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Acetazolamide for Monge's Disease

Efficiency and Tolerance of 6-Month Treatment

¹ Université Paris 13, Laboratoire "Réponses cellulaires et fonctionnelles à l'hypoxie", EA 2363, ARPE, UFR SMBH, Bobigny, France; ² AP-HP, Hôpital Avicenne, Service de Physiologie et Explorations Fonctionnelles, Service de Pharmacie, Bobigny, France; ³ Universidad Peruana Cayetano Heredia, Facultad de Ciencias y Filosofía, Dpto. de Ciencias Biológicas y Fisiológicas, Laboratorio de Fisiología Comparada, Lima, Peru; ⁴ CHU Grenoble, Pôle Urgences, La Tronche, France; and ⁵ AP-HP, Hôpital Jean Verdier, Service de Physiologie et Explorations Fonctionnelles, Bondy, France

Correspondence and requests for reprints should be addressed to Pr. Jean-Paul Richalet, M.D., Dr.Sc., Laboratoire EA 2363, UFR SMBH, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France. E-mail: richalet{at}smbh.univ-paris13.fr

Rationale: Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit.

Objectives: Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function.

Methods: A two-phase study was performed in patients (hematocrit 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated.

Measurements and Main Results: First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O₂ pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance.

Conclusions: Acz reduces erythrocytosis and improves pulmonary circulation in Monge's disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe.

Clinical trial registered with www.clinicaltrials.gov (NCT 00424970).

Key Words: hypoxia • altitude • pulmonary hypertension • chronic mountain sickness

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Chronic mountain sickness, affecting 10% of the population residing at high altitude, is characterized by an excessive number of red cells and pulmonary hypertension. A preliminary study showed that acetazolamide could be an efficient treatment. What This Study Adds to the Field This study showed that prolonged treatment with 250 mg acetazolamide (6 mo) is well tolerated and efficient in reducing hematocrit, increasing the arterial oxygen pressure, and increasing cardiac output.