Phosphodiesterase Inhibitor-Based Vasodilation Improves Oxygen Delivery and Clinical Outcomes Following Stage 1 Palliation.
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 DO2with commonly used surrogate measures.



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-vO2difference (P<0.001) and a lower incidence of CPR requiring extracorporeal membrane oxygenation (E-CPR, P=0.02) within the first 72 postoperative hours. DO2was closely associated with SVR (r2=0.78) but correlated poorly with arterial (SaO2) and venous (SvO2) oxyhemoglobin concentrations, the Sa-vO2difference, and blood pressure.



A vasodilator protocol utilizing milrinone following S1P effectively decreased SVR, improved serum lactate, and decreased postoperative cardiac arrest. DO2correlated more closely with SVR than with Sa-vO2difference, highlighting the importance of measuring VO2in this population.



URL: http://www.clinicaltrials.gov. Unique identifier: NCT02184169.
Department of Cardiology, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
Kimberly I
KI
Mills
Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, MA.|Department of Surgery, Harvard Medical School, Boston, MA.
Aditya K
AK
Kaza
Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA.
Brian K
BK
Walsh
Department of Cardiology, Boston Children's Hospital, Boston, MA.
Hilary C
HC
Bond
Department of Cardiology, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
Mackenzie
M
Ford
Department of Cardiology, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
David
D
Wypij
Department of Cardiology, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
Ravi R
RR
Thiagarajan
Department of Cardiology, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
Melvin C
MC
Almodovar
Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, MA.|Department of Surgery, Harvard Medical School, Boston, MA.
Luis G
LG
Quinonez
Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, MA.|Department of Surgery, Harvard Medical School, Boston, MA.
Christopher W
CW
Baird
Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, MA.|Department of Surgery, Harvard Medical School, Boston, MA.
Sitaram E
SE
Emani
Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, MA.|Department of Surgery, Harvard Medical School, Boston, MA.
Frank A
FA
Pigula
Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA.|Department of Pediatrics, Harvard Medical School, Boston, MA.
James A
JA
DiNardo
Department of Cardiology, Boston Children's Hospital, Boston, MA john.kheir@childrens.harvard.edu.|Department of Pediatrics, Harvard Medical School, Boston, MA.
John N
JN
Kheir
D058366:Blalock-Taussig Procedure; D016887:Cardiopulmonary Resuscitation; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006323:Heart Arrest / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000601:surgery*; D007231:Infant, Newborn; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000378:metabolism; D010166:Palliative Care; D019990:Perioperative Care; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control*; D014655:Vascular Resistance
D010108:Oxyhemoglobins; D058987:Phosphodiesterase 3 Inhibitors; D019344:Lactic Acid; D020105:Milrinone
hypoplastic left heart syndrome; hypoxia; oxygen; oxygen consumption; phosphodiesterase inhibitor