title: Perioperative sildenafil therapy for pulmonary hypertension in infants undergoing congenital cardiac defect closure.
abstract: OBJECTIVE
  Pulmonary hypertension in paediatric patients with ventricular septal defect remains one of the most important determinants of perioperative morbidity and mortality. Sildenafil is an oral, well-tolerated pulmonary vasodilator with few drug interactions. We studied the effect of oral sildenafil, when given before and after surgical closure compared with starting it postoperatively, on the pulmonary artery pressure and patients' outcome.
  
  
  METHODS
  We enrolled 101 infants with large ventricular septal defects who had moderate-to-severe pulmonary hypertension scheduled for surgical closure. They were randomly assigned to the sildenafil group (n = 51, mean age 10 months and mean weight 6.5 kg), in which oral sildenafil was started 2 weeks before surgery to be continued postoperatively, and to the control group (n = 50, mean age 11 months and mean weight 7.3 kg), in which sildenafil was started only postoperatively. It was started at 0.5 mg/kg and increased gradually to a maximum dose of 2 mg/kg in both groups.
  
  
  RESULTS
  Overall hospital mortality was 4.9%. Mean pulmonary artery pressure decreased significantly at all time points of recording in both groups (P < 0.0001). In the sildenafil group, it decreased preoperatively after sildenafil administration from 75.4 to 59.4 mmHg and postoperatively from 50.4 mmHg immediate post-cardiopulmonary bypass to reach 44.2 mmHg before discharge. In the control group, it decreased from 74.6 mmHg to 51 mmHg immediate post-cardiopulmonary bypass to reach 42.7 mmHg before discharge. No adverse effects have been recorded. Although there was no difference in the duration of mechanical ventilation and hospital stay between the two groups, intensive care unit stay was significantly shorter in the sildenafil group. Dobutamine doses were significantly higher in the sildenafil group; however, milrinone and epinephrine have been used more significantly in the control group.
  
  
  CONCLUSIONS
  The low cost, the oral availability and the good tolerability of sildenafil make it a suitable and simple alternative therapy for secondary pulmonary hypertension including persistent postoperative pulmonary hypertension associated with ventricular septal defect in resource limited places. However, starting sildenafil early before surgery does not add a great benefit in terms of improving postoperative pulmonary hypertension or patients' outcome.
authors.affiliation: Department of Cardiovascular & Thoracic Surgery, Ain Shams University, Cairo, Egypt.
authors.forename: Ashraf A H
authors.initials: AA
authors.lastname: El Midany
authors.forename: Ezzeldin A
authors.initials: EA
authors.lastname: Mostafa
authors.forename: Sherif
authors.initials: S
authors.lastname: Azab
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Hassan
mesh_terms: D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D062186:Arterial Pressure / Q000187:drug effects; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D004334:Drug Administration Schedule; D004534:Egypt; D005260:Female; D006345:Heart Septal Defects, Ventricular / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D017052:Hospital Mortality; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D007223:Infant; D007902:Length of Stay; D008297:Male; D019990:Perioperative Care; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000959:Antihypertensive Agents; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
keywords: Congenital heart disease; Pulmonary hypertension; Sildenafil; Ventricular septal defect