Society of Cardiovascular Anesthesiologists

Literature Reviews

Nitroprusside in Critically Ill Patients with Left Ventricular Dysfunction and Aortic Stenosis

Khot UN, Novaro GM, Popovic ZB, Mills RM, Thomas JD, Tuzcu EM, Hammer D, Nissen SE, Francis GS N Engl J Med 2003;348:1756-63

Reviewers: Benjamin A. Kohl, M.D. Albert T. Cheung, M.D.
University of Pennsylvania

Survival in patients with aortic stenosis and left ventricular systolic dysfunction averages only one year without surgery. Aortic valve replacement increases survival and improves ventricular performance. However, managing patients with severe aortic stenosis and heart failure is challenging because traditional medical dogma states that vasodilator therapy to decrease left ventricular afterload is ineffective and dangerous in patients with severe aortic stenosis. Considering the large body of evidence supporting the benefits of afterload reduction in patients with heart failure, Khot and others from the Indiana Heart Physicians Group and the Cleveland Clinic Foundation performed the Use of Nitroprusside in Left Ventricular Dysfunction and Obstructive Aortic Valve Disease (UNLOAD) Study to reexamine the hemodynamic efficacy of vasodilator therapy in critically ill patients with congestive heart failure and severe aortic stenosis.

In the prospective non-randomized study, 25 patients with an aortic valve area <= 0 cm² by echocardiography, left ventricular ejection fraction (EF) <= 0.35, cardiac index (CI) <= 2.2 l/min/m² were administered nitroprusside by intravenous infusion titrated to achieve a mean arterial pressure (MAP) of 60-70 mm Hg. Patients were excluded if their MAP was less than 60 mm Hg or if they were receiving intravenous inotropic or vasopressor therapy on admission. The defined endpoint was a change in the CI from baseline at 6 hours or 24 hours. Patients entered had a mean aortic valve area of 0.6±0.2 cm², peak aortic valve gradient of 65±0.35 mm Hg, mean aortic valve gradient of 39±23 mm Hg, EF of 0.21±0.08, CI of 1.60±0.35 l/min/m² and MAP of 81±13 mm Hg. Nitroprusside was started at an initial dose of only 14±10 mcg/min. At six hours, the mean CI increased to 2.22±0.44 l/min/m² (p<0.001) at a mean nitroprusside dose of 103±67 mcg/min. At 24 hours, the mean CI increased further to 2.52±0.55 l/min/m² (p<0.001) at a mean nitroprusside dose of 128±96 mcg/min. There were no episodes of hypotension, arrhythmias or dyspnea, and serum creatinine decreased slightly after 24 hours of treatment. Survival at 30 days was 76%. There were 4 in-hospital deaths during medical therapy and 1 perioperative death. Of the survivors, 13 had aortic valve replacement, 1 had CABG only, 1 had percutaneous balloon valvuloplasty, and 6 transitioned to chronic medical therapy for heart failure.

The study provided compelling clinical evidence that vasodilator therapy administered cautiously in a highly monitored setting such as an intensive care unit or operating room can be safe and effective for improving hemodynamic performance in patients with severe aortic stenosis and low EF. The study results contradicted the long held belief that cardiac output cannot be increased across a stenotic valve or that systemic vascular tone contributed only minimally to left ventricular afterload in this condition. This revision of conventional medical wisdom expands the therapeutic options available for managing heart failure in patients with aortic stenosis in preparation for or during aortic valve replacement or valvuloplasty. Despite immediate improvements in cardiac output, early mortality was still 16% (4/25). The majority of survivors at 30 days had aortic valve replacement or valvuloplasty. Because there was no control group, it was not possible to determine if the short-term increase in CI from nitroprusside treatment actually decreased mortality or contributed to improvements in clinical outcome in comparison to conventional clinical management. The results of the study also provided evidence to support the use of other medications with vasodilator properties such as nitroglycerin, nicardipine, fenoldopam, nesirtide, or milrinone that may also improve the hemodynamic condition of patients low EF and aortic stenosis in heart failure without subjecting them to the potential risks of nitroprusside toxicity.

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