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Long-term oral diazoxide therapy for pulmonary vascular obstructive disease associated with congenital heart defects
1Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh.
Insights
Diazoxide shows potential for treating pulmonary vascular obstructive disease (PVOD) in children with ventricular septal defects (VSD). While not statistically significant, IV and oral diazoxide suggest a possible benefit for PVOD, with one patient showing sustained improvement.
Area of Science:
- Pediatric Cardiology
- Pulmonary Hypertension
- Pharmacology
Background:
- Pulmonary vascular obstructive disease (PVOD) can develop after surgical correction of ventricular septal defects (VSD).
- Limited treatment options exist for PVOD secondary to VSD.
Purpose of the Study:
- To evaluate the short- and long-term effects of diazoxide on pulmonary vascular resistance (PVR) in children with PVOD post-VSD repair.
Main Methods:
- Six children with biopsy-proven PVOD after VSD closure received intravenous diazoxide.
- Pulmonary artery pressure (PAP), pulmonary flow index (PFI), and PVR were measured.
- Long-term oral diazoxide therapy was administered for approximately 20 months.
Main Results:
- Intravenous diazoxide showed a trend towards decreased PAP and PVR, but without statistical significance.
- Oral diazoxide did not significantly decrease PAP or PVR, though PFI showed a non-significant increase.
- One patient experienced a significant PVR reduction with IV diazoxide and maintained low PVR with oral therapy, showing symptomatic improvement.
Conclusions:
- Oral diazoxide may be a viable treatment for PVOD in children with VSD, particularly if a positive response is observed with intravenous administration.
- Diazoxide appears to be well-tolerated, with hypertrichosis as the main side effect in long-term use.
Abstract:
This report presents the results of short- and long-term effects of diazoxide on the pulmonary vascular resistance (PVR) in patients with pulmonary vascular obstructive disease (PVOD) secondary to delayed surgical correction of ventricular septal defect (VSD). Six children, aged 4 to 10 years, who had closure of VSD and who on lung biopsy showed PVOD, received intravenous diazoxide (1, 2, 4, 5, and 6 mg/kg) after measurements of pulmonary artery pressure (PAP), pulmonary flow index (PFI) by thermodilution technique, and PVR were made. The PAP (51 +/- 19 mm Hg versus 45 +/- 16 mm Hg) and PVR (11.5 +/- 2.7 units versus 8.9 +/- 3.8 units) though decreased, did not attain statistical significance (p greater than 0.1). The PFI (3.2 +/- 1.1 versus 3.4 +/- 0.6 L/min/m) did not change (p greater than 0.1). After oral diazoxide (5 to 10 mg/kg per day) for 20 +/- 3.4 months, the PAP (50.8 +/- 19 mm Hg) and PVR (10.6 +/- 5.8 units) did not decrease (p greater than 0.1), but PFI (4.4 +/- 0.9 L/min/m2), though increased, did not attain significance (p greater than 0.05). However, one of these children who had a fall in PVR from 8.5 to 4.5 units following intravenous diazoxide also had a lower resistance (3.9 units) after 20-months of oral diazoxide therapy and improved symptomatically. No complications other than hypertrichosis were encountered on long-term therapy. Based on this experience, it is suggested that oral diazoxide therapy may be used to improve PVOD if there is favorable response to intravenous diazoxide.