Early Use of Vasopressin in Post-Fontan Management

The treatments for preventing and managing low cardiac output syndrome after congenital heart
surgery with cardiopulmonary bypass include manipulations of vascular volume and infusions of
phosphodiesterase inhibitors (milrinone) and catecholamines (epinephrine and norepinephrine)
for inotropic and vasoactive effects, all of which have associated risks which can contribute
to morbidity and mortality. Vasopressin, a vasoactive drug with efficacy in septic shock, has
also been utilized to improve postoperative hemodynamics after cardiac surgery in children.
It is a common institutional practice to use vasopressin in this patient population, but
usually after escalation through two or three other vasoactive drugs. There have been several
studies in pediatrics and adults which suggest that vasopressin is not inferior to other
vasoconstrictor therapies, and advantageous when looking at specific end points. The
investigators propose to randomize the use of vasopressin to use at an earlier point in our
typical post-operative medication strategy. The proposed study is a double blinded,
randomized, placebo control study of vasopressin infusion immediately after the completion
Fontan operation. The goal is to identify a vasoactive treatment strategy that improves
hemodynamics with lower catecholamine infusion burden, reduces volume of fluid resuscitation,
and reduces in-hospital resource utilization.

Neonatal and pediatric interventions associated with congenital heart disease (CHD) continue
to produce improved outcomes. There are no established guidelines for managing patients after
congenital heart surgery due to lesion-specific unique challenges in the post-operative
period. Volume resuscitation and catecholamine infusions are the traditional treatment
methods to maintain adequate perfusion. However, these two treatment modalities are
associated with increased risk of worsening lung function and prolonged ventilator support
with aggressive fluid resuscitation, increased myocardial oxygen demand, and precipitation of
arrhythmias. Given the multifactorial etiology of postoperative low cardiac output syndrome,
it is often unclear which catecholamine infusion is optimal to improve circulatory function.
Vasopressin, an alternative vasoactive therapy commonly utilized in shock, has been utilized
to improve postoperative hemodynamics in neonatal and pediatric patient populations and has
recently gained more attention.

The use of arginine vasopressin infusion in infants and children after cardiac surgery was
first reported in 1999 in a case series of 11 patients with vasodilatory shock in the
postoperative period. This case series reported initiation of vasopressin for hypotension
refractory to traditional treatment methods and reported a significant rise in hemodynamics
with improved blood pressure in all patients as well as weaning inotropic support in 10/11
patients. Since this study there have been conflicting reports regarding vasopressin levels
and the use of vasopressin to improve hemodynamics. Results from a study published in 2008
evaluated vasopressin levels in 39 patients with CHD in the pre and post-operative periods
and concluded that children do not have deficient levels of vasopressin following surgery
with cardiopulmonary bypass (CPB). In addition, lower levels were not associated with
hypotension. A larger study in 2010 of 121 patients who had congenital heart surgery with CPB
described results suggestive of clinically important hypotension associated with low
vasopressin levels. Several other publications have reported improved blood pressure and
decreased catecholamine usage in patients with CHD. Two of these reports have focused on
vasopressin use in infants with single ventricle physiology. In all of these reported case
series the vasopressin infusion has been initiated in the post-operative period as a rescue
therapy. None of the studies have advocated for initiation of vasopressin immediately
post-operatively and prior to a time period of hemodynamic instability, except for one
retrospective chart review by Alten et al. This study from 2012 initiated vasopressin in the
operating room after CPB in 19 neonates undergoing either an arterial switch for
d-transposition of the great arteries or the Norwood palliation procedure for hypoplastic
left heart syndrome. In this study, all neonates in whom vasopressin was initiated in the
operating room received significantly lower amounts of volume replacement and catecholamine
support in the immediate post-operative period. They also described lower heart rate, lower
incidence of arrhythmias, shorter duration of mechanical ventilation and shorter intensive
care unit stay when compared to lesion-matched control group. More recently in 2016, a single
center retrospectively reviewed their experience with vasopressin and patients undergoing
Fontan operations over a 10 year period and it's effects on chest tube output. They
determined that patients receiving vasopressin perioperatively had less chest tube output and
shorter duration of chest tube drainage in addition to shorter hospital length of stay and
improved fluid balance as compared to historical controls.

There is a gap in the literature describing improved outcomes with a specific targeted
vasoactive and inotropic therapy regimen to use in the post-operative Fontan procedure
patients. This proposed novel study will further provide evidence for outcome based
post-operative medical interventions. The proposed study is a double blinded, randomized
control study of vasopressin infusion versus placebo in the first 24-hours after Fontan
completion. The aim of this study is to evaluate the impact of vasopressin on the early
postoperative course in a relatively homogenous population, with specific attention to
catecholamine use, hemodynamics, pleural drainage, extracardiac organ function (kidney and
liver) and length of stay. Furthermore, the investigators plan to evaluate vasopressin levels
between the two groups.

Inclusion Criteria:

- Planned completion of Fontan palliation

- English or Spanish speaking

- Completion of Informed Consent

Exclusion Criteria:

- Previous failed attempts at Fontan completion with subsequent takedown

- Planned concomitant atrioventricular valvuloplasty or neoaortic valve or arch
reconstruction at the time of Fontan completion

- History of renal failure requiring renal replacement therapy

- Absence of informed consent