Management of Central Venous Access in Children With Intestinal Failure: A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group.

ABSTRACT: Intestinal failure requires the placement and maintenance of a long-term central venous catheter for the provision of fluids and/or nutrients. Complications associated with this access contribute to significant morbidity and mortality, while the loss of access is an increasingly common reason for intestinal transplant referral. As more emphasis has been placed on the prevention of central line-associated bloodstream infections and new technologies have developed, care for central lines has improved; however, because care has evolved independently in local centers, care of central venous access varies significantly in this vulnerable population. The present position paper from the Intestinal Failure Special Interest Group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) reviews current evidence and provides recommendations for central line management in children with intestinal failure.

Approach to Intestinal Failure in Children.

PURPOSE OF REVIEW: Pediatric intestinal failure is a complex condition requiring specialized care to prevent potential complications. In this article, we review the available evidence supporting recent advances in care for children with intestinal failure. RECENT FINDINGS: Multidisciplinary intestinal rehabilitation teams utilize medical and surgical management techniques to help patients achieve enteral autonomy (EA) while preventing and treating the complications associated with intestinal failure. Recent advances in lipid management strategies, minimization of intestinal failure associated liver disease, prevention of central line-associated blood stream infections, and loss of access, as well as development of promising new hormone analogue therapy have allowed promotion of intestinal adaptation. These advances have decreased the need for intestinal transplant. There have been recent advances in the care of children with intestinal failure decreasing morbidity, mortality, and need for intestinal transplantation. The most promising new therapies involve replacement of enteroendocrine hormones.

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome.

OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. RESULTS: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. CONCLUSIONS: Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.

Redefining short bowel syndrome in the 21st century.

In 1968, Wilmore and Dudrick reported an infant sustained by parenteral nutrition (PN) providing a potential for survival for children with significant intestinal resections. Increasing usage of TPN over time led to some patients developing Intestinal Failure Associated Liver Disease (IFALD), a leading cause of death and indication for liver/intestinal transplant. Over time, multidisciplinary teams called Intestinal Rehabilitation Programs (IRPs) began providing meticulous and innovative management. Usage of alternative lipid emulsions and lipid minimization strategies have resulted in the decline of IFALD and an increase in long-term and transplant-free survival, even in the setting of ultrashort bowel (< 20 cm). Autologous bowel reconstructive surgeries, such as the serial tapering enteroplasty procedure, have increased the likelihood of achieving enteral autonomy. Since 2007, the number of pediatric intestinal transplants performed has sharply declined and likely attributed to the newer innovations healthcare. Recent data support the need for changes in the listing criteria for intestinal transplantation given the overall improvement in outcomes. Over the last 50 y, the diagnosis of short bowel syndrome has changed from a death sentence to one of hope with a vast improvement of quality of life and survival.

Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

BACKGROUND: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. METHODS: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. RESULTS: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. CONCLUSION: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Etiology and Medical Management of Pediatric Intestinal Failure.

Pediatric intestinal failure occurs when gut function is insufficient to meet the growing child's hydration and nutrition needs. After massive bowel resection, the remnant bowel adapts to lost absorptive and digestive capacity through incompletely defined mechanisms newly targeted for pharmacologic augmentation. Management seeks to achieve enteral autonomy and mitigate the development of comorbid disease. Care has improved, most notably related to reductions in blood stream infection and liver disease. The future likely holds expansion of pharmacologic adaptation augmentation, refinement of intestinal tissue engineering techniques, and the development of a learning health network for efficient multicenter study and care improvement.

Bone mineral density in children exposed to chronic glucocorticoid therapy.

The objective of this study was to determine the impact of glucocorticoid exposure on lumbar spine bone mineral density (BMD) in children while concurrently measuring their calcium intake, serum 25-OH vitamin D levels, and physical activity. Forty-three patients (4-18 years) with renal glomerular diseases, dermatomyositis, inflammatory bowel disease, juvenile rheumatoid arthritis, post-solid organ transplant, and Duchenne muscular dystrophy were studied. All received at least 5 mg per day of prednisone for more than 6 months. The mean BMD z score was 0 +/- 0.2 (range, -3.8 to +3.3) with 2 patients (5%) having z scores less than -2. The mean daily calcium intake was 1147 +/- 145 g, with 1 patient having hypovitaminosis D (<15 ng/mL). The mean physical activity level was 7.8 +/- 0.8 h/wk. The small reductions in BMD observed in our population suggest that screening is likely not warranted in all children with chronic glucocorticoid exposure.

Utility of liver biopsy in the evaluation of pediatric total parenteral nutrition cholestasis.

BACKGROUND: Cholestasis is a serious complication of total parenteral nutrition (TPN) in neonates. Liver biopsies may be requested to assess the severity of cholestasis and fibrosis. We hypothesized that liver biopsy would not lead to changes in management or improved patient outcomes. METHODS: A single institution retrospective review of infants with TPN cholestasis from January 2008 to January 2016. OUTCOMES: length of stay, complications, change in management and mortality. Statistical analysis was performed using Fisher's exact test. RESULTS: Twenty-seven out of 95 patients with TPN cholestasis underwent liver biopsy. Liver biopsy was associated with increased utilization or ursodeoxycholic acid (p = 0.001). There were no differences in length of stay (LOS) or mortality. One patient had a complication following anesthesia for liver biopsy, there were no bleeding complications recorded. CONCLUSIONS: Liver biopsy in patients with TPN cholestasis was associated with an increase in utilization of ursodeoxycholic acid. The effects of this are not fully understood; however, liver biopsy was not associated with improved patient outcomes such as LOS or mortality.

Treatment of Pediatric Cholestatic Liver Disease.

Cholestatic liver disease affects a small percentage of children, but therapy results in millions of healthcare dollars being spent each year. Close monitoring of nutritional status, pruritus, and complications from portal hypertension should improve the patient's quality of life and survival without liver transplantation. Other comorbid conditions, such as cardiac or renal disease, must also be integrated into the care plan and will affect the overall prognosis of the patient. Portal hypertension leads to ascites, variceal hemorrhage, and infection, which can result in significant mortality if not promptly recognized and treated. Surgical shunts are being used less because the expertise to perform endoscopic sclerotherapy and endoscopic band ligation is available at most medical centers. However, many cholestatic diseases, including biliary atresia, progressive familial intrahepatic cholestasis (PFIC) I, II, and III, and Alagille syndrome, may still require liver transplantation (Table 1). The cost of this procedure can exceed several hundred thousand dollars per patient, without including the annual costs of immunosuppressant therapy and medical monitoring. Meticulous medical management of nutrition and the sequelae of portal hypertension may prolong survival and reduce the potential morbidity and mortality of liver transplantation.