Discontinuation Of Parenteral Nutrition Research Articles

Pediatric Intestinal Failure in the Intestinal Transplant Era: A Retrospective Review of 272 Infants

Background. Pediatric intestinal failure (IF) is a rare but devastating condition defined as the inability of the intestine to support growth and development without supplemental parenteral nutrition (PN). A retrospective study was performed to provide the foundation for the first prospective study of IF in North America. Methods. PIFCon includes 14 sites with multi-disciplinary IF management teams; 9 are also intestinal transplant (ITx) centers. Infants 60 continuous days for IF were included. Demographic, clinical, biochemical, nutritional and outcome data were abstracted from medical charts. Values are presented as median (25th, 75th percentiles) or as (n, %). Enteral autonomy (EA) was defined as the discontinuation of PN for > 3 consecutive mo. Results. 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). The majority were male (156, 57%) and Caucasian (204, 75%). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), intestinal atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), intestinal aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). The cumulative proportions achieving EA at 1 and 3 yr were 0.31 and 0.43, respectively. Commonly used medications were oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Breast milk was given to 52 (19%); the cumulative probabilities of oral solid feeding were .67 at 1 yr and .85 at 3 yr. 25 different infant formulas were used as initial diet; 40 different formulas were used overall. 3.3 new catheter related blood stream infections occurred per person year (PPY) on PN and 0.2 intestinal bleeding episodes PPY of observation. 28 bowel lengthening procedures were performed. Cumulative probability of survival (CPS) was 0.84 at 1 yr and 0.74 at 3 yr. 58 died before and 10 died after ITx. Following study entry, time to death without ITx was 8.2 mo (4.8, 12.6). 137 were alive without ITx when the last data were abstracted from the medical record. 60 received ITx, the cumulative incidence of ITx at 1 and 3 years was .087 and .229, respectively. The CPS 1 year after ITx was 0.84. Conclusions. Children with IF suffer a high rate of mortality and morbidity. EA may require years to achieve. Substantial practice variability is noted among sites. Improved medical, nutritional, and surgical management of IF may reduce time on PN, mortality and need for ITx. Grant support: NIH/NIDDK R21 DK081059-01

Effects of multidisciplinary prenatal care and delivery mode on gastroschisis outcomes

Background/Purpose This study examined the effects of multidisciplinary prenatal care and delivery mode on gastroschisis outcomes, with adjustment for key confounding variables. Methods This retrospective cohort study included all gastroschisis patients treated at a single tertiary children's hospital between 1999 and 2009. Prenatal care, delivery mode (vaginal vs cesarean section before labor vs after labor), patient characteristics, and clinical outcomes were determined by chart review. Time to discontinuation of parenteral nutrition (PN) was the primary outcome of interest. Effects of multidisciplinary prenatal care and delivery mode were evaluated using Cox proportional hazards regression models that included gestational age, birth weight, sex, concomitant intestinal complications, and year of admission. Results Of 167 patients included, 46% were delivered vaginally, 69% received multidisciplinary prenatal care, and median time to PN discontinuation was 38 days. On multivariable modeling, gestational age, uncomplicated gastroschisis, and year of admission were significant predictors of early PN independence. Delivery mode and prenatal care had no independent effect on outcomes, although patients receiving multidisciplinary prenatal care were more likely to be born at term (49% vs 27%, P = .01). Conclusions Gestational age and intestinal complications are the major determinants of outcome in gastroschisis. Multidisciplinary prenatal care may facilitate term delivery.

Parenteral Nutrition–Associated Conjugated Hyperbilirubinemia in Hospitalized Infants

Parenteral nutrition-associated conjugated hyperbilirubinemia (PNAC), commonly defined as direct bilirubin ≥2 mg/dL (34.2 μmol/L), is primarily a pediatric disease with premature infants being the most susceptible. Severe morbidity and increased mortality are associated with bilirubin >10 mg/dL (171.0 μmol/L). The lack of knowledge regarding the cause of PNAC has stymied development of prevention and treatment strategies. A systematic search of published reports was conducted to provide data on histopathology of PNAC and to review prospective, randomized, controlled trials in hospitalized infants. In experiments of young animals, parenteral nutrition (PN) with and without soy oil emulsion is directly linked to hyperbilirubinemia, and the effects are exaggerated by overfeeding. In infants, the most consistently reported risk factor for PNAC is the duration of PN. The only known effective modality is the transition to full enteral feeding and discontinuation of PN. Emerging clinical research is evaluating the role of lipid source (soy vs fish) and motility agents, such as erythromycin. Different trace element preparations are associated with varying severity of cholestasis, a finding that also deserves more study. This article reviews the prevalence, risk factors, clinical presentation, and treatment options for PNAC in neonatal intensive care units.

Recurrent Autoimmune Pancreatitis in a 10‐Year‐Old Boy

Recurrent Autoimmune Pancreatitis in a 10‐Year‐Old Boy

Enteral Feeding and Caloric Intake in Neonates After Cardiac Surgery

Adequate enteral nutrition may be difficult to achieve early in neonates after cardiac surgery, but it is essential for growth, wound healing, and immune function. To assess caloric intake in neonates receiving enteral nutrition after surgery. A retrospective chart review was conducted of daily enteral caloric intake in the cardiac intensive care unit of a tertiary children's hospital. Data on the institution of enteral feeding and the discontinuation of parenteral nutrition were assessed for full-term neonates who had undergone cardiac surgery. Caloric intake was assessed in 100 patients, 52 with biventricular cardiac defects and 48 with a functional single ventricle. The median duration of stay in the cardiac intensive care unit was 13 days (range, 4-69), and patients received enteral feeding exclusively for a median of 5 days (range, 1-43). In total, 705 patient days were evaluated. The median caloric intake per day was 93 kcal/kg (range, 43-142). A goal of 100 kcal/kg was achieved for 48.4% of patient days and 120 kcal/kg for only 19.7% of patient days. Median weight change for the period of enteral feeding was -20 g (range, -775 to 1485 g). Enteral feeding alone is often suboptimal after neonatal cardiac surgery. New strategies to improve caloric intake may enhance postoperative recovery.

Repeat Surgical Bowel Lengthening With the STEP Procedure

Feasibility of repeat lengthening has been demonstrated in animals, but in humans, none of the three clinical case reports have achieved enteral autonomy after secondary lengthening with serial transverse enteroplasty (STEP). Institutional Review Board approved retrospective review of a single center series of repeat intestinal lengthening after prior Bianchi lengthening or STEP. Outcome measures examined include patient survival, weaning from parenteral nutrition, and need for intestinal transplantation. Repeat lengthening with STEP was performed 16 times in 14 patients including 2 adults and 7 male patients after prior Bianchi (n=7) and prior STEP (n=7). Median time after initial lengthening to reSTEP was 12 months (2 months-15 years). Median remnant bowel length before initial lengthening was 35 cm (15-110), before reSTEP was 56.5 cm (27-100) and final length after reSTEP was 90 cm (39-120). Survival is 100% with a median follow-up of 14.5 months (1-65 months). Discontinuation of parenteral nutrition (PN) after reSTEP was achieved in 6 of 14 (43%) patients at a median of 3 months (0.5-13 months) after reSTEP. Intestinal transplant salvage was performed in four patients at 7, 9, 13 months, and 4.6 years, respectively, after reSTEP. All four of those undergoing intestinal transplantation have also subsequently discontinued PN. Repeat lengthening is technically feasible after either of the available surgical lengthening procedures (Bianchi and STEP). In the stable patient, who is unable to wean from PN, repeat lengthening led to discontinuation of TPN in almost half of these carefully selected patients and does not preclude intestinal transplantation.

Intestinal Transplantation Comes of Age

Intestinal transplantation has evolved as a creditable therapeutic option that offers the only chance for cure for patients with intestinal failure who fail parenteral nutrition. The Editors of Transplantation are pleased to publish in this issue the first group of a series of selected articles based on papers presented at the Xth International Small Bowel Transplantation Symposium held in Los Angeles, CA on September 6–8, 2007. All of the articles to be published from this meeting have undergone our standard peer review process. The first articles included in this issue are described below. Additional articles will be published in succeeding issues. The intestine is less tolerant of ischemia than most other transplanted solid organs and, due to frequent significant donor organ size restraints in the majority of intestine recipients, donors are less likely to be procured locally, therefore emphasizing the need to minimize ischemia time. Schaefer et al. (Transplantation 2008; 85: 1300–1310) evaluated the efficacy of intravenous glycine administration in minimizing certain phenomena commonly associated with ischemia–reperfusion injury in a rat intestine model. Their data suggest that perioperative glycine treatment reduces molecular and cellular inflammatory responses within the graft and improves smooth muscle dysfunction posttransplantation. Protocol endoscopy with biopsy has been widely adopted as the standard for small bowel transplant rejection monitoring, but it is invasive, costly, and can be associated with complications. Akpinar et al. studied the use of Fecal Calprotectin levels (FCL) as a possible non-invasive marker for monitoring in small bowel transplant patients (Transplantation 2008; 85: 1281–1286). They present data to show that although no significant FCL difference was found between rejection and inflammation, FCL evolution in individuals could predict rejection days before histopathological diagnosis, suggesting its potential usefulness as a prescreening marker to avoid unnecessary biopsies. Induction immunosuppression is now common practice after intestinal and multivisceral transplantation. Vianna et al. (Transplantation 2008; 85: 1290–1293) describe their experience in 27 patients given antithymocyte globulin, rituximab, and steroids as induction therapy with Tacrolimus and tapered steroids as maintenance. One year patient and graft survival was 81% and 76%. Thirteen patients (48%) experienced 19 episodes of acute rejection; patients with multivisceral grafts experienced fewer episodes of acute rejection. Their data suggest that this induction regimen may have a protective effect against posttransplant lymphoproliferative disease and chronic rejection. Mian et al. (Transplantation 2008; 85: 1287–1289) present a retrospective analysis to determine factors affecting survival of intestinal transplantation in very young pediatric patients. Such patients awaiting intestinal transplantation have a high mortality rate due to long waiting times, scarcity of appropriate size donor organs, and mortality due to sepsis and liver failure. In children under 18 months of age, risks factors affecting survival to intestinal transplantation include small body size and advanced liver disease. No differences in residual small bowel length, presence of the colon, number of line infections or number of central lines were identified in the transplant and not transplanted groups. Intestinal transplantation is only one of a continuous of possible treatments for intestinal failure. Andres et al. (Transplantation 2008; 85: 1294–1299) examined the efficacy of repeat surgical bowel lengthening with the so-called reSTEP procedure (Repeat Serial Transverse Enteroplasty) after previous surgical lengthening procedures. They concluded that in the stable patient who is otherwise unable to wean from parenteral nutrition repeat lengthening via a reSTEP surgery resulted in discontinuation of parenteral nutrition in almost half of a carefully selected group of patients. Most importantly, such repeat procedures did not preclude intestinal transplantation. Anthony Monaco Peter J. Morris

Intestinal Replacement Therapy: Timing and Indications for Referral of Patients to an Intestinal Rehabilitation and Transplant Program

Current treatment options for patients suffering from intestinal insufficiency include all forms of intestinal replacement therapy (IRT). Parenteral nutrition has achieved extended success for the majority of patients requiring interval treatment, however, complications leading to failure of this treatment increases with the duration of therapy. There is currently no consensus as to the appropriate timing for transplantation of the intestine or the timing of referral for evaluation at a center experienced with this therapy. Certain patient characteristics warrant evaluation. Those patients with no jejunoileum who have guaranteed lifelong parenteral dependence, both adult and pediatric, should be immediately referred to a transplant center due to the high likelihood of the development of liver disease. Patients with metastatic infectious complications from catheter sepsis, patients with cholestasis seen intermittently with sepsis episodes, patients who are not successfully weaning and who demonstrate progressive thrombocytopenia, and patients with motility disorder experiencing deterioration should also warrant early referral to an intestinal rehabilitation and transplant program. The objective of evaluation is to maximize the opportunities for rehabilitation while not missing the critical window of opportunity for successful transplantation when needed. We favor an aggressive directed approach to rehabilitation, coupled with psychological preparation for both transplantations and other options. Early referral requires trust between the patient, referring physician, and the transplant team to assure that a rush to judgment will not lead to a premature transplant. The current wait list mortality is high, mandating early referral and listing with an approach aimed at maximizing both the success of gastrointestinal support, as well as of transplantation when necessary.

The role of enteral nutrition in the reversal of parenteral nutrition–associated liver dysfunction in infants

Background Liver dysfunction in children dependent on parenteral nutrition (PN) is well established, and the extent of hyperbilirubinemia has been shown to correlate with morbidity and mortality. The aim of this study was to assess whether increasing provisions of enteral nutrition can improve PN-associated hyperbilirubinemia over time. Methods A retrospective review was conducted on infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004. Inclusion criteria included PN duration more than 1 month, serum direct bilirubin more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with eventual discontinuation of PN. Paired t tests were used for statistical analyses. Results Twelve infants were identified with a PN duration of 5 ± 1 months. Five patients underwent liver biopsy while on PN, and histological evidence of cholestasis was found on all specimens. Peak total and direct bilirubin levels were 10.5 ± 1.9 and 7.0 ± 1.6 mg/dL, respectively, and occurred at time of PN discontinuation. Only 2 patients had improvement in serum bilirubin levels before initiation of full enteral nutrition. After initiation of full enteral nutrition and discontinuation of PN, all patients achieved permanent normalization of bilirubin levels by 4 months ( P < .05) after a 1-month plateau phase. Alkaline phosphatase levels approached reference range within this time but were not significant. Conclusion These data demonstrate for the first time that although PN-dependent infants can achieve normalization of marked hyperbilirubinemia with enteral nutrition, the improvement in liver function usually begins only after full enteral nutrition is tolerated and PN is withdrawn. These findings support the aggressive weaning of PN to enteral nutrition in infants with short bowel syndrome.

ISOLATED HYPERLIPASEMIA ASSOCIATED WITH HYPEREMESIS GRAVIDARUM AND PARENTERAL NUTRITION

Isolated elevation of serum lipase with normal amylase is a rare biochemical finding that has been described in patients with malignant tumors, renal insufficiency, hypertriglyceridemia and macrolipasemia. We present two cases of hyperlipasemia associated with hyperemesis gravidarum (HG). The patients were two African American women on their first pregnancies, without significant medical history, hospitalized for severe HG. Physical exam was unremarkable and laboratory values showed increased serum lipase levels more than three times the upper normal limit with normal serum amylase, and acute pancreatitis was suspected. The elevation persisted for more than a week after the resolution of the symptoms. Parenteral nutrition (PN) appears to be associated with further increase in serum lipase values. The first patient, a 32-year-old woman 16 weeks pregnant G1PO was started on PN at home because of persistent nausea, vomiting, and low caloric intake. The serum lipase of 1082 U/L on admission, increased to a peak level of 3506 U/L during hospitalization with the patient on PN. After discontinuing PN and starting a liquid diet, lipase had a descending trend. The lipase values have normalized after discharge. The second patient, a 19-year-old woman 9 weeks pregnant G1PO presented with a serum lipase of 698 U/L, which increased to speak level of 1491 U/L. Short term PN led to an increase in serum lipase. Subsequently the lipase level decreased with the patient on liquid diet and was reported normal on the follow-up visit. The possibility of isolated hyperlipasemia in patients with HG should be considered to avoid unnecessary diagnostic and therapeutic procedures. It is not clear if the origin of lipase is pancreatic, perhaps due to microlithiasis or nonpancreatic from intestinal, gastric or lingual sources. The transient nature of hyperlipasemia and the normal serum amylase level make the diagnosis of macrolipasemia less likely. Also avoidance or early discontinuation of PN can lead to a normalization of serum lipase level.[figure 1]Figure

Intestinal transplantation for gut failure

In recent years, we have witnessed increasing clinical experience with intestinal transplantation at selected centers. Although early results with this therapy were poor, several important advances have led to improved outcomes. These improvements prompted the Centers for Medicare and Medicaid Services to issue a memorandum on October 4, 2000, according federal reimbursement for intestinal transplantation at selected centers and for selected indications.1 The Centers for Medicare and Medicaid Services stipulated that, to qualify for transplantation, patients must meet a specific definition of intestinal failure and have experienced failure of parenteral nutrition (Table 1). In addition, the Centers for Medicare and Medicaid Services set forth centerspecific criteria for reimbursement, including 1-year patient survival rates of at least 65% and minimum center volume of at least 10 transplants performed per year. Only 4 centers in the United States currently meet these criteria (Mount Sinai Medical Center, University of Pittsburgh Medical Center, University of Miami, and University of Nebraska Medical Center). Thus, intestinal transplantation is currently at a crossroads, transitioning from its historical status as an experimental therapy to standard care for patients with appropriate indications. Presently, appropriate indications, timing of referral, and outcomes of intestinal transplantation are not well recognized among physicians caring for patients who may be candidates for this therapy. Definitions of terms such as “intestinal failure” and “failure of parenteral nutrition” are not standard, and there is no accepted algorithm for integrating parenteral nutrition, intestinal rehabilitation, and transplantation for patients with intestinal failure. Herein we review (1) the applicability of intestinal transplantation for patients with intestinal failure, (2) the current state of medical practice in intestinal transplantation with an emphasis on recent improvements, and (3) current results of this therapy. We also offer for the general gastroenterologist or gastrointestinal surgeon a rational approach to managing intestinal failure and integrating intestinal rehabilitation, parenteral nutrition, and transplantation.2 Brief History

Bone mineral content in children with short bowel syndrome after discontinuation of parenteral nutrition

To determine whether children with short bowel syndrome had evidence of metabolic bone disease, total body bone mineral content was measured by dual-energy x-ray absorptiometry in 18 patients and 36 age-, sex-, and race-matched control subjects. Children with short bowel syndrome had decreased bone mineral content compared with control subjects; however, it was not significant when adjusted for differences in weight and height. Whether these children will have normal bone accretion throughout puberty is not known. (J Pediatr 1998;132:516-9)

Utilization of fat emulsion during total parenteral nutrition in children.

Tolerance for Intralipid fat emulsion during total parenteral nutrition (PN) was studied in 6 children. The Intralipid dose was monitored by the daily determination of plasma Intralipid levels. Fat removal was investigated at the start of and during the PN period by the intravenous fat tolerance test (IVFTT) and by determining the plasma postheparin lipoprotein lipase (LPL) activity. When the plasma Intralipid levels exceeded a value of 100 mg/100 ml, hyper pre-beta lipoproteinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperphospholipidaemia appeared. During PN most patients showed marked increases of postheparin LPL. Return to normal values occurred after discontinuation of PN. Maximal LPL activities were found to correlate significantly with total daily caloric intake (r=0.95, 0.05 less than p less than 0.01). The Intralipid elimination constant hardly changed during PN, with the exception of patient 6, who showed a marked increase (from 7 to 22%). Conclusions of this study are as follows: First a high caloric intake during PN leads to a marked increase of postheparin LPL activity. Second, by monitoring plasma Intralipid levels at 100 mg/100 ml approximately, it is possible to adjust the Intralipid dose in order to prevent hyperlipaemia and to take maximal benefit from rising fat tolerance. Thirdly the IVFTT appeared to be of little value to estimate the child's fat elimination capacity.