Correspondence

Death in a Patient with Primary Pulmonary Hypertension after 20 mg of Nifedipine

N Engl J Med 1993; 329:812-813September 9, 1993

Article

To the Editor:

A favorable long-term effect of large doses of nifedipine or diltiazem has been reported in patients with primary pulmonary hypertension when the therapy was guided by invasive testing1. We had an unfortunate experience after such testing.

A 17-year-old previously healthy woman had dyspnea and fatigue for nine months. A diagnosis of primary pulmonary hypertension with right heart failure was made. The pulmonary-artery pressure was 95/52 mm Hg, the wedge pressure 17 mm Hg, and the cardiac output 1.8 liters per minute. Therapy consisted of warfarin, furosemide, and spironolactone. Single-lung transplantation was considered necessary.

Three weeks later, after the patient had experienced episodes of syncope at rest, a Swan-Ganz catheter was inserted. One hour later, the brachial-artery pressure was 116/62 mm Hg, the heart rate 115 beats per minute, the central venous pressure 17 mm Hg, the mean pulmonary-artery pressure 72 mm Hg, the cardiac output 1.8 liters per minute, and the arterial blood oxygen saturation 92 percent. Dobutamine (6 μg per minute per kilogram of body weight) had been infused for inotropic support for three days.

Nifedipine (20 mg) was given by mouth. The patient felt dizzy 37 minutes later. The brachial-artery pressure was 86/52 mm Hg, the heart rate was 130 beats per minute, the arterial blood oxygen saturation 90 percent, the mean pulmonary-artery pressure 60 mm Hg, the cardiac output 1.9 liters per minute, and the central venous pressure 26 mm Hg. The blood pressure declined further. The patient became unconscious. Atrioventricular and finally electromechanical dissociation ensued. Attempts at resuscitation were unsuccessful. An autopsy revealed idiopathic pulmonary hypertension with intimal and medial hypertrophy of the pulmonary arterioles. The mechanism of death was possibly peripheral vasodilatation and cardiodepression due to nifedipine.

Rich et al. (July 9, 1992, issue)1 consider patients with mean right atrial pressure above 20 mm Hg and cardiac output below 2.0 liters per minute to be too ill for testing with calcium-channel blockers2. Our patient did not meet these exclusion criteria. However, none of the patients of Rich and coworkers who benefited from calcium-channel blockers had as low a cardiac index or as high a right atrial pressure as our patient1. In addition, their patients were treated with digitalis, and the authors recommend diltiazem when the heart rate is above 100 beats per minute. Still, our experience suggests that caution should be used when one is testing with calcium-channel blockers in patients with primary pulmonary hypertension.

Juhani Partanen, M.D.
Markku S. Nieminen, M.D.
Kimmo Luomanmaki, M.D.
University Central Hospital, Helsinki 00290, Finland

2 References

1. 1

   Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327:76-81
   Full Text | Web of Science | Medline

2. 2

   Rich S, Kaufmann E. High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. J Am Coll Cardiol 1991;18:1323-1327
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Rich replies:

To the Editor: The authors describe the unfortunate death of a patient with primary pulmonary hypertension after treatment with 20 mg of oral nifedipine. In writing about our experience of using calcium-channel blockers in patients with primary pulmonary hypertension, we continually underscore the need to exercise caution in patients with marginal hemodynamic status. The patient described in this letter had all the signs of impending cardiogenic shock. Indeed, she required an infusion of dobutamine for hemodynamic support.

Although we have written extensively on our experience using calcium blockers in patients with pulmonary hypertension, it is impossible in published manuscripts to describe every anecdotal experience or caveat1,2. At our institution we have challenged more than 300 patients with calcium-channel blockers and have never had one episode of cardiogenic shock or a death. This underscores the critical importance of testing patients in an experienced setting.

Primary pulmonary hypertension is perhaps the most devastating disease that we encounter in cardiopulmonary medicine. Because it is uncommon, very few centers have gained much experience in treating patients who have it. However, for this reason, many investigators believe that the care of such patients should be left to centers with adequate experience.

We recently reported our experience with adenosine as a testing agent for patients with pulmonary hypertension3. The drug is extraordinarily safe, owing to its half-life of less than seven seconds, and is predictive of the response of calcium-channel blockers.

Stuart Rich, M.D.
University of Illinois at Chicago, Chicago, IL 60612-7323

3 References

1. 1

   Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327:76-81
   Full Text | Web of Science | Medline

2. 2

   Rich S, Kaufmann E. High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. J Am Coll Cardiol 1991;18:1323-1327
   CrossRef | Web of Science | Medline

3. 3

   Schrader BJ, Inbar S, Kaufmann L, Vestal RE, Rich S. Comparison of the effects of adenosine and nifedipine in pulmonary hypertension. J Am Coll Cardiol 1992;19:1060-1064
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Adriano R. Tonelli, Hassan Alnuaimat, Kamal Mubarak. (2010) Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension. Respiratory Medicine 104:4, 481-496
   CrossRef

2. 2

   A. R. Hemnes, P. R. Forfia, H. C. Champion. (2009) Assessment of pulmonary vasculature and right heart by invasive haemodynamics and echocardiography. International Journal of Clinical Practice 63, 4-19
   CrossRef

3. 3

   Nazzareno Galiè, Naushad Hirani, Alessandra Manes, Serena Romanazzi, Massimiliano Palazzini, Luca Negro, Angelo Branzi. (2007) Long-term therapeutic outcomes in pulmonary arterial hypertension. Current Medical Research and Opinion 23:s2, S11-S18
   CrossRef

4. 4

   Jess Mandel. 2006. Approach to the Patient With Pulmonary Hypertension. , 83-98.
   CrossRef

5. 5

   Jess Mandel. 2006. Treatment for Pulmonary Arterial Hypertension. , 99-118.
   CrossRef

6. 6

   &NA;. (1993) Nifedipine danger in primary pulmonary hypertension. Reactions Weekly &NA;:469, 2
   CrossRef

7. 7

   &NA;. (1993) Nifedipine. Reactions Weekly &NA;:469, 10
   CrossRef