{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:41:26Z","timestamp":1787503286274,"version":"build-2736575974"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Respir Crit Care Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sepsis can influence blood volume, its distribution, vascular tone, and cardiac function. Persistent hypotension or the need for vasopressors after volume resuscitation is part of the definition of septic shock. Since increased positive fluid balance has been associated with increased morbidity and mortality in sepsis, timing of vasopressors in the treatment of septic shock seems crucial. However, conclusive evidence on timing and sequence of interventions with the goal to restore tissue perfusion is lacking. The aim of this narrative review is to depict the pathophysiology of hypotension in sepsis, evaluate how common interventions to treat hypotension interfere with physiology, and to give a resume of the results from clinical studies focusing on targets and timing of vasopressor in sepsis. The majority of studies comparing early versus late administration of vasopressors in septic shock are rather small, single-center, and retrospective. The range of \u201cearly\u201d is between 1 and 12\u2009hours. The available studies suggest a mean arterial pressure of 60 to 65\u2009mm Hg as a threshold for increased risk of morbidity and mortality, whereas higher blood pressure targets do not seem to add further benefits. The data, albeit mostly from observational studies, speak for combining vasopressors with fluids rather \u201cearly\u201d in the treatment of septic shock (within a 0\u20133-hour window). Nevertheless, the optimal resuscitation strategy should take into account the source of infection, the pathophysiology, the time and clinical course preceding the diagnosis of sepsis, and also comorbidities and sepsis-induced organ dysfunction.<\/jats:p>","DOI":"10.1055\/s-0041-1733897","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T18:39:12Z","timestamp":1632163152000},"page":"683-688","source":"Crossref","is-referenced-by-count":5,"title":["Should Vasopressors Be Started Early in Septic Shock?"],"prefix":"10.1055","volume":"42","author":[{"given":"Luca","family":"Cioccari","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University of Bern, Bern University Hospital, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan M.","family":"Jakob","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University of Bern, Bern University Hospital, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Takala","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University of Bern, Bern University Hospital, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"issue":"12","key":"ref1","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1007\/s00134-016-4514-1","article-title":"Understanding circulatory failure in sepsis","volume":"42","author":"A Bloch","year":"2016","journal-title":"Intensive Care Med"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","article-title":"Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016","volume":"43","author":"A Rhodes","year":"2017","journal-title":"Intensive Care Med"},{"issue":"18","key":"ref3","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1056\/NEJMoa1401602","article-title":"A randomized trial of protocol-based care for early septic shock","volume":"370","author":"D M Yealy","year":"2014","journal-title":"N Engl J Med"},{"issue":"14","key":"ref4","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJMoa1500896","article-title":"Trial of early, goal-directed resuscitation for septic shock","volume":"372","author":"P R Mouncey","year":"2015","journal-title":"N Engl J Med"},{"issue":"16","key":"ref5","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1056\/NEJMoa1404380","article-title":"Goal-directed resuscitation for patients with early septic shock","volume":"371","author":"S L Peake","year":"2014","journal-title":"N Engl J Med"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00134-016-4675-y","article-title":"Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database","volume":"43","author":"P E Marik","year":"2017","journal-title":"Intensive Care Med"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/CCM.0000000000002189","article-title":"Higher fluid balance increases the risk of death from sepsis: results from a large international audit","volume":"45","author":"Y Sakr","year":"2017","journal-title":"Crit Care Med"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1186\/s13054-014-0691-x","article-title":"Timing of norepinephrine in septic patients: NOT too little too late","volume":"18","author":"J S Rachoin","year":"2014","journal-title":"Crit Care"},{"issue":"07","key":"ref9","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.21037\/jtd.2020.02.21","article-title":"Should we start vasopressors very early in septic shock?","volume":"12","author":"G A Ospina-Tasc\u00f3n","year":"2020","journal-title":"J Thorac Dis"},{"issue":"09","key":"ref10","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1164\/rccm.201806-1034OC","article-title":"Early use of norepinephrine in septic shock resuscitation (CENSER): a randomized trial","volume":"199","author":"C Permpikul","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.annemergmed.2018.03.039","article-title":"Liberal versus restrictive intravenous fluid therapy for early septic shock: rationale for a randomized trial","volume":"72","author":"W H Self","year":"2018","journal-title":"Ann Emerg Med"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00134-018-5085-0","article-title":"The Surviving Sepsis Campaign bundle: 2018 update","volume":"44","author":"M M Levy","year":"2018","journal-title":"Intensive Care Med"},{"issue":"S 01","key":"ref13","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.21037\/jtd.2019.12.84","article-title":"Fluid resuscitation in sepsis: the great 30\u2009mL per kg hoax","volume":"12","author":"P E Marik","year":"2020","journal-title":"J Thorac Dis"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.annemergmed.2018.06.046","article-title":"The 2018 Surviving Sepsis Campaign's treatment bundle: when guidelines outpace the evidence supporting their use","volume":"73","author":"R Spiegel","year":"2019","journal-title":"Ann Emerg Med"},{"issue":"10","key":"ref15","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1097\/CCM.0b013e31825b916b","article-title":"Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis","volume":"40","author":"T D Corr\u00eaa","year":"2012","journal-title":"Crit Care Med"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s001340050509","article-title":"Increased microvascular water permeability in patients with septic shock, assessed with venous congestion plethysmography (VCP)","volume":"24","author":"F Christ","year":"1998","journal-title":"Intensive Care Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0140-6736(85)91447-3","article-title":"Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury","volume":"1","author":"A Fleck","year":"1985","journal-title":"Lancet"},{"issue":"05","key":"ref18","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/SHK.0000000000001197","article-title":"The effects of vasoconstriction and volume expansion on veno-arterial ECMO flow","volume":"51","author":"P W Moller","year":"2019","journal-title":"Shock"},{"issue":"08","key":"ref19","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJMra002709","article-title":"The pathogenesis of vasodilatory shock","volume":"345","author":"D W Landry","year":"2001","journal-title":"N Engl J Med"},{"issue":"06","key":"ref20","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10741-010-9176-4","article-title":"Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms","volume":"15","author":"A Flynn","year":"2010","journal-title":"Heart Fail Rev"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1053\/jcan.2001.22317","article-title":"Myocardial dysfunction in septic shock: Part I. clinical manifestation of cardiovascular dysfunction","volume":"15","author":"A Kumar","year":"2001","journal-title":"J Cardiothorac Vasc Anesth"},{"issue":"05","key":"ref22","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1097\/00003246-199205000-00014","article-title":"Right ventricular dysfunction in septic patients","volume":"20","author":"T Mitsuo","year":"1992","journal-title":"Crit Care Med"},{"issue":"08","key":"ref23","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00134-019-05670-6","article-title":"Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial","volume":"45","author":"T M Merz","year":"2019","journal-title":"Intensive Care Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s13054-015-0980-z","article-title":"Early dynamic left intraventricular obstruction is associated with hypovolemia and high mortality in septic shock patients","volume":"19","author":"J L Chauvet","year":"2015","journal-title":"Crit Care"},{"issue":"05","key":"ref25","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s10557-020-06998-8","article-title":"Vasopressin in patients with septic shock and dynamic left ventricular outflow tract obstruction","volume":"34","author":"M Balik","year":"2020","journal-title":"Cardiovasc Drugs Ther"},{"issue":"17","key":"ref26","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1056\/NEJMoa1312173","article-title":"High versus low blood-pressure target in patients with septic shock","volume":"370","author":"P Asfar","year":"2014","journal-title":"N Engl J Med"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1001\/jama.2019.0071","article-title":"Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: the ANDROMEDA-SHOCK randomized clinical trial","volume":"321","author":"G Hern\u00e1ndez","year":"2019","journal-title":"JAMA"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0140-6736(07)61344-0","article-title":"Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial","volume":"370","author":"D Annane","year":"2007","journal-title":"Lancet"},{"issue":"09","key":"ref29","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1056\/NEJMoa0907118","article-title":"Comparison of dopamine and norepinephrine in the treatment of shock","volume":"362","author":"D De Backer","year":"2010","journal-title":"N Engl J Med"},{"issue":"09","key":"ref30","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1056\/NEJMoa067373","article-title":"Vasopressin versus norepinephrine infusion in patients with septic shock","volume":"358","author":"J A Russell","year":"2008","journal-title":"N Engl J Med"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1186\/s13054-020-03204-x","article-title":"Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis","volume":"24","author":"Y Li","year":"2020","journal-title":"Crit Care"},{"issue":"05","key":"ref32","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1186\/s13054-014-0532-y","article-title":"Early versus delayed administration of norepinephrine in patients with septic shock","volume":"18","author":"X Bai","year":"2014","journal-title":"Crit Care"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jcrc.2019.11.004","article-title":"Delayed vasopressor initiation is associated with increased mortality in patients with septic shock","volume":"55","author":"D Colon Hidalgo","year":"2020","journal-title":"J Crit Care"},{"issue":"06","key":"ref34","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.arcmed.2019.10.003","article-title":"Early use of norepinephrine improves survival in septic shock: earlier than early","volume":"50","author":"M A Elbouhy","year":"2019","journal-title":"Arch Med Res"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13054-020-2756-3","article-title":"Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis","volume":"24","author":"G A Ospina-Tasc\u00f3n","year":"2020","journal-title":"Crit Care"},{"issue":"01","key":"ref36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00134-007-0862-1","article-title":"Liberal vs. conservative vasopressor use to maintain mean arterial blood pressure during resuscitation of septic shock: an observational study","volume":"34","author":"S Subramanian","year":"2008","journal-title":"Intensive Care Med"},{"issue":"03","key":"ref37","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.bja.2017.11.065","article-title":"Norepinephrine exerts an inotropic effect during the early phase of human septic shock","volume":"120","author":"O Hamzaoui","year":"2018","journal-title":"Br J Anaesth"},{"issue":"04","key":"ref38","doi-asserted-by":"crossref","first-page":"R142","DOI":"10.1186\/cc9207","article-title":"Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension","volume":"14","author":"O Hamzaoui","year":"2010","journal-title":"Crit Care"},{"issue":"03","key":"ref39","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1186\/cc13868","article-title":"Timing of vasopressor initiation and mortality in septic shock: a cohort study","volume":"18","author":"V Beck","year":"2014","journal-title":"Crit Care"},{"issue":"10","key":"ref40","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1097\/CCM.0000000000000520","article-title":"Interaction between fluids and vasoactive agents on mortality in septic shock: a multicenter, observational study","volume":"42","author":"J Waechter","year":"2014","journal-title":"Crit Care Med"},{"issue":"10","key":"ref41","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1097\/CCM.0000000000004476","article-title":"Evaluation of vasopressor exposure and mortality in patients with septic shock","volume":"48","author":"R J Roberts","year":"2020","journal-title":"Crit Care Med"},{"issue":"06","key":"ref42","doi-asserted-by":"crossref","first-page":"R181","DOI":"10.1186\/cc8167","article-title":"Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial","volume":"13","author":"M W D\u00fcnser","year":"2009","journal-title":"Crit Care"},{"issue":"07","key":"ref43","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00134-009-1427-2","article-title":"Arterial blood pressure during early sepsis and outcome","volume":"35","author":"M W D\u00fcnser","year":"2009","journal-title":"Intensive Care Med"},{"issue":"08","key":"ref44","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1007\/s00134-005-2688-z","article-title":"Hemodynamic variables related to outcome in septic shock","volume":"31","author":"M Varpula","year":"2005","journal-title":"Intensive Care Med"},{"issue":"01","key":"ref45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13613-018-0448-9","article-title":"Mean arterial pressure and mortality in patients with distributive shock: a retrospective analysis of the MIMIC-III database","volume":"8","author":"J-L Vincent","year":"2018","journal-title":"Ann Intensive Care"},{"issue":"04","key":"ref46","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/CCM.0b013e318206d2a3","article-title":"Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients","volume":"39","author":"X Monnet","year":"2011","journal-title":"Crit Care Med"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1007\/s00134-010-2013-3","article-title":"Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients","volume":"36","author":"J F Georger","year":"2010","journal-title":"Intensive Care Med"}],"container-title":["Seminars in Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1733897.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T18:43:55Z","timestamp":1632163435000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1733897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,20]]},"references-count":47,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2021,9,20]]},"published-print":{"date-parts":[[2021,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1733897","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1069-3424","1098-9048"],"issn-type":[{"value":"1069-3424","type":"print"},{"value":"1098-9048","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,20]]}}}