Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.)

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

Conditions
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Circulatory Shock, Non-cardiac Surgery

Intervention / Treatment
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* Drug: Vasopressin
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vasopressin group<br>Blinded vasopressin | Drug: Vasopressin<br>* 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<br>* Other names: Blinded Vasopressin;|
| Active Comparator: Norepinephrine group<br>Blinded norepinephrine | Drug: Norepinephrine<br>* 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.<br>* Other names: Blinded Norepinephrine;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vasopressin, Norepinephrine, Post-operative, Critical Care