Manganese elimination in hepatobiliary failure

Dear Sir,

We have recently reported on a case of presumed manganese (Mn) toxicity in a patient requiring long-term parenteral nutrition (PN) for intestinal failure associated with acute pancreatitis and hepatobiliary failure. ¹ The report highlighted the non-specific symptoms associated with manganaemia and discussed accumulation within the brain with neurological manifestations. It also highlighted that toxicity can occur in critically ill patients given manganese-supplemented PN, deficiency is rarer than toxicity in critically ill patients, and that the current recommendations may over-estimate daily parenteral requirements.

Manganese distributes very rapidly into tissues and eliminates rapidly from the blood compartment. Total body elimination half-life in humans is reported as 34 (females) to 48 (males) days, ² predominantly via the hepatobiliary system. However, there are limited data on manganese elimination in patients with impaired hepatobiliary function.

In this reported case, total blood manganese concentration was measured at regular intervals over several months, after the Mn had been removed from the PN. ¹ These results were modelled using a PK program (Excel, MS Office 2015). A semi-log plot showed good correlation (r = −0.93), suggesting first-order elimination (Figure 1). The elimination half-life was calculated to be 153.3 days, 3.1-fold greater than in patients with normal liver function.

Figure 1.

Graph to show concentration of manganese in whole blood after removing additional manganese from PN (reference range 72.8–218.5 nmol/L).

These data are consistent with previous findings suggesting that elimination of manganese is significantly impaired in the patient with concomitant hepatobiliary dysfunction.