{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:56:22Z","timestamp":1793228182297,"version":"4.5.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n There is no consensus and wide practice variation in the choice of initial vasoactive agent in children with septic shock.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether receipt of epinephrine compared with norepinephrine as the first vasoactive medication administered is associated with improved outcomes among children with septic shock without known cardiac dysfunction.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This single-center, retrospective cohort study used propensity score matching to examine encounters in which a patient was diagnosed with septic shock and required a vasoactive infusion within 24 hours of ED arrival at a freestanding quaternary care children\u2019s hospital. Participants included patients aged 1 month to 18 years who presented to the ED and were diagnosed with septic shock without known cardiac dysfunction and began an epinephrine or norepinephrine infusion within 24 hours of ED arrival between June 1, 2017, and December 31, 2023. Data were analyzed from March 1 to December 31, 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Epinephrine vs norepinephrine as the first vasoactive medication received.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary outcome was major adverse kidney events by 30 days (MAKE30). Secondary outcomes were 30-day in-hospital mortality, 3-day mortality, need for kidney replacement therapy or persistent kidney dysfunction, endotracheal intubation, mechanical ventilation days, extracorporeal membrane oxygenation, and hospital and intensive care unit length of stay. Primary and secondary outcomes were assessed with the \u03c7\n 2<\/jats:sup>\n test of proportions for binary variables and Wilcoxon rank sum test for continuous variables.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 231 included encounters, the median (IQR) age was 11.4 (5.6-15.4) years, 126 were female (54.6%), and 142 had a medical history that predisposed them to sepsis (61.5%). Most (147 [63.6%]) initially received an epinephrine infusion and 84 (36.4%) received norepinephrine. In the epinephrine group, 9 of 147 (6.1%) met the outcome of MAKE30 and 6 of 147 (4.1%) died within 30 days. In the norepinephrine group, 3 of 84 (3.6%) met MAKE30 and there were no deaths. After inverse probability of treatment weighting, there were no significant differences in the primary outcome, MAKE30. With 2:1 propensity matching, epinephrine was associated with greater 30-day mortality compared with norepinephrine (3.7% vs 0%; risk difference: 3.7%; 95% CI, 0.2%-7.2%).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, those receiving epinephrine had greater 30-day mortality but no difference in MAKE30. Prospective, confirmatory studies are needed to determine if norepinephrine should be the first-line vasoactive agent in pediatric septic shock.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.4720","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:30:35Z","timestamp":1744371035000},"page":"e254720","source":"Crossref","is-referenced-by-count":17,"title":["Epinephrine vs Norepinephrine as Initial Treatment in Children With Septic Shock"],"prefix":"10.1001","volume":"8","author":[{"given":"Matthew A.","family":"Eisenberg","sequence":"first","affiliation":[{"name":"Division of Emergency Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Georgette","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra H.","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Priebe","sequence":"additional","affiliation":[{"name":"Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Division of Infectious Diseases, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Monuteaux","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"issue":"3","key":"zoi250208r1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S2213-2600(18)30063-8","article-title":"The global burden of paediatric and neonatal sepsis: a systematic review.","volume":"6","author":"Fleischmann-Struzek","year":"2018","journal-title":"Lancet Respir Med"},{"issue":"4","key":"zoi250208r2","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1001\/jama.2018.9071","article-title":"Association between the new york sepsis care mandate and in-hospital mortality for pediatric sepsis.","volume":"320","author":"Evans","year":"2018","journal-title":"JAMA"},{"issue":"1","key":"zoi250208r3","doi-asserted-by":"publisher","DOI":"10.1097\/pq9.0000000000000051","article-title":"A quality improvement collaborative for pediatric sepsis.","volume":"3","author":"Paul","year":"2018","journal-title":"Pediatr Qual Saf"},{"issue":"1","key":"zoi250208r4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-1434","article-title":"Development of a quality improvement learning collaborative to improve pediatric sepsis outcomes.","volume":"147","author":"Larsen","year":"2021","journal-title":"Pediatrics"},{"issue":"2","key":"zoi250208r5","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1097\/CCM.0b013e31819323c6","article-title":"Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine.","volume":"37","author":"Brierley","year":"2009","journal-title":"Crit Care Med"},{"issue":"2","key":"zoi250208r6","doi-asserted-by":"publisher","first-page":"e52","DOI":"10.1097\/PCC.0000000000002198","article-title":"Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.","volume":"21","author":"Weiss","year":"2020","journal-title":"Pediatr Crit Care Med"},{"issue":"6","key":"zoi250208r7","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1097\/CCM.0000000000002425","article-title":"American College of Critical Care medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock.","volume":"45","author":"Davis","year":"2017","journal-title":"Crit Care Med"},{"issue":"5","key":"zoi250208r8","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1097\/PCC.0000000000001502","article-title":"Hospital variation in risk-adjusted pediatric sepsis mortality.","volume":"19","author":"Ames","year":"2018","journal-title":"Pediatr Crit Care Med"},{"issue":"9","key":"zoi250208r9","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1097\/PCC.0000000000000225","article-title":"Pediatric severe sepsis in US children\u2019s hospitals.","volume":"15","author":"Balamuth","year":"2014","journal-title":"Pediatr Crit Care Med"},{"key":"zoi250208r10","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.jpeds.2018.03.056","article-title":"Children with chronic disease bear the highest burden of pediatric sepsis.","volume":"199","author":"Prout","year":"2018","journal-title":"J Pediatr"},{"issue":"10","key":"zoi250208r11","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1001\/jamapediatrics.2019.2570","article-title":"Cost of pediatric severe sepsis hospitalizations.","volume":"173","author":"Carlton","year":"2019","journal-title":"JAMA Pediatr"},{"issue":"9","key":"zoi250208r12","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1097\/PCC.0000000000001222","article-title":"The epidemiology of hospital death following pediatric severe sepsis: when, why, and how children with sepsis die.","volume":"18","author":"Weiss","year":"2017","journal-title":"Pediatr Crit Care Med"},{"issue":"11","key":"zoi250208r13","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1097\/CCM.0000000000001260","article-title":"Double-blind prospective randomized controlled trial of dopamine versus epinephrine as first-line vasoactive drugs in pediatric septic shock.","volume":"43","author":"Ventura","year":"2015","journal-title":"Crit Care Med"},{"issue":"11","key":"zoi250208r14","doi-asserted-by":"publisher","first-page":"e502","DOI":"10.1097\/PCC.0000000000000954","article-title":"Double-blind randomized clinical trial comparing dopamine and epinephrine in pediatric fluid-refractory hypotensive septic shock.","volume":"17","author":"Ramaswamy","year":"2016","journal-title":"Pediatr Crit Care Med"},{"issue":"11","key":"zoi250208r15","doi-asserted-by":"publisher","first-page":"e1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.","volume":"49","author":"Evans","year":"2021","journal-title":"Crit Care Med"},{"issue":"9","key":"zoi250208r16","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1056\/NEJM199602293340907","article-title":"Seminars in medicine of the Beth Israel Hospital, Boston: adrenergic receptors\u2013evolving concepts and clinical implications.","volume":"334","author":"Insel","year":"1996","journal-title":"N Engl J Med"},{"issue":"9","key":"zoi250208r17","doi-asserted-by":"publisher","first-page":"e426","DOI":"10.1111\/j.1651-2227.2012.02725.x","article-title":"Noradrenaline use for septic shock in children: doses, routes of administration and complications.","volume":"101","author":"Lampin","year":"2012","journal-title":"Acta Paediatr"},{"issue":"8","key":"zoi250208r18","doi-asserted-by":"publisher","first-page":"e378","DOI":"10.1097\/PCC.0000000000001230","article-title":"Short-term peripheral vasoactive infusions in pediatrics: Where is the harm?","volume":"18","author":"Patregnani","year":"2017","journal-title":"Pediatr Crit Care Med"},{"issue":"3","key":"zoi250208r19","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1590\/1806-9282.60.03.008","article-title":"Norepinephrine infusion increases urine output in children under sedative and analgesic infusion.","volume":"60","author":"Piva","year":"2014","journal-title":"Rev Assoc Med Bras (1992)"},{"issue":"8","key":"zoi250208r20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129305","article-title":"Vasopressors for the treatment of septic shock: systematic review and meta-analysis.","volume":"10","author":"Avni","year":"2015","journal-title":"PLoS One"},{"issue":"5","key":"zoi250208r21","doi-asserted-by":"publisher","first-page":"664","DOI":"10.2215\/CJN.12201018","article-title":"Major adverse kidney events in pediatric sepsis.","volume":"14","author":"Weiss","year":"2019","journal-title":"Clin J Am Soc Nephrol"},{"issue":"8","key":"zoi250208r22","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1001\/jama.2024.0196","article-title":"Development and validation of the Phoenix criteria for pediatric sepsis and septic shock.","volume":"331","author":"Sanchez-Pinto","year":"2024","journal-title":"JAMA"},{"issue":"25","key":"zoi250208r23","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1002\/sim.3697","article-title":"Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.","volume":"28","author":"Austin","year":"2009","journal-title":"Stat Med"},{"issue":"8","key":"zoi250208r24","doi-asserted-by":"publisher","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"147","author":"von Elm","year":"2007","journal-title":"Ann Intern Med"},{"issue":"5","key":"zoi250208r25","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/SHK.0000000000002427","article-title":"Outcomes of pediatric fluid-refractory septic shock according to different vasoactive strategies: a systematic review and meta-analysis.","volume":"62","author":"Marchetto","year":"2024","journal-title":"Shock"},{"issue":"1","key":"zoi250208r26","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13613-019-0545-4","article-title":"Translational gap in pediatric septic shock management: an ESPNIC perspective.","volume":"9","author":"Morin","year":"2019","journal-title":"Ann Intensive Care"},{"issue":"3","key":"zoi250208r27","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1152\/ajplegacy.1948.153.3.586","article-title":"A study of the adrenotropic receptors.","volume":"153","author":"Ahlquist","year":"1948","journal-title":"AM J Physiol"},{"issue":"2","key":"zoi250208r28","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1093\/oxfordjournals.bmb.a070031","article-title":"Peripheral vascular effects of noradrenaline, isopropylnoradrenaline and dopamine.","volume":"19","author":"Allwood","year":"1963","journal-title":"Br Med Bull"},{"issue":"12","key":"zoi250208r29","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1007\/s00134-008-1219-0","article-title":"A comparison of epinephrine and norepinephrine in critically ill patients.","volume":"34","author":"Myburgh","year":"2008","journal-title":"Intensive Care Med"},{"issue":"5","key":"zoi250208r30","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD003709.pub3","article-title":"Vasopressors for hypotensive shock.","author":"Havel","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"issue":"6","key":"zoi250208r31","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1152\/ajpheart.00450.2004","article-title":"Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock.","volume":"287","author":"Minneci","year":"2004","journal-title":"Am J Physiol"},{"issue":"8","key":"zoi250208r32","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1097\/PCC.0000000000003513","article-title":"Management changes after echocardiography are associated with improved outcomes in critically ill children.","volume":"25","author":"Ip","year":"2024","journal-title":"Pediatr Crit Care Med"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2832544\/eisenberg_2025_oi_250208_1743691927.45972.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:30:36Z","timestamp":1744371036000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2832544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.4720","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]}}}