IMPAIRED endothelium-dependent vasodilatation is present in children with high pulmonary flow and pressure which might be exacerbated by cardiopulmonary bypass (CPB). 1,2It has been reported that an increased pulmonary vascular resistance, either directly or as a surrogate of the systemic inflammatory response after cardiopulmonary bypass, has a significant effect on the postoperative recovery of infants after cardiac operations. 3Iloprost is the stable carbacyclin derivative of prostaglandin I2. The use of aerosolized prostaglandin I2has shown to be safe in healthy lambs with regard to coagulation parameters, hemodynamics, and pulmonary toxicity. 4,5Inhaled iloprost has been used as a diagnostic tool to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance, as well as intensive care unit treatment of pulmonary hypertension in a small series of children after cardiac surgery. 6In adults, inhaled iloprost has been successfully used to control pulmonary hypertension after CPB. 7However, no data are available about the intraoperative use of inhaled iloprost in infants younger than 1 yr with pulmonary hypertension undergoing cardiac surgery.
A 6-month-old infant girl, weighing 3.66 kg, was scheduled for atrial and ventricular septal closure. The preoperative medical history included gestational age of 29 weeks at birth, trisomy 21, and bronchopulmonary dysplasia. Preoperative cardiac catheterization revealed an unrestrictive ostium secundum type atrial septum defect and an unrestrictive perimembranous ventricular septal defect, resulting in pulmonary hypertension with a pulmonary-to-systemic perfusion ratio (Qp/Qs) of 1.4 and a pulmonary-to-systemic vascular resistance ratio (Rp/Rs) of 0.6. The preanesthetic medication consisted of aldactone, hydrochlorothiazide, digoxin, and antibiotics. In the operating room, general anesthesia was induced with fentanyl followed by pancuronium bromide and was maintained with fentanyl (total dose, 82 μg × kg−1), isoflurane (maximum end-tidal concentration 0.4 vol%), and midazolam (total dose, 0.4 mg × kg−1) after starting CPB. CPB was performed using nonpulsatile flow (2.4 l × min−1× m−2) with a membrane oxygenator in moderate hypothermia (rectal temperature > 33°C). To maintain full CPB flow at acceptable systemic pressures, the α-adrenergic antagonist urapidil (total dose, 1.0 mg × kg−1) was administered to keep the mean systemic blood pressure below 40 mmHg. Cold crystalloid cardioplegia (Bretschneider [histidine tryptophane ketoglutarate] solution, 110 ml) was given before clamping the aorta. The aortic clamping time was 65 min. During reperfusion of the heart, a loading dose of milrinone (50 μg × kg−1over 60 min) followed by a continuous infusion of 0.5 μg × kg−1× min−1was started. After a total CPB time of 112 min, weaning off CPB was successful at the first attempt. Inhaled iloprost (2.5 μg × kg−1over 20 min) was administered after weaning off CPB, because the mean pulmonary artery pressure/mean systemic blood pressure ratio (Pp/Ps) was increased to 0.72 and arterial oxygen saturation was 76%, despite hyperventilation (Paco2, 30–35 mmHg) with an inspired oxygen fraction of 1.0. Iloprost was prepared from a vial of Ilomedin 50 i.v.® (Schering AG, Berlin, Germany) containing iloprost 50 μg/2.5 ml and was diluted with isotonic saline to obtain a concentration of iloprost 2 μg/ml. For inhalation, 4.5 ml of iloprost 2 μg/ml were administered using an ultrasonic nebulizer. Inhaled iloprost decreased the Pp/Ps to 0.59 and increased the oxygen saturation to 90%. The hemodynamic parameters and oxygen saturation readings are summarized in table 1. The patient was transferred with stable hemodynamic parameters to the pediatric intensive care unit. However, 120 min after terminating inhalational therapy with iloprost, the Pp/Ps increased again to 0.81. The postoperative course was complicated by recurrent pulmonary hypertensive crises during recovery from anesthesia that required prolonged sedation, relaxation, and nonselective pulmonary vasodilators despite the application of inhaled nitric oxide (iNO). We speculate that this may be because of a higher sympathetic activation during recovery from anesthesia and/or a minor response to iNO. Inhaled iloprost, however, has not been used during mechanical ventilation in the pediatric intensive care unit. The patient was ventilated for 6 postoperative days and was discharged to the referring hospital on the seventh postoperative day.
This case report demonstrates that a single dose of inhaled iloprost (2.5 μg × kg−1over 20 min) may be used to decrease Pp/Ps and to improve oxygen saturation in an infant after weaning off CPB; 120 min later the Pp/Ps returned to baseline. A documented hemodynamic effect for 1 to 2 h has previously been described. 8The effective dose of inhaled iloprost in infants is not clear and seems to be dependent on the clinical setting. From previous applications, we speculate that a lower dose of inhaled iloprost is not very effective in infants after weaning off CPB, who were already hyperventilated with 100% oxygen. In accordance with Rimensberger et al. , 6we observed no decrease in systemic blood pressure even though we used a fivefold higher dose. This may be explained by our clinical setting (i.e. , immediately after weaning off CPB; intraoperative use of the systemic vasodilators urapidil and milrinone). Theoretically, different characteristics of the aerosol spray may result in different intrapulmonary drug depletion characteristics, which could explain the lack of spillover into systemic circulation. However, we used a tested ultrasonic nebulizer (Optineb®; Nebu-Tec, Elsenfeld, Germany) that provided an aerosol with a mass median aerodynamic diameter of the droplets of 3.4 μm.
Although iNO is widely used to decrease pulmonary vascular resistance in infants undergoing cardiac surgery, the effects of iNO vary among patients and cumbersome devices are necessary to administer iNO safely. 9,10Furthermore, rebound phenomena have been described with iNO withdrawal, bearing the risk of life-threatening pulmonary hypertensive crisis (e.g. , during transportation to the intensive care unit). 11Inhaled iloprost may, therefore, be an alternative for selective pulmonary vasodilation in infants undergoing cardiac surgery because it is effective, easy to use, and long-acting. Furthermore, from an economic point of view inhaled iloprost may be attractive because iNO became very expensive after approval by the Food and Drug Administration.