Computer‐Assisted Glucose Regulation During Rapid Step‐Wise Increases of Parenteral Nutrition in Critically Ill Patients

Background: Early delivery of calories is important in critically ill patients, and the administration of parenteral nutrition (PN) is sometimes required to achieve this goal. However, PN can induce acute hyperglycemia, which is associated with adverse outcome. We hypothesized that initiation of PN using a rapid “step‐up” approach, coupled with a computerized insulin‐dosing protocol, would result in a desirable caloric intake within 24 hours without causing hyperglycemia. Methods: In our surgical intensive care unit (ICU), glucose is regulated by a nurse‐centered computerized glucose regulation program. When adequate enteral feeding was not possible, PN was initiated according to a simple step‐up rule at an infusion rate of 10 mL/h (approximately 10 kcal/h) and subsequently increased by steps of 10 mL/h every 4 hours, provided glucose was <10 mmol/L, until the target caloric intake (1 kcal/kg/h) was reached. All glucose levels and insulin doses were collected during the step‐up period and for 24 hours after achieving target feeding. Results: In all 23 consecutive patients requiring PN, mean intake was 1 kcal/kg/h within 24 hours. Of the 280 glucose samples during the 48‐hour study period, mean ± standard deviation glucose level was 7.4 ± 1.4 mmol/L. Only 4.5% of glucose measurements during the step‐up period were transiently ≥10 mmol/L. After initiating PN, the insulin requirement rose from 1.1 ± 1.5 units/h to 2.9 ± 2.5 units/h (P < .001). Conclusions: This proof of concept study shows that rapid initiation of PN using a step‐up approach coupled with computerized glucose control resulted in adequate caloric intake within 24 hours while maintaining adequate glycemic control.     

Hyperglycemia During Home Parenteral Nutrition Administration in Patients Without Diabetes

Background: Parenteral nutrition (PN) is a life‐sustaining therapy in appropriate clinical settings. In the hospital setting, some nondiabetic patients develop hyperglycemia and subsequently require long‐term insulin while receiving PN. Whether similar hyperglycemia is seen in the outpatient setting is unclear. Methods: We studied patients enrolled in the Mayo Clinic Home Parenteral Nutrition (HPN) program between January 1, 2010, and December 31, 2012. Patients were excluded if they had diabetes mellitus type 2 (DM2), had previously received HPN, had taken corticosteroids, or were at risk for refeeding syndrome. Results: Of 144 enrolled patients, 93 met inclusion criteria with 39 patients requiring the addition of insulin to HPN. The mean age of the insulin‐requiring group (IR) was higher than that of the non–insulin‐requiring group (NIR) (60.74 ± 13.62 years vs 48.97 ± 17.62 years, P < .001). There were 17 (44%) men in the IR group and 26 (48%) men in the NIR group. Mean blood glucose at baseline before starting the infusion was 131.82 ± 49.55 mg/dL in IR patients and 106.16 ± 59.01 mg/dL in NIR patients (P = .03). In the stepwise multivariate analysis for assessing the risk for developing hyperglycemia, HR for age was 1.020 (1.010–1.031), P < .001. Conclusions: Hyperglycemia is a common finding with the use of PN in both the hospital and ambulatory setting in patients without a previous diagnosis of DM2. Age was the most significant predictor of the requirement of insulin in the present study. When hyperglycemia is managed appropriately with insulin therapy, the long‐term complications can be minimized.     

Glargine Insulin Use Versus Continuous Regular Insulin in Diabetic Surgical Noncritically Ill Patients Receiving Parenteral Nutrition: Randomized Controlled Study

Background: Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE‐in‐PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI‐in‐PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN. Methods: This prospective randomized open‐label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI‐in‐PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5–9. The percentages of blood glucose measurements at goal were compared between groups. Results: Sixty‐seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day (P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI‐in‐PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI‐in‐PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI‐in‐PN (11.4%; P > .1). Conclusion: Both glargine insulin and RI‐in‐PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.     

An insulin protocol for management of hyperglycemia in patients receiving parenteral nutrition is superior to ad hoc management

Background: The authors investigated whether an insulin protocol for parenteral nutrition (PN)–induced hyperglycemia is superior to conventional management relying primarily on sliding‐scale insulin at a large county hospital. Methods: A prospective cohort study with historical controls was completed. Adult patients receiving PN were managed with a protocol that determined insulin doses based on carbohydrate delivery and capillary blood glucose (CBG) if half or more of CBG measurements in the first 24 hours after initiation of PN exceeded 140 mg/dL. Control data were obtained from records of patients who met study eligibility criteria but had been managed before implementation of the insulin protocol. Results: Mean CBG after the start of insulin therapy was 138 ± 37 mg/dL for protocol patients and 159 ± 46 mg/dL for controls (P < .0001). Proportion of CBG values in the target range of 80–140 mg/dL was 60% in the protocol group and 35% in the control group (P < .0001). Hypoglycemia, defined as CBG <80 mg/dL, occurred infrequently but more often in the protocol group (3% vs 1%, P = .012). There was no difference in total daily insulin between groups, although protocol patients received mostly scheduled insulin (93% total daily dose), whereas control patients received predominantly supplemental insulin (66% total daily dose). Conclusions: Protocol‐directed management of PN‐induced hyperglycemia is superior to ad hoc insulin dosing. Linking insulin to carbohydrate in PN leads to improved glycemic control with a low rate of hypoglycemia.     

Hospital Readmissions for Catheter‐Related Bloodstream Infection and Use of Ethanol Lock Therapy

Background: Catheter‐related bloodstream infection (CRBSI) is the most serious long‐term infectious complication of long‐term home parenteral nutrition (PN). Ethanol is being used more commonly as a catheter locking solution in the home PN setting for prevention of CRBSI; however, no current literature reports the use of ethanol lock (ETL) in skilled nursing facility (SNF) patients. Methods: The authors evaluated the number of hospital readmissions for CRBSI and length of stay between SNF (not receiving ETL) and home patients (receiving or not receiving ETL) receiving PN or intravenous fluid therapy. Results: SNF patients had a significantly longer length of stay (LOS) for CRBSI hospital admissions compared with patients receiving PN at home with or without ETL (P < .001; 16 vs 8 vs 8 days). There was no LOS difference for CRBSI between home patients with or without ETL. Home PN patients not receiving ETL were more likely to have a CRBSI from Staphylococcus sp (48% vs 27%; P = .015), whereas SNF PN patients not receiving ETL were more likely to have a CRBSI from Enterococcus sp (16% vs 3%; P = .004). Conclusion: Despite different causative organisms and medical acuity likely affecting the differences observed in LOS, the SNF population is another setting ETL can be used to prevent CRBSI.     

Compatibility of Intravenous Medications With Parenteral Nutrition

Background and Aim: Hospitalized patients requiring parenteral nutrition (PN) often need to receive intravenous (IV) medications as well. Y‐site administration is occasionally necessary, but physicochemical incompatibilities can occur between the medications and PN. The aim of the present study was to assess the physical compatibility between 25 frequently coadministered IV medications and a commercially available ready‐to‐use total PN. Methods: PN (NuTRIflex Lipid Special; B. Braun Medical AG, Sempach, Switzerland) and medications were mixed in 1:1 (v/v) proportions, and the stability was assessed at the time of mixing and after 1 and 4 hours. The stability of lipid emulsion was observed by microscopic investigation, visual inspection, dynamic laser light scattering, and laser light obscuration. The binary admixtures of PN (without lipid emulsion) and medications were used to detect discoloration, visibly detectable precipitates, and subvisual particles. Results: Two of 25 medications were incompatible with the lipid emulsion (serum albumin 20% and tropisetron), 2 showed signs of degradation (discoloration) over time (esomeprazole and pantoprazole), and 1 precipitated at high concentrations (5‐fluorouracil). The other 20 medications were considered compatible when administered by Y‐site. Conclusion: The present study validated the compatibility of 1 commercially available PN and 20 medications. These results offer new solutions to support the implementation of complex therapeutic schemes in practice, when coadministration via Y‐site cannot be avoided.     

Teduglutide‐Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome

Background: Teduglutide, a glucagon‐like peptide‐2 (GLP‐2) analogue, is available for long‐term use by parenteral nutrition (PN)–dependent adults to promote intestinal adaptation but is not approved for use in pediatric patients. The objective of this study was to assess teduglutide‐stimulated induced intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation in a neonatal piglet model of short bowel syndrome (SBS). Materials and Methods: Neonatal piglets (48 hours old; n = 72) underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment groups, in a 2 × 2 factorial design, with PN or PEN (80% standard PN/20% standard enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received nutrient infusions for 4 hours, 48 hours, or 7 days. Results: Teduglutide improved (P < .05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon; apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). These effects were complemented and synergistically enhanced by PEN in both site and timing of action. Structural adaptations preceded functional adaptations, but crypt depth remained a strong indicator of adaptation, regardless of time. Conclusions: The combination of teduglutide and PEN enhances intestinal adaptation beyond that of either therapy alone.     

Provision of balanced nutrition protects against hypoglycemia in the critically ill surgical patient

Background: Intensive insulin therapy lowers blood glucose and improves outcomes but increases the risk of hypoglycemia. Typically, insulin protocols require a dextrose solution to prevent hypoglycemia. The authors hypothesized that the provision of balanced nutrition (enteral nutrition [EN] or parenteral nutrition [PN]) would be more protective against hypoglycemia (≤50 mg/dL) than carbohydrate alone. Methods: A retrospective analysis was performed of patients treated with intensive insulin therapy and surviving ≥24 hours. The computer‐based insulin protocol requires infusion of D10W at 30 mL/h if EN or PN is not provided. Nutrition provision was assessed in 2‐hour increments, comparing periods of blood glucose control with and without balanced nutrition. The risk of hypoglycemia for each blood glucose measurement was estimated by multivariable regression. Results: In total, 66,592 glucose measurements were collected on 1392 patients. Hypoglycemic events occurred in 5.8/1000 glucose tests after 2 hours without balanced nutrition compared to 2.2/1000 tests when balanced nutrition was given in the preceding 2 hours. In multivariable regression models, balanced nutrition was the strongest protective factor against hypoglycemia. Patients who did not receive balanced nutrition in the preceding 2 hours had a 3 times increase in the odds of a hypoglycemic event at their next glucose check (odds ratio = 3.6, P < .001). Providing carbohydrate alone was not protective. Conclusions: Balanced nutrition is associated with reduced risk of hypoglycemia. These results suggest that balanced nutrition should be given when insulin therapy is initiated. Future studies should evaluate the efficacy of EN vs PN in preventing hypoglycemia.     

Management of Parenteral Nutrition in Hospitalized Adult Patients

Despite the high prevalence of malnutrition in adult hospitalized patients, surveys continue to report that many clinicians are undertrained in clinical nutrition, making targeted nutrition education for clinicians essential for best patient care. Clinical practice models also continue to evolve, with more disciplines prescribing parenteral nutrition (PN) or managing the cases of patients who are receiving it, further adding to the need for proficiency in general PN skills. This tutorial focuses on the daily management of adult hospitalized patients already receiving PN and reviews the following topics: (1) PN basics, including the determination of energy and volume requirements; (2) PN macronutrient content (protein, dextrose, and intravenous fat emulsion); (3) PN micronutrient content (electrolytes, minerals, vitamins, and trace elements); (4) alteration of PN for special situations, such as obesity, hyperglycemia, hypertriglyceridemia, refeeding, and hepatic/renal disease; (5) daily monitoring and adjustment of PN formula; and (6) PN‐related complications (PN‐associated liver disease and catheter‐related complications).     

Parenteral nutrition administration leads to specific alterations in the expression of adipocytokines and peroxisome proliferator-activated receptors in a rat model

Background: Similar to metabolic syndrome, parenteral nutrition (PN) administration has also been associated with biologic abnormalities of glucose and lipids. Such complications include hyperglycemia, hypertriglyceridemia, liver dysfunction, and hepatobiliary complications. Because metabolic syndrome has been associated with altered expression of adipocytokines, and peroxisome proliferator‐activated receptors (PPARs), the present study hypothesized that PN would also lead to alterations in adipocytokines and related gene abundances. Methods: Male Wister rats received either intravenous (IV) saline and chow (control) or PN. To determine the contribution of lipids to metabolic changes, the following 2 PN groups were studied: PN with IV lipid (PN+L) and PN without lipid (PN–L). Rats were studied after 7 days. Results: A marked increase in hepatic glycogen staining was found in the PN–L group, and conversely, a marked increase in hepatic lipid staining was observed in the PN+L group. Both PN groups demonstrated a 30% increase in serum adiponectin levels in comparison to controls. In the liver, ACDC mRNA expression significantly increased (10%–20%), while ADIPOR1 expression significantly declined in the PN groups compared with controls. PPAR expression significantly declined (10%–30%) in the PN+L group compared with controls. In contrast to metabolic syndrome, PN+L led to a decrease in tumor necrosis factor α and interleukin 6 levels in the liver. Conclusions: The study shows that PN led to specific alterations in the abundance of adipocytokines and PPARs. These changes give critical insight into many of the metabolic derangements in lipid metabolism, which patients may experience with PN.     

National Trends and In‐Hospital Outcomes of Adult Patients With Inflammatory Bowel Disease Receiving Parenteral Nutrition Support

Background: Patients with inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are susceptible to protein‐calorie malnutrition secondary to decreased oral intake, malabsorption, and increased metabolic expenditure. In this study, we seek to assess the national frequencies of parenteral nutrition (PN) use among hospitalized patients with IBD and to determine their in‐hospital outcomes. Methods: We analyzed the Nationwide Inpatient Sample from 1988–2006 to determine the frequency of PN usage among patients with UC or CD and to determine their in‐hospital outcomes. A multivariate analysis was performed to identify factors predictive of increased inpatient mortality in this population. Results: From 1988–2006, the annual incidence of PN use among hospitalized patients with CD was 4.29 per 100,000 and among those with UC was 3.80 per 100,000, with trends being relatively stable through the indexed period. The mean length of hospitalization among patients with UC receiving PN was longer compared with patients with CD. Factors predictive of an increased risk for mortality include the following: age >50 years, acute kidney injury, hospital‐acquired pneumonia, Clostridium difficile colitis, prolonged postoperative ileus requiring PN use, pulmonary embolism, malnutrition, and patients with UC relative to CD. Conclusion: Traditionally, patients with CD are at a higher risk for developing malnutrition than patients with UC; however, there is a 2‐fold higher risk for inpatient mortality and a longer length of hospitalization among patients with UC compared with those with CD. This pattern suggests that the use of PN, particularly among patients with UC, serves as a surrogate marker of higher disease acuity and severity.     

Methods to identify and compare parenteral nutrition administered from hospital-compounded and premixed multichamber bags in a retrospective hospital claims database

Purpose: Use of parenteral nutrition (PN) is indicated for patients who are unable to meet their needs enterally. PN may be administered via custom‐compounded mix or commercially available ready‐to‐use multichamber bags (MCB), but little is known about potential differences in clinical outcomes between these delivery systems. This study was undertaken to assess the feasibility of comparing custom‐compounded and MCB PN in a large hospital claims database. Methods: Hospital claims data from the Premier Perspective Comparative Hospital Database (PCD) reported from 2005 through 2007 were analyzed. The authors searched the data for patients who received any PN products, including compounded PN and MCB PN. Coding algorithms for identifying patient characteristics, risk factors, and outcomes of interest were explored. Results: Using hospital billing claims, the authors identified patients in the database treated with premixed PN from multichamber bags (“MCB only,” n = 4699) and patients treated with custom‐compounded PN solution (“compounded PN,” n = 64,315). Methods of identifying PN administration groups, patient characteristics and risk factors, outcomes of interest, and data limitations are described. Conclusions: Exploratory analysis suggests that comparisons of PN administered via compounding and MCB are possible using the Premier data. The ability to control for many identifiable risk factors allows data to be presented for the use of PN and related outcomes in both a clinically sensible and relevant manner, albeit with some limitations.     

Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric‐Onset Intestinal Failure

Background: Intestinal failure (IF)–associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. Methods: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture‐independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Results: Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Conclusions: Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.     

Dosing and monitoring of trace elements in long-term home parenteral nutrition patients

Background: Trace elements (TEs) dosing and monitoring in home parenteral nutrition (PN) patients vary with their underlying conditions. Methods: This retrospective observational study evaluated parenteral TE dosing, serum TE concentrations and monitoring, and dose‐concentration relationships between TE doses and serum TE concentrations in 26 adult and adolescent home PN patients. Results: There was a total of 40,493 PN days. Average parenteral zinc doses of 9.1 mg/d and 7.6 mg/d resulted in the majority of serum zinc concentrations (90%) within normal range in patients with and without short bowel syndrome (SBS), respectively. Selenium at about 70 mcg/d resulted in about 60% of serum selenium concentrations within normal range, with 38% of values below normal in patients with and without SBS alike. Copper at 1 mg/d resulted in 22.5% of serum copper concentrations above the normal range. The majority of serum manganese (94.6%) and chromium (96%) concentrations were elevated. Serum TE concentrations were infrequently monitored. Significant relationships existed between doses and serum concentrations for zinc (P < .0001), manganese (P = .012), and chromium (P < .0001) but not for selenium or copper. Conclusions: TE doses in home PN should be individualized and adjusted based on regular monitoring of TE status. In long‐term home PN patients, higher zinc and selenium doses may be necessary to maintain their normal serum concentrations. Lower copper doses and restrictions of manganese and chromium supplementation may be needed to avoid their accumulation. Relationships between TE doses and serum TE concentrations vary for each TE and underlying clinical conditions.     

When early enteral feeding is not possible in critically ill patients: results of a multicenter observational study

Background: Early enteral nutrition (EN) is the preferred strategy for feeding the critically ill; however, it is not always possible to initiate EN within the recommended 24 to 48 hours. When these situations arise, controversy exists whether to start feeding early via the parenteral route or to delay feeding until EN can be provided. Methods: A multicenter, international, observational study examined nutrition practices in intensive care units (ICUs). Eligible patients were critically ill patients with a medical diagnosis who remained in the ICU for >72 hours and received EN >48 hours after admission. Data were collected on site, including patient characteristics, daily nutrition practices, and outcomes at 60 days. Nutrition and clinical outcomes were compared between 3 groups of patients: (1) early parenteral nutrition (PN) (<48 hours after admission) and late EN (>48 hours after admission), (2) late PN and late EN, and (3) late EN and no PN. Results: Of the 703 patients who met our inclusion criteria, 541 (77.0%) medical patients received late EN and no PN. In patients receiving late EN and PN, 83 (11.8%) received early PN and 79 (11.2%) received late PN. Adequacy of calories and protein from total nutrition was highest in the early PN group (74.1% ± 21.2% and 71.5% ± 24.9%, respectively) and lowest in the late EN group (42.9% ± 21.2% and 38.7% ± 21.6%) (P < .001). The proportion of patients dead or remaining in hospital was significantly higher for early PN compared with late EN and PN (unadjusted hazard ratio for early PN = 0.55; 95% confidence interval, 0.37–0.83, P = .015). However, this difference did not remain significant (P = .65) after adjustment for baseline characteristics. Conclusions: The results suggest that initiating PN early, when it is not possible to feed enterally early, may improve provision of calories and protein but is not associated with better clinical outcomes compared with late EN or PN.     

Plasma Aluminum Concentrations in Pediatric Patients Receiving Long‐Term Parenteral Nutrition

Background: Patients receiving long‐term parenteral nutrition (PN) are at increased risk of aluminium (Al) toxicity because of bypass of the gastrointestinal tract during PN infusion. Complications of Al toxicity include metabolic bone disease (MBD), Al‐associated encephalopathy in adults, and impaired neurological development in preterm infants. Unlike the United States, there are no regulations regarding Al content of large‐ and small‐volume parenterals in Canada. We, therefore, aimed to present our data on plasma Al concentration and Al intake from our cohort of pediatric patients receiving long‐term PN. Methods: Plasma Al concentration was retrospectively gathered from the patient charts of all 27 patients with intestinal failure (IF) receiving long‐term PN at The Hospital for Sick Children, Toronto, Canada, and compared with age‐ and sex‐matched controls recruited for comparison. In addition, Al concentration was measured in PN samples collected from 10 randomly selected patients with IF and used to determine their Al intake. Results: The plasma Al concentration of patients with IF receiving long‐term PN was significantly higher than that of control participants (1195 ± 710 vs 142 ± 63 nmol/L; P < .0001). In the subgroup of 10 patients for whom Al intake from their PN solution was determined, mean ± SD Al intake from PN was 15.4 ± 15 µg/kg, 3 times the Food and Drug Administration upper recommended intake level, and Al intake was significantly related to plasma Al concentration (P = .02, r² = 0.52). Conclusion: Pediatric patients receiving long‐term PN for IF in Canada are at risk for Al toxicity.