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Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock
A B Groeneveld1, K J Hartemink, M C de Groot
1Medical Intensive Care Unit, Academic Hospital and Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands. johangroeneveld@compuserve.com
Abstract:
Activation of the nitric oxide (NO) pathway over that of endothelin in the vessel wall, as judged from circulating endothelin and nitrate-nitrite (NN) levels, may partly account for the hypotension associated with vasodilation, diminished catecholamine sensitiveness and O2 extraction, and lactic acidemia in human septic shock. In a prospective study, 14 consecutive patients with septic shock and a pulmonary artery catheter in place were included. For 3 days after admission, serial measurements of hemodynamic variables and plasma levels of endothelin and NN were done. The patients had a hyperdynamic circulation. Except for a higher final blood lactate level and more treatment with vasoconstricting catecholamines in nonsurvivors, global hemodynamic and O2-related variables did not differ between outcome groups. On the day of admission, circulating endothelin and NN levels were elevated and related to elevated levels of tumor necrosis factor-alpha and interleukin-6. The levels of endothelin increased in time in nonsurvivors as compared with survivors. The NN levels declined in survivors but not in nonsurvivors. The systemic vascular resistance indices (SVRI), global O2 extraction ratios, and blood lactate levels directly related to the endothelin levels. SVRI and global O2 extraction ratios inversely, and the lactate blood levels directly, related to NN levels, and the hemodynamic and metabolic parameters related directly to the ratio between endothelin and NN plasma levels on the days of the study. The vessel wall factors did not relate to the creatinine levels. The results suggest that the hemodynamic and metabolic peripheral abnormalities of human septic shock are mediated in part by cytokine-activated endothelin and NO systems in the vessel wall. They also suggest that increased production rather than diminished renal clearance accounts for elevated levels of NN and endothelin and that the latter are associated with a poor outcome.