Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery

Non-cardiac Surgery Clinical Trial

— VANCSIII  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03483753
• Other study ID #: 62586316.6.0000.0065
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: January 2019
• Est. completion date: October 2, 2023

Study information

• Verified date: October 2023
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2, 2023
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Circulatory Shock
• Non-cardiac Surgery
• Shock

Intervention

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
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

References & Publications (12)

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. — View Citation

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. 200 — View Citation

Gkisioti S, Mentzelopoulos SD. Vasogenic shock physiology. Open Access Emerg Med. 2011 Jan 6;3:1-6. doi: 10.2147/OAEM.S10388. eCollection 2011. — View Citation

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. — View Citation

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, Z — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	All-cause mortality	mortality rate of any cause	30 days after randomization
Secondary	Acute myocardial infarction	to compare between groups the incidence of acute myocardial infarction	30 days after randomization
Secondary	Cardiogenic shock	to compare between groups the incidence of cardiogenic shock	30 days after randomization
Secondary	Ventricular and / or supraventricular arrhythmia	to compare between groups the incidence of Ventricular and / or supraventricular arrhythmia	30 days
Secondary	Acute respiratory distress syndrome (ARDS)	to compare between groups the incidence of Acute respiratory distress syndrome (ARDS)	30 days
Secondary	Stroke and transient ischemic attack	to compare between groups the incidence of Stroke and transient ischemic attack	30 days
Secondary	Delirium	to compare between groups the incidence of Delirium	30 days
Secondary	Acute renal failure (AKIN 1 or more)	to compare between groups the incidence of Acute renal failure (AKIN 1 or more)	30 days
Secondary	Length of time in the Intensive Care Unit (ICU) and hospital	Length of time in the Intensive Care Unit (ICU) and hospital	30 days
Secondary	Length of mechanical ventilation	Length of mechanical ventilation	30 days
Secondary	Septic shock	to compare between groups the incidence of septic shock	30 days
Secondary	hospital and ICU readmission rate	hospital and ICU readmission rate	30 days
Secondary	Reoperation	number of patients who required reoperation	30 days
Secondary	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