Pathophysiology of hypotension in patients with fulminant hepatic failure.

Abstract

SUMMARY Studies on the incidence and pathophysiology of hypotension in fulminant hepatic failure showed that 82 out of 94 patients developed arterial hypotension with a systolic blood pressure of less than 80 mmHg. Such episodes accounted for 16 % of the total time spent in grade IV coma. Factors such as haemorrhage, cardiac or respiratory abnormalities, extracorporeal perfusion, or hypotension which occurred during the terminal stages of the illness, could be implicated for only 400% of this time, leaving 600% as unexplained. Further investigation of these unexplained factors showed that peripheral vasodilatation rather than primary heart failure was responsible, and in all but three patients construction of ventricular function curves showed a normal ventricular response to volume expansion with a corresponding increase in blood pressure. A small, but significant, slowing of the heart rate occurred during these periods of unexplained hypotension. This, together with the association that was found between the occurrence of hypotension and cerebral oedema with coning, suggests that central vasomotor depression may be important in its pathogenesis.Although the occurrence of hypotension in fulminant hepatic failure is well recognised (Ritt et al., 1969;Rueff and Benhamou, 1973), there is little published information concerning its pathogenesis or even its frequency. Its importance lies in the secondary hypoxic brain damage that may ensue from the associated reduction in cerebral blood flow and cerebral oxygen delivery. The present analysis is based on a series of 94 patients in whom we have documented the total duration of the hypotension, its significance in relation to the patient's clinical course, and the apparent factors underlving it. Particular attention has been paid to those patients in whom hypotension could not be explained on the basis of blood loss, respiratory difficulties, or cardiac arrhythmias. The cardiac output and indirect left atrial pressure have been measured in these patients and ventricular function curves constructed to determine the relative roles of heart failure and peripheral vasodilatation. The possibility of a central origin for the hypotension, perhaps related to the cerebral oedema which appears so frequently in this condition, was also investigated (Gazzard et al., 1975). MethodsThe 94 patients were admitted to the Liver Failure

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

“…The ability to infuse relevant amino acids with stable isotope labels to measure the conversion of arginine to citrulline as a surrogate for NO production was employed in this model to evaluate the role of NO in initiating the hemodynamic disturbances, which is not possible to do in a clinical setting, as patients will invariably present late in the course of the condition. These findings lead us to speculate that there may be some other mechanism involved in the pathophysiology of the vascular abnormality seen in the onset of ALF as seen in patients (39) and also this model (50). This result is in contrast to other published articles where increases in the metabolites of NO were described (34).…”

“…Without liver transplantation, mortality from ALF is about 50% (4). A hallmark of ALF is the presentation of systemic hypotension and a hyperdynamic circulation (39). This is associated with increased guanylate cyclase (GC) activation by nitric oxide (NO) (33), which converts guanidine triphosphate to cyclic guanidine monophosphate and is thought to cause the vasodilatation seen in ALF (34).…”

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

“…26 Acetaminophen-induced acute liver failure (AALF) is characterized by progressive vasodilatory shock and multiple organ failure and shares striking similarities with septic shock. [27][28][29] Both conditions result in uncontrolled activation of the inflammatory cascade, despite being triggered by different events.…”

Contractile response of femoral arteries in pigs with acute liver failure

“…Although the occurrence of arterial hypotension is widely recognized (2), the exact pathogenesis has still to be defined. Compensatory activation of neurohumoral reflexes involving the sympathetic nervous system and renin-angiotensin axis normally counteract for the loss of vascular tone (3).…”