Biren P. Modi

Safety and Efficacy of a Fish-Oil–Based Fat Emulsion in the Treatment of Parenteral Nutrition–Associated Liver Disease

BACKGROUND. Parenteral nutrition–associated liver disease can be a progressive and fatal entity in children with short-bowel syndrome. Soybean-fat emulsions provided as part of standard parenteral nutrition may contribute to its pathophysiology. METHODS. We compared safety and efficacy outcomes of a fish-oil–based fat emulsion in 18 infants with short-bowel syndrome who developed cholestasis (serum direct bilirubin level of >2 mg/dL) while receiving soybean emulsions with those from a historical cohort of 21 infants with short-bowel syndrome who also developed cholestasis while receiving soybean emulsions. The primary end point was time to reversal of cholestasis (3 consecutive measurements of serum direct bilirubin level of ≤2 mg/dL). RESULTS. Among survivors, the median time to reversal of cholestasis was 9.4 and 44.1 weeks in the fish-oil and historical cohorts, respectively. Subjects who received fish-oil–based emulsion experienced reversal of cholestasis 4.8 times faster than those who received soybean emulsions and 6.8 times faster in analysis adjusted for baseline bilirubin concentration, gestational age, and the diagnosis of necrotizing enterocolitis. A total of 2 deaths and 0 liver transplantations were recorded in the fish-oil cohort and 7 deaths and 2 transplantations in the historical cohort. The provision of fish-oil–based fat emulsion was not associated with essential fatty acid deficiency, hypertriglyceridemia, coagulopathy, infections, or growth delay. CONCLUSIONS. Parenteral fish-oil–based fat emulsions are safe and may be effective in the treatment of parenteral nutrition–associated liver disease.

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.

A Standardized Assessment of Thyroid Nodules in Children Confirms Higher Cancer Prevalence Than in Adults

CONTEXT Thyroid cancer is the most common endocrine malignancy, but due to its rare occurrence in the pediatric population, the cancer risk of childhood thyroid nodules is incompletely defined, and optimal management of children with suspected nodules is debated. OBJECTIVE The aim was to study the presenting features and cancer risk of sporadic childhood thyroid nodules using a standardized clinical assessment and management plan. DESIGN AND SETTING Boston Childrens Hospital and Brigham and Womens Hospital collaborated to create a multidisciplinary pediatric thyroid nodule clinic and implement a standardized assessment plan. Upon referral for a suspected nodule, serum TSH was measured and hypothyrotropinemic patients underwent (123)I scintigraphy. All others underwent thyroid ultrasonography, and if this confirmed nodule(s) ≥ 1 cm, ultrasound-guided fine-needle aspiration was performed. Medical records were retrospectively reviewed and compared to a control population of 2582 adults evaluated by identical methods. PATIENTS AND RESULTS Of 300 consecutive children referred for the initial evaluation of suspected thyroid nodules from 1997 to 2011, 17 were diagnosed with autonomous nodules by scintigraphy. Neck ultrasonography performed in the remainder revealed that biopsy was unnecessary in over half, either by documenting only sub-centimeter nodules or showing that no nodule was present. A total of 125 children met criteria for thyroid biopsy, which was performed without complication. Their rate of cancer was 22%, significantly higher than the adult rate of 14% (P = .02). CONCLUSIONS Neck ultrasonography and biopsy were key to the evaluation of children with suspected thyroid nodules. Although the relative cancer prevalence of sonographically confirmed nodules ≥ 1 cm is higher in pediatric patients than adults, most children referred for suspected nodules have benign conditions, and efforts to avoid unnecessary surgery in this majority are warranted.

Mortality and Management of Surgical Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Prospective Cohort Study

BACKGROUND Necrotizing enterocolitis (NEC) is a leading cause of death in very low birth weight (VLBW) neonates. The overall mortality of NEC is well documented. However, those requiring surgery appear to have increased mortality compared with those managed medically. The objective of this study was to establish national birth-weight-based benchmarks for the mortality of surgical NEC and describe the use and mortality of laparotomy vs peritoneal drainage. STUDY DESIGN There were 655 US centers that prospectively evaluated 188,703 VLBW neonates (401 to 1,500 g) between 2006 and 2010. Survival was defined as living in-hospital at 1-year or hospital discharge. RESULTS There were 17,159 (9%) patients who had NEC, with mortality of 28%; 8,224 patients did not receive operations (medical NEC, mortality 21%) and 8,935 were operated on (mortality 35%). On multivariable regression, lower birth weight, laparotomy, and peritoneal drainage were independent predictors of mortality (p < 0.0001). In surgical NEC, a plateau mortality of around 30% persisted despite birth weights >750 g; medical NEC mortality fell consistently with increasing birth weight. For example, in neonates weighing 1,251 to 1,500 g, mortality was 27% in surgical vs 6% in medical NEC (odds ratio [OR] 6.10, 95% CI 4.58 to 8.12). Of those treated surgically, 6,131 (69%) underwent laparotomy only (mortality 31%), 1,283 received peritoneal drainage and a laparotomy (mortality 34%), and 1,521 had peritoneal drainage alone (mortality 50%). CONCLUSIONS Fifty-two percent of VLBW neonates with NEC underwent surgery, which was accompanied by a substantial increase in mortality. Regardless of birth weight, surgical NEC showed a plateau in mortality at approximately 30%. Laparotomy was the more frequent method of treatment (69%) and of those managed by drainage, 46% also had a laparotomy. The laparotomy alone and drainage with laparotomy groups had similar mortalities, while the drainage alone treatment cohort was associated with the highest mortality.

Pediatric Intestinal Failure: Nutrition, Pharmacologic, and Surgical Approaches

Intestinal failure (IF) is a condition where there is insufficient functional bowel to allow for adequate nutrient and fluid absorption to sustain adequate growth in children. Several etiologies can predispose to IF, including necrotizing enterocolitis, gastroschisis, and intestinal atresias. Intestinal rehabilitation can be seen as a 3-pronged strategy merging nutrition, pharmacologic, and surgical approaches to achieve the ultimate goal of enteral nutrition. Nutrition approaches should seek to facilitate transition from parenteral nutrition (PN) to enteral nutrition because prolonged use of PN is associated with severe morbidity and mortality. Enteral nutrition, on the other hand, promotes and enhances an adaptive response in the intestine. Medications used in the treatment of IF may help alleviate symptoms of diarrhea, bacterial overgrowth, and gastrointestinal dysmotility. Surgical procedures, such as longitudinal intestinal lengthening and tapering (LILT) or serial transverse enteroplasty (STEP), can increase mucosal surface area and may enhance intestinal adaptation. IF is a difficult disease process with a complex patient population and is best guided through this 3-pronged approach by a multidisciplinary team featuring surgeons, gastroenterologists, dietitians, pharmacists, and nurses.

Adrenal insufficiency in the critically ill neonate and child.

Purpose of review Adrenal insufficiency, common in critically ill patients of all ages, has recently gained prominence as a significant pathologic entity in pediatrics. This review describes the current diagnostic approach to detecting adrenal insufficiency and the clinical consequences in critically ill children and infants. It also discusses the current therapeutic approach to adrenal insufficiency in critically ill patients. Recent findings Relative adrenal insufficiency and its clinical implications have recently come into focus with observational studies demonstrating a high prevalence in pediatric septic shock patients and a significant associated morbidity. Neonatal studies have clarified diagnostic testing and defined clinical outcomes associated with adrenal insufficiency in preterm infants. Comparisons of bioavailable and total cortisol levels demonstrate the utility of total cortisol testing in pediatric septic shock patients. Summary Adrenal insufficiency contributes to morbidity in critically ill neonates and children. Diagnostic testing by adrenocorticotropin stimulation tests should be done in patients unresponsive to standard treatment of shock. Prospective, randomized clinical trials in critically ill neonates and children with adrenal insufficiency are required to determine if these populations will benefit from glucocorticoid replacement therapy.

A.S.P.E.N. Clinical Guidelines Nutrition Support of Neonates Supported with Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) utilizes a modified heart-lung machine with a membrane oxygenator in the setting of profound cardiorespiratory failure. ECMO has been used successfully in pediatric and adult applications, though the most frequent indication is neonatal respiratory failure in conditions such as persistent pulmonary hypertension, congenital diaphragmatic hernia, congenital heart disease, and meconium aspiration. ECMO use is associated with improved mortality, however the nutritional and metabolic burden in these children is considerable. ECMO does not provide a “metabolic rest.” Rather, neonates on ECMO have demonstrated some of the highest rates of protein catabolism reported. Appropriate provision of nutrition support in ECMO patients is predicated upon a clear understanding of the changes in their metabolism, metabolic reserves, and nutrition requirements. The purpose of this Clinical Guideline is to address the nutrition support of neonatal patients treated with ECMO.

Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome

INTRODUCTION Serial transverse enteroplasty (STEP) has been shown to improve bowel function in short bowel syndrome. The effect of the STEP procedure on intestinal motility is not known, but some have hypothesized that it could disrupt bowel innervation and thus impair intestinal motility. METHODS Growing Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal of 50 cm of jejunum, (2) 90% bowel resection +/- STEP to the proximal dilated bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each operation, baseline and post-octreotide small intestinal motility was studied with continuously perfused manometry catheters using non-anticholinergic anesthesia. In addition, awake monitoring was performed using strain gauge analysis 1 week after the third operation. Characteristics of phase III of the migrating motor complex (MMC) were compared between and within groups using t test, chi(2), and analysis of variance, with significance set at P < .05. RESULTS Manometry data from the third surgery revealed no differences between groups or compared with baseline within groups for the presence and characteristics of phase III of the MMC. Specifically, the mean amplitude and frequency of phase III after octreotide, and both the mean baseline and mean octreotide-stimulated motility indices were equivalent. The duration of phase III after octreotide stimulation was significantly increased in the STEP animals, suggesting a potential benefit of the STEP procedure. Strain gauge analysis, performed in awake animals, confirmed no differences between the groups for basal and octreotide-stimulated characteristics of phase III of the MMC. CONCLUSIONS These preliminary data suggest that the STEP procedure in a porcine model of short bowel syndrome does not interfere with baseline or hormonally stimulated motility within the small bowel. These findings further support the STEP procedure as a safe option for the surgical management of short bowel syndrome.

Pediatric intestinal failure and vascular access.

Emerging developments in the care of intestinal failure (IF) patients have drastically improved their overall prognosis, with recently reported survival rates over 90%. IF patients remain an extremely complex population who benefit from specialized, multidisciplinary care. Advances in the provision of parenteral and enteral nutrition, progress in the management of IF-associated liver disease with parenteral fish oil and catheter-associated blood stream infection with ethanol lock therapy, and the availability of novel surgical interventions, such as the serial transverse enteroplasty procedure, have made this a dynamic health care field with the promise of ongoing improvements in outcomes for these patients.

High diagnostic yield of gastrointestinal endoscopy in children with intestinal failure.

PURPOSE Children with intestinal failure (IF) often have gastrointestinal (GI) symptoms, including bleeding, increased stool output, and feeding intolerance. The use of endoscopic assessment of these symptoms has not been previously reported. This report evaluates the diagnostic yield of GI endoscopy in the setting of IF. METHODS After institutional review board approval, we reviewed the medical records (including endoscopy, pathology and microbiology data) of patients with IF who underwent GI endoscopies between September 1999 and March 2007. RESULTS Twenty-seven patients underwent 61 GI endoscopies: 34 esophagogastroduodenoscopies, 17 colonoscopies, 7 flexible sigmoidoscopies, and 3 ileoscopies. Indications for endoscopy, which were not mutually exclusive, included chronic diarrhea (39%, n = 24), GI bleeding (36%, n = 22), suspected bacterial overgrowth (36%, n = 22), and suspected peptic disease (15%, n = 9). Based on gross endoscopic appearance, histopathology, or microbiology, 43 (70%) procedures yielded abnormalities. These included infectious (20%, n = 12), anatomical (18%, n = 11), peptic (15%, n = 9), allergic (15%, n = 9), and other (2%, n = 1) findings. Eleven (73%) of 15 duodenal cultures grew a spectrum of 17 bacterial species. Overall, 24 (89%) of 27 patients had gross endoscopic, histopathologic, or microbiologic abnormalities. CONCLUSIONS In pediatric patients with IF, diagnostic upper and lower GI endoscopies yield high rates of abnormalities and can help guide clinical management.