Children hepatic encephalopathy

Charlton CP, Buchanan E, Holden CE, et al. Intensive enteral feeding in advanced cirrhosis Reversal of malnutrition without precipitation of hepatic encephalopathy. Arch Dis Child 1992 67 603-607. 

Ong, J.P., et al., et al.2003. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med, 114(3) pp. 188-193 Puliyel, J.M. and V. Bhambhani, 2003. Ketoacid levels may alter osmotonicity in diabetic ketoacidosis and precipitate cerebral edema. Arch Dis Child, 88(4) p. 366 Roberts, J.S., et al.2006. Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children. Crit Care Med, 34(8) pp. 2217-2223 Ryan, C.J., et al.2001. Multisorbent plasma perfusion in fulminant hepatic failure effects of duration and frequency of treatment in rats with grade 111 hepatic coma. Artif Organs, 25(2) pp. 109-118... 

Population PK screening in Phase II and Phase III is useful in assessing the impact of altered hepatic function (as a covariate) in PKs, if those patients are not excluded from Phase II and III trials, and if there is sufficient PK information collected about the patients to characterize them reasonably well. If a population PK approach is used, patients in Phase II and III studies are assessed for encephalopathy, ascites, serum bilirubin, serum albumin, and prothrombin time (which are components of the Child-Pugh score) or a similar group of measures of hepatic function. The population PK study, then, would include the following features ... 

Ondansetron could be used, but the dose should be reduced to 8 mg daily in divided doses, as this patient has severe hepatic impairment (Child-Pugh C). Ondansetron should be used with caution as it can cause constipation, which may worsen encephalopathy. A laxative should be co-prescribed if necessary. 

Hepatic disease In 24 subjects, 6 of whom were healthy and 19 of whom had varying degrees of hepatic impairment received a single injection of liraglutide 0.75 mg subcutaneously into a thigh, and plasma concentrations were measured for 72 hours [57 ]. The Child Pugh criteria were used to define hepatic impairment. Patients with encephalopathy, liver transplants, and other clinical significant diseases were excluded. The AUC was lower in those with severe hepatic impairment than in the healthy individuals, and there was a relation between albumin concentration and AUC. However, there were too few observations to determine whether lower albumin concentrations were the sole determinant of the reduction in AUC in those with hepatic impairment or whether other factors were... 

---