Rapid development of severe copper deficiency in a patient with Crohn's disease receiving parenteral nutrition.

A 32-year-old man with active Crohn's disease and recurrent small bowel strictures underwent abdominal surgery and was subsequently given total parenteral nutrition (TPN). Severe cholestasis developed and copper was removed from the TPN. Although serum ceruloplasmin levels were within normal limits, 8 weeks after copper removal, he developed pancytopenia. Serum copper levels were severely depressed. Bone marrow biopsy was consistent with copper deficiency; cytoplasmic vacuolization of both myeloid and erythroid precursors, megaloblastic erthropoiesis, and marked hypocellularity were observed. IV replacement with copper sulfate resulted in improvement in the patient's anemia, neutropenia, and thrombocytopenia, but the patient died suddenly from cardiac tamponade. Postmortem examination revealed fibrinous and hemorrhagic pericarditis. Despite the rare occurrence of overt copper deficiency, this case emphasizes the need to recognize copper deficiency as an important etiology of iron-resistant anemia in patients receiving TPN. Furthermore, the relative rapidity with which our patient developed pancytopenia suggests that, in view of the established recommendation that copper be removed from TPN in cholestatic conditions, serum copper levels must be measured periodically.     

Parenteral nutrition support in major abdominal trauma patients

32 out of 111 patients with major abdominal trauma were studied to evaluate the effects of total parenteral nutrition (TPN). There were 24 men and 8 women with average age of 31 years. 25 cases were recorded as blunt trauma. The others had penetrating wounds. An Abdominal Trauma Index (ATI) was used to score the injury severity. 68% (22 32 ) of the patients had a score of more than 15, and 25% (8 32 ) had a score over 25. TPN was carried out in 11 patients with complicated injuries of the pancreas and duodenum, in 15 cases with small bowel fistula secondary to extended intestinal trauma, and in 6 patients with severe intraabdominal abscesses after injury. The TPN mixture contained 32-42 kcal/kg/day of nonprotein energy and 0.21-0.30 g/kg/day of nitrogen. The average period of TPN support was 26 days. No TPN-related complication developed except 2 cases of catheter-related sepsis. The results demonstrated no significant change in body weight during TPN support. Weekly cumulative nitrogen balances were increased significantly after the use of TPN (from 15.5 g/week at the first week to 48.2 g/week at the fourth week, p < 0.01). There were increases in serum albumin, prealbumin, fibronectin and transferrin following TPN support (from 30.6 g/L, 142.8 mg/L, 103.3 mg/L and 1.2 g/L at day 0 to 35.7 g/L, p < 0.01, 256.3 mg/L, p < 0.01, 184.5 mg/L, p < 0.01, and 1.9 g/L, p < 0.05, at day 21 respectively). Blood sugar, cholesterol and triglyceride remained normal. In 4 patients with duodenal fistula and 6 cases with small bowel fistula (n = 15), the fistulae closed spontaneously. There were no deaths during TPN. We conclude that total parenteral nutrition is of value in the treatment of severe abdominal traumatic patients.     

Pancytopenia after removal of copper from total parenteral nutrition

Patients who develop cholestatic jaundice during chronic total parenteral nutrition (TPN) can develop significant hematologic complications due to hypocupremia if copper supplementation is withheld. A 36-year-old female with short bowel syndrome developed progressive liver dysfunction 6 months after initiation of TPN. Trace elements were omitted from her TPN because of cholestasis and persistent hyperbilirubinemia. Despite chronic diarrhea, absorption of some dietary copper was anticipated from her oral diet. Fifteen months later, the patient became red cell transfusion dependent, and her neutrophil and platelet counts steadily declined. After 19 months of receiving TPN without trace elements, her serum copper level was 25 microLg/dL (normal: 70 to 155 microg/dL). Provision of trace elements for 2 months was associated with increased serum copper, neutrophil and platelet counts and independence from red cell transfusions. When the serum copper level reached 186 microg/dL, copper supplementation was discontinued. Over the next 3 months, serum copper level fell to 10 microg/dL, neutrophil and platelet counts fell precipitously, and red cell transfusions were resumed. Once again, copper, neutrophil and platelet levels promptly rebounded with parenteral copper supplementation. Although anemia and neutropenia are well-recognized hematologic consequences of copper deficiency, thrombocytopenia rarely has been reported. This is the first report of pancytopenia secondary to TPN-related copper deficiency in which the association was confirmed when hypocupremia recurred.     

Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply

In order to prevent essential fatty acid (EFA) deficiency induced by fat-free total parenteral nutrition (TPN), 10 infants on TPN were rubbed three times daily for 20 days using oenethera oil (80% EFA). Total EFA amount provided cutaneously was 1900 mg/kg/d. Plasma and red blood cells phospholipids were determined on days 1 and 20 in these 10 treated and six untreated infants on TPN and compared with those of normal control infants. On day 1, plasma nonessential FA including 20:3 n-9(p less than 0.01) were increased in both TPN groups while 18:2 n-6 and 18:3 n-3 (p less than 0.001 and p less than 0.01) were decreased. On the 20th day, EFA deficiency had worsened with a decrease in plasma level of 20:4 n-6 (p less than 0.02) and a higher than normal triene/tetraene ratio : 3.4 +/- 1.1 and 2.3 +/- 0.6 vs 0.1 +/- 0.1 (p less than 0.02). As for red blood cells phospholipids, 16:0 was increased and 18:2 n-6 and 20:3 n-6 were decreased (p less than 0.05) on day 1. On day 20, these FA were more abnormal while 20:3 n-9 became significantly increased (p less than 0.05). No difference was observed between the TPN groups at any time. These results show that cutaneous application of large amounts of EFA-rich oil is unable to prevent or cure TPN induced EFA deficiency.     

Hypocupremia in patients receiving total parenteral nutrition

Although hypocupremia is a well-known consequence of long-term total parenteral nutrition (TPN), its incidence as well as the duration of TPN necessary to induce it are still unsettled. The purpose of this study is to review the changes in serum copper level in 25 patients receiving TPN for a period longer than 2 wk (mean duration 6 wk) at the Istituto Nazionale Tumori of Milan and to evaluate the possible relationship of cupremia with the basic disease. Main indications for TPN included enterocutaneous fistulas (11 patients), cancer cachexia (10 patients), radiation enteropathy (two patients), and severe postoperative stricture following esophagogastric resection (two patients). Mean value of serum copper at the beginning of the study was 143 micrograms/100 ml (normal value 65-165 micrograms/100 ml), and the regression analysis showed a mean fall of 5.64 micrograms/100 ml/wk. Hypocupremia occurred in four patients (three with intestinal fistulas and one with radiation obstructive enteritis) at 5th, 6th, 9th, and 6th wk of TPN, respectively. No patient with cancer cachexia developed hypocupremia. No patient with hypocupremia had clinical evidence of a copper deficiency syndrome. We conclude that 1) hypocupremia does not occur within the first month of TPN; 2) its incidence is about 16% in patients intravenously fed for period longer than 2 wk; 3) it is more frequent in patients with enterocutaneous fistulas, whereas it never occurs in patients with cancer cachexia, and 4) it is not necessarily associated to a clinicometabolic syndrome of copper deficiency. Finally, the "nutritional" meaning of serum copper should be questioned in cancer patients since it could represent a "tumor marker."     

Clinical studies on zinc metabolism during total parenteral nutrition as related to zinc deficiency

In 99 adult patients receiving controlled total parenteral nutrition (TPN), a study was made on the time course of concentrations of zinc in plasma, erythrocyte and urine in relation to the development of zinc deficiency. Zinc deficiency developed in 11 cases receiving TPN solutions not containing zinc. The plasma zinc level was significantly lower at the time of onset of zinc deficiency than in normal subjects, before the procedure of TPN, or at the time of symptomatic relief achieved by administration of zinc. The erythrocyte zinc level was slightly but not significantly lower at time of onset of zinc deficiency than in normal subjects, before TPN or at time of symptomatic relief. The urinary zinc level at time of onset of zinc deficiency was significantly lower than that in normal subjects or at the time of symptomatic relief but not significantly lower than that before TPN. A comparison between patients developing and those not developing zinc deficiency within 4 wk of the outset of TPN showed that only the plasma zinc level was significantly lower in the former than the latter group. The urinary zinc level also tended to be lower, although not significantly, in the former than the latter group but varied widely. No difference was present between the groups as to the erythrocyte zinc level. Zinc deficiency developed in none of those patients who had a plasma zinc level of 50 micrograms/dl or more but in five of 10 (50%) patients with less than 50 micrograms/dl and in all three with less than 30 micrograms/dl of zinc in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limitation of central vein thrombosis in total parenteral nutrition by continuous infusion of low-dose heparin.

The use of continuous, low-dose heparin in total parenteral nutrition (TPN) formulas to limit central venous thrombosis was retrospectively evaluated. Seven of 129 patients (5.4%) developed central vein thrombosis when TPN solutions provided less than 6,000 units (usually 1,000 units/liter) heparin per day. In the subsequent period when heparin was increased to 6,000 units per day, 10 of 858 (less than 1.2%) patients developed a TPN-related thrombosis (P less than 0.0005). The incidence of antithrombin III (AT III) deficiency in a subset of high-risk patients scheduled to receive TPN was 51% (23 of 55). Twelve of the 23 had clinical evidence of thrombosis, whereas only 3 of 22 patients with normal AT III levels did (P less than 0.01) A major contributing factor to the development of thrombosis in TPN appears to be depression in antithrombin III levels, which is commonly found in patients who require this therapy. Low-dose heparin appears to reduce the incidence of thrombosis with TPN when provided continuously in sufficient amounts.     

Limitation of central vein thrombosis in total parenteral nutrition by continuous infusion of low-dose heparin

The use of continuous, low-dose heparin in total parenteral nutrition (TPN) formulas to limit central venous thrombosis was retrospectively evaluated. Seven of 129 patients (5.4%) developed central vein thrombosis when TPN solutions provided less than 6,000 units (usually 1,000 units/liter) heparin per day. In the subsequent period when heparin was increased to 6,000 units per day, 10 of 858 (less than 1.2%) patients developed a TPN-related thrombosis (P less than 0.0005). The incidence of antithrombin III (AT III) deficiency in a subset of high-risk patients scheduled to receive TPN was 51% (23 of 55). Twelve of the 23 had clinical evidence of thrombosis, whereas only 3 of 22 patients with normal AT III levels did (P less than 0.01) A major contributing factor to the development of thrombosis in TPN appears to be depression in antithrombin III levels, which is commonly found in patients who require this therapy. Low-dose heparin appears to reduce the incidence of thrombosis with TPN when provided continuously in sufficient amounts.     

Water-soluble vitamins in cancer patients on parenteral nutrition: a prospective study

Forty-three patients with mild weight loss were studied prospectively to determine whether the parenteral water-soluble vitamin doses in a commercially available preparation (MVI concentrate; USV Laboratories, Tarrytown, NY) maintained serum, red blood cell (RBC), and urinary concentrations of water-soluble vitamins in stressed cancer patients receiving total parenteral nutrition (TPN). Patients were divided into three groups: (1) oral diet, no intravenous vitamins given; (2) TPN plus 5 ml MVI; and (3) TPN plus 10 ml MVI. Vitamins C, B1, B2, B3, B6, and niacin were measured initially and weekly during a 6-week study period. Caloric and nitrogen balances were quantified. Most of the patients in all three groups had normal blood or urine levels of all water-soluble vitamins. No clinical evidence of vitamin deficiency or MVI toxicity was detected. The recommended parenteral dosages of vitamin C (100 mg/day) and B3 (15 mg/day) provided measurably adequate levels in all patients. Levels of vitamins B1, B2, B6, and niacin that were less than the normal range were noted in 4-40% of patients receiving the recommended daily dosages of 3 mg, 3.6 mg, 4 mg, and 40 mg, respectively. These deficiencies appeared to improve in group III patients who received twice the recommended parenteral vitamin dosages, although they did not completely disappear. Niacin deficiency appeared to be the most prevalent, occurring in 40% of patients studied. Since intravenous doses of B1, B2, B6, and niacin are safe and well tolerated, it appears that increased daily amounts of these vitamins should be given to cancer patients on parenteral nutrition.     

Serum concentration of folates during total parenteral nutrition in Crohn's disease

Folate status as evidenced by the fasting serum (S-) concentration of folates was determined in a consecutive series of 15 patients with Crohn's disease (CD) given total parenteral nutrition (TPN)—nil per os—for between 23 and 97 days (mean, 56 days). At introduction of TPN three patients displayed sub-normal S-folate levels—below 4.0 nmol/1—(group 1), whereas 12 patients recorded S-folates above 4.0 nmol/l (group 2). During the TPN each patient received one ampoule of water-soluble vitamins, including 0.2 mg of folic acia per 24 h. S-folates were normalised during the TPN in group 1 and maintained a level near the middle of the reference range (4–23 nmol/l) in group 2. It would thus appear that during 6–8 weeks of TPN the vitamin regimen studied, including 0.2 mg of folic acid per 24 h, is able to maintain the S-folate concentration within the reference range in CD patients with no evidence of folate deficiency and to prevent signs of folate deficiency in CD patients with an initially sub-normal S-folate concentration.     

Serum concentration of cobalamines during total parenteral nutrition in Crohn's disease

The vitamin B12 status was assessed by measuring the fasting serum (S-) concentration of cobalamines in a consecutive series of 12 patients with Crohn's disease (CD) given total parenteral nutrition (TPN)--nil per os--for between 21 and 97 days (mean, 49 days). At introduction of TPN the S-cobalamine concentration was less than 300 pmol/liter in four patients (group I) and more than 300 pmol/liter in eight (group II). Each day during TPN fat- and water-soluble vitamins, including 2 micrograms of cyanocobalamin, were given. In group I there was a small increase in the S-cobalamine level during the first 2 to 4 weeks of TPN, whereas in group II the values approached the middle of the reference range (190-680 pmol/liter) after 6 to 8 weeks of TPN. It would thus appear that the vitamin regimen studied, including 2 micrograms of cyanocobalamin per 24 hr, is able to maintain the S-cobalamine concentration within the reference range during 6 to 8 weeks of TPN in CD patients with no evidence of vitamin B12 deficiency, and to prevent the development of vitamin B12 deficiency during 2 to 4 weeks of TPN in CD patients with a S-cobalamine level initially below 300 pmol/liter.     

Adverse effects of high dose carnitine supplementation of total parenteral nutrition on protein and fat oxidation in the critically ill

The aim of the present study was to investigate the effects of continuous and acute L-carnitine supplementation of total parenteral nutrition (TPN) on protein and fat oxidation in severe catabolism. A critically ill and severely malnourished male patient received TPN (non protein energy = 41 kcal/kg/day, provided equally as fat and glucose) over 38 days, without L-carnitine for 23 days and with carnitine supplements (15 mg/kg/day) for the following 15 days. Subsequently, he was given carnitine-free enteral nutrition for 60 more days. A four-hour infusion of 100 mg L-carnitine was given on day 11 of each TPN period. Indirect calorimetry was carried out after 11 days of either carnitine-free or supplemented TPN and at the initiation of enteral nutrition. Additional measurements were performed 4 hours and 24 hours after the acute infusions of carnitine. The rate of protein oxidation and the respiratory quotient were found to be higher, and the rate of fat oxidation to be lower, with carnitine-supplemented TPN, than with either carnitine-free TPN or enteral nutrition. Acute infusion of carnitine resulted in an increased rate of protein oxidation and a reduced rate of fat oxidation on both TPN-regimens. These unfavourable effects on protein metabolism may be due to an impairment of fat oxidation by excess amounts of carnitine.     

Supplementation of essential trace elements during total parenteral nutrition--effects on trace element-deficient rats

Thirty-one male SD rats, six weeks old, were fed a trace element-deficient diet for two weeks and then divided into three groups and maintained for 1 week as follows: group A with total parenteral nutrition (TPN) without supplementation of trace elements, group B with TPN supplemented with the following 5 trace elements ... iron, zinc, copper, manganese and iodine, and group C with a diet free of the above five trace elements. Another group of eight rats was fed a diet supplemented with the above five trace elements for three weeks as a control (group D). Feeding or TPN without supplementation of trace elements evoked microcytic hypochromic anemia and significant decreases in iron concentrations in plasma and tissues (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to cure anemia and a significant increase in the iron concentration in tibia (group B). Decreases in the zinc or copper concentrations in plasma and tissues during TPN without trace elements were prevented by supplementation of trace elements in the TPN solution (group B). The plasma zinc and copper concentrations correlated well with their levels in liver, kidney and tibia. Manganese deficiency was not recognized in this investigation (groups A and C), though supplementation of trace elements in the TPN solution increased tissue manganese concentration (group B). Feeding or TPN without supplementation of trace elements induced decreases in plasma triiodothyronine and thyroxine (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to increase plasma thyroxine (group B).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet]

TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE-5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element-related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN.     

Infusion of enteral vs parenteral nutrients using high-concentration branch-chain amino acids: effect on wound healing in the postoperative rat

Starting total parenteral nutrition (TPN) the day after acute surgical stress has beneficial effects on body weight, nitrogen balance, and colonic anastomosis bursting pressure in normally nourished rats. In view of the reported favorable utilization of high-concentration branch-chain amino acids (BCAA) following severe stress, we compared enteral (TEN) to parenteral (TPN) nutrient infusions containing increased BCAA starting the day of operation. Twenty-four male Sprague-Dawley rats, in two groups paired by weight under IP pentobarbital anesthesia underwent jugular vein catheter (CVP) insertion, laparotomy, gastrostomy, colon anastomosis, dorsal skin incision and SC polyvinyl alcohol sponge insertion. The rats were maintained for 6 days with continuous IV infusion in the TPN group (gastrostomy plugged) and continuous gastric infusion for the TEN group (CVP plugged). Urine and feces were collected daily. The infusions contained 1000 to 1002 Kcal, 847 to 845 nonprotein Kcal, 38 to 39 g of amino acids, 206 to 209 g of carbohydrates, and 2.8 to 2.9 g of rat per liter in the TEN and TPN, respectively, with identical ratios of dietary essential amino acids to nonessential amino acids (52/48), and 28.34% BCAA in the TPN and 33.10% BCAA in the TEN. There were 491 mg/100 mL of glutamine in the TEN and 170 mg of glutamic acid in the TPN. Amino acids were infused at 8.59 g/kg per day for TEN and 8.34 g/kg per day for TPN. The vitamins, minerals, and trace minerals were essentially the same in the TEN and TPN except for the absence of iron, iodine, selenium, and molybdenum in the TPN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma and red blood cell vitamin E status of patients on total parenteral nutrition

Plasma and red blood cell (RBC) tocopherol isomer (alpha, beta, delta, and gamma) concentrations were measured prior to, and following total parenteral nutrition (TPN), with Intralipid. Before feeding, nine of 13 patients had plasma total tocopherol levels less than 0.6 mg/dl (normal range 0.63-1.24 mg/dl) and 10 of 13 had total RBC tocopherol levels less than 0.2 mg/dl (normal range (0.20-0.39 mg/dl). Following 7 days TPN plasma vitamin E status increased significantly (p less than 0.001). However, this was due mostly to increases in the circulating level of beta + gamma-tocopherols. RBC vitamin E status was also significantly increased (p less than 0.001) following TPN, however, this was again due to incorporation of non-alpha-tocopherols. In a second study a alpha-tocopherol supplement, Vitlipid N, (9.1 mg alpha-tocopherol/day) was included in the feed. In these patients, large increases in plasma concentrations of non-alpha-tocopherol isomers were accompanied by an apparent improvement in alpha-tocopherol status (0.64 vs 0.44 mg/dl after 7 days). However, RBC alpha-tocopherol concentration did not change appreciably in these patients following either 7 or 14 days feeding. It is concluded that RBC vitamin E status is markedly influenced by the available plasma tocopherol pool and that provision of a small supplement of alpha-tocopherol is not sufficient to compete with the high concentration of non-alpha-isomers present in Intralipid. TPN utilizing fat emulsions containing high levels of non-alpha-tocopherol isomers (even when accompanied by alpha-tocopherol supplements) does not improve alpha-tocopherol status.     

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.     

Neonatal metabolic acidosis: effect of chloride from normal saline flushes

Metabolic Acidosis is a reported complication of total parenteral nutrition (TPN). A large number of infants receiving TPN in an NICU were noted to have metabolic acidosis. We evaluated the effect of lowering the chloride intake on the incidence of metabolic acidosis in low birth weight (LBW) infants on TPN. Standard TPN solutions were adjusted to provide about 2-3 mEq/kg/day chloride instead of 5-7 mEq/kg/day provided previously. Most infants on TPN received approximately another 1-3 mEq/kg/day from intravenous and arterial line flushes with normal saline. Ten infants who had been on the original TPN solutions were compared to 10 infants who were on the revised TPN solutions. Serum pH, bicarbonate, and base deficit were used to measure acidosis. Medical records were reviewed for the number of days the infants had abnormal values. Serum chloride levels were also recorded. While similar in gestational age, birth weight, age during study period, days on TPN, and days on orally supplemented parenteral nutrition, the group with higher chloride intake had significantly more days of metabolic acidosis. They also had significantly higher serum chlorides. It is concluded that a total chloride load in excess of 6 mEq/kg/day in LBW infants receiving TPN is associated with more metabolic acidosis. Also, if saline is used for clearing of intravenous and arterial lines, standard TPN solutions should be formulated with consideration of the total chloride load.     

Latent copper deficiency in patients receiving low-copper enteral nutrition for a prolonged period

BACKGROUND: Copper deficiency has been reported in patients supported with long-term enteral nutrition. Occasionally, this leads to anemia and leukopenia. There is no detailed report relating to the onset time of copper deficiency and how the symptoms develop. This report describes the relation between copper deficiency symptoms and duration of enteral nutrition. METHODS: The study included 55 patients, with 82 measurements, at the neurologic ward of Nagoya Daini Red Cross Hospital. The mean age was 71 +/- 11 years. The daily average dosage of energy was 938 kcal/d. A commercial nutrient for enteral administration that contains 0.13 mg/1000 mL copper was used. Baseline measures on individual patients were taken every month. Blood was collected at 8 am before and after the start of enteral nutrition. Levels of copper, zinc, ceruloplasmin, hemoglobin, and white blood cells were measured. RESULTS: The serum level of copper in the patients was 94.0-181.0 microg/dL before the start of enteral nutrition. The level of serum copper remained within the normal range for about 3 months. The level of serum copper in the patients decreased gradually and was less than the normal level after 3 months, with the exception of 1 patient. The serum level of copper in the patients was 3.0-123.0 microg/dL 3 months after the start of enteral nutrition. The levels of serum copper were below normal in 25 cases out of 82 measurements. However, the number of patients with symptoms of copper deficiency was only 2. Copper deficiency symptoms appeared at 41 and 77 months, the average being 59 months. CONCLUSIONS: Almost all patients showed a latent copper deficiency about 3 months after the start of enteral nutrition. However, only a few patients developed overt symptoms of copper deficiency.