Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial

Abstract Background Shock is a condition with high mortality even with early intervention and treatment. Usual care for shock and hypotension in the Emergency Department (ED) is intravenous fluid resuscitation which can lead to fluid overload and other complications. When fluid therapy fails or risk...

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Main Authors: Lasse Paludan Bentsen, Thomas Strøm, Jakob Lundager Forberg, Gerhard Tiwald, Peter Biesenbach, Malik Kalmriz, Jens Henning Rasmussen, Nikolaj Raaber, Sören Möller, Mette Løkke, Gitte Boier Tygesen, Hanne Nygaard, Josephine Hyldgaard Brok, Julie Westergaard Andersen, Nikolett Bajusz, Mikkel Brabrand
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
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Online Access:https://doi.org/10.1186/s13049-025-01369-4
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author Lasse Paludan Bentsen
Thomas Strøm
Jakob Lundager Forberg
Gerhard Tiwald
Peter Biesenbach
Malik Kalmriz
Jens Henning Rasmussen
Nikolaj Raaber
Sören Möller
Mette Løkke
Gitte Boier Tygesen
Hanne Nygaard
Josephine Hyldgaard Brok
Julie Westergaard Andersen
Nikolett Bajusz
Mikkel Brabrand
author_facet Lasse Paludan Bentsen
Thomas Strøm
Jakob Lundager Forberg
Gerhard Tiwald
Peter Biesenbach
Malik Kalmriz
Jens Henning Rasmussen
Nikolaj Raaber
Sören Möller
Mette Løkke
Gitte Boier Tygesen
Hanne Nygaard
Josephine Hyldgaard Brok
Julie Westergaard Andersen
Nikolett Bajusz
Mikkel Brabrand
author_sort Lasse Paludan Bentsen
collection DOAJ
description Abstract Background Shock is a condition with high mortality even with early intervention and treatment. Usual care for shock and hypotension in the Emergency Department (ED) is intravenous fluid resuscitation which can lead to fluid overload and other complications. When fluid therapy fails or risk of complications are high, the next treatment step is the use of vasopressors for stabilisation. Noradrenaline therapy for hypotension and shock are commonly used in ED’s outside Scandinavia, but the evidence on the optimal initiation time is sparse. The lack of noradrenaline therapy in Scandinavia provides a unique environment to investigate the possible implications of early initiation. The aim of this trial is to investigate whether the use of early initiated noradrenaline compared to ED fluid therapy can improve blood pressure goals and by that, reduce the need for ICU admittance. Methods This protocol describes a pragmatic, multi-center, superiority randomized controlled trial, randomizing patients with hypotension to intervention or control. Eligible patients are ≥ 18-year-old who have received at least 500 ml intravenous fluids (including prehospital administration), and without suspected cardiogenic, haemorrhagic, anaphylactic, or neurogenic causes, or require direct ICU admittance due to non-hemodynamic severe organ failure. The intervention group receives noradrenaline initiated at 0.05 mcg/kg/min with a maximum of 0.15 mcg/kg/min through a peripheral venous catheter for up to 24 h. The control group receives usual care. Treatment is targeted for a systolic blood pressure ≥ 100 mmHg, a mean arterial pressure ≥ 65 mmHg or a clinician defined blood pressure target. We require a sample size of 320 patients to show a significant difference in proportion of patients achieving shock control within 90 min (primary endpoint). Key secondary outcomes include ICU free days alive within 30-days and 30-day all-cause mortality. Discussion Previous prospective randomized trials on early peripheral noradrenaline treatment for shock are sparse and are investigated in settings where noradrenaline use is already usual care. Since noradrenaline are not used as standard treatment for shock in Scandinavian EDs, this provides a unique opportunity not only to investigate the early initiation of noradrenaline for shock, but also comparing it directly to ED fluid only approach. Trial registration: EU CT ID 2023-504584-16-00. ClinicalTrials.gov NCT05931601. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05931601
format Article
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issn 1757-7241
language English
publishDate 2025-04-01
publisher BMC
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series Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
spelling doaj-art-aa10de5c2ffb4398ad2c0c7548e26bef2025-08-20T03:06:57ZengBMCScandinavian Journal of Trauma, Resuscitation and Emergency Medicine1757-72412025-04-0133111310.1186/s13049-025-01369-4Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trialLasse Paludan Bentsen0Thomas Strøm1Jakob Lundager Forberg2Gerhard Tiwald3Peter Biesenbach4Malik Kalmriz5Jens Henning Rasmussen6Nikolaj Raaber7Sören Möller8Mette Løkke9Gitte Boier Tygesen10Hanne Nygaard11Josephine Hyldgaard Brok12Julie Westergaard Andersen13Nikolett Bajusz14Mikkel Brabrand15Department of Emergency Medicine, Odense University HospitalDepartment of Clinical Research, University of Southern DenmarkDepartment of Emergency Medicine, Helsingborg HospitalEmergency Department, Zealand University HospitalDepartment of Clinical Research, University of Southern DenmarkEmergency Department, Gødstrup Regional HospitalDepartment of Emergency Medicine, Copenhagen University Hospital, Bispebjerg and Frederiksberg HospitalDepartment of Emergency Medicine, Aarhus University HospitalDepartment of Clinical Research, University of Southern DenmarkDepartment of Emergency Medicine, Odense University HospitalEmergency Department, Gødstrup Regional HospitalDepartment of Emergency Medicine, Copenhagen University Hospital, Bispebjerg and Frederiksberg HospitalDepartment of Emergency Medicine, Odense University HospitalDepartment of Emergency Medicine, Odense University HospitalEmergency Department, Zealand University HospitalDepartment of Emergency Medicine, Odense University HospitalAbstract Background Shock is a condition with high mortality even with early intervention and treatment. Usual care for shock and hypotension in the Emergency Department (ED) is intravenous fluid resuscitation which can lead to fluid overload and other complications. When fluid therapy fails or risk of complications are high, the next treatment step is the use of vasopressors for stabilisation. Noradrenaline therapy for hypotension and shock are commonly used in ED’s outside Scandinavia, but the evidence on the optimal initiation time is sparse. The lack of noradrenaline therapy in Scandinavia provides a unique environment to investigate the possible implications of early initiation. The aim of this trial is to investigate whether the use of early initiated noradrenaline compared to ED fluid therapy can improve blood pressure goals and by that, reduce the need for ICU admittance. Methods This protocol describes a pragmatic, multi-center, superiority randomized controlled trial, randomizing patients with hypotension to intervention or control. Eligible patients are ≥ 18-year-old who have received at least 500 ml intravenous fluids (including prehospital administration), and without suspected cardiogenic, haemorrhagic, anaphylactic, or neurogenic causes, or require direct ICU admittance due to non-hemodynamic severe organ failure. The intervention group receives noradrenaline initiated at 0.05 mcg/kg/min with a maximum of 0.15 mcg/kg/min through a peripheral venous catheter for up to 24 h. The control group receives usual care. Treatment is targeted for a systolic blood pressure ≥ 100 mmHg, a mean arterial pressure ≥ 65 mmHg or a clinician defined blood pressure target. We require a sample size of 320 patients to show a significant difference in proportion of patients achieving shock control within 90 min (primary endpoint). Key secondary outcomes include ICU free days alive within 30-days and 30-day all-cause mortality. Discussion Previous prospective randomized trials on early peripheral noradrenaline treatment for shock are sparse and are investigated in settings where noradrenaline use is already usual care. Since noradrenaline are not used as standard treatment for shock in Scandinavian EDs, this provides a unique opportunity not only to investigate the early initiation of noradrenaline for shock, but also comparing it directly to ED fluid only approach. Trial registration: EU CT ID 2023-504584-16-00. ClinicalTrials.gov NCT05931601. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05931601https://doi.org/10.1186/s13049-025-01369-4ShockHypotensionVasopressorNorepinephrineNoradrenalineFluid therapy
spellingShingle Lasse Paludan Bentsen
Thomas Strøm
Jakob Lundager Forberg
Gerhard Tiwald
Peter Biesenbach
Malik Kalmriz
Jens Henning Rasmussen
Nikolaj Raaber
Sören Möller
Mette Løkke
Gitte Boier Tygesen
Hanne Nygaard
Josephine Hyldgaard Brok
Julie Westergaard Andersen
Nikolett Bajusz
Mikkel Brabrand
Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Shock
Hypotension
Vasopressor
Norepinephrine
Noradrenaline
Fluid therapy
title Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
title_full Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
title_fullStr Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
title_full_unstemmed Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
title_short Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
title_sort early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department vasoshock a protocol for a pragmatic multi center superiority randomized controlled trial
topic Shock
Hypotension
Vasopressor
Norepinephrine
Noradrenaline
Fluid therapy
url https://doi.org/10.1186/s13049-025-01369-4
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