Clifford Lo

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.

Integrating nutrition as a theme throughout the medical school curriculum

More than one-third of adult Americans are obese. A major portion of the diseases that cause the highest morbidity and mortality, eg, heart disease, cancer, diabetes, stroke, and hypertension, can be attributed to diet. Yet, despite the demand for more nutrition education, few medical schools have an adequate nutrition curriculum. Many medical schools are reducing the number of lecture hours in favor of problem-based tutorial discussions, so an addition of another mandatory lecture course is not likely. The organization of nutrition as a theme throughout the 4-y medical school curriculum can pull together many hours of nutrition information taught during various courses, eg, biochemistry, physiology, pathophysiology, clinical clerkships, and electives. Emphasis should be placed on the identification of available resources (eg, faculty throughout the medical school and affiliated hospitals, textbooks, research, and clinical experiences) and applied to practical clinical situations so that students are able to identify, assess, and appropriately manage the frequent nutritional problems seen in outpatients and inpatients. Strategies and techniques such as curriculum analysis, computer-aided instruction modules, Internet Web sites, case-based tutorial discussions, use of physician nutrition specialists and dietitians, administratively separate nutrition units, observed structured clinical examinations, and faculty development are listed and discussed in this article.

Aminosyn PF or trophamine : which provides more protection from cholestasis associated with total parenteral nutrition ?

Summary: Cholestasis often occurs in infants on total parenteral nutrition (TPN) for long periods. Amino acid formulations developed specifically for infants, namely Aminosyn PF and Trophamine, may protect against cholestasis associated with total parenteral nutrition (CATPN). The development of cholestasis may also be caused by other risk factors such as prematurity, surgery, sepsis, and extracorporeal membrane oxygenation (ECMO). To evaluate the relative effectiveness of the pediatric amino acid formulations in reducing CATPN, the courses of 70 infants < 1 year of age who received TPN for at least 14 days were reviewed. Cholestasis was defined as a conjugated scrum bilirubin ≥ 2 mg/dl subsequent to the initiation of TPN; CATPN was considered present when other factors related to cholestasis were ruled out. Liver function tests were recorded 24 h before starting TPN and at day 7, 15, and 21 during TPN infusion. Thirty infants (42.8%) developed cholestasis. CATPN was judged to have occurred in 15 (21.4%) of 70 infants, while 15 (21.4%) developed cholestasis secondary to other factors. Of the 15 CATPN patients, 7 had received Trophamine, 6 had received Aminosyn PF, and 2 had received both solutions. Aminosyn PF and Trophamine, along with other potential risk factors for CATPN such as antecedent surgery, sepsis, ECMO, prematurity, and nitrogen/calorie intake were analyzed by regression-analysis methods. None was statistically significant except the length of TPN (p = 0.0063). In conclusion, we cannot support the view that Trophamine is more effective than Aminosyn PF in the prevention of CATPN.

Effectiveness of a clinical practice guideline for parenteral nutrition: a 5-year follow-up study in a pediatric teaching hospital

OBJECTIVE To determine the effectiveness of a clinical practice guideline (CPG) on the use of parenteral nutrition (PN) at a tertiary care pediatric hospital. METHODS Review of prospectively collected data on hospital-wide PN use 2 years before and 5 years after the establishment of the CPG. Effectiveness of the CPG was measured as the percentage of PN courses lasting fewer than 5 days and the number of PN starts per 1000 patient days. RESULTS During the study period, 5745 PN courses were administered. The mean (SD) number of PN starts per 1000 inpatient days was 8.86 (0.78) before the CPG and 9.54 (2.49) afterwards (p = .28). The percentage courses of PN lasting for fewer than 5 days declined from 26.3% before the CPG to 18.4% afterwards (p < .0001). A multivariate model confirmed that the rate of short-term PN starts declined after the CPG was issued. The mean (SD) number of PN courses shorter than 5 days in the 2 years before the CPG was 2.33 (0.42) per 1000 patient days versus 1.75 (0.45) in the 5 years after the CPG was instituted (p = .005), which is a 25% decline. The services with the highest volume of PN use showed the most significant decreases in short-term PN use. A cost savings to the hospital of more than

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease

50,000 may have been realized. CONCLUSIONS In a large pediatric tertiary care hospital, a CPG was successfully deployed. CPGs can favorably affect the use rates and costs of parenteral nutrition.

Low Serum Citrulline Concentration Correlates With Catheter-Related Bloodstream Infections in Children With Intestinal Failure

BACKGROUND Parenteral nutrition-associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. METHODS Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Childrens Hospital Boston (Mass). Inclusion criteria included PN duration of greater than 3 months with subsequent tolerance of full enteral nutrition and evidence of PN-associated liver injury. Time to normalize ALT and direct bilirubin were estimated using Kaplan-Meier and Cox proportional hazards methods. RESULTS Mean age PN cessation was 6 months (range, 2-14 months). Median PN duration was 18 weeks (interquartile range [IQR], 13-33 weeks), and median follow-up was 24 weeks (IQR, 14-48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks, respectively (P = .001). CONCLUSION Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

Aspartate aminotransferase to platelet ratio index correlates with hepatic cirrhosis but not with fibrosis in pediatric patients with intestinal failure.

BACKGROUND Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure. METHODS Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ <30 days, creatinine clearance <20 mL/minute, or a history of organ transplant/immunosuppression. RESULTS A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively). CONCLUSIONS Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.

Success rates and cost-effectiveness of antibiotic combinations for initial treatment of central-venous-line infections during total parenteral nutrition.

Background and Objectives: Patients with intestinal failure (IF) require parenteral nutrition (PN) support to obtain enough nutrients to sustain growth; long-term PN use is associated with significant liver damage. The aim of this study was to analyze the use of a noninvasive test, the aspartate aminotransferase to platelet ratio index (APRI), in the diagnosis of liver disease in pediatric patients with IF. Methods: Medical records of all Boston Childrens Hospital patients who received PN and underwent a liver biopsy from January 2006 until November 2010 were reviewed. Patients with IF with a clinical diagnosis were selected. APRI was calculated as (aspartate aminotransferase [U/L]/upper normal limit) × 100/platelets (109 cells/L). Presence of fibrosis and cirrhosis was estimated using the METAVIR score in liver biopsies. Results: Sixty-two liver biopsies from 48 patients (22 girls) were studied. Mean APRI values in the different METAVIR categories (0–1, 2–3, 4) were 1.80, 1.17, and 4.24, respectively (analysis of variance P = 0.053; Bonferroni test for cirrhosis vs fibrosis P = 0.048). APRI could significantly predict cirrhosis (odds ratio 1.2; 95% confidence interval [CI] 1.001–1.43) but not fibrosis (METAVIR 2–3, odds ratio 1.00; 95% CI 0.86–1.18). Area under the receiver operating characteristic curve for cirrhosis was 0.67 (95% CI 0.45–0.89; P = 0.13). Conclusions: APRI, a noninvasive, easy-to-obtain bedside test, significantly predicts cirrhosis but not fibrosis in pediatric patients with IFALD. Because the clinicians need a noninvasive test to differentiate among different stages of liver fibrosis rather than differentiating cirrhosis from normal, we cannot recommend the use of this test in pediatric patients with IFALD for this purpose.

Immune deficiencies in chronic intestinal pseudo-obstruction

BACKGROUND Central-venous-line infections can be successfully treated with appropriate antibiotics, thus avoiding the need for catheter removal. Based on our experience, vancomycin, gentamicin, piperacillin, ceftazidime, and amphotericin, alone or in combination, are usually administered, pending sensitivity results. This empirical list, however, has never been verified against actual sensitivity results nor has it been tested for cost or efficacy. METHODS Medical records of inpatients on hyperalimentation over 1 year were reviewed. Success rate, therapy duration, and drug acquisition cost and charge were assessed for central-venous-line infections. Antibiotics then were paired and evaluated in terms of charge and efficacy against all microorganisms as determined by sensitivity results. RESULTS In 500 inpatients receiving hyperalimentation for 9,698 patient-days, 8.4 central-venous-line infections/1,000 patient-days occurred. Staphylococcus non-aureus, Candida species, Enterococcus faecium, and Staphylococcus aureus predominantly were isolated. Of the infections, 51 (67%) were sensitive to one or more of the initial antibiotics. A 2-week course of antibiotics successfully treated 50 (66%) catheter infections without line removal. Appropriate initial therapy on average reduced treatment duration by 8 to 10 days and drug charges by