Chromium deficiency after long-term total parenteral nutrition

Summary A 63-year-old female developed unexplained hyperglycemia and glycosuria during administration of a total parenteral nutrition regimen on which she had been stable for several months. Because the patient had no history of diabetes or evidence of an infection, chromium deficiency was considered. Plasma chromium level was 0.1 g/dl (laboratory reference interval: 1.8–3.8 g/dl). Fourteen days of supplemental intravenous chromium chloride (200 g/day) allowed complete withdrawal of exogenous insulin with no further hyperglycemia or glycosuria. Correction of unexplained glucose intolerance following vigorous chromium supplementation indicates that the patient had chromium deficiency. Subsequent plasma chromium levels remained unchanged, possibly reflecting the sensitivity limits of the assay that was used, the uncertainty that exists regarding appropriate reference intervals for this element, and the fact that plasma levels do not always correlate with total body stores. The patient did not manifest peripheral neuropathy, which was present in one of the two previously reported cases, nor encephalopathy, which was reported in the other. We conclude that this patient developed chromium deficiency as a result of inadequate administration of chromium in the parenteral formula (6 g/day) plus excessive enteric losses, and she presented with glucose intolerance as the only clinical manifestation of the deficiency. Caution should be exercised when interpreting plasma chromium in patients with suspected deficiency.At the time of this case report, Dr. Brown was Nutritional Support Pharmacist, North Carolina Memorial Hospital, Chapel Hill, North Carolina 27514.     

Hepatic copper in patients receiving long-term total parenteral nutrition

GOALS: To assess the possibility of iatrogenic hepatic copper overload in adult patients on long-term total parenteral nutrition (TPN). BACKGROUND: TPN predisposes to hepatic copper accumulation through disturbances of the enterohepatic bile acid pool, but iatrogenic copper overload through TPN solutions may occur as well. STUDY: Quantitative hepatic copper and multiple clinical, biochemical, and histopathologic parameters were compared between patients with long-term TPN associated liver disease (n = 28) and patients with drug-induced cholestatic liver disease (n = 10). RESULTS: Eighty-nine percent of TPN patients and all controls had mildly elevated hepatic tissue copper, but 29% of TPN patients had levels above the diagnostic threshold for Wilson's disease. Quantitative hepatic copper correlated positively with serum aspartate aminotransferase (P = 0.001, r = 0.59), total bilirubin (P < 0.001, r = 0.65), and direct bilirubin (P < 0.001, r = 0.63) in TPN patients, but not in controls. The amount of hepatic copper did not correlate with the duration of TPN (median, 1.9 years; range, 0.3-18.0 years) or serum copper levels. TPN patients with significant cholestasis accumulated more copper than patients with no or only minimal cholestasis (P = 0.002). CONCLUSIONS: Significant hepatic copper overload in TPN patients occurs through chronic cholestasis in TPN-associated liver disease and is independent from the total duration of TPN. Iatrogenic copper overload through trace elements in TPN solutions does not seem to be a significant factor.     

Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition

An adult patient with chronic idiopathic intestinal pseudo-obstruction maintained on home parenteral nutrition for 6 consecutive years died from cardiomyopathy and ventricular fibrillation. Postmortem examination of the heart revealed widespread myocytolysis and replacement fibrosis similar to that seen in the selenium deficient cardiomyopathy in China (Keshan disease) and animal models. Selenium deficiency in this patient was documented with extremely low concentrations of selenium and decreased activity of the selenoprotein, glutathione peroxidase, in blood, heart, liver, and skeletal muscle. Reports of selenium deficient diets causing myocardial damage in humans and animals and the findings in our patient strongly suggest that his fatal cardiomyopathy was caused by selenium deficiency.     

Preoperative total parenteral nutrition for bowel resection in Crohn's disease

To examine the effect of preoperative total parenteral nutrition (TPN) on patients with Crohn's disease undergoing bowel resection, an historical cohort was assembled of 103 patients resected between 1982 and 1984 by a single surgical team. Preoperative, perioperative, and postoperative variables were compared between patients receiving TPN and patients not receiving TPN. Analysis was stratified for three surgical procedures: segmental small bowel resection, ileocecectomy, and segmental or total colectomy. The effect of TPN was most pronounced in patients having small bowel surgery. For segmental small bowel resection, 12 of 17 patients had TPN, and these patients had 20.4 ±14.3 cm less bowel resected than did those in the non-TPN group, an effect not dependent on duration of TPN. For ileocectomy patients, 31 of 62 patients received TPN, and these patients had 11.2±4.2 cm less small bowel resected than the non-TPN group, an effect not dependent on the duration of TPN. For large bowel resection patients, 6 of 24 patients had TPN, and there was no difference in length of bowel resection, preoperative and perioperative variables, or recurrence. The total hospital stay was 13.5±2.6 days longer for those having TPN;3.5±1.9 days of the longer stay was postoperative. In conclusion, TPN was associated with reduced length of small bowel resection at the expense of longer hospital stay.This research supported in part by the Gastrointestinal Research Foundation Junior Board.     

Total parenteral nutrition in Crohn's disease

The effect of total parenteral nutrition on 19 patients suffering from severe active Crohn's disease was studied. Total parenteral nutrition was effective as primary therapy in 56 per cent. In the remaining patients, it was highly effective as supportive therapy, enabling them to undergo uneventful major surgery.     

Jejunal motility during cyclic total parenteral nutrition in patients with Crohn's disease.

Our aim was to study the jejunal motility (a) in seven patients receiving longterm (median: 24 days) cyclic total parenteral nutrition (CTPN) for an acute exacerbation of Crohn's disease involving the ileum and/or the colon without any sign of occlusion and (b) in six healthy volunteers undergoing the same parenteral nutrition for one day after an overnight fast. Continuous recordings, lasting 20 hours, were carried out in patients after correction of their nutritional status and significant improvement of the Crohn's disease activity index. In five of the seven patients, we recorded seven to 14 phase III episodes (PIII) (median: 10), both more frequent and slower during the nocturnal part of the recording time as compared with diurnal. Seven to 18 PIIIs (median: 12) were found in controls. The overall duration of the motor activity was not different between these five patients and controls. In the remaining two patients, no PIII episode was recorded and 79% and 57% respectively of the whole recording time consisted of irregular motor activity. Our work therefore, shows that: (a) PIIIs remain and have a circadian variation in their periodicity and propagation velocity, in most of our patients undergoing longterm CTPN (b) CTPN does not determine a longer duration of motor rest of the small bowel in patients than in controls submitted for a short period of time to the same parenteral intake.     

Effective intravenous cyclosporin therapy in a patient with severe Crohn's disease on parenteral nutrition.

We report a patient with severe Crohn's disease and the short bowel syndrome on parenteral feeding who was not responding to conventional therapy and underwent treatment with cyclosporin (CyA) given initially intravenously and subsequently orally in each of two courses. Plasma drug concentrations were largely kept within the therapeutic range but wide variability was observed on oral therapy. Improvement both clinically and by objective assessment, was observed on intravenous CyA therapy, but was not sustained when the drug was given orally for several months. None of the side effects observed resisted treatment or was severe enough to warrant discontinuation of therapy. These findings suggest that there may be a place for intravenous CyA therapy in patients with severe Crohn's disease who do not respond to conventional therapy or to oral treatment with CyA.     

Control of gastric pH with ranitidine in patients with Crohn's disease receiving total parenteral nutrition. Comparison of two intravenous regimens

Eleven patients with Crohn's disease in remission who were receiving total parenteral nutrition (TPN) underwent continuous intragastric 24-h pH monitoring before and during ranitidine administration. The patients were randomly allocated to receive 200 mg/ day (group 1) or 400mg/day (group 2) of ranitidine by continuous infusion. The mean basal 24-h gastric pH was sustained at a low value. After raintidine administration, the mean pH increased significantly both in group 1 (from 2.13 to 3.28) and in group 2 (from 1.91 to 3.36), with the mean holding-time at pH-3 also increasing significantly in both groups. There were no differences in the mean pH or holding-time at pH-3 between the two groups during ranitidine administration; however, the plasma ranitidine concentration was significantly higher in group 2. These findings indicate that the continuous infusion of a standard dose of ranitidine exerted a maximal inhibitory effect on the sustained hyperacidity induced by TPN, but that this infusion was unable to maintain the intragastric pH level at above 3.5.     

Hyperglycemia correlates with outcomes in patients receiving total parenteral nutrition

BACKGROUND: Hyperglycemia is associated with higher mortality rates after myocardial infarction, stroke, and in critically ill patients. This study was made to determine the associations between hyperglycemia and adverse outcomes in patients receiving total parenteral nutrition (TPN). METHODS: A retrospective cohort study included total 457 patients (age, 66.4 +/- 16.3 years) receiving TPN in 2004. The patients were divided by mean glucose level into quartiles: quartile 1 (<114 mg/dL, Q1), quartile 2 (114 to 137 mg/dL, Q2), quartile 3 (137 to 180 mg/dL, Q3), and quartile 4 (>180 mg/dL, Q4). A logistic regression analysis was performed to determine whether the degree of hyperglycemia was associated with the adverse outcomes. RESULTS: The odds ratio of death was significantly increased in quartile 2 (OR, 2.1 [95% CI: 1.1 to 4.0]) (P = 0.02), quartile 3 (OR, 2.3 [95% CI: 1.2 to 4.5]) (P = 0.01), and quartile 4 (OR, 5.0 [95% CI: 2.4 to 10.6]) (P < 0.01) as compared with quartile 1. Each 10-mg/dL increase in mean blood glucose level was associated with an increased risk factor of infection (OR, 1.09 [95% CI: 1.05 to 1.13]) (P < 0.01), cardiac complications (OR, 1.10 [95% CI: 1.03 to 1.17]) (P < 0.01), acute renal failure (OR, 1.07 [95% CI: 1.03 to 1.11]) (P < 0.01), and respiratory failure (OR, 1.08 [95% CI: 1.02 to 1.14]) (P < 0.01). The risk of adverse outcomes increased with hyperglycemia, independent of age, sex, body weight, prior diagnosis of diabetes, ICU stay, insulin therapy, blood sugar readings before TPN treatment, and frequency of blood sugar measurements. CONCLUSIONS: Hyperglycemia in patients receiving TPN correlates with morbidities and mortality. A prospective, randomized, controlled study instituting aggressive hyperglycemic control is required to determine whether the control of blood glucose can improve outcomes in patients receiving TPN.     

Treatment of Crohn's disease with home parenteral nutrition.

Home parenteral nutrition was used to treat 9 patients with severe Crohn's enterocolitis. Seven patients had a short bowel syndrome after multiple resections of bowel. In 2 patients home parenteral nutrition was used as primary therapy. The treatment was well tolerated and proved successful in 8 of 9 patients. Three patients have been able to discontinue parenteral infusions and currently are in remission. The main complications were associated with the access device which was replaced in 3 patients. Five patients currently have abnormal liver function tests without progressive liver disease. It is concluded that home parenteral nutrition is an important new therapeutic modality which can reduce or even eliminate the need for repeated or prolonged hospitalization of patients with short bowel syndrome complicating severe Crohn's disease. In addition, the technique of home parenteral nutrition, because it is relatively simple and safe, lends itself to early intervention in severe fulminant cases of Crohn's disease. This approach can result in healing of fistulae and abscesses and greatly shortening the period of hospitalization. The patient is more rapidly rehabilitated, and his fear of early relapse and recurrent malnutrition is minimized, thus facilitating a prolonged period of bowel rest which can lead to eventual remission. Home parenteral nutrition should be kept in mind as a possible alternative to early surgical intervention in selected cases of severe Crohn's disease.     

Acute pancreatitis associated with high-concentration lipid emulsion during total parenteral nutrition therapy for Crohn's disease

A 17-yr-old boy with Crohn's disease and growth retardation developed an acute abdominal crisis while receiving total parenteral nutritional support. Acute pancreatitis was confirmed surgically. After recovery, in an attempt to provide adequate calories and to elucidate the inciting agent, he was rechallenged with his original total parenteral nutritional solution which contained 500 ml/day of a 20% fat emulsion. Symptoms and signs of acute pancreatitis quickly returned. Total parenteral nutrition was continued without the fat emulsion and symptoms and signs disappeared. This case suggests that acute pancreatitis was due to intolerance of high-concentration lipid emulsion.     

Concentration of selenium in plasma and erythrocytes during total parenteral nutrition in Crohn's disease.

Plasma- and erythrocyte-selenium concentrations were determined in five consecutive patients with Crohn's disease given preoperative total parenteral nutrition - nil per os - for a mean period of 34 days per patient. No blood components were administered during the total parenteral nutrition. Before the total parenteral nutrition the plasma-selenium level and, to a less extent, the erythrocyte-selenium levels were below the reference values. After three weeks of total parenteral nutrition both concentrations had fallen. There were, however, clinical and biochemical signs of improvement during the total parenteral nutrition, as indicated by an increase in body weight, P-albumin and P-transferrin. In one female patient given 39 days of preoperative total parenteral nutrition containing 0.06 mumol (5 micrograms) selenium per 24 h the decreasing levels of plasma-selenium and erythrocyte-selenium were both correlated to the duration of the total parenteral nutrition (r = 0.87 and 0.96, respectively). The results suggest that total parenteral nutrition patients may be at risk for selenium deficiency, and that a supplementary administration of selenium via total parenteral nutrition may be required.