Endothelin production in sepsis and the adult respiratory distress syndrome

Objective
Septic shock is characterised by a decrease in systemic vascular resistance. Nevertheless, regional increases in vascular resistance can occur which may predispose to organ dysfunction, including the adult respiratory distress syndrome (ARDS). Because endothelial damage is a major feature of acute lung injury, we examined whether the potent endothelial vasoconstrictor peptide endothelin-1 plays a pathophysiological role in sepsis of ARDS.

Design
Plasma endothelin was measured in mixed venous, pulmonary capillary and arterial blood, and the relationship with outcome measures was determined.

Setting
The intensive care unit of a university teaching hospital.

Patients and participants
A consecutive series of well-characterised patients with sepsis syndrome, both with (n=11) and without (n=15) ARDS, and ventilated controls without sepsis or ARDS (n=7).

Measurements and results
Plasma endothelin was significantly elevated in patients with sepsis alone and in patients with sepsis and ARDS. Plasma endothelin did not differ among mixed venous, pulmonary capillary and systemic arterial blood. On multiple regression analysis, plasma endothelin correlated positively with organ failure score and with oxygen consumption, and negatively with the PaO2∶FiO2 ratio. There was no correlation with plasma creatinine, suggesting that decreased renal clearance did not account for the high plasma endothelin concentrations.

Conclusions
Although the lung does not appear to be the major site of endothelin production in critically ill patients with sepsis, increased endothelin production may contribute to regional increases in vacular resistance, hypoperfusion, and the development of organ failure, including ARDS, in patients with sepsis.