Combined Inhaled Pulmonary Vasodilators in Cardiac Surgery: A Scoping Review

Pulmonary hypertension is a risk factor for increased morbidity and mortality in cardiac surgery. The use of a combination of inhaled vasodilator agents could have an improved effect on pulmonary vascular resistance in the perioperative cardiac surgery setting without causing the systemic side effect of hypotension observed with intravenous agents. There is currently limited evidence regarding the use of combination therapy for pulmonary hypertension in the context of cardiac surgery. A scoping review was conducted to retrieve relevant literature on the use of a combination of inhaled vasodilator agents in the treatment of pulmonary hypertension and/or right ventricular dysfunction in adults and children undergoing cardiac surgery. The authors searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2025 for relevant articles. They identified 23 studies including 432 patients. The combined inhaled therapies reported in the literature are nitric oxide or milrinone combined with prostacyclin analogues. Of the 23 studies, 18 reported a hemodynamic benefit of the drugs in decreasing pulmonary hypertension and improving right ventricular function. Decreased intraoperative and postoperative vasopressor and/or inotropic use also was observed. Moreover, the impact on clinical outcomes, such as difficulty in weaning from cardiopulmonary bypass and length of intensive care unit stay, showed conflicting results. No study has reported an impact on mortality, length of hospital stay, or other intraoperative or postoperative complications. Combined therapies are promising therapeutic alternatives for the management of pulmonary hypertension and/or right ventricular dysfunction in cardiac surgery, but more studies are required to determine their systemic effects and impact on clinical outcomes.