Vasopressin Proves Superior to Norepinephrine in Vasoplegic Shock

Jessica Swain, Mercer University College of Pharmacy

Vasoplegic syndrome is a complication of cardiopulmonary bypass, and has an incidence between 5% and 25% in cardiac surgery patients.  Vasoplegic syndrome or shock is characterized by hypotension, high or normal cardiac outputs and low systemic vascular resistance, and increased requirements for fluids and vasopressors during or after cardiopulmonary bypass.  Vasoactive infusions, such as phenylephrine or norepinephrine, have been used as treatments for intraoperative or postoperative vasoplegic syndrome. [1]

Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial [2]
Design Prospective, randomized, double-blind; N= 300
Objective To evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome
Study Groups Vasopressin (n= 149); norepinephrine (n= 151)
Methods Vasopressin and norepinephrine were mixed in identical 250-mL intravenous bags of 5% dextrose in water.  Infusion was started at 5 mL/h and increased by 2.5 mL/h every 10 minutes during the first hour to achieve maximum target rate of 30 mL/h.  Infusion was titrated to maintain a mean arterial pressure (MAP) of at least 65 mmHg.  If target MAP was not reached and further therapy was needed, open-label norepinephrine was started in addition to the study drug.  Severe postoperative complications were defined as stroke, requirement of mechanical ventilation for longer than 48 hours, deep sternal wound infection, reoperation, or acute renal failure.
Duration January 2012 to March 2014
Primary Outcome Measure Composite of mortality or severe postoperative complications within 30 days after randomization, length of ICU and hospital stay, and incidence of atrial fibrillation
Baseline Characteristics
Norepinephrine Vasopressin
Mean age, years 55 54
Male, n (%) 80 (53) 83 (55)
Mean weight, kg 70 73
Diabetes, n (%) 67 (44) 71 (47.6)
Hypertension, n (%) 77 (51) 74 (49.7)
History of acute myocardial infarction, n (%) 66 (43.7) 56 (37.6)
Congestive heart failure, n (%) 50 (33.1) 65 (43.6)
COPD, n (%) 65 (43) 54 (36.2)
Results
Norepinephrine Vasopressin p-value
Composite of primary outcome, n (%) 74 (49) 48 (32.2) 0.0014
30-day mortality 24 (15.9) 23 (15.4) 0.98
Mechanical

ventilation >48h

13 (8.6) 8 (5.4) 0.28
Sternal wound

infection

15 (9.9) 7 (4.7) 0.09
Reoperation 10 (6.6) 10 (6.7) 0.31
Stroke 4 (2.6) 4 (2.7) 0.97
Acute renal

failure

54 (35.8) 15 (10.3) <0.0001
Norepinephrine Vasopressin p-value
Length of ICU stay, days 6 5 0.005
Length of hospital stay, days 13 10 0.0016
Norepinephrine Vasopressin p-value
Atrial fibrillation, n (%) 124 (82.1) 95 (63.8) 0.0004
Adverse Events Common Adverse Events: not disclosed
Serious Adverse Events (vasopressin): digital ischemia (2%); mesenteric ischemia (2%); hyponatremia (8.1%); postoperative acute myocardial infarction (7.4%)
Percentage that Discontinued due to Adverse Events: not disclosed
Study Author Conclusions Vasopressin reduced the incidence of severe complications in patients with vasoplegic shock after cardiac surgery and reduced lengths of ICU and hospital stays.  Vasopressin also reduced occurrence of atrial fibrillation.

Vasopressin may be preferable to norepinephrine in the management of patients with vasoplegic syndrome after cardiac surgery.  The use of vasopressin in vasoplegic shock has the potential to decrease costs for patients due to the decreased length of stay and reduction in severe complications seen in this trial.  This study was conducted at one referral center for cardiac surgery in Sao Paulo, Brazil and may not have generalizability into other patient populations.  

References

[1] Fischer GW, Levin MA. Vasoplegia during cardiac surgery: current concepts and management. Semin Thorac Cardiovasc Surg. 2010;22(2):140-4.

[2] Hajjar LA, Vincent JL, Barbosa gomes galas FR, et al. Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial. Anesthesiology. 2017;126(1):85-93.

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