Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study

Abstract Background The Surviving Sepsis Campaign guidelines suggest adding arginine vasopressin (AVP) when norepinephrine (NE) doses reach 0.25–0.50 µg/kg/min in septic shock patients. However, relying solely on a NE threshold has limitations, as other factors may be valuable in guiding AVP therapy...

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Main Authors: Max Melchers, Vivienne de Smet, Chrissie Rooijakkers, Jonathan Huising, Wander Vermeulen, Beyza Nur Nisa Köktaş, Karlijn Johanna van de Vusse, Kimia Milani Sabzewar, Shakti Bedanta Mishra, Carina Bethlehem, Dirk P. Boer, Nedim Cimic, Mirella van Duijnhoven, Tim Frenzel, Jordi Liesveld, Gianluca Paternoster, Susanne Stads, Jan J. Weenink, Barbara Festen-Spanjer, Peter Pickkers, Arthur Raymond Hubert van Zanten
Format: Article
Language:English
Published: SpringerOpen 2025-04-01
Series:Annals of Intensive Care
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Online Access:https://doi.org/10.1186/s13613-025-01472-w
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author Max Melchers
Vivienne de Smet
Chrissie Rooijakkers
Jonathan Huising
Wander Vermeulen
Beyza Nur Nisa Köktaş
Karlijn Johanna van de Vusse
Kimia Milani Sabzewar
Shakti Bedanta Mishra
Carina Bethlehem
Dirk P. Boer
Nedim Cimic
Mirella van Duijnhoven
Tim Frenzel
Jordi Liesveld
Gianluca Paternoster
Susanne Stads
Jan J. Weenink
Barbara Festen-Spanjer
Peter Pickkers
Arthur Raymond Hubert van Zanten
author_facet Max Melchers
Vivienne de Smet
Chrissie Rooijakkers
Jonathan Huising
Wander Vermeulen
Beyza Nur Nisa Köktaş
Karlijn Johanna van de Vusse
Kimia Milani Sabzewar
Shakti Bedanta Mishra
Carina Bethlehem
Dirk P. Boer
Nedim Cimic
Mirella van Duijnhoven
Tim Frenzel
Jordi Liesveld
Gianluca Paternoster
Susanne Stads
Jan J. Weenink
Barbara Festen-Spanjer
Peter Pickkers
Arthur Raymond Hubert van Zanten
author_sort Max Melchers
collection DOAJ
description Abstract Background The Surviving Sepsis Campaign guidelines suggest adding arginine vasopressin (AVP) when norepinephrine (NE) doses reach 0.25–0.50 µg/kg/min in septic shock patients. However, relying solely on a NE threshold has limitations, as other factors may be valuable in guiding AVP therapy during septic shock. Therefore, we aimed to identify additional patient characteristics associated with AVP hemodynamic responsiveness. Methods A multicenter, prospective, observational study was conducted among adult ICU patients who met the predefined criteria for septic shock (not reaching the individual target mean arterial pressure despite adequate fluid resuscitation and NE base dose > 0.25 µg/kg/min) and received AVP therapy. AVP hemodynamic responsiveness was the primary study outcome, defined as stabilization or decrease of NE infusion rate two hours after initiating AVP. Secondary outcomes included shock duration and rebound hypotension following termination of AVP infusion. Univariate and multivariable regression analyses were performed to detect associations between characteristics and outcomes. Results Between May 2020 and October 2023, 200 septic shock patients originating from 11 different ICUs were included. Of these, 153 (79%) met the definition for AVP hemodynamic responsiveness. Obesity and hyperlactatemia was negatively associated with AVP-response (adjusted Odds Ratio [aOR] 0.30, 95%CI 0.14–0.65 and aOR 0.86, 95%CI 0.75–0.99, respectively), while a NE infusion rate ≥ 0.30 µg/kg/min showed positive odds of AVP response (aOR 2.33, 95%CI 1.06–5.14). Incidence of new-onset atrial fibrillation was lower in AVP responders than non-responders (4% vs. 14%, p = 0.013). Higher body mass index (BMI) , NE infusion rate and duration prior to AVP initiation was associated with longer shock duration (aOR 1.06, 95%CI 1.02–1.11, aOR 1.12, 95%CI 1.01–1.25, and 1.01 95% CI 1.00–1.03, respectively), while higher pH associated with lower likelihood of prolonged shock (aOR 0.80, 95%CI 0.64–0.99). Rebound hypotension occurred in 9% when AVP was terminated, and AVP duration > 24 h was negatively associated with rebound hypotension (OR 0.22, 95%CI 0.05–0.85). Conclusions Arterial lactate, pH, BMI, and NE duration and dose were associated with AVP responsiveness and shock duration during septic shock, and rebound hypotension occurred in 9% during recovery. Our findings suggest that beyond NE thresholds, specific factors could be considered to optimize adjunctive AVP therapy in septic shock patients. Graphical Abstract
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spelling doaj-art-e1e043ff8029476eb271c18e973aedd92025-08-20T02:55:36ZengSpringerOpenAnnals of Intensive Care2110-58202025-04-0115111410.1186/s13613-025-01472-wHemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry studyMax Melchers0Vivienne de Smet1Chrissie Rooijakkers2Jonathan Huising3Wander Vermeulen4Beyza Nur Nisa Köktaş5Karlijn Johanna van de Vusse6Kimia Milani Sabzewar7Shakti Bedanta Mishra8Carina Bethlehem9Dirk P. Boer10Nedim Cimic11Mirella van Duijnhoven12Tim Frenzel13Jordi Liesveld14Gianluca Paternoster15Susanne Stads16Jan J. Weenink17Barbara Festen-Spanjer18Peter Pickkers19Arthur Raymond Hubert van Zanten20Department of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Siksha ‘O’ Anusandhan University HospitalDepartment of Intensive Care, Medical Center LeeuwardenDepartment of Intensive Care, Maasstad HospitalDepartment of Intensive Care, Tjongerschans HospitalDepartment of Intensive Care, Viecuri Medical CenterDepartment of Intensive Care, Radboud University Medical CenterDepartment of Intensive Care, Rivierenland HospitalDepartment of Health Science Anesthesia and ICU School of Medicine, University of Basilicata San Carlo HospitalDepartment of Intensive Care, Ikazia HospitalDepartment of Intensive Care, Spaarne GasthuisDepartment of Intensive Care, Gelderse Vallei HospitalDepartment of Intensive Care, Radboud University Medical CenterDepartment of Intensive Care, Gelderse Vallei HospitalAbstract Background The Surviving Sepsis Campaign guidelines suggest adding arginine vasopressin (AVP) when norepinephrine (NE) doses reach 0.25–0.50 µg/kg/min in septic shock patients. However, relying solely on a NE threshold has limitations, as other factors may be valuable in guiding AVP therapy during septic shock. Therefore, we aimed to identify additional patient characteristics associated with AVP hemodynamic responsiveness. Methods A multicenter, prospective, observational study was conducted among adult ICU patients who met the predefined criteria for septic shock (not reaching the individual target mean arterial pressure despite adequate fluid resuscitation and NE base dose > 0.25 µg/kg/min) and received AVP therapy. AVP hemodynamic responsiveness was the primary study outcome, defined as stabilization or decrease of NE infusion rate two hours after initiating AVP. Secondary outcomes included shock duration and rebound hypotension following termination of AVP infusion. Univariate and multivariable regression analyses were performed to detect associations between characteristics and outcomes. Results Between May 2020 and October 2023, 200 septic shock patients originating from 11 different ICUs were included. Of these, 153 (79%) met the definition for AVP hemodynamic responsiveness. Obesity and hyperlactatemia was negatively associated with AVP-response (adjusted Odds Ratio [aOR] 0.30, 95%CI 0.14–0.65 and aOR 0.86, 95%CI 0.75–0.99, respectively), while a NE infusion rate ≥ 0.30 µg/kg/min showed positive odds of AVP response (aOR 2.33, 95%CI 1.06–5.14). Incidence of new-onset atrial fibrillation was lower in AVP responders than non-responders (4% vs. 14%, p = 0.013). Higher body mass index (BMI) , NE infusion rate and duration prior to AVP initiation was associated with longer shock duration (aOR 1.06, 95%CI 1.02–1.11, aOR 1.12, 95%CI 1.01–1.25, and 1.01 95% CI 1.00–1.03, respectively), while higher pH associated with lower likelihood of prolonged shock (aOR 0.80, 95%CI 0.64–0.99). Rebound hypotension occurred in 9% when AVP was terminated, and AVP duration > 24 h was negatively associated with rebound hypotension (OR 0.22, 95%CI 0.05–0.85). Conclusions Arterial lactate, pH, BMI, and NE duration and dose were associated with AVP responsiveness and shock duration during septic shock, and rebound hypotension occurred in 9% during recovery. Our findings suggest that beyond NE thresholds, specific factors could be considered to optimize adjunctive AVP therapy in septic shock patients. Graphical Abstracthttps://doi.org/10.1186/s13613-025-01472-wSepsisShockNorepinephrineArginine vasopressinIntensive care unitBody mass index
spellingShingle Max Melchers
Vivienne de Smet
Chrissie Rooijakkers
Jonathan Huising
Wander Vermeulen
Beyza Nur Nisa Köktaş
Karlijn Johanna van de Vusse
Kimia Milani Sabzewar
Shakti Bedanta Mishra
Carina Bethlehem
Dirk P. Boer
Nedim Cimic
Mirella van Duijnhoven
Tim Frenzel
Jordi Liesveld
Gianluca Paternoster
Susanne Stads
Jan J. Weenink
Barbara Festen-Spanjer
Peter Pickkers
Arthur Raymond Hubert van Zanten
Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
Annals of Intensive Care
Sepsis
Shock
Norepinephrine
Arginine vasopressin
Intensive care unit
Body mass index
title Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
title_full Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
title_fullStr Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
title_full_unstemmed Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
title_short Hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock: insights from a prospective multicenter registry study
title_sort hemodynamic effects of adjunct arginine vasopressin to norepinephrine in septic shock insights from a prospective multicenter registry study
topic Sepsis
Shock
Norepinephrine
Arginine vasopressin
Intensive care unit
Body mass index
url https://doi.org/10.1186/s13613-025-01472-w
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