Nitric Oxide in Conjunction With Milrinone Better Stabilized Pulmonary Hemodynamics After Fontan Procedure

Abstract

Inhaled nitric oxide (iNO) has been used for patients with increased pulmonary vascular resistance (PVR) shortly after Fontan operation, but repeat deterioration of PVR during or shortly after its withdrawal remains a major concern. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, can also reduce PVR for postoperative patients with pulmonary hypertension. We hypothesized that iNO, in conjunction with milrinone, can provide additive benefits for pulmonary hemodynamics and reduce the occurrence of iNO withdrawal failure/rebound. Thirty-one patients with marked elevation of transpulmonary pressure gradient (TPG, >10 mm Hg) or central venous pressure (CVP, >15 mm Hg) after modified fenestrated Fontan operation were prospectively randomized into two groups, that is, group iNO (iNO at approximately 10 ppm, n = 15) and group iNO + Mil (iNO at approximately 10 ppm and milrinone at 0.5 microg/kg/min, n = 16). Hemodynamics, arterial blood oxygenation, and occurrence of withdrawal failure/rebound were compared between the two groups. Combined application of iNO and milrinone resulted in (i) more significant decrement of CVP (19.6 +/- 3.5% in group iNO + Mil vs. 15.2 +/- 4.6% in group iNO, P < 0.05) and TPG (18.2 +/- 4.8% in group iNO + Mil vs. 15.3 +/- 2.6% in group iNO, P < 0.05), (ii) more significant increment of systolic systemic arterial pressure (8.7 +/- 2.7% in group iNO + Mil vs. 5.2 +/- 3.1% in group iNO, P < 0.05), and (iii) more significant improvement of arterial oxygen saturation (9.3 +/- 3.2% in group iNO + Mil vs. 6.8 +/- 2.8% in group iNO, P < 0.01). Occurrence of iNO withdrawal failure during its weaning or rebound after its discontinuation was significantly lower in group iNO + Mil. The combined use of iNO and milrinone provided additive benefits as compared with exclusive use of iNO for patients with elevated PVR after Fontan procedure.

Nitric oxide, oxidative stress and inflammation in pulmonary arterial hypertension

“…Currently phase III trials are underway. Similar improvements in pulmonary hemodynamics have been reported when inhaled nitric oxide was combined with milirinone, a PDE-3 inhibitor (53). And finally there are several drugs currently undergoing clinical trials that are targeted at stimulating NO-independent soluable guanylyl cyclases.…”

Successful one-lung ventilation in a patient with the Fontan circulation undergoing thoracotomy: a case report

“…We did not administer NO during the operation because we planned early extubation suitable for the Fontan circulation, and repeated the deterioration of PVR after its withdrawal remained a concern. Cai et al [8] reported that the combined use of NO and milrinone optimally stabilized the pulmonary hemodynamics after a Fontan operation.…”

Phosphodiesterases: Emerging Therapeutic Targets for Neonatal Pulmonary Hypertension

“…In both series, the infants were already receiving iNO at the time that the milrinone was started, and significant improvements in oxygenation were observed with milrinone treatment (Bassler et al 2006; McNamara et al 2006). Similarly, in pediatric patients ( n = 46, average age 5 years) undergoing a Fontan procedure, postoperative use of milrinone in conjunction with iNO resulted in greater improvements in the transpulmonary gradient and arterial oxygen saturation versus those children treated with iNO alone or milrinone alone (Cai et al 2008a, b). These clinical case series all support an interesting potential role for milrinone in the treatment of neonatal pulmonary hypertension, especially when used in conjunction with iNO.…”