Continuous Parenteral Nutrition Research Articles

Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice.

We have developed a mouse model of parenteral nutrition-associated liver disease (PNALD) in which parenteral nutrition (PN) infusion results in cholestatic liver injury. In the liver, the master circadian genes Arntl/Bmal drive rhythmic gene expression and regulate circadian expression of hepatic functions including bile acid synthesis. The aim of this study was to examine the effect of continuous PN on ileal and hepatic expression of circadian regulatory (CR) genes, farnesoid X receptor (FXR) signaling, and bile acid synthesis in mice. Wild-type mice were exposed to ad libitum Chow or continuous soy oil lipid emulsion-based PN infusion through a central venous catheter for 4 days (PN). Water was provided ad libitum, but no nutrients were provided enterally. On day 4, separate groups of Chow and PN-fed mice were euthanized every 6 h (7 AM, 1 PM, 7 PM, and 1 AM), and ileal, hepatic tissue and serum harvested. From tissue samples, the relative expression of circadian transcription factors and FXR signaling was assessed. Administration of 4-day PN increased hepatic injury, inflammatory cytokine expression, and gut permeability. In the ileum, PN activated FXR and induced expression of Fgf15 and Nr0b2. In the liver, expression of FXR-downstream targets was dysregulated. PN administrations impacted hepatic and ileal circadian transcription factor mRNA expression, which was discordant between the two organs. Dysregulation of circadian regulatory machinery is in part due to discordance of the gut-liver axis during PN. Pharmacological targeting of CR as a therapeutic strategy for PNALD thus deserves further investigation.NEW & NOTEWORTHY This study used a novel short-term model of parenteral nutrition (PN) that is translationally relevant. We find that short-term PN is sufficient to induce hepatic and ileal changes in circadian transcription factor expression and to prevent normal concordant coordination of circadian transcription factors between the ileum and liver. These data suggest that targeting circadian transcription may have some clinical benefit in patients receiving parenteral nutrition.

Pericardial Effusion and Superficial Abdominal Abscess as Complications of Malposed PICC Line in a Preterm Neonate: A Case Report

In neonatal critical care units, peripherally inserted central catheter lines are frequently used to provide venous access for continuous parenteral nutrition and medications in newborns. In this case report, a male neonate weighing 1270 grams was on Continuous Positive Airway Pressure (CPAP) for hyaline membrane disease and initially received Total Parenteral Nutrition (TPN) through a Peripherally Inserted Central Catheter (PICC) in the left long saphenous vein on the second day. The baby developed tachycardia, respiratory distress requiring mechanical ventilation, and erythematous swelling over the paraumbilical region. A diagnosis of pericardial effusion and superficial abdominal abscess secondary to a malposed PICC line in a preterm, very low birth weight neonate was made. Suspecting a misplaced line, it was immediately removed, and the patient showed improvement over the next 24 hours. Within the next 48 hours, the patient was extubated to CPAP. Therefore, daily inspection by an expert, as well as confirmation of the central line tip, will aid in preventing delays in detecting complications.

Nutritional Screening of Sick Neonates in NICU and Its Relation to Short Term Outcome

Background Malnutrition during infancy has long-term physical and psychological adverse effect on development. Neonatal nutritional assessment is important to determine the daily energy and nutritional requirements needed for optimum growth and development. Objectives Assessment of the validity of Nutrition risk screening tools, and to stratify neonates admitted to the NICU according to their nutritional risk and correlate this to their outcome. Methods A cross-sectional study was conducted in NICU at Ain Shams University Hospitals. All neonates admitted to the NICU in a set period of 6 months from December 2017 to June 2018 were enrolled in the study after written and verbal consents were taken from parents.All neonates were subjected to the following: Anthropometric measurements (weight, length, head circumference, mid arm circumference, skin fold thickness and ponderal index at admission), Dietary assessment and laboratory investigations. The number of patients at this study were classified according to ‘Ohio neonatal nutrition screening tool (NNST) into a three risk groups: •low risk group: no = 121 •moderate risk: no = 15 •High risk: no = 14 Results The study showed that full intake enteral nutrition was reached in 100% of low and moderate risk groups and in only 64.3% of high risk group. Continuous parenteral nutrition was required in 100% of moderate and high risk groups and in only 7.4% of the low risk group. It also showed that the length of hospital stay was increased in the moderate risk group to 22 days (16-26) and in the high risk group to 8.5 days (3-16) while in the low risk group was only 5 days (4-7).Considering the hospital discharged patients: 100% of the moderate risk group, 99.2% of the low risk group and only 21.4% of the high risk group were discharged. According to the septic score, sepsis was recorded in 85.7% in the high risk group, 66.7% in the moderate risk group and only in 24% of the low risk group. Conclusion Nutritional screening tools were able to identify neonates at nutritional risk, as it showed that High risk group patients had higher rate of mortality and higher risk of Sepsis and thus they were in need for further assessment and support by nutrition specialist.

Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding.

Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition. Following preterm delivery (on day 105 of 115 gestation), pigs were fitted with umbilical artery and jugular vein catheters and provided continuous parenteral nutrition. Four days after birth, pigs were assigned to receive intermittent Leu (1600 µmol kg-1 h-1 ; n = 8) or alanine (1600 µmol kg-1 h-1 ; n = 8) parenteral pulses every 4 h for 28 h. Anabolic signaling and fractional protein synthesis were determined in skeletal muscle. Leu concentration in the longissimus dorsi and gastrocnemius muscles increased in the leucine (LEU) group compared with the alanine (ALA) group (P < 0.0001). Despite the Leu-induced disruption of the Sestrin2·GATOR2 complex, which inhibits mTORC1 activation, in these muscles (P < 0.01), the abundance of mTOR·RagA and mTOR·RagC was not different. Accordingly, mTORC1-dependent activation of 4EBP1, S6K1, eIF4E·eIF4G, and protein synthesis were not different in any muscle between the LEU and ALA groups. Intermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition.

Etiologies and treatments of chronic intestinal failure-short bowel syndrome (SBS) in Japanese adults: a real-world observational study

PurposeShort bowel syndrome (SBS) with intestinal failure (SBS-IF) requires long-term parenteral nutrition (PN). This study investigated the real-world etiologies of SBS, treatment patterns, and PN-related outcomes among adult patients with SBS-IF in Japan.MethodsThis retrospective, observational cohort study was based on data from April, 2008 to January, 2020 from one of the largest hospital-based claim databases in Japan. Analyzed patients were aged ≥ 16 years, had received continuous PN for ≥ 6 months, and had SBS or undergone SBS-related surgery with a diagnosis of a causative disease. The primary endpoint was PN weaning.ResultsWe analyzed data for 393 patients. The most frequent causes of SBS-IF were ileus (31.8%), Crohn’s disease (20.1%), and mesenteric ischemia (16.0%). Of 144/393 (36.6%) patients who were weaned off their PN, 48 (33.3%) were subsequently restarted on PN. Of 276/393 (70.2%) patients whose PN was initiated in hospital, 156 (56.5%) transitioned to home management. The mean duration of initial PN was 450.4 and 675.5 days for patients who were able or unable to be weaned off PN, respectively. Sepsis (67.4%), catheter-related bloodstream infections (49.1%), and liver disorders (45.0%) were the most reported PN-related complications.ConclusionsMost patients with SBS-IF in Japan could not be weaned off PN and suffered life-threatening complications.

Sepsis versus anaphylaxis—differentiating shock etiology: a case report involving Smoflipid

: This case study illustrates a clinically observed interaction between Smoflipid and the development of anaphylactic shock in a patient on long-term parenteral nutrition. This patient had a history of a well-differentiated retroperitoneal liposarcoma, now resected, which was complicated by duodenal perforation and intraperitoneal drain placement; due to significant gastrointestinal tract dysfunction the patient was maintained on continuous parenteral nutrition via a peripherally inserted central catheter (PICC) line. Following a routine and drain exchange, the patient was admitted to the hospital. The patient subsequently developed anaphylactic-like shock symptomatology, necessitating admission to the critical care unit. Intermittent dual vasopressor use was required. There was also an intermittently visible rash that was noted. The etiology of the shock state was unclear. After review of the patient’s case and clinical course, a potential etiology of his shock state was the inpatient protocolized substitution of Smoflipid instead of Intralipid in the parenteral nutrition regimen. After consultation with Allergic Diseases, Nutrition, and Pharmacy the Smoflipid was discontinued and the patient’s regimen was reverted to the standing home regimen including Intralipid. Following discontinuation of Smoflipid and resumption of Intralipid, the shock physiology resolved. The patient was subsequently transferred from the critical care unit and discharged soon thereafter by the primary surgical service. A formal Allergic Disease evaluation was completed in the outpatient setting. Continuous parenteral nutrition therapy was maintained at home using the previous home Intralipid regimen without issue. This case illustrates a multidisciplinary approach including Surgery, Allergic Diseases, Nutrition, Pharmacy, and Critical Care to address the patient’s acute shock state. In addition, a review of different shock states is presented. A literature review evaluating side effects of Smoflipid and an association of shock to its use is presented.

Evaluation of the Safety of Rapid Parenteral Nutrition Titration

Initiation of parenteral nutrition (PN) can cause complications including hyperglycemia (HGL), electrolyte abnormalities, and refeeding syndrome (RFS). These concerns lead many to titrate over several days, but our practice is to titrate PN to goal within 8hours. The aim of this study was to evaluate the safety of titrating PN to goal within 8hours. This was a single-center, retrospective study of adult patients initiated on continuous PN with titration to goal rate in <8hours. The primary composite outcome included the incidence of HGL, hypomagnesemia, hypophosphatemia, or hypokalemia within 24hours of PN initiation. Secondary outcomes included analyses of patients with risk factors for HGL and RFS, critically ill patients, and individual components of the composite outcome. Three hundred forty-two patients were included, with a primary outcome incidence of 24.6% (HGL 17.4%; hypokalemia 1.8%; hypomagnesemia 0.6%; hypophosphatemia 8.5%). The primary outcome was more common in the HGL group (34.3% vs 14.7%, P < 0.01) and in the ICU group (40.9% vs 20.7%, P < 0.01). Mean 24-hour blood glucose > 180mg/dL occurred more in the HGL group (27.9% vs 7.6%, P < 0.01) and in the ICU group (34.8% vs 13.8%, P < 0.01). In patients with no risk factors, the primary outcome was 11.9%. Rapid PN titration was likely safe in patients without risk factors for HGL or RFS. Further evaluation of protocolized HGL management is needed to determine the risk of HGL in patients with HGL risk factors.

Effects of cyclic parenteral nutrition on parenteral nutrition-associated cholestasis in newborns.

Parenteral nutrition (PN) is one of the main nutritional methods used in newborns; however, long-term PN may induce PN-associated cholestasis (PNAC). This study aims to evaluate the effect of cyclic PN in the prevention and improvement of PNAC in newborns requiring long-term PN. A retrospective cohort study was conducted on patients admitted at the Seoul National University Children's Hospital neonatal intensive care unit between October 2010 and September 2015 and referred to the nutrition support team with total parenteral nutrition for more than 14 days. The primary outcome was the incidence of PNAC. The incidence of hypoglycemia, changes in direct bilirubin (DB) concentrations, and length of hospital stay were investigated. A total of 124 patients were observed in this study. Among these, 100 patients received continuous PN, whereas 24 patients received both continuous and cyclic PN. PNAC occurred in 31.5% (39/124) of study population. The incidence rates of PNAC were 27.4% during continuous PN period and 20.8% during cyclic PN period. Cyclic PN was an independent factor that significantly decreased PNAC incidence (OR=0.154; 95% CI, 0.045-0.529, p=0.003). DB concentrations significantly decreased (p=0.049) with therapeutic cyclic PN, but remained normal with prophylactic cyclic PN. No significant difference in hypoglycemia incidence and length of hospital stay was observed in both continuous PN and continuous to cyclic PN groups. Cyclic PN could be effective in the prevention and improvement of PNAC and also safe in terms of hypoglycemia in newborns.

Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease

Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This animal model serves as an experimental model to further investigate the pathogenesis of PNALD inflicted by steatosis and cholestasis.

Dysregulation of bile acid homeostasis in parenteral nutrition mouse model.

Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD.

CLINICAL NUTRITION WEEK 2015: Long Beach, CA February 14–17, 2015

CLINICAL NUTRITION WEEK 2015: Long Beach, CA February 14–17, 2015

Continuous Parenteral and Enteral Nutrition Induces Metabolic Dysfunction in Neonatal Pigs

We previously showed that parenteral nutrition (PN) compared with formula feeding results in hepatic insulin resistance and steatosis in neonatal pigs. The current aim was to test whether the route of feeding (intravenous [IV] vs enteral) rather than other feeding modalities (diet, pattern) had contributed to the outcome. Neonatal pigs were fed enterally or parenterally for 14 days with 1 of 4 feeding modalities as follows: (1) enteral polymeric formula intermittently (FORM), (2) enteral elemental diet (ED) intermittently (IEN), (3) enteral ED continuously (CEN), and (4) parenteral ED continuously (PN). Subgroups of pigs underwent IV glucose tolerance tests (IVGTT) and hyperinsulinemic-euglycemic clamps (CLAMP). Following CLAMP, pigs were euthanized and tissues collected for further analysis. Insulin secretion during IVGTT was significantly higher and glucose infusion rates during CLAMP were lower in CEN and PN than in FORM and IEN. Endogenous glucose production rate was suppressed to zero in all groups during CLAMP. In the fed state, plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide (GLP)-1, and GLP-2 were different between feeding modalities. Insulin receptor phosphorylation in liver and muscle was decreased in IEN, CEN, and PN compared with FORM. Liver weight was highest in PN. Steatosis and myeloperoxidase (MPO) activity tended to be highest in PN and CEN. Enterally fed groups had higher plasma GLP-2 and jejunum weight compared with PN. PN and enteral nutrition (EN) when given continuously as an elemental diet reduces insulin sensitivity and the secretion of key gut incretins. The intermittent vs continuous pattern of EN produced the optimal effect on metabolic function.

Randomized Controlled Trial of Early Parenteral Nutrition Cycling to Prevent Cholestasis in Very Low Birth Weight Infants

To compare the incidence of cholestasis in very low birth weight infants receiving cycled versus continuous parenteral nutrition, and to determine factors that predispose to parenteral nutrition-associated cholestasis (PNAC). Preterm infants weighing ≤ 1250 g (n = 70) at birth were randomly assigned within the first 5 postnatal days to either cycle (n = 34) or continuous (n = 36) parenteral nutrition. Liver function tests were obtained at baseline, and sequentially thereafter. Cholestasis was defined as direct bilirubin >2 mg/dL. Infants with major congenital anomalies, congenital hepatic disease, clinically apparent congenital viral infection, and those who required major abdominal surgery were excluded. The incidence of PNAC was similar in the 2 groups (cycle 32% vs continuous 31%; P = 1.0). Bilirubin and transaminases were similar in both groups by repeated measures of ANOVA. Gestational age, birth weight, and Apgar scores were significantly lower, and Clinical Risk Index for Babies II scores were significantly higher in infants who developed PNAC. Using backward selection logistic regression, bronchopulmonary dysplasia, duration of parenteral nutrition, and days to full enteral nutrition emerged as factors independently associated with PNAC. Early prophylactic parenteral nutrition cycling in very low birth weight infants in this study did not reduce cholestasis. Time to full feedings is a significant predictor for PNAC in very low birth weight infants. Preterm infants with bronchopulmonary dysplasia are more likely to have PNAC as a comorbidity. The Clinical Risk Index for Babies II score may help identify those preterm infants who might benefit from future prospective prevention trials.

Fungal infection in patients after liver transplantation in years 2003 to 2012

Fungal infections after liver transplantation have received considerable interests because of their association with substantial morbidity and mortality. This study investigated risk factors of fungal infection after liver transplantation. Retrospective analysis was performed based on clinical data from 120 patients with fungal infection after liver transplantation from January 1, 2003 to May 30, 2012. χ2 test was used to analyze risk factors for fungal infections. The fungal infection rate after liver transplantation is 13.5% (120/886) and the case fatality rate reaches 70.8%; most are infected by Candida albicans (67.5%), with infection located in the lung (73.3%). Acute physiology and chronic health evaluation scores of the infected group are higher than those of the control group 24 hours after the surgery (27.1±5.2 vs. 21.9±5.0). The percentage of primary liver cancer patients in the infected group was lower than in the control group (26.7% vs. 45.8%). Compared to the control group, the infected group had a higher percentage of patients with HBV, gestational diabetes mellitus, and multiple organ dysfunction syndrome. Percentages of patients with long continuous parenteral nutrition time, poorly controlled high blood sugar, long-term mechanical ventilation, and antibiotics use were higher in the infected group than in the control group. Preoperative original attack, postoperative critical condition, chronically high blood sugar, long-term use of antibiotics, and mechanical ventilation are probably vital risk factors for fungal infection after liver transplantation.

Abnormal plasma peptide YY 3–36 levels in patients with liver cirrhosis

Objective Peptide YY 3–36 (PYY 3–36) is a gut hormone with anorectic action that also affects energy expenditure. Anorexia and malnutrition are often observed in patients with decompensated liver cirrhosis (LC), whereas patients with LC after insertion of transjugular portosystemic stent shunts (TIPS) show normal eating behavior. The underlying mechanism of anorexia in decompensated LC and its resolution in patients with TIPS is still unclear. We thus investigated fasting and postprandial PYY 3–36 serum levels in patients with decompensated LC, patients with compensated LC with in situ TIPS, and healthy controls. Methods We analyzed fasting PYY 3–36 levels in six patients with decompensated LC (four men and two women, 55 ± 11 y of age), nine patients with TIPS (seven men and two women, 48 ± 11 y of age), and 10 controls (eight men and two women, 43 ± 9 y of age) postprandially after a standardized meal of 300 kcal and during 1-h continuous parenteral nutrition. Energy expenditure was determined by indirect calorimetry. Results At baseline PYY 3–36 was comparable in controls and patients with TIPS (91 ± 10 and 89 ± 25 ng/L) but was increased in patients with decompensated LC (165 ± 44 ng/L, P < 0.01). Although the cumulative postprandial PYY 3–36 increase was similar in controls (mean 2089 ng/240 min per liter) and patients with decompensated LC (mean 1735 ng/240 min per liter), no postprandial PYY 3–36 increase was observed in patients with TIPS (mean −579 ng/240 min per liter). Parenteral nutrition did not significantly affect PYY 3–36 levels in any group. Fasting PYY 3–36 values were negatively related to resting energy expenditure ( r = −0.443, P = 0.030). PYY 3–36 was not associated to liver parameters (e.g., bilirubin, alanine aminotransferase). Conclusion Our results demonstrate an abnormal neuroendocrine regulation of PYY 3–36 in patients with decompensated LC and those with TIPS.

Utility of liver function tests including aminotransferase-to-platelet ratio index in monitoring liver dysfunction in short-gut infants of varying ages and intestinal lengths

Background/Purpose Aspartate aminotransferase-to-platelet ratio index (APRI) has good correlation with liver fibrosis progression in the infant and toddler short-gut population. This study applies laboratory liver function testing, including APRI, to monitor liver dysfunction over time for short-gut infants, with further analysis of at-risk subpopulations. Methods Study inclusion criteria included infants younger than 1 year at initial intestinal resection with subsequent continuous parenteral nutrition dependence of 3 months minimum. Bilirubin, aspartate aminotransferase, alanine aminotransferase, APRI, and biopsies were collected for 26 weeks postresection. Subgroup analysis was stratified by (1) estimated gestational age, (2) age at intestinal resection (AGE), and (3) remaining intestinal length. Results Thirty-one children were included, all with AGE younger than 2 months at initial intestinal resection (mean, 13 days). Aminotransferase-to-platelet ratio index was the only marker associated with fibrosis progression (median, APRI by METAVIR grade: F0/F1/F2, 1.9; F3, 5.7; F4, 14.7 [ P = .02]). At 8 and 18 weeks postresection, there are separations seen within study subgroups, indicating the onset and progression of liver dysfunction. Conclusion Aminotransferase-to-platelet ratio index is associated with liver fibrosis progression in this population. There are marked changes in liver dysfunction at 8 and 18 weeks postresection, with subgroup differences within estimated gestational age, AGE, and remaining intestinal length.

Metabolic Effects of Cyclic Parenteral Nutrition Infusion in Adults and Children

Cyclic (discontinuous) infusion of parenteral nutrition (PN) presents a clear practical advantage over continuous 24-hour infusion in patients receiving long-term or home PN. It is important for nutrition support clinicians to recognize the metabolic consequences of cyclic infusion. A literature search was conducted through PubMed (1948 to December 2009) and MEDLINE (1950 to November 2009) using the search term parenteral nutrition plus any of the following: cycling, cycle, cyclic, discontinuous, intermittent, bolus. Prospective clinical studies characterizing the metabolic effects of cyclic PN infusion in humans and their references were reviewed. Twenty-five studies met inclusion criteria and were included in the review. Sample sizes were 4-65 (18 studies examined < or =20 patients, 9 examined < or =10 patients). Eight studies had important design elements that limit interpretability. Cyclic and continuous PN infusions result in similar nitrogen balance and circulating counterregulatory hormone concentrations. Following PN infusion, carbohydrate oxidation decreases, fat oxidation increases, and the respiratory quotient decreases. In acutely ill mechanically ventilated patients, carbon dioxide production increases. Cyclic infusion may stabilize liver function tests in some patients with mild hyperbilirubinemia (< or =20 ng/mL) on continuous PN infusion. Abrupt infusion initiation may cause hyperglycemia. Abrupt discontinuation may cause hypoglycemia, predominantly in children younger than 2-3 years old, which may decrease with infusion tapering. Cyclic PN infusion is not associated with increased daily calcium, phosphorus, magnesium, or vitamin D losses. These results indicate a favorable risk-benefit profile of cyclic PN infusion in most patients receiving long-term or home PN, in support of current practices.

Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (TPN) that was either high in glucose [C; 75% nonprotein calories (NPC)] or in lipid (HL; 75% NPC) in the presence or absence of a low dose (one-third basal) chronic intraportal infusion of glucagon (GN; 0.25 ng.kg(-1).min(-1)). During the 3 days of TPN, all groups received the same insulin algorithm; the total amount of glucose infused (GIR) was varied to maintain isoglycemia ( approximately 120 mg/dl). On day 3 of TPN, hepatic metabolism was assessed. Glucose and insulin levels were similar in all groups. GIR was decreased in HL and C + GN ( approximately 30%) and was further decreased in HL + GN (55%). Net hepatic glucose uptake was decreased approximately 15% in C + GN, and HL and was decreased approximately 50% in HL + GN. Lipid alone or combined with glucagon decreased glucose uptake by peripheral tissues. Despite impairing whole body glucose utilization, HL did not limit whole body energy disposal. In contrast, glucagon suppressed whole body energy disposal irrespective of the diet composition. In summary, failure to appropriately suppress glucagon secretion adds to the dietary fat-induced impairment in both hepatic and peripheral glucose disposal. In addition, unlike increasing the percentage of calories as fat, inappropriate glucagon secretion in the absence of compensatory hyperinsulinemia limits whole body nutrient disposition.

Comparison of Urine Urea Nitrogen Collection Times in Critically Ill Patients

Twenty-four-hour urine urea nitrogen (UUN) collections are used to assess nitrogen loss in critically ill patients but are often difficult to obtain accurately. This prospective study compared 6- and 12-hour UUN collections with 24-hour UUN collections in critically ill patients receiving continuous nutrition support. ICU patients admitted from September 1999 through January 2003 who had UUN collections as part of routine care were recruited into the study. Patients were not receiving oral diets, were receiving continuous parenteral or enteral nutrition, and had indwelling urinary catheters. We excluded patients with hepatic or renal failure. Urine samples were collected every 6 hours starting at 6:00 am and kept refrigerated until the 24-hour collection was complete. Samples were analyzed using an automated urease enzymatic reaction. Samples were multiplied by a factor of 4 (6-hour samples) or 2 (12-hour samples) to estimate 24-hour totals and then compared with actual 24-hour totals. Twenty-four patients (18 men) completed the study; 21 patients had 6-hour samples (84 samples), and 24 patients had 12-hour samples (24 samples). Estimated 24-hour UUN from 6-hour (14.7-15.7 g/d) and 12-hour (15.2 g/d) samples did not differ significantly (p > .5) from actual 24-hour totals (15.1 g/d). Shortened UUN collection times may be used to estimate 24-hour nitrogen losses in critically ill patients receiving continuous nutrition support.

Endotoxin and cytokine released during parenteral nutrition.

Apart from its benefits, parenteral nutrition (PN)-related complications have been reported. Studies have shown that PN could alter cytochrome P450 (CYP) activity. One of the possible mechanisms is through cytokine and nitrite release, which is triggered by endotoxin. The purpose of this study is to investigate the potential release of endotoxin, cytokines, and nitrite during PN. Rats were randomly assigned into either (a) the PN group, which received continuous PN infusion only; or (b) the control group, which received normal chow with saline infusion. The infusions were administered continuously for 7 days, and then blood was collected and microsomes were prepared from the excised livers. Endotoxin levels in the PN group were significantly higher in portal vein but not in inferior vena cava when compared with those of the controls. TNF-alpha and IL-6 levels were significantly higher in the PN group (p < .05). However, IL-1 beta levels were not significantly different in the 2 groups (p > .05). The nitrite levels, the end product of nitric oxide formation, were found to be almost 2 times higher after PN (p < .05). It is confirmed that a 7-day infusion treatment of PN in rat may be linked to bacterial translocation, which leads to increased levels of endotoxin. This increase could trigger cytokine release, which could down regulate CYP activities.