International Latin American Survey on Pediatric Intestinal Failure Team

There is little data on the experience of managing pediatric Intestinal Failure (IF) in Latin America. This study aimed to identify and describe the current organization and practices of the IF teams in Latin America and the Caribbean. An online survey was sent to inquire about the existence of IF teams that managed children on home parenteral nutrition (HPN). Our questionnaire was based on a previously published European study with a similar goal. Twenty-four centers with pediatric IF teams in eight countries completed the survey, representing a total number of 316 children on HPN. The median number of children on parenteral nutrition (PN) at home per team was 5.5 (range 1–50). Teams consisted of the following members: pediatric gastroenterologist and a pediatric surgeon in all teams, dietician (95.8%), nurse (91.7%), social worker (79.2%), pharmacist (70.8%), oral therapist (62.5%), psychologist (58.3%), and physiotherapist (45.8%). The majority of the centers followed international standards of care on vascular access, parenteral and enteral nutrition, and IF medical and surgical management, but a significant percentage reported inability to monitor micronutrients, like vitamins A (37.5%), E (41.7%), B1 (66.7%), B2 (62.5%), B6 (62.5%), active B12 (58.3%); and trace elements—including zinc (29.2%), aluminum (75%), copper (37.5%), chromium (58.3%), selenium (58.3%), and manganese (58.3%). Conclusion: There is wide variation in how IF teams are structured in Latin America—while many countries have well-established Intestinal rehabilitation programs, a few do not follow international standards. Many countries did not report having an IF team managing pediatric patients on HPN.     

Etiology and Management of Pediatric Intestinal Failure: Focus on the Non-Digestive Causes

Background: Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF results from intrinsic diseases of the gastrointestinal tract (digestive IF) (DIF); few cases arise from digestive vascular components, gut annexed (liver and pancreas) and extra-digestive organs or from systemic diseases (non-digestive IF) (NDIF). The present review revised etiology and treatments of DIF and NDIF, with special focus on the pathophysiological mechanisms, whereby NDIF develops. Methods: We performed a comprehensive search of published literature from January 2010 to the present by selecting the following search strings: “intestinal failure” OR “home parenteral nutrition” OR “short bowel syndrome” OR “chronic pseudo-obstruction” OR “chronic intestinal pseudo-obstruction” OR “autoimmune enteropathy” OR “long-term parenteral nutrition”. Results: We collected overall 1656 patients with well-documented etiology of IF: 1419 with DIF (86%) and 237 with NDIF (14%), 55% males and 45% females. Among DIF cases, 66% had SBS and among NDIF cases 90% had malabsorption/maldigestion. Conclusions: The improved availability of diagnostic and therapeutic tools has increased prevalence and life expectancy of rare and severe diseases responsible for IF. The present review greatly expands the spectrum of knowledge on the pathophysiological mechanisms through which the diseases not strictly affecting the intestine can cause IF. In view of the rarity of the majority of pediatric IF diseases, the development of IF Registries is strongly required; in fact, through information flow within the network, the Registries could improve IF knowledge and management.     

Single‐Center,Adult Chronic Intestinal Failure Cohort Analyzed According to the ESPEN‐Endorsed Recommendations,Definitions, and Classifications

Background/Aims: The objective of this study was to describe a clinically well‐defined, single‐center, intestinal failure (IF) cohort based on a template of definitions and classifications endorsed by the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods: A cross‐sectional, retrospective, adult IF cohort, receiving parenteral support (PS), was extracted from the Copenhagen IF database at the tertiary IF center, Copenhagen University Hospital, Rigshospitalet, Denmark. Results: Rigshospitalet provided PS to 188 adult patients with IF on December 31, 2011. Six patients received only fluids and electrolytes, while 97% required parenteral energy (17 ± 12 kcal/kg/d). Although 92% of the cohort had undergone intestinal resection, only 53% were classified as patients with short bowel syndrome (SBS) according to the pathophysiological classification. In the remaining cohort, patients were distributed as 5% with intestinal fistula, 12% with intestinal dysmotility, 5% with mechanical obstruction, and 14% with mucosal diseases. Twelve percent had a combination of pathophysiological causes. The patients with SBS (n = 100) were subdivided according to bowel anatomy into group 1 (jejuno/ileostomy, n = 82), group 2 (jejuno‐colonic‐anastomosis, n = 16), and group 3 (jejuno‐ileo‐colonic‐anastomosis, n = 2). When evaluating the cohort requirements for PS using the ESPEN chronic IF classification based on the need for fluid volume and energy, 53% of the patients with IF were distributed in the maximum categories. Conclusion: The orphan condition of IF with its large patient heterogeneity mandates establishment of uniform definitions and a harmonization of classifications. As illustrated, the ESPEN‐endorsed definitions and classifications are well designed and may serve as a common uniform template to facilitate both intra‐ and intercenter comparisons between reference centers and thus outcome results.     

Vitamin D Deficiency in Children With Intestinal Failure Receiving Home Parenteral Nutrition

Background: Vitamin D plays important roles in both skeletal and nonskeletal health. Limited data suggest that patients with intestinal failure (IF) receiving home parenteral nutrition (PN) are at risk for vitamin D deficiency due to inadequate oral intake, poor absorption, and chronic illness. The purpose of this study was to document vitamin D status in pediatric patients with IF receiving home PN. Materials and Methods: We performed a 2‐year retrospective review of children with IF followed at our center who had been on home PN for ≥6 months and had ≥1 serum 25‐hydroxyvitamin D (25‐OHD) level checked as part of routine clinical care. Patients were then categorized as deficient (<20 ng/mL), insufficient (20–29 ng/mL), or normal (≥30 ng/mL) based on their lowest vitamin D level. Demographic data and clinical characteristics were also assessed. Results: Eleven of 27 children (41%) had ≥1 insufficient 25‐OHD level, including one child with vitamin D deficiency. Diagnosis of short bowel syndrome (compared with dysmotility or malabsorption syndromes) was associated with decreased likelihood of suboptimal vitamin D status, with an odds ratio of 0.12 (95% confidence interval, 0.02–0.8, P = .028). Osteopenia was noted in 59% of the cohort. There was a trend toward higher risk for osteopenia in patients with low 25‐OHD levels compared with those with normal 25‐OHD levels (82% vs 44%, P = .109). Conclusion: Suboptimal 25‐OHD levels are common in children with IF on home PN. This emphasizes the critical importance of routine surveillance of serum vitamin D levels and consideration of enteral supplementation when indicated.     

Long-Term Outcomes in Patients with Intestinal Failure Due to Short Bowel Syndrome and Intestinal Fistula

Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001–2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years; p < 0.001). A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies.     

Poor Social Support and Unemployment Are Associated With Negative Affect in Home Parenteral Nutrition–Dependent Patients With Chronic Intestinal Failure

Background: Home parenteral nutrition (HPN) provides life‐sustaining treatment for people with chronic intestinal failure (CIF). Poor quality of life is reported in association with the burden of HPN and the underlying condition leading to intestinal failure (IF). However, levels of negative affect (NA), incorporating anxiety and depression, have not been reported in CIF. This study examined the occurrence and risk factors for NA in a large CIF population using the validated Hospital Anxiety & Depression Scale (HADS) and Multidimensional Scale of Perceived Social Support (MSPSS) questionnaires. Methods: A survey pack including HADS and MSPSS were distributed to patients managed by a specialist IF center. Data from these measures were analyzed against factors including underlying disease, length of time receiving HPN, employment status, and demographics. Results: Of 85 patients who completed this study, 56% had clinical levels of anxiety and/or depression. Linear regression analysis confirmed significant correlations between social support and HADS scores, with poorer perceived social support associated with higher levels of NA (?0.26 MSPSS + 33.24; R² = 0.29; P < .0001). There were also significant associations between unemployment and higher anxiety (P = .004), depression (P = .008), and NA scores (P = .003). By contrast, there were no significant associations between patient age, duration of time receiving parenteral nutrition, pathophysiological mechanisms of CIF, and NA levels. Conclusions: Clinical anxiety and depression are common, affecting more than half of patients with CIF. Patients with poor social networks and those of working age who have ceased employment are particularly vulnerable and should be prioritized for psychological support because of their elevated risk.     

Longitudinal Bone Mineralization Assessment in Children Treated With Long‐Term Parenteral Nutrition for Severe Intestinal Failure

Background: Metabolic bone disease is common in children receiving home parenteral nutrition (HPN) for intestinal failure (IF). Long‐term evolution of bone mass in pediatric IF is poorly documented. The aims of this study were (1) to determine the prevalence of low bone mass (LBM) in children receiving HPN for IF, (2) to evaluate the evolution of total bone mineral content (TBMC) during HPN with dual‐energy x‐ray absorptiometry (DXA), and (3) to identify related factors. Methods: All children referred in our HPN center from 2004 to 2014 were eligible. Inclusion criteria were HPN dependence due to noninflammatory IF, at least 2 TBMC assessments, and HPN duration of at least 2 years at last DXA. TBMC was expressed in z score for ideal weight for height (WFH). LBM was defined by a TBMC WFH z score ≤–2 standard deviations (SD). Results: A total of 175 DXAs for 31 children were performed, mean of 5.6 ± 2.9 assessments per child. The median time between first and last DXA recorded was 6.2 years (0.7–16.6). At the first DXA, 14 children (45%) had a LBM. TBMC increased by +0.1 ± 0.04 SD per year of HPN (P = .012). The risk of LBM decreased with an odds ratio of 0.9 per year of HPN (95% confidence interval, 0.92–0.99; P = .018). Lean mass z score and calcium parenteral intakes were related to the TBMC improvement. Conclusion: LBM is common in pediatric IF, but bone status could improve during HPN in these children.     

Challenging the 48‐Hour Rule‐Out for Central Line–Associated Bloodstream Infections in the Pediatric Intestinal Failure Population

Introduction: While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line–associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. Methods: A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. Results: Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C‐reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. Conclusion: Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.     

Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1–4 and 14–18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.     

Parenteral ω‐3 Fatty Acid Lipid Emulsions for Children With Intestinal Failure and Other Conditions

Background: There is growing interest in the use of ω‐3 fatty acid (n‐3FA) lipid emulsions to prevent complications associated with parenteral nutrition. The authors systematically reviewed the evidence on the benefits and safety of n‐3FA compared with standard lipid emulsions in children with intestinal disease, critical illness, trauma, or postoperative complications. Materials and Methods: The authors searched 4 bibliographic databases from their inception to March 2011, conference proceedings, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodological quality, and rated the strength of the evidence. One reviewer extracted and a second reviewer verified data. The authors summarized findings qualitatively and conducted meta‐analysis when appropriate. Results: Five randomized controlled trials with unclear risk of bias and 3 high‐quality prospective cohort studies were included. The studies examined premature, low birth weight infants (n = 6) and children with heart disease (n = 1) or intestinal failure (n = 1). The strength of evidence was consistently low or very low across all lipid emulsion comparisons and outcomes. In young children, n‐3FA emulsions resulted in improvement in some biochemical outcomes of intestinal failure–associated liver disease but no difference in mortality. Few studies examined patient‐important outcomes, such as length of hospital and intensive care stay; need for transplantation, growth, and cognitive development; or the long‐term effects and potential harms associated with these therapies. Conclusions: Currently, there is a lack of sufficient high‐quality data to support the use of parenteral n‐3FA lipid emulsions in children. Future trials examining long‐term clinical outcomes and harms are needed.     

Self‐Evaluation of Quality of Life Among Patients Receiving Home Parenteral Nutrition: A Validation Study

Background : Home parenteral nutrition (HPN) can increase survival and quality of life (QOL) in cases of chronic intestinal failure. The present study compares a gold standard—a validated QOL assessment by Baxter et al (hereafter, HPN‐QOL)—with a shorter questionnaire for QOL evaluation (hereafter, New QOL). Materials and Methods : Both questionnaires were completed by 58 patients attending the nutrition clinic of the Rabin Medical Center (Israel). A z score was used to equate means and variances. Statistical analysis was based on Pearson correlation between variances. Stepwise regression was used to evaluate the best value predictor in the New QOL for QOL during HPN. Cronbach’s α was used for internal consistency, and confirmatory factor analysis was used for structural validity. Results : Results from the sections of the New QOL that relate to the patient’s general health, level of independence, and experience with handling the parenteral nutrition therapy are highly correlated with the HPN‐QOL (r = 0.43 and r = 0.50, respectively). In addition, there was good correlation between the questionnaires with reference to the patient’s social state, mental state, and everyday functioning (r = ?0.43, New QOL; r = ?0.39, HPN‐QOL). However, the New QOL results show no correlation between the patient’s physical symptoms and QOL during HPN. This was hypothesized to result from the nature of the study population. Conclusion : The results of our new questionnaire are well correlated with the gold standard HPN‐QOL. The New QOL appears to be simple and easy to use.     

Increased Intestinal Absorption in the Era of Teduglutide and Its Impact on Management Strategies in Patients With Short Bowel Syndrome–Associated Intestinal Failure

Short bowel syndrome–associated intestinal failure (SBS‐IF) as a consequence of extensive surgical resection of the gastrointestinal (GI) tract results in a chronic reduction in intestinal absorption. The ensuing malabsorption of a conventional diet with associated diarrhea and weight loss results in a dependency on parenteral nutrition and/or intravenous fluids (PN/IV). A natural compensatory process of intestinal adaptation occurs in the years after bowel resection as the body responds to a lack of sufficient functional nutrient‐processing intestinal surface area. The adaptive process improves bowel function but is a highly variable process, yielding different levels of symptom control and PN/IV independence among patients. Intestinal rehabilitation is the strategy of maximizing the absorptive capacity of the remnant GI tract. The approaches for achieving this goal have been limited to dietary intervention, antidiarrheal and antisecretory medications, and surgical bowel reconstruction. A targeted pharmacotherapy has now been developed that improves intestinal absorption. Teduglutide is a human recombinant analogue of glucagon‐like peptide 2 that promotes the expansion of the intestinal surface area and increases the intestinal absorptive capacity. Enhanced absorption has been shown in clinical trials by a reduction in PN/IV requirements in patients with SBS‐IF. This article details the clinical considerations and best‐practice recommendations for intestinal rehabilitation, including optimization of fluids, electrolytes, and nutrients; the integration of teduglutide therapy; and approaches to PN/IV weaning.