Prevalence and determinants of elevated plasma norepinephrine concentration in compensated cirrhosis

Elevation of plasma norepinephrine concentration in patients with cirrhosis and ascites is attributed to sympathetic activation due to arterial underfilling. Plasma norepinephrine should thus be normal in patients without sodium retention. We examined the prevalence and determinants of elevated plasma norepinephrine concentration in compensated cirrhosis.

Forty-six studies were performed on 37 patients; nine were studied twice. Between studies, elevated plasma norepinephrine concentration fell to normal in eight patients. Standard clinical and laboratory methods were used for all measurements.

Plasma norepinephrine was elevated (> 1.89 nmol/L) in 31 studies. Patients with normal and elevated values were similar with respect to arterial pressure, cardiac output, systemic resistance, heart rate, plasma renin activity, and plasma atrial natriuretic factor concentration. Liver function, as indicated by plasma clearance of cholic acid, antipyrine, and caffeine, was similar in the two groups, but patients with elevated norepinephrine concentration had significantly increased plasma caffeine concentrations. Plasma norepinephrine concentration significantly correlated with plasma caffeine concentration but not with any hemodynamic or neurohormonal variables. Arterial pressure fell in repeatedly studied patients in whom plasma norepinephrine concentration declined. Moreover, the changes in arterial pressure and plasma norepinephrine concentration were significantly, directly correlated.

Sympathetic activation is common in "compensated" cirrhosis. This is not because of arterial underfilling. Indeed, blood pressure and norepinephrine concentration maintained a normal physiological relationship in repeatedly studied patients. Elevated plasma caffeine concentration as a consequence of impaired hepatic metabolic function may contribute to sympathetic activation in some patients.