Nitric oxide: a new area in intensive care.

Abstract

The relaxing effects of nitric oxide on smooth muscles, first identified in 1987, inaugurated a new area of therapeutic efficacity in intensive care. Nitric oxide is synthesized by endothelial cells, macrophages, brain cells and other cells following immunological activation and plays a role in normal blood pressure homeostasis, neuromodulation, cytotoxicity and intracellular message transmission. Since inappropriate vasodilatation or shock may result from cytokine- or endotoxin-induced overproduction of nitric oxide, experiments have been conducted on the effect of nitric oxide synthase inhibitors on shock-induced hypotension. In animal models, results have demonstrated a new method for treating septic shock since infusing nitric oxide inhibitors can rapidly re-establish haemodynamics. Nevertheless, due to possible interference with the immune defense system further studies on the physiological, pharmacological and metabolic effects are required before routine antishock therapy can be used in the intensive care unit. Inversely, in pulmonary hypertension there may be an insufficient production of endogenous nitric oxide. Thus administration via inhalation would represent a promising replacement therapy. In addition, since nitric oxide is rapidly inactivated by haemoglobin, its vasodilatory effect is restricted to the pulmonary vasculature resulting in lowered pulmonary artery pressure without systemic vasodilatation. Effective protocols have been developed for primary pulmonary hypertension of the newborn and acute respiratory distress syndrome. The bronchodilatory effect of nitric oxide is another area suggesting an alternative approach to treating different causes of bronchoconstriction including asthma. The results of early clinical trials are awaited. When used in low concentrations under continuous monitoring, nitric oxide is a safe new therapeutic option for the treatment of pulmonary hypertension and nitric oxide inhibitors may have an important role to play in the management of septic shock.