Therapeutic approaches to the problem of biliary sludge and gallstone formation during total parenteral nutrition

Prolonged total parenteral nutrition is associated with the development of biliary sludge, which consists of super-saturated bile containing cholesterol crystals, bilirubin granules and a very high concentration of mucin glycoprotein. Reduced gallbladder contractility in TPN patients appears to be essential for the pathogenesis of sludge, which represents an important stage in the formation of gallstones, a common and well recognised complication of TPN. Possible approaches to the prevention of these biliary complications of TPN include: 1) inhibition of prostaglandin mediated mucin hypersecretion with aspirin, NSAIDs or possibly by n-3 essential fatty acids; 2) stimulation of gallbladder contractility by early oral feeding or the use of CCK; and 3) reduction of cholesterol saturation and mucin secretion by ursodeoxycholic acid.     

The Effect of Intravenous Fat and Total Parenteral Nutrition on Biliary Physiology

Patients on long-term total parenteral nutrition (TPN) have an increased incidence of gallstones. To determine the pathophysiologic mechanisms responsible for gallstone formation in these patients, we fed three groups of prairie dogs intravenously for 10 days with continuous infusions of isocaloric, isovolemic, and isonitrogenous solutions with either 0, 25, or 50% of nonprotein calories provided as Intralipid. A fourth group of prairie dogs was hyperalimented with the 25% solution for 28 days. Control animals were fed Purina rat Chow ad libitum. Each animal's bile salt pool was labeled with iv ³H-cholic acid 16 hr prior to collecting gallbladder and hepatic bile specimens. The ratio of gallbladder to hepatic bile ³H-cholic acid specific activity (dpm/mol of bile acid), an index of gallbladder stasis, was significantly (p <0.05) lower in TPN animals (<0.65 ± 0.19) compared to controls (1.07 ± 0.11).This finding indicates that gallbladder stasis developed in all animals fed by TPN. TPN did not alter gallbladder or hepatic bile lithogenic index. Two of five 28-day TPN animals developed biliary sludge, and one of these animals formed pigment gallstones. TPN without lipid decreased serum cholesterol concentration. As the lipid concentration of the TPN solution was increased, serum cholesterol increased. These data indicate that TPN induces gallbladder stasis regardless of caloric source but does not increase bile lithogenic index despite a dose-related rise in serum cholesterol as the percent of calories provided as lipid is increased. We conclude that TPN-induced gallbladder disease results from gallbladder stasis and not from increased bile cholesterol saturation. (Journal of Parenteral and Enteral Nutrition 8 :263–268, 1984)     

Gastric pepsin and acid secretion during total parenteral nutrition and constant-rate enteral nutrition in infancy

Total Parenteral Nutrition (TPN) and constant rate enteral nutrition (CREN) are widely used: their effects on gastric function, especially pepsin secretion, are unknown. Basal and pentagastrin-stimulated pepsin (BPO, MPO) and acid (BAO, MAO) secretions were measured in three groups of infants: controls (14 infants fed normally), TPN groups (seven infants on TPN), CREN groups (14 infants on CREN). The MAO and MPO of the TPN group were significantly lower than controls (p less than 0.02), and the ratio of pentagastrin-stimulated PO/AO did not change, suggesting a large decrease of acid gastric function in the TPN group. BPO was not different from controls and BAO was significantly higher because of amino acids perfusion. The data for CREN group were not different from those of the control group, despite the fact that 11 infants were on TPN before CREN. These results demonstrate that TPN causes decreases in both acid and pepsin secretions in human infants. When TPN children are placed on CREN, these secretions return to normal.     

The effect of exclusive parenteral nutrition,constant rate enteral nutrition,partial meal feeding,normal oral feeding and etiology on the plasma pancreatic polypeptide levels in children

Plasma pancreatic polypeptide (PP) levels were determined by radioimmunoassay in 100 children. Of the 81 children on Total Parenteral Nutrition (TPN), 32 were studied after cyclic TPN (cTPN), 66 after Partial Meal Feeding plus Parenteral Nutrition, 25 after Constant Rate Enteral Nutrition and 18 during Normal Oral Feeding. Nineteen controls received normal alimentation.PP levels during TPN (172 ± 17 pg/ml), cTPN (150 ± 23) and Constant Rate Enteral Nutrition (200 ± 27) were similar to each other and to pre-prandium (p), Normal Oral Feeding (198 ± 22) and controls (196 ± 40). PP increased (p < 0.05) in post-prandium (pp), Partial Meal Feeding (233 ± 23) compared to TPN, cTPN, p Normal Oral Feeding and p controls, but remained at half that of pp Normal Oral Feeding (387 ± 58) and pp controls (410 ± 91, p < 0.001). The p PP levels were significantly reduced in chronic intestinal pseudo-obstruction (CIPO) (90 ± 22, p < 0.02) and short bowel (length < 100 cm) (76 ± 17, p < 0.001), as compared to controls.This study indicates that TPN or Constant Rate Enteral Nutrition do not modify basal PP levels. Normal Oral Feeding and Partial Meal Feeding produce a significant pp stimulation of PP release. Intestinal pathology can interfere with p plasma PP levels.     

Effect of intravenous fat on cholecystokinin secretion and gallbladder motility in man.

During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction.     

Tolerance to starvation in children on long-term total parenteral nutrition

To evaluate the consequences of long-term cyclic total parenteral nutrition (TPN) on metabolic pathways which contribute to energy metabolism, adaptation to starvation was studied in a group of seven children 2-7 years old, on long-term cyclic TPN. In addition to clinical monitoring, the following biological parameters were measured: blood levels of glucose, free fatty acids, ketone bodies and carnitine, and urinary excretion of dicarboxylic acids. Five of the seven children had good clinical tolerance up to 30 h of fasting. This indicated that metabolic changes arising from prolonged cyclic TPN are easily reversed when such children are fasting. The other two children had to be refed after 22 and 24 h, respectively. Both had metabolic signs of impaired hepatic fatty acid oxidation or ketogenesis. These metabolic changes might reflect the liver failure caused by TPN in these children, and stresses the fact that prolonged starvation has to be carefully monitored in patients with liver dysfunction secondary to TPN.     

肠外瘘病人肠内营养支持临床应用研究

目的：观察肠内营养在肠外瘘病人应用的时机、条件、途径及肠内营养制品的选择,研究肠内营养在肠外瘘病人中的作用。方法：收集１７０例肠外瘘病人诊断、住院总天数及全肠外营养（ＴＰＮ）、全肠内营养（ＴＥＮ）、肠内＋肠外营养（ＰＮ＋ＥＮ）、经口饮食的天数,计算不同营养支持方法期间,非蛋白质热量、蛋白质的供给量和并发症的发生率。收集ＴＰＮ、ＴＥＮ支持前和支持后满１５天病人的血清白蛋白浓度。另对４０例肠外瘘病人进行为期１５天的前瞻性观察,了解肠内营养对白蛋白、前白蛋白、转铁蛋白、纤维连结蛋白、总蛋白、球蛋白和肝酶谱的影响。结果：１７０例病人的总住院天数为１３５５３天,其中１６４人曾使用ＴＰＮ６０４０天（４４．６％）;１２９人使用ＴＥＮ３６７６天（２７．１％）;８３人使用肠内＋肠外营养４８９天（３．６％）;１２８人经口饮食２３３     

不同配方TPN对胆源性胰腺炎胆囊收缩及胆汁酸成分的影响

目的：探讨各种完全胃肠外营养（TPN）对胆源性胰腺炎胆囊收缩及胆汁酸成分改变的作用。方法：选择胆源性胰腺炎住院病人共86例,在常规治疗相同的基础上,随机分成四组,TPN支持分别为仅用糖盐水（GNS组）、糖盐水加用7％凡命（VM组）、糖盐水加用20％英脱利匹特（IL组）、糖盐水加用7％凡命及20％英脱利匹特（VM＋IL组）。B超测量胆囊体积及计算最大胆囊排空率（MGER）,气相色谱法检测胆汁游离脂肪酸（FFA）。结果：发现VM＋IL组及VM组与GNS及IL组比较MGER显著升高,差异显著（P＜0．05）;VM＋IL组及IL组与GNS组比较,各种胆汁FAA构成比较差异显著（P＜0．05）。结论：TPN中加入VM＋IL或VM会促进胆囊排空,加入VM＋IL或IL会减轻胆汁FFA变化程度,均对胆石形成或增大可能有预防作用。     

Does the route of feeding modify gastric emptying in rats?

BACKGROUND: It has been shown that the pattern of previous nutrient intake can influence gastric emptying. However, the effect of the absence of enteral stimulation in the setting of a normal energy supply on gastric emptying has not been examined. The aim of this study was to determine whether the absence of enteral stimulation during total parenteral nutrition (TPN) could modify gastric emptying in rats. METHODS: Two experiments were performed. First, gastric emptying of a peptone meal was compared between rats receiving TPN, oral liquid diet (same solution as TPN), or regular diet (control group) for 10 days. In the second experiment, gastric emptying of two test meals (40% peptone and 25% glucose) was studied before and after rats received TPN or intragastric nutrition (same solution as TPN) for 10 to 12 days. RESULTS: In experiment 1, gastric emptying of 40% peptone in the TPN and liquid diet groups was slower than that in the control group. This difference was significant between the TPN group and the control group (p < .01) but not between the liquid diet and control groups (p = .076). Gastric emptying of this meal in the TPN and liquid diet groups was similar. In experiment 2, no difference in gastric emptying of 40% peptone or 25% glucose was found between rats receiving TPN and those receiving intragastric nutrition for 10 to 12 days. CONCLUSIONS: The composition of diet not the route of feeding is important in the modification of gastric emptying by the pattern of previous nutrient intake.     

Gallbladder contraction after hormonal manipulations in normal subjects and patients under total parenteral nutrition.

Total parenteral nutrition (TPN) induces biliary dilatation, sludge and formation of gallstones. Cholecystokinin (CCK) induces gallbladder (GB) contraction. During thyrotropin-releasing hormone (TRH) testing for thyroid function, we observed that patients felt a strong micturition reflex attributable to smooth muscle contraction of the bladder. The possibility of GB contraction after TRH administration was studied compared to cholecystokinin-octapeptide (CCK-OP) and/or fatty meal administration. The effect of intravenous (IV) CCK-OP, TRH and a combination of the two on GB volume was studied in normal volunteers without GB or liver disease and in patients receiving TPN for greater than 2 weeks. Subjects included six normal volunteers who received an oral fatty meal only, 18 other normal volunteers (Group A) and 18 TPN patients (Group B). Gallbladder contraction was estimated by ultrasound prior to and after administration of the fatty meal; in the other 36 subjects, GB contraction was calculated prior to and after administration of CCK-OP, TRH, or both. Results are expressed as a percentage of the GB basal volume using each subject as his or her own control. Group A and Group B were each divided into three equal subgroups receiving IV CCK-OP (A1, B1), TRH (A2, B2), or both (A3, B3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of dietary fat composition on postprandial plasma bile acid and cholecystokinin concentrations in healthy premenopausal women

Bile acids derived from intestinal bacterial metabolism and transported to the breast in plasma may influence risk of breast cancer. The purpose of the present study was to test the hypothesis that fatty acid chain length and degree of unsaturation differ with regard to their influence on the postprandial release of cholecystokinin (CCK) and the subsequent increase in plasma bile acid concentrations that occur following a meal. A randomized crossover design was used to compare five high-fat test meals (50 g fat) with a low-fat test meal (15 g) on plasma bile acid and CCK concentrations in eighteen healthy premenopausal women. The high-fat meals were enriched in oleate or palmitate, or linoleate or medium-chain triacylglycerols (MCT) or a blend of oleate and long-chain n-3 fatty acids. The postprandial increase in plasma CCK concentration was lower on the MCT meal compared with all meals and was greater following the linoleate compared with the low-fat meal. Plasma bile acid concentrations increased 2-3-fold postprandially but the increase was lower following the MCT meal compared with the other meals and was greater on the linoleate meal compared with the low-fat meal. The postprandial increases in plasma chenodeoxycholic acid concentration showed a trend to rise with increasing unsaturation of the test meal. In conclusion, meals rich in linoleate are a potent stimulus for CCK release and lead to prolonged elevations of plasma bile acids and meals containing MCT inhibit CCK release and the subsequent increase in plasma bile acid concentrations.     

Individual neuropeptides regulate gut-associated lymphoid tissue integrity, intestinal immunoglobulin A levels, and respiratory antibacterial immunity

BACKGROUND: Total parenteral nutrition (TPN) leads to atrophy of the gut-associated lymphoid tissue (GALT) and a significant decrease in intestinal immunoglobulin A (IgA) levels, a major constituent of mucosal immunity. Bombesin (BBS) prevents TPN-induced GALT atrophy and maintains intestinal IgA levels. BBS, a neuropeptide analogous to gastrin-releasing peptide in humans, stimulates the release of other gut neuropeptides including cholecystokinin (CCK), gastrin, and neurotensin (NT). This study investigates the ability of CCK, gastrin, or NT to individually prevent TPN-induced GALT atrophy and preserve respiratory immunity. METHODS: Experiment 1: Male mice were randomly assigned to receive chow, TPN, TPN plus CCK, TPN plus gastrin, or TPN plus NT. After 5 days of feeding, Peyer's patches (PP) from the proximal and distal small bowel were harvested and analyzed for cell yields. PP cells were also analyzed for GALT cell type. Small bowel IgA levels were measured by enzyme-linked immunosorbent assay (ELISA). Experiment 2: Mice were randomly assigned to receive either liposomes containing Pseudomonas antigen or liposomes without antigen. After 10 days, mice were randomly assigned to the same five treatment groups, fed for 5 days, and then given intratracheal Pseudomonas. Mortality was assessed after 48 hours. RESULTS: Experiment 1: GALT cell reductions due to IV-TPN were greater in the distal than proximal small bowel. All three neuropeptides prevented most TPN-induced GALT atrophy due mainly to the maintenance of the B-cell and T-cell populations in the PP of the distal bowel. Intestinal IgA levels were significantly higher in the animals treated with neuropeptides than animals treated with TPN only; however, these IgA levels were not maintained at levels observed in chow-fed animals. Experiment 2: Immunization resulted in significantly lower mortality in animals fed chow, TPN plus CCK, and TPN plus gastrin. TPN alone and TPN plus NT resulted in loss of immunity and mortality rate at comparable levels to unimmunized animals. CONCLUSIONS: Supplementation of IV-TPN with CCK, gastrin, and NT prevents GALT atrophy, primarily in the distal bowel. Intestinal IgA levels improve but not to normal levels. CCK and gastrin reversed IV-TPN-induced effects on antibacterial pneumonia in immunized animals while NT did not.     

Alterations in hepatic mitochondrial function during total parenteral nutrition in immature rats

To evaluate the effects of total parenteral nutrition (TPN) on hepatic mitochondrial function in immature rats, changes in hepatic energy charge levels and oxidative phosphorylation rates of hepatic mitochondria were studied along with the examination of serum chemical test. Male Wistar rats weighing 30 to 45 g were used and randomized into TPN (n = 8), enteral (n = 7), and control groups (n = 8). Parenteral and enteral groups were fed with TPN solution containing 19.3% dextrose, 3.19% amino acids, 1.05% fat emulsion, minerals and vitamins, and the control group with rat chow. The number of calories per kilogram per day was 550 x 1/4 on the 1st day, 550 x 1/2 on the 2nd, 550 x 3/4 on the 3rd, and 550 x 1 on the 4th day, based on the body weight on the 1st day. After the 5th day, 550 Kcal/kg/day was given, based on the body weight of the respective day. After 13-day feeding, hepatic energy charge (EC), phosphorylation rate (PR) of hepatic mitochondria and serum chemical examination were carried out. EC was 0.871 +/- 0.016 in the control group, 0.830 +/- 0.019 in the enteral, and 0.785 +/- 0.011 in TPN group (p less than 0.001, compared with control group). PR was 138.9 +/- 1.9, 133.0 +/- 6.7, 111.0 +/- 4.3, respectively, (p less than 0.05, compared with control and enteral groups). There was no difference between the three groups on SGOT, SGPT, and total bilirubin. TPN group showed a deterioration of hepatic phosphorylation rate and energy charge in spite of normal serum transaminase levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Imbalance between jejunum and ileum in the response of brush border hydrolases to oral feeding after intravenous alimentation in rats

The effect of oral refeeding after total parenteral nutrition (TPN) on brush border hydrolases was measured in the proximal jejunum and ileum of adult rats. The animals received intravenously for 4 days a mixture of Intralipid 10% and Vamine-Glucose. At the end of TPN, oral feeding was reinstituted and the rats were fed with an isocaloric standard diet (60% carbohydrate, 17% protein, 3% lipid). Sucrase, isomaltase, lactase, and aminopeptidase N activities were measured at the end of TPN and at 1, 3, and 5 days after TPN. Sham-operated rats nourished orally with the standard diet were used as controls. In both intestinal segments, lactase activity showed no significant changes at the end of TPN or during oral realimentation. Isomaltase, and especially sucrase activities, exhibited an important drop at the end of TPN. After TPN, a complete restoration of isomaltase and sucrase activities was obtained in the jejunum only. During oral refeeding a 40% deficit in sucrase activity persisted in the ileum throughout the experimental period, whereas normal isomaltase activity was restored in this segment. Aminopeptidase N activity was lowered by TPN and recovered normal values within a few hours after oral realimentation. Thus, reinstitution of oral feeding after TPN should take into account that the intestine is capable of digesting normal amounts of dietary protein but has a reduced tolerance for carbohydrates.     

Hepatic transport of bile salt and bile composition following total parenteral nutrition with and without lipid emulsion in the rat

The effect of total parenteral nutrition (TPN) on bile flow and composition and on hepatic bile acid transport maximum (Tm) and bile salt-independent bile flow (BSIF) was studied in the rat following seven days TPN containing 33% calories from Intralipid (IL) or Liposyn (LP) or 0% calories from lipid. All TPN regimes markedly reduced bile flow. In no case did TPN cause an increase in bile cholesterol concentration or saturation relative to bile acid and phospholipid. Bile acid Tm was reduced in rats receiving either 0% lipid or 33% IL; BSIF was reduced only in the 0% lipid group. Rats receiving 33% LP had a higher bile flow than the other TPN regimes while bile acid Tm and BSIF were similar to controls. It is proposed that in established TPN, bile flow is reduced largely as a result of decreased hepatic bile acid excretion. In the rat, TPN has no deleterious effect on the molar concentration of cholesterol, phospholipid or bile acid in bile secreted by the hepatocyte. The significant differences between the effect of the two lipid emulsions on hepatobiliary function require further study.     

Effects of intravenous nutrition on lipoprotein metabolism, body composition, weight gain and uremic state in experimental uremia in rats

The effect on serum lipids, lipoprotein fractions, body composition, weight gain and uremic state of including fat in intravenous nutrition was evaluated in rats with chronic uremia. Uremic rats were given high energy (1385 kJ.kg body weight-1.day-1), low nitrogen (0.6 g N.kg body weight-1.day-1) total parenteral nutrition (TPN) for 12 d with either glucose or glucose plus 30% lipids (Intralipid) as the energy source. Additional uremic and nonuremic groups were fed a standard diet orally. During TPN, serum triglyceride and cholesterol levels were slightly higher in rats fed lipid-based TPN compared to those administered glucose-based TPN or fed the oral diet; but there were no differences 8 h after feeding. The serum lipoprotein fractions showed accumulation of lipids in LDL resulting from the lipid-based TPN but no differences in VLDL. In orally fed uremic rats, more lipids were found in HDL than in the TPN-treated rats. The fractional clearance of the fat emulsion was normal and independent of the nutrition composition. Uremic rats administered lipid-based TPN for 21 d had the same weight gain as orally fed, nonuremic control rats (23 +/- 3 vs. 22 +/- 2%); glucose-based TPN did not support normal growth (10 +/- 1%). Uremic rats fed orally did not grow and retained significantly more body water than TPN-fed uremic rats. In uremic animals, lipid-based TPN also was associated with normal body composition despite significantly lower levels of carnitine in plasma, skeletal muscle and heart tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatobiliary complications associated with TPN: an enigma.

Despite the fact that the clinical experience with TPN has been gathered from patients of all age groups suffering from a variety of underlying diseases running very different clinical courses and often complicated by a number of septic metabolic and therapeutic problems, certain points can be made with regard to predisposing factors. 1) Prematures and neonates are particularly at risk. 2) Cholestasis occurs earlier and has a greater chance of leading to chronic liver disease in surgical patients. 3) Hepatobiliary abnormalities are more likely to develop after a prolonged period of TPN and are less frequent in patients who are also receiving oral feedings. Definition of the mechanism of hepatobiliary complications remains a problem. Although calcium bilirubinate appears to be responsible for sludge and stones, there is as yet no explanation for the presence of large amounts of indirect-reacting bilirubin in gallbladder and hepatic bile in patients on TPN. The pathogenesis of cholestatic liver disease remains an enigma; the lack of normal gastrointestinal stimuli for bile formation, abnormalities of bile acid metabolism, and sepsis might play roles, but attention has recently been attracted to amino acid toxicity and this possibility deserves further study.     

Hepatobiliary complications associated with TPN: an enigma

Despite the fact that the clinical experience with TPN has been gathered from patients of all age groups suffering from a variety of underlying diseases running very different clinical courses and often complicated by a number of septic metabolic and therapeutic problems, certain points can be made with regard to predisposing factors. 1) Prematures and neonates are particularly at risk. 2) Cholestasis occurs earlier and has a greater chance of leading to chronic liver disease in surgical patients. 3) Hepatobiliary abnormalities are more likely to develop after a prolonged period of TPN and are less frequent in patients who are also receiving oral feedings. Definition of the mechanism of hepatobiliary complications remains a problem. Although calcium bilirubinate appears to be responsible for sludge and stones, there is as yet no explanation for the presence of large amounts of indirect-reacting bilirubin in gallbladder and hepatic bile in patients on TPN. The pathogenesis of cholestatic liver disease remains an enigma; the lack of normal gastrointestinal stimuli for bile formation, abnormalities of bile acid metabolism, and sepsis might play roles, but attention has recently been attracted to amino acid toxicity and this possibility deserves further study.     

Fibronectin levels in stressed and septic patients fed with total parenteral nutrition

Plasma fibronectin concentrations were measured in healthy persons as well as in septic and stressed patients. A decrease in plasma fibronectin concentration was shown in volunteers receiving a low energy (600 kcal), amino acids- and lipid-deficient diet. Increased fibronectin levels were measured in stressed and septic patients, not receiving enteral nutrition, after adequate total parenteral nutrition (TPN during 1 week). It is concluded that total parenteral nutrition facilitates improved fibronectin synthesis in stressed and septic patients. Total parenteral nutrition containing an amino acid mixture rich in branched amino acids (50.2% BCAA) is not superior to TPN containing a standard amino acid mixture (15.6% BCAA) in this respect.     

Use of total parenteral nutrition in pediatric bone marrow transplantation

To evaluate the extent of the nutritional stress of pediatric bone marrow transplantation (BMT) and to evaluate the use of total parenteral nutrition (TPN), 35 consecutive pediatric patients who received BMT were studied retrospectively. Voluntary cessation of oral nutrition in almost all patients was observed, and significant decreases of serum albumin levels were seen after BMT. In 85% of these patients, TPN was necessary in response to severe wasting and fasting. No deaths were related to indwelling central venous catheters during the period of 2968 catheter-use days in these severely myelosuppressed patients. The mean of the total daily energy intake was 104% of basal energy expenditure (BEE), and 70% of patients lost their weight. Predicted energy requirement to maintain body weight after BMT would be 128% of BEE from a simple linear regression step in this study. Significant correlations were found between the marrow recovery time and the initial nutritional state, expressed as the percentage of ideal weight height ratio, as well as benign nature of the disease. The use of TPN did not show any beneficial effects on the time course of marrow recovery, although it showed favorable effects on the maintenance of body weight.