Phosphodiesterase Inhibitor-Based Vasodilation Improves Oxygen Delivery and Clinical Outcomes Following Stage 1 Palliation

J Am Heart Assoc. 2016 Nov 2;5(11):e003554. doi: 10.1161/JAHA.116.003554.


Background: Systemic vasodilation using α-receptor blockade has been shown to decrease the incidence of postoperative cardiac arrest following stage 1 palliation (S1P), primarily when utilizing the modified Blalock-Taussig shunt. We studied the effects of a protocol in which milrinone was primarily used to lower systemic vascular resistance (SVR) following S1P using the right ventricular to pulmonary artery shunt, measuring its effects on oxygen delivery (DO2) profiles and clinical outcomes. We also correlated Fick-based assessments of DO2 with commonly used surrogate measures.

Methods and results: Neonates undergoing S1P were treated according to best clinical judgment prior to (n=32) and following (n=24) implementation of a protocol that guided operative, anesthetic, and postoperative management, particularly as it related to SVR. A majority of the subjects (n=51) received a modified right ventricular to pulmonary artery shunt. In a subset of these patients (n=21), oxygen consumption (VO2) was measured and used to calculate SVR, DO2, and oxygen debt. Neonates treated with the protocol had significantly lower SVR (P=0.02), serum lactate (P<0.001), and Sa-vO2 difference (P<0.001) and a lower incidence of CPR requiring extracorporeal membrane oxygenation (E-CPR, P=0.02) within the first 72 postoperative hours. DO2 was closely associated with SVR (r2=0.78) but correlated poorly with arterial (SaO2) and venous (SvO2) oxyhemoglobin concentrations, the Sa-vO2 difference, and blood pressure.

Conclusions: A vasodilator protocol utilizing milrinone following S1P effectively decreased SVR, improved serum lactate, and decreased postoperative cardiac arrest. DO2 correlated more closely with SVR than with Sa-vO2 difference, highlighting the importance of measuring VO2 in this population.

Clinical trial registration: URL: Unique identifier: NCT02184169.

Keywords: hypoplastic left heart syndrome; hypoxia; oxygen; oxygen consumption; phosphodiesterase inhibitor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blalock-Taussig Procedure
  • Cardiopulmonary Resuscitation
  • Extracorporeal Membrane Oxygenation
  • Female
  • Heart Arrest / epidemiology
  • Heart Arrest / prevention & control*
  • Humans
  • Hypoplastic Left Heart Syndrome / surgery*
  • Infant, Newborn
  • Lactic Acid / metabolism
  • Male
  • Milrinone / therapeutic use*
  • Oxygen Consumption
  • Oxyhemoglobins / metabolism
  • Palliative Care
  • Perioperative Care
  • Phosphodiesterase 3 Inhibitors / therapeutic use*
  • Postoperative Complications / epidemiology
  • Postoperative Complications / prevention & control*
  • Vascular Resistance


  • Oxyhemoglobins
  • Phosphodiesterase 3 Inhibitors
  • Lactic Acid
  • Milrinone

Associated data