Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1770-1777

Intravenous Almitrine Combined with Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome

LLUIS GALLART, QIN LU, LOUIS PUYBASSET, G. S. UMAMAHESWARA RAO, PIERRE CORIAT, JEAN-JACQUES ROUBY, and The NO Almitrine Study Group

Unité de Réanimation Chirurgicale (Department of Anesthesiology), Hôpital de la Pitié-Salpétrière, University of Paris VI, France; Servei d'Anestesiologia, Hospital Universitari del Mar, Barcelona, Spain; and Department of Anaesthesia, National Institute of Mental Health and Neurosciences, Bengalore, India

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase Pa_O2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 µg · kg¹ · min¹, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 µg · kg¹ · min¹ of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O₂, Pa_O2 increased by 75 ± 8 mm Hg after iNO, by 101 ± 12 mm Hg after almitrine 4 µg · kg¹ · min¹, and by 175 ± 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, Pa_O2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure () increased by 1.4 ± 0.2 mm Hg with almitrine 4 µg/kg/ min (p < 0.001) and decreased by 3.4 ± 0.4 mm Hg with iNO and by 1.5 ± 0.3 mm Hg with the combination (p < 0.001). The maximum increase in Pa_O2 was obtained at almitrine concentrations  4 µg · kg¹ · min¹, whereas almitrine increased dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 µg · kg¹ · min¹ dramatically increases Pa_O2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O₂. The long-term consequences of this immediate beneficial effect remain to be determined.

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