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 or ARDS.


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


METHODS
The intensive care unit of a university teaching hospital.


METHODS
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).


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 vascular [correction of vacular] resistance, hyperfusion, and the development of organ failure, including ARDS, in patients with sepsis.
Sanai
L
L
University Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK.
Haynes
W G
WG
MacKenzie
A
A
Grant
I S
IS
Webb
D J
DJ
D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D009102:Multiple Organ Failure; D010101:Oxygen Consumption; D011652:Pulmonary Circulation / Q000502:physiology; D011659:Pulmonary Gas Exchange; D012044:Regression Analysis; D012128:Respiratory Distress Syndrome / Q000097:blood*; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood*; D014655:Vascular Resistance / Q000502:physiology
D019332:Endothelin-1