{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:07:38Z","timestamp":1777637258029,"version":"3.51.4"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) serves as a crucial salvage therapy for refractory shock; however, the optimal strategy for vasopressor management during extracorporeal circulatory support remains unclear. Norepinephrine is a cornerstone agent for maintaining perfusion pressure, yet the association between its dose intensity and patient outcomes remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the association between the norepinephrine-equivalent dose during the initial phase of VA-ECMO support and clinical outcomes in patients with refractory shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective cohort study, 135 patients with refractory shock supported by VA-ECMO in the intensive care unit (ICU) of our hospital from January 2020 to January 2025 were included. Patients were divided into a low-dose group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f68) and a high-dose group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f67) based on the median value of the mean norepinephrine-equivalent dose within 72\u202fh after ECMO initiation. Baseline characteristics, 30-day all-cause mortality, a composite endpoint of hemodynamic stability (proportion of time meeting target thresholds between 24 and 72\u202fh of ECMO support), successful ECMO weaning rate, ICU length of stay, total duration of vasopressor support, and indicators of tissue perfusion and organ function [24\u202fh lactate clearance,\n                      <jats:italic>\u0394<\/jats:italic>\n                      Sequential Organ Failure Assessment (SOFA) score, and the incidence of acute kidney injury] were compared between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, the high-dose group had significantly higher SOFA scores (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f4.156,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) and serum lactate levels (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f4.893,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) compared to the low-dose group. Survival analysis demonstrated a significantly lower 30-day cumulative survival rate in the high-dose group (log-rank \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f9.873,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.002). After adjustment using multivariable Cox regression, a high vasopressor dose remained an independent risk factor for mortality (HR\u202f=\u202f1.92, 95% CI 1.13\u20133.25,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.015). Regarding secondary outcomes, the proportion of patients achieving hemodynamic stability was significantly lower in the high-dose group (\u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f10.897,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001). This group also exhibited a lower successful ECMO weaning rate (\u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f8.352,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004), a longer ICU stay (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f2.341,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.021), and a prolonged duration of vasopressor support (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f3.894,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Tissue perfusion metrics revealed that the 24\u202fh lactate clearance rate was lower in the high-dose group (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f\u22123.125,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.002), and the improvement in SOFA score at 72\u202fh was worse (\n                      <jats:italic>t<\/jats:italic>\n                      \u202f=\u202f2.894,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004). Furthermore, the incidence of acute kidney injury (\u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f4.012,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.045) and the new-onset severe arrhythmias (\u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f5.124,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.024) were higher in the high-dose group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with refractory shock supported by VA-ECMO, a higher norepinephrine-equivalent dose during the initial support period is independently associated with an increased risk of death and worse clinical outcomes. This suggests the need for careful evaluation and optimization of vasopressor intensity, even when ECMO provides circulatory support.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1804565","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:05:27Z","timestamp":1777442727000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of norepinephrine dosage for hemodynamic stability during ECMO support in refractory shock: a retrospective study"],"prefix":"10.3389","volume":"13","author":[{"given":"Lele","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"ezad229","DOI":"10.1093\/ejcts\/ezad229","article-title":"Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry","volume":"64","author":"Anselmi","year":"2023","journal-title":"Eur J Cardiothorac Surg"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"ytae125","DOI":"10.1093\/ehjcr\/ytae125","article-title":"Has the role of veno-arterial extracorporeal membrane oxygenation in patients with cardiogenic shock following acute myocardial infarction been fully determined? A case report","volume":"8","author":"Nguyen","year":"2024","journal-title":"Eur Heart J Case Rep"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.3390\/medicina60111747","article-title":"The Jack-in-the-box: pericardial decompression syndrome managed by a multidisciplinary approach with early initiation of Veno-arterial extracorporeal membrane oxygenation: a case report","volume":"60","author":"Orban","year":"2024","journal-title":"Medicina"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"190.e5","DOI":"10.1016\/j.ajem.2024.09.034","article-title":"Severe caffeine poisoning with mexiletine successfully treated by extracorporeal methods","volume":"86","author":"Kohara","year":"2024","journal-title":"Am J Emerg Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3390\/jcm14010213","article-title":"The Management of Postpartum Cardiorespiratory Failure in a patient with COVID-19 and sickle cell trait requiring Extraorporeal membrane oxygenation support and Airflight transportation","volume":"14","author":"Pelouze","year":"2025","journal-title":"J Clin Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1093\/ehjacc\/zuac133","article-title":"Heart rate control and haemodynamic improvement with ivabradine in cardiogenic shock patient on mechanical circulatory support","volume":"11","author":"Colombo","year":"2022","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41420-023-01447-5","article-title":"Venlafaxine antagonizes the noradrenaline-promoted colon cancer progression by inhibiting the norepinephrine transporter","volume":"9","author":"Zhang","year":"2023","journal-title":"Cell Death Discov"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41586-024-07810-5","article-title":"Substrate binding and inhibition mechanism of norepinephrine transporter","volume":"633","author":"Ji","year":"2024","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1111\/aor.14646","article-title":"Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios","volume":"47","author":"Sugimura","year":"2023","journal-title":"Artif Organs"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/s41586-024-07638-z","article-title":"Transport and inhibition mechanisms of the human noradrenaline transporter","volume":"632","author":"Hu","year":"2024","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e20230068","DOI":"10.5935\/0004-2749.20230068","article-title":"Effects of tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective serotonin-norepinephrine reuptake inhibitors on the ocular surface","volume":"86","author":"Ismayilov","year":"2022","journal-title":"Arq Bras Oftalmol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"13464","DOI":"10.1038\/s41598-023-40719-z","article-title":"A matched case-control study on the effectiveness of extracorporeal cytokine adsorption in critically ill patients","volume":"13","author":"Jerman","year":"2023","journal-title":"Sci Rep"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"4081","DOI":"10.1111\/jocn.16561","article-title":"The influence of intensive care unit culture and environment on nurse decision-making when managing vasoactive medications: a qualitative exploratory study","volume":"32","author":"Hunter","year":"2023","journal-title":"J Clin Nurs"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"669","DOI":"10.5005\/jp-journals-10071-24231","article-title":"Comparison of norepinephrine and Terlipressin vs norepinephrine alone for Management of Septic Shock: a randomized control study","volume":"26","author":"Sahoo","year":"2022","journal-title":"Indian J Crit Care Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/s41586-024-07719-z","article-title":"Molecular basis of human noradrenaline transporter reuptake and inhibition","volume":"632","author":"Tan","year":"2024","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1111\/jpc.16226","article-title":"Noradrenaline use for neonatal circulatory support","volume":"58","author":"Hong","year":"2022","journal-title":"J Paediatr Child Health"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1021\/acschemneuro.5c00241","article-title":"A chemically stable Photocaged noradrenaline","volume":"16","author":"Buczynski","year":"2025","journal-title":"ACS Chem Neurosci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41586-022-04782-2","article-title":"Spatiotemporal dynamics of noradrenaline during learned behaviour","volume":"606","author":"Breton-Provencher","year":"2022","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/s41586-024-07437-6","article-title":"Dimerization and antidepressant recognition at noradrenaline transporter","volume":"630","author":"Zhang","year":"2024","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.aucc.2023.09.009","article-title":"Nurse management of noradrenaline infusions in intensive care units: an observational study","volume":"37","author":"Hunter","year":"2024","journal-title":"Aust Crit Care"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s13054-023-04583-7","article-title":"The vasopressin loading for refractory septic shock (VALOR) study: a prospective observational study","volume":"27","author":"Nakamura","year":"2023","journal-title":"Crit Care"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1443990","DOI":"10.3389\/fped.2024.1443990","article-title":"A pilot randomized controlled trial comparing noradrenaline and adrenaline as a first-line vasopressor for fluid-refractory septic shock in neonates","volume":"12","author":"Garegrat","year":"2024","journal-title":"Front Pediatr"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"547","DOI":"10.2131\/jts.50.547","article-title":"Successful multimodal treatment of venlafaxine overdose-induced catecholamine-refractory shock: a case report","volume":"50","author":"Hayakawa","year":"2025","journal-title":"J Toxicol Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"tkae081","DOI":"10.1093\/burnst\/tkae081","article-title":"Haemodynamic management of septic shock","volume":"13","author":"Kotani","year":"2025","journal-title":"Burns Trauma"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1804565\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:05:31Z","timestamp":1777442731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1804565\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":24,"alternative-id":["10.3389\/fmed.2026.1804565"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1804565","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"article-number":"1804565"}}