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Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants
Karan R Kumar1,2, Elizabeth C Ciociola3, Kayla R Skinner2
1Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Insights
Combination pulmonary vasodilator therapy is increasingly used in infants, with inhaled nitric oxide and sildenafil being common. However, significant practice variations exist, highlighting the need for further research into optimal treatment strategies for infant pulmonary hypertension.
Area of Science:
- Neonatal pharmacology
- Pediatric critical care
- Pulmonary hypertension research
Background:
- Combination pulmonary vasodilator therapy is rising in pediatric critical care.
- Infant-specific data on combination therapy for pulmonary hypertension remains limited.
- This study addresses the pharmacoepidemiology of combination therapy in critically ill infants.
Purpose of the Study:
- To describe the use of combination pulmonary vasodilator therapy in critically ill infants.
- To analyze drug utilization patterns, including frequency, timing, and duration.
- To compare characteristics and outcomes of infants receiving combination versus monotherapy.
Main Methods:
- Retrospective analysis of a multicenter database (1997-2020).
- Inclusion of inborn infants receiving inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for >2 consecutive days.
- Comparison of clinical variables and drug use between combination and monotherapy groups.
Main Results:
- 9% of 7681 infants received combination therapy.
- Combination therapy infants had lower gestational age, birth weight, and higher mortality.
- Inhaled nitric oxide and sildenafil were most frequent; dual therapy with these was most common.
- Combination therapy use increased over time, with significant practice variation.
Conclusions:
- Combination pulmonary vasodilator therapy, particularly inhaled nitric oxide and sildenafil, is increasingly utilized in infants.
- Significant variations in clinical practice necessitate further research.
- Optimal combinations, sequencing, dosing, and indications require further investigation.
Background:
New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods:
We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination's frequency, timing, and duration and graphically represented drug use over time.
Results:
Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion:
Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
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