Experimental and clinical results in shock lung treatment with vitamin E.

ABSTRACT

The adult respiratory distress syndrome (ARDS) is not confined only to late shock states but is a typical finding in intoxications with such oxidizing agents as O3, NO2, chlorate, or paraquat. Under experimental conditions, alpha-tocopherol in a high enteric dosage (2 x 50 mg/kg) was able to prevent alterations of pulmonary surface tension parameters (p less than 10(-5)) induced by microembolization of pulmonary vessels in awake rabbits. Parameters of gas exchange (PaO2' A-aDO2) were significantly less impaired (p less than 0.01) in the tocopherol group. Since there was no additional oxidative stress, the protective effect of tocopherol suggests an involvement of pathophysiologically occurring peroxidation mechanisms. Arachidonic acid (AA) metabolism is known to be a physiological oxygenation process yielding products with utmost biological efficacy. In a model of isolated, ventilated, and continuously perfused rabbit lungs, release or addition of AA resulted in an increase of pulmonary vascular resistance and permeability. The former could be ascribed to cyclooxygenase products, the latter to lipoxygenase products, of AA. The alpha-tocopherol effect in this model was a complex one the antioxidative chromane structure (Trolox) as well as superoxide dismutase (SOD) decreased both pulmonary vascular resistance and permeability induced by AA metabolism dose dependently to a large degree, whereas the phytyl side chain augmented both effects. Pharmacological efficacy of high-dose alpha-tocopherol is not yet completely understood. Since 1977, we have applied all-rac-alpha-tocopheryl acetate (6-8 x 300-500 mg/day by gastric tube) to patients with manifest or threatening ARDS in addition to the required conventional complex therapy. Out of 176 patients being artificially ventilated for at least four days in the Internal Intensive Care Unit, Giessen University, 87 received tocopherol and 89 did not. There was no statistically valid stratification or randomization of the patients. In general, the tocopherol-treated patients were considered to have the worse prognosis, as is confirmed by higher maximum FIO2 and PEEP values. Thirty-four tocopherol patients (39%) and 15 nontocopherol patients (17%) survived. Surviving tocopherol patients were ventilated for a mean of 10.0 +/- 7.7 days (with maxima of 25, 28, and 41 days), whereas surviving nontocopherol patients were ventilated only for 5.5 +/- 1.1 days (none of these for more than 8 days). Absorption of alpha-tocopherol by these severely ill patients was shown by gas chromatography. A well-prepared clinical trial for tocopherol therapy of ARDS is suggested.