Safety and Efficacy of Vasopressin After Fontan Completion: A Randomized Pilot Study

Abstract

Background: Arginine vasopressin is a nonapeptide hormone with effects on intracellular water transport and arterial tone that is used in distributive shock and following cardiopulmonary bypass. We sought to evaluate the safety and efficacy of vasopressin infusion on hemodynamics and fluid balance in the early postoperative period after Fontan completion.

Methods: We conducted a randomized, double-blinded, placebo-controlled study of vasopressin infusion for 24 hours after cardiopulmonary bypass for Fontan completion. Patient characteristics, hospital outcomes, and measures of hemodynamic parameters, urine output, chest tube drainage, fluid balance, laboratory data, and plasma arginine vasopressin concentrations were collected at baseline and for 48 postoperative hours. Data were analyzed using mixed-effect regressions.

Results: Twenty patients were randomized, 10 to vasopressin and 10 to placebo. Transpulmonary gradient (6.4 ± 0.5 vs 8.3 ± 0.5 mm Hg, P = .011) and chest tube drainage (23 ± 20 vs 40 ± 20 mL/kg, P = .028) for 48 hours after surgery were significantly lower in the vasopressin arm compared to placebo. Arginine vasopressin concentrations were elevated above baseline after surgery until 4 hours post cardiac intensive care unit admission in both arms, and higher in the vasopressin arm during postoperative infusion. No differences in sodium concentration, liver function, or renal function were noted between groups.

Conclusions: Vasopressin infusion after Fontan completion appears safe and was associated with reduced transpulmonary gradient and chest tube drainage in the early postoperative period. A larger multiinstitutional study may show further outcome benefit.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Cumulative chest tube drainage, urine output, and fluid balance over first 48 intensive care unit hours. The chest tube drainage was significantly lower in the vasopressin treatment group (P = .028). Data are displayed as group hourly means (dots) and 5%-95% confidence intervals (shading). (CT, chest tube.)

Figure 2.

Hemodynamic measures over first 48 intensive care unit hours. The transpulmonary pressure gradient was significantly lower in the vasopressin treatment group (P = .011). Data are displayed as group hourly means (dots) and 5%-95% confidence intervals (shading).

Figure 3.

Vasoactive support over first 48 intensive care unit hours. The milrinone infusion rate was significantly higher in the vasopressin treatment group during the first intensive care unit day (P = .009). Data are displayed as group hourly means (dots) and 5%-95% confidence intervals (shading).

Figure 4.

Study timeline and arginine vasopressin plasma levels in placebo and active vasopressin infusion treatment groups. Arginine vasopressin levels were elevated from baseline in both groups at study hours T6 and T12. Vasopressin treatment resulted in a sustained elevation in arginine vasopressin in the active treatment group through T28. Data are duration of study drug infusion (grey shading), plasma AVP mean concentration (dots), and 5%-95% confidence intervals (color shading). (ICU, intensive care unit; POD, postoperative day.)