Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery (VANCSIII)

Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery: a Randomized and Controlled Trial

The purpose of the present study is to evaluate the effect of vasopressin compared to norepinephrine on the clinical complications of patients with vasospastic shock after noncardiac surgeries.

Study Overview

• Status: Withdrawn
• Conditions: Non-cardiac Surgery; Circulatory Shock
• Intervention / Treatment: Drug: Vasopressin; Drug: Norepinephrine

Detailed Description

The Systemic Inflammatory Response Syndrome (SIRS) is a common complication after non-cardiac surgery, impacting negatively on patient outcome and with high incidence rates. Vasoplegic syndrome is the most serious complication of SIRS and can happen after any type of surgery. The etiology of the vasoplegic syndrome has not yet been fully elucidated, but is known to occur more frequently in patients at high surgical risk, submitted to major surgeries, or in the presence of perioperative complications and patients with comorbidities. In this circumstance, the depletion of vasopressin stocks is described, which may contribute to the refractoriness of the shock and the lack of response to the catecholaminergic drugs. The standard treatment of perioperative vasoplegia has been adequate volume replacement and administration of vasopressors, with norepinephrine being the most commonly used. However, it is known that norepinephrine may have deleterious effects on the body and in 20% of patients with vasospastic shock it is ineffective. Previous studies have suggested benefits of adding vasopressin in refractory situations, especially in septic shock. Recently the VANCS study (Vasopressin or norepinephrine in the vasopregic shock after cardiac surgery: double-blind, controlled and randomized study) demonstrated superiority of vasopressin in the reversion of vasoplegic shock after cardiac surgery, as well as a lower incidence of renal insufficiency, atrial fibrillation and shorter hospitalization time. (Anesthesiology. 2017 Jan;126(1):85-93.)

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Tais F Szeles, MD; Phone Number: +5519992859415; Email: taisfelix@usp.br
• Study Contact Backup: Name: Ludhmila A Hajjar, MD, PhD; Phone Number: +55993194401; Email: ludhmila@terra.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age greater than 18 years;
• Patients undergoing high-risk non-cardiac surgery;
• vasopressor need within 24 hours after surgery, defined as mean arterial pressure (MAP) <65 mmHg after volume resuscitation with at least 1 liter of crystalloid solution (Ringer's lactate) and maintaining a cardiac index> 2.2 ml / min / m²;
• Signature of the informed consent form.

Exclusion Criteria:

• Allergy to vasoactive drugs;
• Previous use of vasopressor;
• Gestation;
• Presence of Raynaud's phenomenon, altered Allen's test, systemic sclerosis or vasospastic diathesis;
• Severe hyponatremia (Na <130 mEq / L);
• Acute mesenteric ischemia;
• Acute coronary syndrome;
• Participation in another study;
• Refusal to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Norepinephrine group; Blinded norepinephrine	Drug: Norepinephrine; Blinded Norepinephrine will be started if there is persistent hypotension, characterized by mean arterial pressure <65 mmHg after fluid replacement. Continuous infusion of the drug at doses ranging from 0.1 mcg / kg / min to 1.0 mcg / kg / min.; Other Names: Blinded Norepinephrine
Experimental: Vasopressin group; Blinded vasopressin	Drug: Vasopressin; Blinded Vasopressin will be started if there is persistent hypotension, characterized by mean arterial pressure <65 mmHg after fluid replacement. Continuous infusion of the drug at doses ranging from 0.01 U / min to 0.06 U / min; Other Names: Blinded Vasopressin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence between groups of a composite outcome of all-cause mortality, cardiovascular and renal complications after high-risk non-cardiac surgeries	Cardiovascular complications include: stroke, acute myocardial infarction, cardiogenic shock, nonfatal myocardial injury, and ventricular or supraventricular arrhythmias. Renal complications: Acute renal failure with AKIN stage 1 or higher or renal support therapy.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	mortality rate of any cause	30 days after randomization
Acute myocardial infarction	to compare between groups the incidence of acute myocardial infarction	30 days after randomization
Cardiogenic shock	to compare between groups the incidence of cardiogenic shock	30 days after randomization
Ventricular and / or supraventricular arrhythmia	to compare between groups the incidence of Ventricular and / or supraventricular arrhythmia	30 days
Acute respiratory distress syndrome (ARDS)	to compare between groups the incidence of Acute respiratory distress syndrome (ARDS)	30 days
Stroke and transient ischemic attack	to compare between groups the incidence of Stroke and transient ischemic attack	30 days
Delirium	to compare between groups the incidence of Delirium	30 days
Acute renal failure (AKIN 1 or more)	to compare between groups the incidence of Acute renal failure (AKIN 1 or more)	30 days
Length of time in the Intensive Care Unit (ICU) and hospital	Length of time in the Intensive Care Unit (ICU) and hospital	30 days
Length of mechanical ventilation	Length of mechanical ventilation	30 days
Septic shock	to compare between groups the incidence of septic shock	30 days
hospital and ICU readmission rate	hospital and ICU readmission rate	30 days
Reoperation	number of patients who required reoperation	30 days
Incidence of severe adverse events	to compare the incidence of severe adverse outcomes defined as mesenteric ischemia, digital ischemia, hyponatremia (Na<130mEq/L), myocardial infarction or stroke	30 days

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Juliano P Almeida, MD, PhD, University of Sao Paulo; Principal Investigator: Tais F Szeles, MD, University of Sao Paulo

Publications and helpful links

General Publications

• Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373.
• Dubin A, Pozo MO, Casabella CA, Palizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13(3):R92. doi: 10.1186/cc7922. Epub 2009 Jun 17.
• Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available.
• Levin MA, Lin HM, Castillo JG, Adams DH, Reich DL, Fischer GW. Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome. Circulation. 2009 Oct 27;120(17):1664-71. doi: 10.1161/CIRCULATIONAHA.108.814533. Epub 2009 Oct 12.
• Gkisioti S, Mentzelopoulos SD. Vasogenic shock physiology. Open Access Emerg Med. 2011 Jan 6;3:1-6. doi: 10.2147/OAEM.S10388. eCollection 2011.
• Teboul JL, Monnet X. Detecting volume responsiveness and unresponsiveness in intensive care unit patients: two different problems, only one solution. Crit Care. 2009;13(4):175. doi: 10.1186/cc7979. Epub 2009 Aug 10.
• Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR 3rd, Hirshberg EL, Grissom CK, Morris AH. Survival after shock requiring high-dose vasopressor therapy. Chest. 2013 Mar;143(3):664-671. doi: 10.1378/chest.12-1106.
• Morales D, Madigan J, Cullinane S, Chen J, Heath M, Oz M, Oliver JA, Landry DW. Reversal by vasopressin of intractable hypotension in the late phase of hemorrhagic shock. Circulation. 1999 Jul 20;100(3):226-9. doi: 10.1161/01.cir.100.3.226.
• Russell JA. Vasopressin, Norepinephrine, and Vasodilatory Shock after Cardiac Surgery: Another "VASST" Difference? Anesthesiology. 2017 Jan;126(1):9-11. doi: 10.1097/ALN.0000000000001435. No abstract available.
• Hajjar LA, Vincent JL, Barbosa Gomes Galas FR, Rhodes A, Landoni G, Osawa EA, Melo RR, Sundin MR, Grande SM, Gaiotto FA, Pomerantzeff PM, Dallan LO, Franco RA, Nakamura RE, Lisboa LA, de Almeida JP, Gerent AM, Souza DH, Gaiane MA, Fukushima JT, Park CL, Zambolim C, Rocha Ferreira GS, Strabelli TM, Fernandes FL, Camara L, Zeferino S, Santos VG, Piccioni MA, Jatene FB, Costa Auler JO Jr, Filho RK. Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial. Anesthesiology. 2017 Jan;126(1):85-93. doi: 10.1097/ALN.0000000000001434.
• Takenaka K, Ogawa E, Wada H, Hirata T. Systemic inflammatory response syndrome and surgical stress in thoracic surgery. J Crit Care. 2006 Mar;21(1):48-53; discussion 53-5. doi: 10.1016/j.jcrc.2005.07.001.
• Haga Y, Beppu T, Doi K, Nozawa F, Mugita N, Ikei S, Ogawa M. Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery. Crit Care Med. 1997 Dec;25(12):1994-2000. doi: 10.1097/00003246-199712000-00016.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2019
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Norepinephrine; Post-operative; Vasopressin; Critical Care
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Natriuretic Agents; Hemostatics; Coagulants; Sympathomimetics; Vasoconstrictor Agents; Antidiuretic Agents; Norepinephrine; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: 62586316.6.0000.0065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes