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Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery
Christian Stocker1, Daniel J Penny, Christian P Brizard
1Department of Intensive Care, Royal Children's Hospital, Flemington Road, 3052, Parkville, Victoria, Australia.
Insights
Intravenous sildenafil enhanced inhaled nitric oxide's (iNO) pulmonary vasodilator effects in infants post-cardiac surgery. However, sildenafil caused systemic hypotension and worsened oxygenation, with no improvement from iNO.
Area of Science:
- Cardiology
- Pediatric Intensive Care
- Pharmacology
Background:
- Pulmonary hypertension is a risk in infants post-cardiac surgery.
- Inhaled nitric oxide (iNO) is a primary treatment for neonatal pulmonary hypertension.
- The effects of intravenous sildenafil in conjunction with iNO in this population are not fully understood.
Purpose of the Study:
- To investigate the acute effects of intravenous sildenafil on hemodynamics and oxygenation.
- To examine the interaction between sildenafil and iNO in infants at risk of pulmonary hypertension after cardiac surgery.
Main Methods:
- A prospective, randomized trial was conducted in a pediatric intensive care unit.
- Fifteen ventilated infants undergoing cardiac surgery repair were enrolled.
- Infants received either iNO followed by intravenous sildenafil, or sildenafil followed by iNO, with hemodynamic and blood gas measurements taken at intervals.
Main Results:
- Both iNO and sildenafil individually reduced pulmonary vascular resistance index (PVRI).
- The combination of iNO and sildenafil resulted in further PVRI reduction.
- Sildenafil administration led to decreased systemic blood pressure and systemic vascular resistance, and impaired arterial oxygenation.
Conclusions:
- Intravenous sildenafil potentiates the pulmonary vasodilator effects of iNO in infants post-cardiac surgery.
- Sildenafil administration resulted in systemic hypotension and worsened oxygenation, which was not ameliorated by iNO.
Objective:
To investigate the acute effects of intravenous sildenafil on haemodynamics and oxygenation, and its interaction with inhaled nitric oxide (iNO) in infants at risk of pulmonary hypertension early after cardiac surgery.
Design:
Prospective, randomised trial.
Setting:
Paediatric intensive care unit of a children's hospital.
Patients And Participants:
Sixteen ventilated infants early after closure of ventricular or atrioventricular septal defects, were randomly assigned to one of two groups. The study was completed in 15 infants.
Interventions:
Studies were commenced within 7 h of separation from bypass. Seven infants received iNO (20 ppm) first, with the addition of intravenous sildenafil (0.35 mg/kg over 20 min) after 20 min. Eight infants received sildenafil first, iNO was added after 20 min. Vascular pressures, cardiac output and a blood gas were recorded at 0, 20 and 40 min.
Measurements And Results:
In infants receiving iNO first, iNO lowered the pulmonary vascular resistance index (PVRI) from 3.45 to 2.95 units (p=0.01); sildenafil further reduced PVRI to 2.45 units p<0.05). In those receiving sildenafil first, PVRI was reduced from 2.84 to 2.35 units (p<0.05) with sildenafil, and fell to 2.15 units (p=0.01) with the addition of iNO. In both groups, sildenafil reduced the systemic blood pressure and systemic vascular resistance (p<0.01) and worsened arterial oxygenation and the alveolar-arterial gradient (p<0.05).
Conclusion:
Intravenous sildenafil augmented the pulmonary vasodilator effects of iNO in infants early after cardiac surgery. However, sildenafil produced systemic hypotension and impaired oxygenation, which was not improved by iNO.
