Trace minerals in critically ill patients: a forgotten cause of delayed recovery?

Introduction

The aim of this pilot study was to assess the possible deficiency of the standard nutrition protocol, based on the daily recommended doses (DRD) in the literature [1], in the surgical ICU for trace minerals. An intervention with extra supplements given in addition to the standard formula was evaluated.

Methods

A prospective, observational pilot study in a surgical ICU of a tertiary referral centre. Forty-eight intensive care patients with two or more organ failures were included in the study (APACHE II score 24.2 ± 7.9). All patients received total parenteral nutrition according to a standard protocol. Plasma measurements of manganese, selenium and zinc were performed before and after 7 days of extra supplementation with a commercial formula containing one DRD1 of each element (Addamel^® N; Fresenius Kabi, 's-Hertogenbosch, The Netherlands). Twenty-five patients were also screened for copper and chromium levels and their response to supplements.

Results

The overall daily caloric intake in the week before inclusion into the study was 1693 ± 841 kcal and during the study period 2211 ± 543 kcal (P = 0.002). Copper as a substantial element in the normal function of oxidative enzyme systems (so-called 'cupro-enzymes') and in plasma primarily bound to ceruloplasmine, an acute phase protein, is difficult to interpret in critically ill patients. However, levels at the start were normal (14.5 ± 6.3 μmol/l, n = 10.0–30.0 μmol/l) and could be raised significantly (17.4 ± 4.6 μmol/l, P = 0.004). Ceruloplasmin levels were within the normal range and did not change significantly over the study period (0.34 ± 0.11 g/l, n = 0.24–0.62 to 0.37 ± 0.10 g/l, P = 0.414). Manganese is part of the mitochondrial superoxide dismutase and important for the metabolic effects of vitamin K. In our population normal starting levels were found (30.5 ± 13.7 nmol/l, n = 2–37 nmol/l) and were raised significantly (37.0 ± 16.3 nmol/l, P = 0.021). Selenium as a co-factor in the erythrocyte glutathion peroxidase complex has a protective role against peroxides. (Very) low baseline levels were found (0.53 ± 0.22 μmol/l, n = 0.8–1.8 μmol/l) and the supplement, although double the DRD, could not normalize this (0.71 ± 0.28 μmol/l), but the improvement was statistically significant (P < 0.0001). Albumin as the transport protein for selenium was low and did not change significantly (20.9 ± 6.0 g/l, n = 35–50 to 21.1 ± 6.5 g/l, P = 0.959). Zinc metabolism and physiology are subject to debate. Zinc deficiency, however, is known for impaired wound healing, alopecia and immunologic dysfunctions. Almost all patients were deficient at the start (8.6 ± 3.6 μmol/l, n = 11.5–23.5 μmol/l), and then supplementation did result in significant improvement, but only just to normal levels (11.4 ± 2.6 μmol/l, P < 0.0001). Chromium is a cofactor in insulin metabolism and glucose utilisation. Plasma levels are difficult to assess, because of their biologic significance. However, starting levels were high (86 ± 52 nmol/l, n = 9.6–50 nmol/l) and were raised nonsignificantly (90 ± 45 nmol/l). The chromium-transporting protein transferrin was low and did not change significantly (1.3 ± 0.9 g/l, n = 2.0–3.5 to 1.3 ± 0.4 g/l, P = 0.475).

Conclusions

A significant percentage of ICU patients have trace mineral deficiencies, despite well-dosed parenteral (and/or enteral) feeding regimens. Low plasma levels are not unequivocal to interpret [2], but our results support a more prominent role for research and re-evaluation of the current recommended nutrition standards for ICU patients.