British Journal of Anaesthesia, 2000, Vol. 84, No. 5 659
© 2000 The Board of Management and Trustees of the British Journal of Anaesthesia
Abstract |
Soluble adhesion molecules and endothelin in patients with fulminant hepatic failure: evidence for endothelial activation and injury
1 University Department of Anaesthetics, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh EH3 9YW, UK
2 University Department of Surgery, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh EH3 9YW, UK
Abstract
Fulminant hepatic failure (FHF) causes multiple organ dysfunction notably cardiovascular collapse, renal failure, and cerebral oedema. Endothelial–leucocyte interaction is implicated in the pathogenesis of organ dysfunction in the critically ill and is mediated via intercellular adhesion molecules. We have previously demonstrated early activation of circulating leucocytes in patients with FHF.
In this study we investigated endothelial activation by measuring circulating concentrations of endothelin and soluble selectins in patients with FHF.
We studied 14 patients with FHF (13 paracetamol-induced, 1 non-ABC hepatitis). All had grade III/IV encephalopathy, and were sedated, paralysed and mechanically ventilated. No patient had microbiological evidence of sepsis at the time of study. Arterial blood was centrifuged and stored at –70°C for subsequent analysis. Cardiovascular variables, oxygenation indices, prothrombin time, and multiple organ dysfunction scores (MODS) were recorded at the time of sampling. Analysis for soluble E, L, and P selectin and for endothelin-1 was by sandwich ELISA using commercial kits. All analyses were done in duplicate and concentrations averaged. For comparison venous blood was drawn from eight healthy volunteers.
Median prothrombin time in patients was 105 s (range 40–200). Seven patients fulfilled King’s College criteria for poor prognosis of whom four died and three survived following liver transplantation. Of the remaining seven patients two died. The median MODS score was 12 (8–17). Concentrations of soluble selectins and endothelin are presented in Table 1. No relation was observed between selectin or endothelin concentration and cardiovascular parameters, oxygenation index, the presence of renal failure, norepinephrine requirement or survival. sL-selectin concentration correlated inversely with MODS (r=0.6, P<0.04).
Our data indicate significantly increased circulating concentrations of sE-selectin, sP-selectin and endothelin-1 in patients with FHF. These molecules originate primarily from endothelial cells and are released in response to activation or injury. Concentrations of sL-selectin, which is leucocyte-derived, were normal overall but correlated inversely with MODS score. This was interesting because sL-selectin concentrations have been inversely correlated with organ failure in at risk patients who develop ARDS. We conclude that endothelial activation occurs in FHF.