{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:58:03Z","timestamp":1787018283764,"version":"build-2736575974"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Animal studies of cardiac arrest suggest that shorter epinephrine dosing intervals than currently recommended (every 3\u20135 min) may be beneficial in select circumstances.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between epinephrine dosing intervals and pediatric cardiac arrest outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-center retrospective cohort study of children (&amp;lt;18 years of age) who received \u2a7e1 minute of cardiopulmonary resuscitation and \u2a7e2 doses of epinephrine for an index in-hospital cardiac arrest. Exposure was epinephrine dosing interval \u2a7d2 minutes (frequent epinephrine) versus &amp;gt;2 minutes. The primary outcome was survival to hospital discharge with a favorable neurobehavioral outcome (Pediatric Cerebral Performance Category score 1\u20132 or unchanged). Logistic regression evaluated the association between dosing interval and outcomes; additional analyses explored duration of cardiopulmonary resuscitation (CPR) as a mediator. In a subgroup, the effect of dosing interval on diastolic blood pressure was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Between January 2011 and December 2018, 125 patients met inclusion\/exclusion criteria; 33 (26%) received frequent epinephrine. Frequent epinephrine was associated with increased odds of survival with favorable neurobehavioral outcome (adjusted odds ratio, 2.56; 95% confidence interval, 1.07\u20136.14; P\u2009=\u20090.036), with 66% of the association mediated by CPR duration. Delta diastolic blood pressure was greater after the second dose of epinephrine among patients who received frequent epinephrine (median [interquartile range], 6.3 [4.1 to 16.9] vs. 0.13 [\u22122.3 to 1.9] mm Hg; P\u2009=\u20090.034).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients who received at least two doses of epinephrine, dosing intervals \u2a7d2 minutes were associated with improved neurobehavioral outcomes compared with dosing intervals &amp;gt;2 minutes. Mediation analysis suggests that improved outcomes are largely due to frequent epinephrine shortening duration of CPR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202012-4437oc","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T18:10:01Z","timestamp":1626372601000},"page":"977-985","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":32,"title":["The Effect of Epinephrine Dosing Intervals on Outcomes from Pediatric In-Hospital Cardiac Arrest"],"prefix":"10.1093","volume":"204","author":[{"given":"Martha F.","family":"Kienzle","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan W.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Faerber","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Katcoff","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P.","family":"Landis","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis A.","family":"Topjian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J.","family":"Kilbaugh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay M.","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2026030321572183400_bib1","doi-asserted-by":"crossref","first-page":"e005580","DOI":"10.1161\/CIRCOUTCOMES.119.005580","article-title":"Annual incidence of adult and pediatric in-hospital cardiac arrest in the United States","volume":"12","author":"Holmberg","year":"2019","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"2026030321572183400_bib2","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1097\/CCM.0b013e31828cf0c0","article-title":"Ratio of PICU versus ward cardiopulmonary resuscitation events is increasing","volume":"41","author":"Berg","year":"2013","journal-title":"Crit Care Med"},{"key":"2026030321572183400_bib3","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1161\/CIRCULATIONAHA.119.041667","article-title":"Trends in survival after pediatric in-hospital cardiac arrest in the United States","volume":"140","author":"Holmberg","year":"2019","journal-title":"Circulation"},{"key":"2026030321572183400_bib4","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1097\/CCM.0000000000001484","article-title":"Incidence and outcomes of cardiopulmonary resuscitation in PICUs","volume":"44","author":"Berg","year":"2016","journal-title":"Crit Care Med"},{"key":"2026030321572183400_bib5","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1056\/NEJMoa1109148","article-title":"Trends in survival after in-hospital cardiac arrest","volume":"367","author":"Girotra","year":"2012","journal-title":"N Engl J Med"},{"key":"2026030321572183400_bib6","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1001\/jama.1990.03440080084029","article-title":"Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation","volume":"263","author":"Paradis","year":"1990","journal-title":"JAMA"},{"key":"2026030321572183400_bib7","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1161\/CIRCULATIONAHA.117.032270","article-title":"Association between diastolic blood pressure during pediatric in-hospital cardiopulmonary resuscitation and survival","volume":"137","author":"Berg","year":"2018","journal-title":"Circulation"},{"key":"2026030321572183400_bib8","doi-asserted-by":"crossref","first-page":"S469","DOI":"10.1161\/CIR.0000000000000901","article-title":"Part 4: Pediatric basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care","volume":"142","author":"Topjian","year":"2020","journal-title":"Circulation"},{"key":"2026030321572183400_bib9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/01.CIR.75.2.491","article-title":"The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine","volume":"75","author":"Brown","year":"1987","journal-title":"Circulation"},{"key":"2026030321572183400_bib10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0196-0644(85)80440-6","article-title":"Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs","volume":"14","author":"Kosnik","year":"1985","journal-title":"Ann Emerg Med"},{"key":"2026030321572183400_bib11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.resuscitation.2016.01.032","article-title":"Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study","volume":"101","author":"Hardig","year":"2016","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.resuscitation.2020.06.024","article-title":"Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs","volume":"156","author":"Putzer","year":"2020","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.resuscitation.2017.05.023","article-title":"Epinephrine dosing interval and survival outcomes during pediatric in-hospital cardiac arrest","volume":"117","author":"Hoyme","year":"2017","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib14","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.resuscitation.2013.10.004","article-title":"Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: a retrospective review of prospectively collected data","volume":"85","author":"Warren","year":"2014","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.resuscitation.2015.12.008","article-title":"The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: a retrospective cohort study","volume":"103","author":"Wang","year":"2016","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.annemergmed.2019.04.031","article-title":"The association of the average epinephrine dosing interval and survival with favorable neurologic status at hospital discharge in out-of-hospital cardiac arrest","volume":"74","author":"Grunau","year":"2019","journal-title":"Ann Emerg Med"},{"key":"2026030321572183400_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resuscitation.2019.03.032","article-title":"Hemodynamic effects of chest compression interruptions during pediatric in-hospital cardiopulmonary resuscitation","volume":"139","author":"Morgan","year":"2019","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib18","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1161\/CIR.0b013e3182340239","article-title":"Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association","volume":"124","author":"Becker","year":"2011","journal-title":"Circulation"},{"key":"2026030321572183400_bib19","doi-asserted-by":"crossref","first-page":"e746","DOI":"10.1161\/CIR.0000000000000710","article-title":"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)","volume":"140","author":"Nolan","year":"2019","journal-title":"Circulation"},{"key":"2026030321572183400_bib20","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCULATIONAHA.112.125625","article-title":"Duration of cardiopulmonary resuscitation and illness category impact survival and neurologic outcomes for in-hospital pediatric cardiac arrests","volume":"127","author":"Matos","year":"2013","journal-title":"Circulation"},{"key":"2026030321572183400_bib21","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1542\/peds.2006-1724","article-title":"Higher survival rates among younger patients after pediatric intensive care unit cardiac arrests","volume":"118","author":"Meaney","year":"2006","journal-title":"Pediatrics"},{"key":"2026030321572183400_bib22","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1001\/jama.295.1.50","article-title":"First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults","volume":"295","author":"Nadkarni","year":"2006","journal-title":"JAMA"},{"key":"2026030321572183400_bib23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jamapediatrics.2016.2535","article-title":"Survival rates following pediatric in-hospital cardiac arrests during nights and weekends","volume":"171","author":"Bhanji","year":"2017","journal-title":"JAMA Pediatr"},{"key":"2026030321572183400_bib24","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1001\/jama.2015.9678","article-title":"Time to epinephrine and survival after pediatric in-hospital cardiac arrest","volume":"314","author":"Andersen","year":"2015","journal-title":"JAMA"},{"key":"2026030321572183400_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v059.i05","article-title":"Mediation: R package for causal mediation analysis","volume":"59","author":"Tingley","year":"2014","journal-title":"J Stat Softw"},{"key":"2026030321572183400_bib26","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1161\/CIRCULATIONAHA.117.030488","article-title":"Association between prompt defibrillation and epinephrine treatment with long-term survival after in-hospital cardiac arrest","volume":"137","author":"Patel","year":"2018","journal-title":"Circulation"},{"key":"2026030321572183400_bib27","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1056\/NEJMoa032440","article-title":"A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest","volume":"350","author":"Perondi","year":"2004","journal-title":"N Engl J Med"},{"key":"2026030321572183400_bib28","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1378\/chest.97.6.1458","article-title":"Epinephrine and norepinephrine in cardiopulmonary resuscitation. Effects on myocardial oxygen delivery and consumption","volume":"97","author":"Lindner","year":"1990","journal-title":"Chest"},{"key":"2026030321572183400_bib29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/00003246-199303000-00020","article-title":"Effects of graded doses of epinephrine on both noninvasive and invasive measures of myocardial perfusion and blood flow during cardiopulmonary resuscitation","volume":"21","author":"Chase","year":"1993","journal-title":"Crit Care Med"},{"key":"2026030321572183400_bib30","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/00003246-199402000-00020","article-title":"High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: a prospective, randomized study","volume":"22","author":"Berg","year":"1994","journal-title":"Crit Care Med"},{"key":"2026030321572183400_bib31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.resuscitation.2007.12.013","article-title":"Cerebral cortical microvascular flow during and following cardiopulmonary resuscitation after short duration of cardiac arrest","volume":"77","author":"Ristagno","year":"2008","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib32","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1097\/01.CCM.0000280427.76175.D2","article-title":"Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation","volume":"35","author":"Ristagno","year":"2007","journal-title":"Crit Care Med"},{"key":"2026030321572183400_bib33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s13054-020-03297-4","article-title":"Epinephrine\u2019s effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation","volume":"24","author":"Mavroudis","year":"2020","journal-title":"Crit Care"},{"key":"2026030321572183400_bib34","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1161\/01.CIR.99.10.1379","article-title":"Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs","volume":"99","author":"Wenzel","year":"1999","journal-title":"Circulation"},{"key":"2026030321572183400_bib35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0300-9572(98)00018-5","article-title":"Hemodynamic effects of repeated doses of epinephrine after prolonged cardiac arrest and CPR: preliminary observations in an animal model","volume":"36","author":"Cairns","year":"1998","journal-title":"Resuscitation"},{"key":"2026030321572183400_bib36","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/CIRCULATIONAHA.115.016082","article-title":"Extracorporeal cardiopulmonary resuscitation (E-CPR) during pediatric in-hospital cardiopulmonary arrest is associated with improved survival to discharge: a report from the American Heart Association\u2019s Get With The Guidelines-Resuscitation (GWTG-R) Registry","volume":"133","author":"Lasa","year":"2016","journal-title":"Circulation"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/204\/8\/977\/67014162\/ajrccm_204_8_977.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/204\/8\/977\/67014162\/ajrccm_204_8_977.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:57:34Z","timestamp":1772593054000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/204\/8\/977\/8492348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,10,15]]},"published-print":{"date-parts":[[2021,10,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202012-4437oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10]]},"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"2020-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}