Prostaglandin E

Intravenous PGE1 causes both pulmonary and systemic vasodilation and, in some critically ill patients, increases cardiac output and oxygen delivery.41 Although the effect on the pulmonary circulation is usually small, vasodilation is more marked under hypoxic conditions, and the nebulised drug improves ventilation-perfusion matching.21 PGE1 also inhibits platelet aggregation and neutrophil adhesion. The initial trial of PGE142 showed improved survival in trauma patients with respiratory failure. However, this benefit could not be reproduced in a subsequent multicentre trial43 in patients suffering from lung injury precipitated by surgery, trauma, or sepsis. The dose of PGE1 was limited by side effects, particularly systemic hypotension. More recent trials have used liposome technology to increase drug delivery while mitigating side effects.44 45 The use of a liposome itself is associated with immune modulating effects including downregu-lation of neutrophil adhesion molecules. A combined PGE1-liposome preparation in a rodent model of ALI reduced pulmonary neutrophil infiltration and capillary leak.46 However, although the phase II and III trials of liposomal PGE1 showed that patients with ARDS receiving the drug had more rapid improvements in the Pao2/Fio2 ratio, neither a survival benefit nor a reduced requirement for ventilatory support was found in the treatment group.44 45 Retrospective subgroup analysis suggested that high dose therapy might reduce the time to extubation.

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