Novel role of midodrine in pulmonary hypertension in liver transplant candidates

Abstract

Pulmonary hypertension (PH) in liver transplant candidates is associated with high morbidity and mortality in the pre-and post-liver transplantation period. There is a high incidence of acute right heart failure and death at the time of reperfusion when PH is not wellcontrolled preoperatively.(1,2) Portopulmonary hypertension (PoPH) is a rare form of pulmonary arterial hypertension (PAH) in patients with portal hypertension, with or without end-stage liver disease. The official definition includes the presence of portal hypertension with mean pulmonary arterial pressure (mPAP) 25 mm Hg, pulmonary artery wedge pressure (PAWP) 15 mm Hg, and pulmonary vascular resistance (PVR) > 3 Wood units (240 dyne/seconds/cm 25 ) as measured during right heart catheterization (RHC). Although the exact pathophysiology continues to be debated, the current understanding faults the shear stress acting on the pulmonary arteries by the high cardiac output (CO) state as one of the culprits for the vascular remodeling.(1,3)Pulmonary venous hypertension (PVH), increasingly recognized in liver transplant candidates, has a hemodynamic profile consistent with mPAP 25 mm Hg and PAWP > 15 mm Hg on RHC. The etiology of PVH in this population has been attributed either to high CO states or increased blood volume due to fluid shifts. Notably, a majority of these patients have concomitant left heart disease, commonly diastolic dysfunction.(4) Vigorous diuresis is often limited by azotemia inherent in managing this group of patients.The above-mentioned entities are thought to exist independent of each other. However, we have noted instances where interchange in the hemodynamic profiles between PoPH and PVH are seen in liver transplant candidates, particularly during periods of high CO. We describe 3 patients illustrating the novel role of midodrine in patients with this phenomenon. Patient 1A 47-year-old male with a history of cirrhosis presumed secondary to fatty liver disease presented with an echocardiogram showing a normal left ventricular ejection fraction (LVEF) and size, a severely dilated right ventricle (RV), a severely reduced RV function, and septal flattening. He was diagnosed with PoPH after RHC (Table 1). He was listed for liver transplantation after a decrease in mPAP < 35 mm Hg with 20 mg of sildenafil 3 times a day (tid), 5 mg of ambrisentan daily, and intravenous (IV) epoprostenol of 6 ng/ kg/minute.During his routine 3-month RHC while being listed, an increase in his PAWP to 23 mm Hg with an elevated CO (9.6 L/minute) was noted, which is consistent with PVH (Table 1). No significant hemodynamic changes were observed with increased diuresis, which necessitated the use of 10 mg of midodrine tid to increase systemic vascular resistance (SVR) in an effort to decrease his CO. Three weeks after initiation of midodrine, his hemodynamic profile returned to one more consistent with PoPH (Table 1). Despite an Abbreviations: CO, cardiac output; IV, intravenous; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary arterial pressu...

Midodrine use in critically ill patients: a narrative review

“…Aside from its well established uses for orthostatic hypotension and neurocardiogenic syncope, 60 midodrine has been used off-label for multiple clinical indications over the past 20 years. Case reports and case series report its use to maintain normotension in patients with a spinal cord injury 61 and following acute myocardial infarction, 62 to correct dysautonomia in chronic fatigue syndrome, 63 to decrease left ventricular outflow tract obstruction by improving filling in hypertrophic cardiomyopathy, 64 to decrease severity of shunt and hypoxemia in patients with right-to-left intracardiac shunting, 65 to increase systemic vascular resistance and reduce pulmonary pressures in porto-pulmonary hypertension, 66 and to decrease lymphatic flow in refractory chylothorax. 67 , 68 …”