Inhaled Pulmonary Vasodilators and Thoracic Organ Transplantation: Does Evidence Support Its Use and Cost Benefit?

Abstract

In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of perioperative morbidity and mortality. In lung transplantation, primary graft dysfunction remains a major obstacle because it can cause bronchiolitis obliterans and mortality. Pulmonary vasodilators have been used as an adjunct therapy for heart or lung transplantation, mainly to treat pulmonary hypertension, right ventricular failure, and associated refractory hypoxemia. Among pulmonary vasodilators, inhaled nitric oxide is unique in that it is selective in pulmonary circulation and causes fewer systemic complications such as hypotension, flushing, or coagulopathy. Nitric oxide is expected to prevent or attenuate primary graft dysfunction by decreasing ischemia-reperfusion injury in lung transplantation. However, when considering the long-term benefit of these medications, little evidence supports their use in heart or lung transplantation. Current guidelines endorse inhaled vasodilators for managing immediate postoperative right ventricular failure in lung or heart transplantation, but no guidance is offered regarding agent selection, dosing, or administration. This review presents the current evidence of inhaled nitric oxide in lung or heart transplantation as well as comparisons with other pulmonary vasodilators including cost differences in consideration of economic pressures to contain rising pharmacy costs.

Nitric Oxide in Cardiac Surgery: A Review Article

“…Therefore, despite almost 30 years of application history, we still do not have a solid evidence base and clear recommendations for the use of NO in cardiac surgery [ 259 ]. There is insufficient evidence to reach a consensus on the dosage, duration of therapy or impact on patient outcomes for conventional NO indications [ 260 ]. Relatively recent clinical data on the effectiveness of NO in the framework of perioperative organ-protection strategies in cardiac surgery lead the clinician and scientist to a real “terra incognita” [ 261 ].…”

Perioperative Management of Heart Transplantation: A Clinical Review

“…41 However, there is currently no clear evidence that this medication may improve long-term outcome in patients, and the cost/benefit ratio is questioned. 42 Finally, it was recently suggested, in a retrospective cohort of cardiac surgical patients with pulmonary hypertension or right ventricular failure, that the combination of inhaled milrinone and epoprostenol was associated with beneficial effects on hemodynamics. 43 The severe forms of primary graft dysfunction are traditionally managed with venoarterial ECMO, but up to 45% of patients with primary graft dysfunction have isolated right ventricular dysfunction.…”

Thoracic Transplant Anesthesiology: Keeping Up With Advances and Developments of Allied Specialties

“…25 Krebs and Morita did an excellent review of the scientific rationale and clinical evidence supporting the continued use of inhaled pulmonary vasodilators. 26 The authors concluded that inhaled pulmonary vasodilators are very useful in short-term therapy for acute right heart failure and pulmonary hypertensive crisis. No definite evidence exists to support the utility of inhaled nitric oxide in the prevention or treatment of PGD in humans.…”