA, Nadkarni VM, Clark AE, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Incidence and outcomes of cardiopulmonary resuscitation in PICUs. Crit Care Med 2016; 44:798–808

Girotra S, Spertus JA, Li Y, et al.; American Heart Association Get With the Guidelines–Resuscitation Investigators: Survival trends in pediatric in-hospital cardiac arrests: An analysis from get with the guidelines-resuscitation. Circ Cardiovasc Qual Outcomes 2013; 6:42–49

Topjian AA, Raymond TT, Atkins D, et al.; Pediatric Basic and Advanced Life Support Collaborators: Part 4: Pediatric basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2020; 142:S469–S523

Panchal AR, Bartos JA, Cabañas JG, et al.; Adult Basic and Advanced Life Support Writing Group: Part 3: Adult basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2020; 142:S366–S468

Paradis NA, Martin GB, Rivers EP, et al.: Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA 1990; 263:1106–1113

Berg RA, Sutton RM, Reeder RW, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) PICqCPR (Pediatric Intensive Care Quality of Cardio-Pulmonary Resuscitation) Investigators: Association between diastolic blood pressure during pediatric in-hospital cardiopulmonary resuscitation and survival. Circulation 2018; 137:1784–1795

Berg RA, Morgan RW, Reeder RW, et al.: Diastolic blood pressure threshold during pediatric cardiopulmonary resuscitation and survival outcomes: A multicenter validation study. Crit Care Med 2023; 51:91–102

Andersen LW, Berg KM, Saindon BZ, et al.; American Heart Association Get With the Guidelines–Resuscitation Investigators: Time to epinephrine and survival after pediatric in-hospital cardiac arrest. JAMA 2015; 314:802–810

Hoyme DB, Patel SS, Samson RA, et al.; American Heart Association Get With the Guidelines–Resuscitation Investigators: Epinephrine dosing interval and survival outcomes during pediatric in-hospital cardiac arrest. Resuscitation 2017; 117:18–23

Donnino MW, Salciccioli JD, Howell MD, et al.; American Heart Association’s Get With The Guidelines-Resuscitation Investigators: Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: Retrospective analysis of large in-hospital data registry. BMJ 2014; 348:g3028

Bakhsh A, Safhi M, Alghamdi A, et al.: Immediate intravenous epinephrine versus early intravenous epinephrine for in-hospital cardiopulmonary arrest. BMC Anesthesiol 2021; 21:147

Fukuda T, Kondo Y, Hayashida K, et al.: Time to epinephrine and survival after paediatric out-of-hospital cardiac arrest. Eur Heart J Cardiovasc Pharmacother 2018; 4:144–151

Fukuda T, Ohashi-Fukuda N, Inokuchi R, et al.: Timing of intravenous epinephrine administration during out-of-hospital cardiac arrest. Shock 2021; 56:709–717

Okubo M, Komukai S, Callaway CW, et al.: Association of timing of epinephrine administration with outcomes in adults with out-of-hospital cardiac arrest. JAMA Netw Open 2021; 4:e2120176

Sigal AP, Sandel KM, Buckler DG, et al.: Impact of adrenaline dose and timing on out-of-hospital cardiac arrest survival and neurological outcomes. Resuscitation 2019; 139:182–188

Lin YR, Li CJ, Huang CC, et al.: Early epinephrine improves the stabilization of initial post-resuscitation hemodynamics in children with non-shockable out-of-hospital cardiac arrest. Front Pediatr 2019; 7:220

Kienzle MF, Morgan RW, Faerber JA, et al.: The effect of epinephrine dosing intervals on outcomes from pediatric in-hospital cardiac arrest. Am J Respir Crit Care Med 2021; 204:977–985

Wang CH, Huang CH, Chang WT, et al.: The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: A retrospective cohort study. Resuscitation 2016; 103:125–130

Warren SA, Huszti E, Bradley SM, et al.; American Heart Association's Get With the Guidelines-Resuscitation (National Registry of CPR) Investigators: Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: A retrospective review of prospectively collected data. Resuscitation 2014; 85:350–358

Fukuda T, Kaneshima H, Matsudaira A, et al.: Epinephrine dosing interval and neurological outcome in out-of-hospital cardiac arrest. Perfusion 2022; 37:835–846

Grunau B, Kawano T, Scheuermeyer FX, et al.: The association of the average epinephrine dosing interval and survival with favorable neurologic status at hospital discharge in out-of-hospital cardiac arrest. Ann Emerg Med 2019; 74:797–806

Meert K, Telford R, Holubkov R, et al.: Paediatric in-hospital cardiac arrest: Factors associated with survival and neurobehavioural outcome one year later. Resuscitation 2018; 124:96–105

Brown CG, Werman HA, Davis EA, et al.: The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine. Circulation 1987; 75:491–497

Kosnik JW, Jackson RE, Keats S, et al.: Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs. Ann Emerg Med 1985; 14:204–208

Hardig BM, Götberg M, Rundgren M, et al.: Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study. Resuscitation 2016; 101:77–83

Putzer G, Martini J, Spraider P, et al.: Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs. Resuscitation 2020; 156:223–229

Sutton RM, Wolfe HA, Reeder RW, et al.; ICU-RESUS and Eunice Kennedy Shriver National Institute of Child Health: Effect of physiologic point-of-care cardiopulmonary resuscitation training on survival with favorable neurologic outcome in cardiac arrest in pediatric ICUs: A randomized clinical trial. JAMA 2022; 327:934–945

Nolan JP, Berg RA, Andersen LW, et al.: Cardiac arrest and cardiopulmonary resuscitation outcome reports: Update of the Utstein resuscitation registry template for in-hospital cardiac arrest: A consensus report from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia). Circulation 2019; 140:e746–e757

Morgan RW, Landis WP, Marquez A, et al.: Hemodynamic effects of chest compression interruptions during pediatric in-hospital cardiopulmonary resuscitation. Resuscitation 2019; 139:1–8

Fiser DH: Assessing the outcome of pediatric intensive care. J Pediatr 1992; 121:68–74

Pollack MM, Holubkov R, Glass P, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Functional status scale: New pediatric outcome measure. Pediatrics 2009; 124:e18–e28

Matos RI, Watson RS, Nadkarni VM, et al.; American Heart Association’s Get With The Guidelines–Resuscitation (Formerly the National Registry of Cardiopulmonary Resuscitation) Investigators: Duration of cardiopulmonary resuscitation and illness category impact survival and neurologic outcomes for in-hospital pediatric cardiac arrests. Circulation 2013; 127:442–451

Nadkarni VM, Larkin GL, Peberdy MA, et al.; National Registry of Cardiopulmonary Resuscitation Investigators: First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults. JAMA 2006; 295:50–57

Bhanji F, Topjian AA, Nadkarni VM, et al.; American Heart Association’s Get With the Guidelines–Resuscitation Investigators: Survival rates following pediatric in-hospital cardiac arrests during nights and weekends. JAMA Pediatr 2017; 171:39–45

Topjian AA, Clark AE, Casper TC, et al.: Early lactate elevations following resuscitation from pediatric cardiac arrest are associated with increased mortality. Pediatr Crit Care Med 2013; 14:4–11

Ferguson LP, Durward A, Tibby SM: Relationship between arterial partial oxygen pressure after resuscitation from cardiac arrest and mortality in children. Circulation 2012; 126:335–342

Topjian AA, Sutton RM, Reeder RW, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) Investigators: The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest. Resuscitation 2019; 141:88–95

Topjian AA, Moler FW, Telford R, et al.: Association of early postresuscitation hypotension with survival to discharge after targeted temperature management for pediatric out-of-hospital cardiac arrest secondary analysis of a randomized clinical trial. JAMA Pediatr 2018; 172:143–153

Moler FW, Silverstein FS, Holubkov R, et al.; THAPCA Trial Investigators: Therapeutic hypothermia after in-hospital cardiac arrest in children. N Engl J Med 2017; 376:318–329

López-Herce J, Del Castillo J, Matamoros M, et al.: Post return of spontaneous circulation factors associated with mortality in pediatric in-hospital cardiac arrest: A prospective multicenter multinational observational study. Crit Care 2014; 18:607

Wintergerst KA, Buckingham B, Gandrud L, et al.: Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 2006; 118:173–179

Srinivasan V, Spinella PC, Drott HR, et al.: Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med 2004; 5:329–336

Slovis JC, Morgan RW, Landis WP, et al.: The physiologic response to rescue therapy with vasopressin versus epinephrine during experimental pediatric cardiac arrest. Resusc Plus 2020; 4:100050

Mavroudis CD, Ko TS, Morgan RW, et al.: Epinephrine’s effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation. Crit Care 2020; 24:583

O’Brien CE, Santos PT, Reyes M, et al.: Association of diastolic blood pressure with survival during paediatric cardiopulmonary resuscitation. Resuscitation 2019; 143:50–56

Morgan RW, Berg RA, Reeder RW, et al.; ICU-RESUS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigator Groups: The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes. Crit Care 2023; 27:105

Ortmann LA, Reeder RW, Raymond TT, et al.: Epinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: A multicenter study utilizing time-stamped epinephrine dosing records. Resuscitation 2023; 188:109855