An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure-Associated Liver Disease in Infants With Intestinal Failure.

BACKGROUND: SMOFlipid has a more diverse lipid profile than traditional Intralipid and has become the standard lipid for patients in our intestinal rehabilitation program. Our objective was to compare outcomes in neonates with intestinal failure (IF) who received SMOFlipid against those receiving Intralipid. METHODS: This was a retrospective cohort study of infants with IF with a minimum follow-up of 12 months in 2008-2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels. Statistical analysis included the Mann-Whitney U and χ2 tests, with an α value < 0.05 considered significant. Approval was obtained from our institutional review board. RESULTS: Thirty-seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z-scores were improved for patients receiving SMOFlipid at 3 months (-0.932 vs -2.092; P = 0.028) and 6 months (-0.633 vs -1.614; P = 0.018). There were no differences in PN-supported patients or demographics between the groups. CONCLUSION: Use of SMOFlipid resulted in decreased development of IF-associated liver disease in patients with IF when assessed using biochemical tests.

Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion.

BACKGROUND: Pediatric intestinal failure (PIF) is a life-altering chronic condition with significant morbidity and mortality. Omegaven® therapy has been used to treat children with advanced intestinal failure associated liver disease. Our objective was to determine the evolution of hepatic fibrosis in PIF patients who received Omegaven® and describe their clinical outcome. METHODS: A retrospective review in PIF patients who received Omegaven® was performed. Patients were included if they had liver biopsies completed before Omegaven® therapy and after resolution of hyperbilirubinemia. Biopsy results were evaluated to determine the degree of fibrosis, inflammation, and cholestasis. Clinical and biochemical data was collected. RESULTS: Six patients were identified. Assessment of fibrosis at last follow-up demonstrated improvement in 2 patients and progression or stable fibrosis in 4/6. All patients demonstrated reduction in cholestasis and inflammation. One patient received a liver/intestine transplant and a second is listed, both of them with progressive fibrosis. One patient achieved full enteral nutrition, while the rest remain partially parenteral nutrition dependent. CONCLUSION: Use of Omegaven® is associated with reduced cholestasis and inflammation, but with persistence or worsening of fibrosis in some patients. A subset of patients with progressive fibrosis may develop portal hypertension and progressive liver disease.

Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid.

BACKGROUND: To examine whether SMOFlipid prevents progression of intestinal failure-associated liver disease (IFALD) in parenteral nutrition (PN)-dependent infants with early IFALD (conjugated bilirubin 17-50 µmol/L, 1-3 mg/dL). STUDY DESIGN: Pilot multicenter blinded randomized controlled trial comparing SMOFlipid with Intralipid. Patients received the trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin. RESULTS: Twenty-four infants (mean age, 6 weeks) participated in the trial (13 Intralipid and 11 SMOFlipid). At the time of trial enrollment, patients in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks and did not differ according to treatment ( P = .99). At trial conclusion, patients who received SMOFlipid had a lower conjugated bilirubin than those who received Intralipid (mean difference, -59 µmol/L; P = .03). Patients receiving SMOFlipid were also more likely to have a decrease in serum conjugated bilirubin to 0 µmol/L than those in the Intralipid group over the entire observation period (hazard ratio, 10.6; 95%; P = .03). The time to achievement of full enteral tolerance did not differ statistically (hazard ratio, 1.3; P = .59) between the groups. There was no significant difference in safety outcomes between the groups. CONCLUSIONS: Compared with Intralipid, SMOFlipid reduces the risk of progressive IFALD in children with intestinal failure. This trial was registered at clinicaltrials.gov as NCT00793195.

Change of Outcomes in Pediatric Intestinal Failure: Use of Time-Series Analysis to Assess the Evolution of an Intestinal Rehabilitation Program.

BACKGROUND: The clinical picture of pediatric intestinal failure has changed over the past 15 years, while effectiveness evolving treatment options remains unclear. This study explored evolution in care and quantified independent effects of new treatment options. STUDY DESIGN: Consecutive patients (n = 196) with neonatal or infantile intestinal failure, born between July 1996 and December 2011, were derived from an intestinal rehabilitation program (IRP) patient registry. Change over time was analyzed using multivariable Box-Jenkins method-based autoregressive integrative moving average models (ARIMA), robust linear regression, and nonparametric trend analysis. Four systematically introduced treatment options (IRP, serial transverse enteroplasty, omega-3 lipid emulsions, and ethanol locks) were evaluated. Analyses were adjusted for patient characteristics and disease severity. The primary outcome was disease-specific mortality from liver failure and sepsis. Secondary outcomes included parenteral nutrition weaning, transplantations, catheter complications, and liver disease. RESULTS: Patient characteristics remained unchanged over time, except for decreasing small bowel length (-0.5%/quarter; 95% CI -0.85, -0.16) and ICU admission time (-0.6 days/quarter; 95% CI -1.03, -0.18). Disease-specific mortality diminished significantly over time (-0.02 deaths/quarter; 95% CI -0.03, -0.01) by IRP and omega-3 lipids introduction (-0.6 deaths/quarter each, 95% CI -1.23, -0.02 and -0.77, -0.45, respectively). Serial transverse enteroplasty and ethanol locks had no significant impact. Parenteral nutrition weaning and transplantations remained unchanged, while catheter sepsis and complication rates decreased by 0.3 episodes/1,000 catheter-days each (95% CI -0.43, -0.2 and -0.45, -0.24, respectively). CONCLUSIONS: Introduction of IRP and omega-3 lipids independently decreased disease-specific mortality. For the first time, time series analysis was applied to evaluate effectiveness of treatment options in intestinal rehabilitation.

Ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients with intestinal failure: preliminary experience.

BACKGROUND: Catheter-related bloodstream infections (CRBSI) cause morbidity and mortality in patients with intestinal failure dependent on parenteral nutrition. Ethanol lock of central venous catheters may decrease CRBSI, but limited pediatric data are available. METHODS: Home parenteral nutrition patients with at least one previous CRBSI were initiated on a 70% ethanol lock protocol for a minimum of 4 hours. Infection rates (per 1000 catheter days) before and after initiation of ethanol locks were compared using a paired t test. RESULTS: Ten patients (4 girls; median age, 44 months [range, 31-129 months]) began ethanol lock therapy after a total of 91 CRBSIs (37 gram-positive, 30 gram-negative, and 24 fungal) with a mean of 10.2 ± 6.2 per 1000 catheter days. Patients received ethanol lock for an average of 227 ± 64 days with only 3 CRBSI occurring (CRBSI rate of 0.9 ± 1.8 per 1000 catheter days [P = .005]). Central venous catheter replacements decreased from 5.6 per 1000 days to 0.3 per 1000 days posttherapy (P = .038). Ethanol lock was discontinued in 2 of 10 patients because of catheter thrombosis. CONCLUSION: Preliminary results demonstrate a significant decrease in CRBSI with a 70% ethanol lock protocol. Catheter thrombosis may be a limitation that needs to be addressed. With such a dramatic therapeutic effect, a randomized trial is feasible and should be performed.

Human growth hormone and glutamine for patients with short bowel syndrome.

BACKGROUND: There has been clinical enthusiasm for treating short bowel patients with human recombinant growth hormone and/or glutamine in hopes of reducing parenteral nutrition dependency. It has been more than a decade since Byrne and colleagues reported enhanced absorption of nutrients, improved weight gain, and reduction in parenteral nutrition requirements with the administration of a combination of human growth hormone (HGH) and glutamine in patients with short bowel syndrome. Other studies have reported inconsistent results. OBJECTIVES: The purpose of this systematic review was to evaluate the efficacy of growth hormone with or without glutamine supplementation for adult patients with short bowel syndrome. SEARCH STRATEGY: Electronic searches were performed to identify all publications describing randomised controlled trials of the use of human growth hormone with or without glutamine for the treatment of patients with short bowel syndrome. SELECTION CRITERIA: Randomised controlled trials of human growth hormone with or without glutamine for patients with short bowel syndrome were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the published studies. The statistical analyses were performed using RevMan 5 software. Follmann's method was used for cross-over studies. MAIN RESULTS: Five studies were included in the review. Human growth hormone with or without glutamine appears to provide benefit in terms of increased weight (MD 1.66 Kg; 95% CI 0.69 to 2.63;P = 0.0008), lean body mass (MD 1.93 Kg; 95% CI 0.97 to 2.90; P = 0.0001) energy absorption (MD 4.42 Kcal; 95% CI 0.26 to 8.58; P = 0.04) and nitrogen absorption (MD 44.85 g; 95%CI 0.20 to 9.49; P = 0.04) for patients with short bowel syndrome. The single RCT that focused on parenteral nutrition (PN) requirements demonstrated decreased PN volume and calories and number of infusions in patients who received HGH with or without glutamine supplementation. Only patients who received HGH with glutamine maintained statistically significant PN reductions at 3 month follow-up. AUTHORS' CONCLUSIONS: The results suggest a positive effect of human growth hormone on weight gain and energy absorption. However, in the majority of trials, the effects are short-lived returning to baseline shortly after cessation of therapy. The temporary benefit calls into question the clinical utility of this treatment. To date, the evidence is inconclusive to recommend this therapy. Consideration should be made to studying patients during the active phase of intestinal adaptation rather than in the setting of chronic intestinal failure. The role of HGH in paediatric short bowel syndrome remains unknown.

Is the use of parenteral omega-3 lipid emulsions justified in surgical neonates with mild parenteral nutrition-associated liver dysfunction?

PURPOSE: Although evidence suggests that parenteral omega-3 lipid emulsions (O-3LEs) may be beneficial in treating advanced parenteral nutrition (PN)-associated liver disease, our objective was to determine if O-3LEs are justified in those with early liver disease. METHODS: This is a retrospective analysis of prospectively collected data on all surgical neonates, who received more than 1 day of PN postoperatively between 2001 and 2004 with observation through 2005 (era before O-3LE introduction). We examined the proportion of those who developed mild and advanced liver dysfunction. RESULTS: Of the 292 infants in the cohort, 104 (36%) developed mild liver dysfunction (conjugated bilirubin, 34 micromol/L [cBili34]) after a mean of 22 days. Thirty-one (30%) of the cBili34 patients reached a serum conjugated bilirubin of 100 micromol/L, and 13 (13%) developed liver failure. Of these, 4 underwent transplantation, and 5 died of hepatic disease. Overall, 86 of the cBili34 patients (83%) were weaned off PN. CONCLUSION: With more than 80% of cBili34 patients being weaned from PN without adverse hepatic sequelae, it is difficult, in the absence of definitive evidence of efficacy and safety for O-3LEs together with increased costs, to justify the routine use of O-3LEs in this low-risk population outside formal research protocols.

Percutaneous cholangiography for the treatment of parenteral nutrition-associated cholestasis in surgical neonates: preliminary experience.

OBJECTIVE: Parenteral nutrition-associated cholestasis (PNAC) occurs in up to 60% of surgical neonates with intestinal failure, and 10% will develop end-stage liver failure. Our aim was to evaluate the effectiveness of percutaneous transhepatic transcholecystic cholangiography (PTTC) in the treatment of PNAC in surgical neonates. METHODS: A retrospective double cohort study of surgical neonates with PNAC was conducted. Patients with PNAC who received PTTC were compared to controls matched by gestational age, birth weight, sex, and parenteral nutrition duration. Percutaneous transhepatic transcholecystic cholangiography was performed under general anesthesia with ultrasound guidance. Analysis was performed using paired Student's t test and McNemar chi2 test. RESULTS: Nine PTTC patients and 9 controls were similar in mean age (35.5 +/- 3.1 vs 35.6 +/- 4.2 weeks, P = .85), birth weight (2531 +/- 879 vs 2692 +/- 1052 g, P = .28), sex (all males), and parenteral nutrition duration (51.2 +/- 29.8 vs 53.3 +/- 33.3 days, P = .74). Percutaneous transhepatic transcholecystic cholangiography was performed in 9 patients at mean corrected age of 5.5 +/- 3.4 weeks and weight of 3621 +/- 546 g. All control patients and 8 (88.9%) of 9 PTTC patients had eventual resolution of hyperbilirubinemia. Percutaneous transhepatic transcholecystic cholangiography patients experienced a more rapid rate of resolution of their cholestasis, and the mean time to resolution of conjugated bilirubin was less in the PTTC group (8.5 +/- 3.2 vs 18.5 +/- 7.6 weeks, P = .02). CONCLUSION: Therapeutic PTTC results in a 50% reduction in the time to PNAC resolution. Percutaneous transhepatic transcholecystic cholangiography may have a role as active therapy to slow progression of PNAC in surgical neonates with intestinal failure.