Sildenafil e hipertensión pulmonar neonatal

Julio 2009

Successful Weaning of Nitric Oxide Facilitated by a Single Dose of Sildenafil in a Baby With Persistent Pulmonary Hypertension of the Newborn
 

Kai Konig y cols; Mercy Hospital for Women Department of Paediatrics Melbourne, Victoria, Australia

Pediatric Pulmonology 44:837 (2009)

To the Editor:
 

We present the case of a 41 + 2 weeks gestation female infant that was born via vacuum extraction through thick meconium liquor in a rural hospital following an uneventful pregnancy. Apgar scores were 5, 6, and 6 at 1, 5, and 10 min, respectively. The baby was in significant respiratory distress and was intubated at 12 min of age, requiring FiO2 of 1.0 and peak inspiratory pressures (PIP) as high as 30 cmH2O. Inhaled nitric oxide (iNO) was initiated at 25 ppm, umbilical catheters placed, volume expansion and inotropes given, and sedation and muscle relaxation commenced. At 8 hr of age, the baby was transported via air ambulance to our neonatal intensive care unit.

The baby had significant pulmonary hypertension of the newborn (PPHN) with maximum right ventricular systolic pressures (RVSP) of 120mmHg on echocardiography. She required inotrope and vasopressor support for 8 days, endotracheal ventilation with high-frequency oscillation and conventional ventilation for 20 days, and sedation for 21 days, iNO was first weaned after 6 days with slowly improving RVSPs.

After 16 days on iNO, the infant was trialled off for the first time and failed, indicated by an increased oxygen requirement up to FiO2 0.8. A second weaning attempt failed 3 days later for the same reason. Prior to the third attempt she was given a single dose of oral Sildenafil 0.4 mg/kg to facilitate weaning. When iNO was ceased following Sildenafil, the infant’s oxygen requirement of FiO2 0.25 did not change. She was extubated to CPAP, and after 4 days she was weaned to room air. The patient was discharged after 30 days. On echocardiography prior discharge, the RVSP had dropped to 32mmHg. At a 6 months follow-up visit, she was neurologically normal and appropriately developed for her age.

Rebound pulmonary hypertension (PHT) commonly occurs in the process of withdrawing iNO.1–3 Atz and Wessel firstly reported the ameliorating effects of Sildenafil in iNO withdrawal in three infants after cardiac surgery.4 In 2006, Namachivayam et al.5 reported the results of a randomized controlled trial using a single dose of 0.4 mg/kg Sildenafil to prevent rebound PHT in 30 infants and children on iNO, in the paediatric intensive care unit. Most patients were post-cardiac surgery. This study demonstrated that one dose  of Sildenafil prevented all infants in the Sildenafil group from developing rebound PHT. In the control group however, 10 patients developed elevated pulmonary arterial pressures and 4 of those could not been weaned off iNO. Adverse effects were not reported. Our case of a baby with meconium aspiration and subsequent severe PPHN exemplifies that weaning of iNO treatment in this patient population can be problematic.

Sildenafil may be considered as a facilitating agent in the weaning process of iNO in neonates with severe PPHN, although it is recognized that further studies are needed in
this patient population.
 

Referencias

1. Miller OI, Tang SF, Keech A, Celermajer DS. Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 1995;346:51–52.

2. Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg 1996;62:1759– 1764.

3. Schulze-Neick I, Werner H, Penny DJ, Alexi-Meskishvili V, Lange PE. Acute ventilatory restriction children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension. Intensive Care Med 1999;25:76–80.

4. Atz AM,Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;91:307–310.

5. Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 2006;174:1042–1047.