Sildenafil for Pulmonary Embolism?

Abstract & Commentary

By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.

Synopsis: In a patient with severe pulmonary embolism and clinical deterioration despite thrombolytic therapy in whom more invasive therapy could not be undertaken, administration of oral sildenafil was associated with better hemodynamics and other clinical improvement.

Source: Ganiere V, et al. Dramatic beneficial effects of sildenafil in recurrent massive pulmonary embolism. Intensive Care Med. 2006;32:452-454.

A 58-year-old woman presented with 3 days of dyspnea and was shown by CT scan to have pulmonary thromboemboli. She was anticoagulated with low-molecular-weight heparin and was stable for 2 days, but then developed acute respiratory failure, was intubated, and transferred to the ICU. A transesophageal echocardiogram showed right ventricular dysfunction and an estimated pulmonary arterial systolic pressure of 100 mm Hg. Thrombolytic therapy was instituted, and over the next 2 days the patient was administered increasing doses of norepinephrine and dobutamine. Pulmonary arterial catheterization was performed, revealing a cardiac index of 2.1 L/min/m2, a mean pulmonary arterial pressure of 56 mm Hg, and a pulmonary vascular resistance index of 700 dynes/cm-5/m2. The patient’s family declined a proposed transfer to another facility where surgical therapy and nitric oxide were available.

She was then given 50 mg sildenafil by nasogastric tube, and 2 hours later the cardiac index had increased to 3.2 L/min/m2, with a decrease in mean pulmonary artery pressure to 46 mm Hg and a fall in pulmonary vascular resistance index to 425 dynes/cm-5/m2. The patient had previously been normotensive, and systemic arterial pressure did not fall with sildenafil administration. Sildenafil 50 mg 3 times daily was administered for several weeks and then slowly withdrawn. Echocardiography showed an estimated pulmonary arterial systolic pressure of 65 mm Hg at 3 months and 80 mm Hg at 9 months.

Commentary

Sildenafil, an enhancer of nitric oxide-mediated pulmonary vasodilation, is now approved by the US Food and Drug Administration for treating chronic pulmonary arterial hypertension. This case report from Switzerland illustrates the possibility of its use in selected instances of severe acute pulmonary hypertension.

There are a number of uncertainties about this case. The title of the article says "recurrent massive pulmonary embolism," but no documentation of recurrence was obtained, and it is not clear whether the patient was ever hypotensive, a criterion for most definitions of massive pulmonary thromboembolism.1 In these days of direct visualization of thromboemboli via CT angiography, the clots are often described as "massive" based on their number and size. However, there is a difference between anatomic extent and hemodynamic effects. To my knowledge the only clinical trials of thrombolysis or other intervention in massive pulmonary embolism have used either initial or refractory hypotension to define this condition. This patient also probably had chronic pulmonary hypertension, as shown by the very high initial pulmonary arterial systolic pressure (100 mm Hg) and the markedly elevated mean pulmonary arterial pressures obtained on follow-up echocardiograms up to 9 months after the episode of thromboembolism.

These quibbles about the case notwithstanding, it seems inevitable that sildenafil will be tried in the ICU (although its use in this context is not currently approved). Its use has already been reported in right-sided heart failure due to exacerbation of chronic pulmonary arterial hypertension,2 and there are reports of the administration of sildenafil in tandem with inhaled nitric oxide.3,4 However, a case report does not a clinical trial make, and intensivists would be wise to await the results of further investigations before trying this potentially promising, easy-to-administer therapy in their own practices.

References

  1. Kucher N, et al. Massive pulmonary embolism. Circulation. 2006;113:577-582.
  2. Ng J, et al. Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil? Br J Anaesth. 2005;94:774-777.
  3. Lewis GD, et al. Pulmonary thromboembolism superimposed on a congenital ventricular septal defect in a 50-year-old man: inhaled nitric oxide and sildenafil to the rescue. Cardiol Rev. 2004;12:188-190.
  4. Bigatello LM, et al. Sildenafil can increase the response to inhaled nitric oxide. Anesthesiology. 2000;92:1827-1829.