Nitric-oxide-lowering effect of terlipressin in decompensated cirrhosis: comparison to the molecular adsorbent recirculating system and correlation with clinical status.
Systemic vasodilatation and arterial hypotension, refractory to adrenergic vasopressors, portend a poor prognosis in patients with decompensated cirrhosis. The production of large amounts of nitric oxide, consequent to endotoxin-induced tumour necrosis factor (TNF)-alpha-mediated upregulation of inducible nitric oxide synthase (iNOS), has been suggested to be central to this phenomenon. Terlipressin has recently been shown in an animal model of cirrhosis to suppress endotoxin-induced TNF-alpha-mediated upregulation of iNOS, thereby preventing overproduction of nitric oxide and restoring normal vascular tone. We present the first evidence that this effect of terlipressin may also occur clinically, in a patient with Child-Pugh class C cirrhosis, endotoxaemia, a raised circulating TNF-alpha concentration, and marked systemic vasodilatation with refractory arterial hypotension. Beneficial effects of terlipressin on circulating nitrate and nitrite concentrations, haemodynamic status, plasma renin levels and indocyanine green clearance were comparable to those of the molecular adsorbent recirculating system (MARS). Our findings suggest that terlipressin may be the vasopressor agent of choice in patients with decompensated cirrhosis and provide a rationale for combination terlipressin and MARS therapy when the therapeutic response to either treatment alone is suboptimal.
Kurtovic
Jelica
J
Gastrointestinal and Liver Unit, The Prince of Wales Hospital and University of New South Wales, Sydney, Australia.
Boyle
Martin
M
Bihari
David
D
Riordan
Stephen M
SM
D000368:Aged; D019446:Endotoxemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000188:drug therapy; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D019164:Liver, Artificial; D008236:Lypressin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D016060:Sorption Detoxification / Q000379:methods*; D000077585:Terlipressin; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D008236:Lypressin; D000077585:Terlipressin