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Improved survival in a multidisciplinary short bowel syndrome program

PURPOSE Pediatric short bowel syndrome (SBS) remains a management challenge with significant mortality. In 1999, we initiated a multidisciplinary pediatric intestinal rehabilitation program. The purpose of this study was to determine if the multidisciplinary approach was associated with improved survival in this patient population. METHODS The Center for Advanced Intestinal Rehabilitation includes dedicated staff in surgery, gastroenterology, nutrition, pharmacy, nursing, and social work. We reviewed the medical records of all inpatients and outpatients with severe SBS treated from 1999 to 2006. These patients were compared to a historical control group of 30 consecutive patients with severe SBS who were treated between 1986 and 1998. RESULTS Fifty-four patients with severe SBS managed by the multidisciplinary program were identified. Median follow-up was 403 days. The mean residual small intestinal length was 70 +/- 36 vs 83 +/- 67 cm in the historical controls (P = NS). Mean peak direct bilirubin was 8.1 +/- 7.9 vs 9.0 +/- 7.4 mg/dL in controls (P = NS). Full enteral nutrition was achieved in 36 (67%) of 54 patients with severe SBS vs 20 (67%) of 30 patients in the control group (P = NS). The overall survival rate, however, was 89% (48/54), which is significantly higher than in the historical controls (70%, 21/30; P < .05). CONCLUSIONS A multidisciplinary approach to intestinal rehabilitation allows for fully integrated care of inpatients and outpatients with SBS by fostering coordination of surgical, medical, and nutritional management. Our experience with 2 comparable cohorts demonstrates that this multidisciplinary approach is associated with improved survival.

Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure

PURPOSE We sought to determine whether a regimen of 70% ethanol locks could reduce the rate of central venous catheter (CVC) infections in parenteral nutrition-dependent children with intestinal failure. METHODS We performed a retrospective review of 23 parenteral nutrition-dependent children in our multidisciplinary intestinal rehabilitation clinic who started ethanol lock therapy between September 2007 and June 2009. The treatment regimen consisted of a 70% ethanol lock instilled 3 times per week in each catheter lumen. The rate of CVC infections before and after initiation of ethanol lock therapy was compared using the Wilcoxon signed ranks test with significance set at P < .05. RESULTS The most common diagnoses leading to intestinal failure were necrotizing enterocolitis (26.1%), gastroschisis (21.7%), and intestinal atresia (14.3%). Ethanol locks were well tolerated with no reported adverse side effects. The infection rate decreased from 9.9 per 1000 catheter days prior to initiation of ethanol locks to 2.1 per 1000 catheter days during therapy (P = .03). CONCLUSIONS A regimen of ethanol lock therapy administered three days per week appears to be a safe and effective means of reducing the rate of CVC infections in parenteral nutrition-dependent children with intestinal failure.

Overview of pediatric short bowel syndrome.

Short bowel syndrome (SBS) is a malabsorptive state occuring as a result of surgical resection or congenital disease of a significant portion of the small intestine (1). The amount of resection or remaining bowel generally dictates the degree of malabsorption and consequentely the need for specialized enteral nutrition or parenteral nutrition (PN). Intestinal failure in the context of SBS is defined as a dependence on PN to maintain minimal energy and fluid requirement for growth in children. Common causes of SBS in infants and children include necrotizing enterocolitis, midgut volvulus, intestinal atresia, and gastroschisis. Early identification of patients at risk for long-term PN dependency is the first step toward avoiding severe complications. Close monitoring of nutritional status, steady and early introduction of enteral nutrition, and aggressive prevention, diagnosis, and treatment of infections such as central venous catheter sepsis and bacterial overgrowth can significantly improve the prognosis. Intestinal transplantation is an emerging treatment that may be considered when intestinal failure is irreversible and children are experiencing serious complications related to TPN administration.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome.

PURPOSE The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] > or =2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. METHODS After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. RESULTS A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral omega-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). CONCLUSIONS In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.

High Prevalence of Multiple Micronutrient Deficiencies in Children with Intestinal Failure: A Longitudinal Study

OBJECTIVE To determine the prevalence of micronutrient deficiencies in children with intestinal failure as they transitioned from parenteral nutrition (PN) to enteral nutrition (EN). STUDY DESIGN We reviewed medical records of all patients with severe intestinal failure treated from 1999 to 2008 at a multidisciplinary intestinal rehabilitation program who had undergone micronutrient biochemical monitoring. RESULTS The cohort of 30 children (mean age, 5 years; range, 2 to 9 years; 18 boys) had median PN duration of 23 weeks (IQR, 13 to 34 weeks). Median transition from PN to full EN lasted 12 weeks (IQR, 8 to 20 weeks); during this transition, 33% of patients had at least one vitamin deficiency and 77% at least one mineral deficiency. After transition to 100% EN, 70% had at least one vitamin deficiency and 77% had at least one mineral deficiency, with the most common deficiencies being vitamin D (68%), zinc (67%), and iron deficiency (37%). After transition to 100% EN, multivariate analysis identified regular use of a multivitamin supplement (P=.004) and intact ileocecal valve (P=.02) as protective against the development of vitamin deficiencies, independent of bowel length, gestational age, and days on PN. CONCLUSIONS Children with intestinal failure exhibit a high prevalence of micronutrient deficiencies during intestinal rehabilitation. Regular monitoring and aggressive supplementation in children with intestinal failure is warranted.

Risk Factors for Parenteral Nutrition–associated Liver Disease Following Surgical Therapy for Necrotizing Enterocolitis

Objective:The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition–associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. Patients and Methods:From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥2 mg/dL or ALT ≥2 × the upper limit of normal in the absence of sepsis after ≥14 days of exposure to PN. Results:Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97–12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56–3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5–4.7; P = 0.001) times greater in patients with ≥4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. Conclusions:The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.

Risk Factors for Intestinal Failure in Infants with Necrotizing Enterocolitis: A Glaser Pediatric Research Network Study

OBJECTIVE To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.

Multiple Micronutrient Deficiencies in a Child With Short Bowel Syndrome and Normal Somatic Growth

Children with short bowel syndrome (SBS) are at risk for a variety of macro- and micronutrient deficiencies and other complications as a result of loss of small bowel surface area (1). The amount and location of small intestine loss in SBS will generally define the degree of nutrient malabsorption and the likelihood of micro-nutrient deficiencies. Duodenal resection, for example, can result in iron and folate deficiencies. Extensive jejunal resection can lead to malabsorption of carbohydrates, proteins, and calcium. The terminal ileum is the primary site of absorption of vitamin B12 and bile salts. Bile salt malabsorption can in turn present with steatorrhea and deficiencies of vitamins A, D, E, and K. Ileocolonic resection can predispose to several problems as a result of the loss of the ileocecal valve, resulting in loss of the ileal break, increased risk of anastomotic ulcers, and bacterial overgrowth. The extent of nutrient malabsorption in SBS is generally assessed by history and physical examination, including assessment of growth parameters. Normal somatic growth generally implies adequate energy and macronutrient absorption. We describe a patient with SBS who developed severe iron-deficiency anemia and multiple micronutrient deficiencies despite normal growth, full oral intake, and limited ileal resection.

[13C]Methionine Breath Test to Assess Intestinal Failure-Associated Liver Disease

Oxidation of L[1-13C]methionine ([13C]-Met) in liver mitochondria can be quantified by measuring exhaled 13CO2. We hypothesized that 13CO2 recovery after i.v. administered [13C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-13C]-Met breath tests ([13C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [13C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for 13CO2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO2) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [13C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [13C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [13C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [13C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [13C]-MBT may also help quantify progression or improvement of IFALD.

Daily metabolic rate in healthy infants

BACKGROUND Previous estimates of daily metabolic rate in infants were based on short-term unstandardized measurements of energy expenditure (EE). OBJECTIVE Determine 24-hour metabolic profiles in infants. METHODS Energy expenditure (kcal/min by indirect calorimetry) and physical activity (oscillations in weight/min/kg body weight) were measured in 10 healthy infants (5.0+/-0.8 months, 68+/-3 cm, 7.3+/-0.8 kg) for 24 hours in the Enhanced Metabolic Testing Activity Chamber while allowing parental interaction. Energy intake, 24-hour EE, resting metabolic rate (RMR), and sleeping metabolic rate (SMR) (kcal/kg/day) were determined. In addition, extrapolated 24-hour EE, RMR, and SMR from the first 4 and 6 hours of data were compared with 24-hour measurements. RESULTS Twenty-four-hour energy intake, EE, RMR, and SMR (mean+/-SD) were 78.2+/-17.6, 74.7+/-3.8, 65.1+/-3.5, and 60.3+/-3.9, respectively. EE and physical activity showed a decrease at 11:30 pm and a return to daytime levels by 5:30 am, suggesting a metabolic circadian rhythm. Extrapolated 24-hour EE, RMR, and SMR from the first 4 hours (72.2+/-6.6, 65.9+/-8.7, and 64.9+/-6.4) and 6 hours (74.8+/-6.7, 65.8+/-6.6, and 64.8+/-5.6) were similar to 24-hour measurements. CONCLUSIONS An apparent circadian rhythm in metabolic rate and physical activity was detected by 24-hour measurements. Furthermore, shorter-term measurements of the variables were comparable with 24-hour values.