Correlation of Cholestasis With Serum Copper and Whole‐Blood Manganese Levels in Pediatric Patients

Abstract

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

Copper Supplementation in Premature Infants With Parenteral Nutrition–Associated Cholestasis

“…Another explanation may be lack of optimal delivery of hepatic copper to blood because of low concentrations of serum ceruloplasmin commonly seen in premature infants. The later explanation in conjunction with decreased biliary excretion of copper associated with cholestasis in premature infants may result in accumulation of copper in hepatocytes without a concurrent increase in serum copper . Excess copper is hepatotoxic; therefore, further administration of parenteral copper can lead to worsening of hepatic function.…”

Prevention and Treatment of Intestinal Failure-Associated Liver Disease in Children

“…Based upon limited expert opinion, there is concern for copper and manganese toxic accumulation in the liver in the setting of cholestasis. Serum levels of manganese and copper are not reliably associated with degree of cholestasis 69 . Nevertheless, there is reason to believe excessive manganese intake can cause liver dysfunction.…”

Manganese Provision in Parenteral Nutrition: An Update

“…Mn concentrations cannot be reliably interpreted unless glassware has been acid‐washed to minimize contamination . Researchers have considered whether the confounding effect of contamination can be avoided by measuring the more reliable serum copper (Cu) as a surrogate test of Mn status . However, the serum Cu concentration did not correlate with whole blood Mn, nor has measurement of Mn metalloenzymes in blood found a place in the assessment of Mn status.…”