Duration Of Total Parenteral Nutrition Research Articles

Continuous infusion idarubicin and intravenous busulphan as conditioning regimen to autologous stem cell transplantation for patients with acute myeloid leukaemia

The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty-five patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 x 10E6/kg. The median number of days to PMN >500/cmm and platelets >20000/cmm was 10 and 13, respectively. In order to perform a comparison in terms of haematological and non haematological toxicity, a group of 30 patients, who were previously autografted after conditioning with IDA and oral Bu was considered. Selection of factors for a matched pair analysis included median age, percentage of subjects aged over 60 years, median CD34+ cell received, cytogenetic and molecular findings and per cent of secondary AML. As compared to previous series, the occurrence of severe mucositis was dramatically reduced (80% vs. 12%, p < 0.0001). In addition, need and duration of total parenteral nutrition (TPN), iv antibiotic therapy and hospitalization were also significantly reduced. We conclude that replacement of oral with intravenous BU results in a more favourable toxicity profile. A longer follow-up is required to assess a potential advantage in terms of disease free survival (DFS).

Colestasis asociada a la nutrición parenteral prolongada en el período neonatal: posible eficacia del ácido ursodesoxicólico

Introduction The morbidity associated with prematurity occasionally leads to the use of prolonged parenteral nutrition, with the subsequent development of cholestasis being one of its complications. Patients and methods This is a two year retrospective study which compared biochemical markers of liver damage and cholestasis in premature babies who received or did not receive urso-deoxycholic acid for parenteral nutrition associated cholestasis. Results Of a total of 24 recruited patients 17 received urso-deoxycholic acid and 7 did not. In the treated group significant decreases ( P<0.05) in gamma-glutamyltranspeptidase and conjugated bilirubin were found after four and five weeks of treatment, respectively. Moreover, a significant correlation ( P<0.01) between conjugated bilirubin and duration of total parenteral nutrition was established. Conclusions Patients who were promptly treated with urso-deoxycholic acid showed a more rapid decrease in biochemical markers of cholestasis, but not of cytotoxicity in the hepatobiliary complications secondary to prolonged parenteral nutrition. However, the present study has limitations derived from its design and therefore it would be desirable launch a randomized trial with sufficient power to evaluate the benefits derived from prophylactic or therapeutic use of urso-deoxycholic acid in the hepatobiliary conditions associated with the prolonged use of parenteral nutrition in the premature infants.

Use of transanastomotic feeding tubes during esophageal atresia repair

Purpose Esophageal atresia (EA) with tracheoesophageal fistula (TEF) type C accounts for 85% of all EA. In our center, patients were previously started on total parenteral nutrition (TPN) postoperatively and oral feedings initiated only after a contrast esophagogram. Our aim is to assess the benefit of intraoperatively placed transanastomotic feeding tubes (TAFTs). Methods A 7-year retrospective review analyzed the outcomes of children with EATEF type C as they relate to the use of TAFT. Demographics, associated anomalies, operative findings, complications, duration of TPN, resumption of oral feeding, length of stay, and follow-up were examined. Results Twenty-one patients had EATEF type C. Eleven (55%) and 9 (45%) patients were identified as nonfeeding tube (NFT) and TAFT groups, respectively. There were no differences in gestational age, birth weight, associated anomalies, and interval to operative intervention or operative time. Excluding one patient with a severe cardiac malformation in the NFT group, there were no significant differences in anastomotic leak (8% vs 22%), stenosis (36% vs 22%), TPN duration (20 days vs 12 days), and cholestasis (36% vs 11%). Conclusion Transanastomotic feeding tube may lead to shorter TPN duration and decreased cholestasis, but a larger prospective study would be required to prove these benefits and ensure that it does not increase anastomotic leaks. This could be done through an expanded Canadian Pediatric Surgery Network study.

Erythromycin establishes early oral feeding in neonates operated for congenital intestinal atresias

The recovery of gastrointestinal function following surgery for congenital intestinal atresias can be prolonged and may increase morbidity and hospital stay. This study was conducted to investigate the prokinetic effect of erythromycin in neonates undergoing surgery for small bowel atresias. A randomized-controlled trial was conducted at the Departments of Paediatrics and Paediatric Surgery, Military Hospital, Rawalpindi, Pakistan, from January to December 2007 to study the prokinetic effect of erythromycin (3 mg/kg per dose 4 times daily). Thirty consecutive neonates undergoing primary anastomosis for congenital small bowel atresias were randomly divided into two groups: group I (erythromycin) and group II (control). The groups were similar in terms of gestational age, sex, mode of delivery, birth weight and types of atresias. Postoperative recovery of intestinal functions was measured as time taken to achieve full enteral feed (150 ml/kg per 24 h), duration of total parenteral nutrition (TPN) and hospital stay. Neonates receiving oral erythromycin achieved full enteral feeding early (13.07 vs. 16.13 days) required TPN for shorter duration (10.53 vs. 13.73 days) and their hospital stay was less (16.2 vs. 18.0 days) as compared to the neonates in the control group who did not receive any erythromycin. The differences were statistically significant. The administration of oral erythromycin following primary anastomosis for small intestinal atresias results in early recovery of intestinal function, fewer days on TPN and a trend for shorter hospital stay.

Infections in gastroschisis: organisms and factors

This study aimed to define the incidence, causative organisms and predisposing factors leading to infection related morbidity in newborns with gastroschisis. All gastroschisis patients admitted over the 5-year period (1999-2004) were retrospectively reviewed. Surveillance samples, wound, blood, urine and fecal cultures were analyzed. Duration of total parenteral nutrition, antibiotic therapy, feeding regimes and demographic data were also analyzed. Multiple logistic regression was employed using the SPSS system and p < 0.05 was considered as significant. Seventy-two neonates were identified with 53% having abnormal gut carriage mostly due to Enterobacter and Klebsiella. Wound infection occurred in 20% of cases. Abnormal gut carriage predisposed to the development of wound infection. Line sepsis occurred in 21% of neonates. Endogenous coagulase negative Staphylococcus caused 74% of septic episodes. There was no correlation between abnormal gut carriage and the development of line sepsis. Overall survival was 96%. The cause of infections in gastroschisis patients appears to be multifactorial. A multidisciplinary team can play an important role in reducing the incidence of infections. Strict aseptic protocols and auditing practice can be the invaluable tools in decreasing morbidity rates.

Erythromycin for the prevention and treatment of feeding intolerance in preterm infants

Functional immaturity of gastrointestinal motility predisposes preterm infants to feeding intolerance. Erythromycin is a motilin agonist that exerts its prokinetic effect by stimulating propagative contractile activity in the interdigestive phase. To evaluate the efficacy of erythromycin in the prevention and treatment of feeding intolerance in preterm infants. Systematic literature search was performed according to the Cochrane Neonatal Collaborative Review Group search strategy. Randomized controlled trials of erythromycin in preterm infants to promote gastrointestinal motility were identified from the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007), MEDLINE (1966 - December 2007), EMBASE (1980 - December 2007), CINAHL (1982 - December 2007), cross-references, abstracts, and journal hand searching. The initial selection criteria limited the review to studies using erythromycin at 3 - 12 mg/kg/day in preterm infants less than 36 weeks gestational age with feeding tolerance. However, a significant number of studies using erythromycin at a higher dose (> 12 mg/kg/day) or as prophylaxis for those at risk of feeding intolerance were identified. A post hoc decision was made to include these studies in the review. Studies were categorized into prevention and treatment studies, and data from each category were analyzed separately. Within each category, subgroup analyses were performed based on low (3 to 12mg/kg/day) and high doses (> 12mg/kg/day) of erythromycin. Primary outcome was days to full enteral feeding. Secondary outcomes included adverse effects associated with erythromycin, duration of total parenteral nutrition (TPN), weight gain, necrotizing enterocolitis (NEC), and length of hospital stay. Ten randomized controlled studies (three prevention and seven treatment studies) were included. Studies varied greatly in the definition of feeding intolerance and how outcomes were measured, analyzed and reported, so meta-analysis of most outcomes was impossible. It was observed, however, that the studies using erythromycin at higher treatment doses (40 to 50 mg/kg/day) or in infants > 32 weeks' GA reported more positive effects in improving feeding intolerance.Meta-analysis of high dose prevention studies showed no significant difference in NEC (typical RR 0.59, 95% CI 0.11, 3.01; typical RD -0.021, 95% CI -0.087, 0.045). Meta-analysis of high dose treatment studies showed no significant difference in septicemia (typical RR 0.83, 95% CI 0.47, 1.45; typical RD -0.04, 95% CI -0.17, 0.08). There is insufficient evidence to recommend the use of erythromycin in low or high doses for preterm infants with or at risk of feeding intolerance. Future research is needed to determine if there is a more precise dose range where erythromycin might be effective as a prokinetic agent in preterm infants > 32 weeks' GA.

Risk factors for albicans and non-albicans candidemia in the intensive care unit*

To determine risk factors for bloodstream infections (BSI) with Candida non-albicans (C-NA) species and Candida albicans (CA) among critically ill patients. Case-control study. Adult medical and surgical intensive care units (ICUs) at two university hospitals. Consecutive patients with C-NA and CA BSIs from 1995-2005 formed the two case groups. Controls were patients without candidemia who were randomly selected in a ratio of 5:1 and matched by study hospital, ICU type (medical vs. surgical) and by ICU admission date within a 3-month period. Data collected included demographics, comorbidities, exposure to antibiotics and antifungals, and ICU factors such as total parenteral nutrition (TPN), blood product transfusions, invasive procedures, central venous catheters, hemodialysis, and mechanical ventilation. We built multivariable logistic regression models, which identified risk factors for C-NA or CA BSIs compared with controls. Variables were adjusted for time-at-risk. There were 67 patients with C-NA BSIs, 79 patients with CA BSIs, and 780 controls. In multivariable models, factors associated with an increased risk of C-NA compared with controls included major pre-ICU operations [odds ratio; (95% confidence interval)] [2.12; (1.14-3.97)], gastrointestinal procedures [2.24; (1.49-3.38)], enteric bacteremia [3.43; (1.39-8.48)], number of hemodialysis days [6.20; (2.67-14.4)], TPN duration [2.87; (1.40-5.90)], and mean number of red blood cell transfusions [2.72; (1.33-5.58)]. Factors associated with an increased risk of CA BSIs compared to controls were very similar and included major ICU operations [1.26; (1.14-3.97)], enteric bacteremia [3.45; (1.38-8.63)], number of hemodialysis days [3.84; (1.75-8.40)], TPN duration [11.0; (5.52-21.7)] and mean number of red blood cell transfusions [1.97; (0.98-3.99)]. We found multiple common risk factors for both non-C. albicans and C. albicans BSIs, however we could not differentiate between these two groups based on clinical characteristics alone.

Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients

In this multicenter study, 30 patients undergoing matched related or unrelated allogeneic stem-cell transplantation for leukemia were treated with palifermin, and retrospectively compared to a matched control group. Palifermin recipients transplanted with an unrelated donor showed a significant reduction of severity, incidence and duration of oral mucositis WHO grades 2-4. In addition, in the palifermin group the use of opioid analgesics and the duration of total parenteral nutrition decreased, whether stem cells were used from matched related or unrelated donors. No beneficial influence of palifermin on the incidence and severity of acute GVHD (aGVHD) was apparent. The incidence and duration of febrile neutropenia, documented infections, hematopoietic recovery or overall survival remained unchanged. The most common adverse effects included rash or erythema, generally mild and transient in appearance. Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas--regardless of donor status--no effect on the incidence and severity of aGVHD was seen.

Percutaneously Inserted Central Catheter for Total Parenteral Nutrition in Neonates: Complications Rates Related to Upper Versus Lower Extremity Insertion

The objective of this study was to compare the complication rates of upper versus lower extremity percutaneously inserted central catheters used for total parenteral nutrition in neonates. During a 48-month study period, 396 neonates were identified as having had percutaneously inserted central venous catheters. A total of 370 catheters were inserted from the upper and 107 from the lower extremity. Data retrieved and analyzed were birth weight, gestational age, age at placement, duration in place, duration of total parenteral nutrition, type of infusates, catheter-related bloodstream infection, phlebitis, leakage, occlusion, necrotizing enterocolitis, intraventricular hemorrhage, serum creatinine, liver function tests, and length of hospitalization. The median birth weight and gestational age were 940 g and 28 weeks. The rate of catheter-related bloodstream infection was 11.6% for the upper and 9.3% in the lower extremity catheters. The most common organism was coagulase-negative Staphylococcus for both upper and lower extremity catheters and significantly higher with catheters from the upper extremity. Lower extremity catheters were in place longer, and the time from insertion to complication was also longer. The rate of cholestasis was higher for the upper extremity catheters. Multiple regression analysis showed that the most significant contributor to cholestasis was duration of time the catheters were in place and the duration of total parenteral nutrition administration. Receiver operating characteristics curve demonstrated higher sensitivity for duration of catheters in predicting cholestasis with duration of total parenteral nutrition being more specific. Lower extremity percutaneously inserted central venous catheters had lower rates of catheter-related bloodstream infection, longer time to first complication, and lower cholestasis despite longer duration of total parenteral nutrition. When possible, lower extremity inserted catheters should be used for the administration of total parenteral nutrition.

Ten-year experience in the management of total colonic aganglionosis

Purpose The aim of this study was to review the 10 years' experience in the management of patients with total colonic aganglionosis (TCA) and follow-up of their health condition. Methods Cases of 25 patients with TCA in the Children's Hospital of Fudan University from 1996 to 2005 were reviewed and analyzed. The confirmed diagnosis was established by an intraoperative frozen-section biopsy of the rectum, colon, appendix, and ileum. The data included in this study accounted for sex, age, signs of presentation, any familiar history of Hirschsprung disease (HD) or associated abnormalities, and ileal involvement. Plain x-ray films, barium enema, and anorectal manometry were provided for evaluation. The results of surgical management were analyzed for weight at definite operation, blood requirement during operation, the total parenteral nutrition duration, and the pre- and postoperative complications of these patients. Follow-up data were collected regarding growth development, stool frequency, stool consistency, fecal soiling, incontinence, enterocolitis, and anal stricture. Results Among 25 patients, 8 (32%) females and 17 (68%) males were diagnosed as having TCA. Sixteen patients (64%) were evaluated at the neonatal period, whereas 9 patients (36%) were evaluated after the neonatal period. All 25 patients received at least 1 plain abdominal radiograph or barium enema at the university hospital before operation. However, there was no specific pathognomonic finding that may provide a definite diagnosis. Nineteen (76%) patients underwent initial laparotomy at our institute and 6 patients (24%) were operated on beforehand at other hospitals. Twenty-three (92%) patients were diagnosed as having TCA and underwent ileostomy, whereas 2 (8%) patients underwent primary pull-through procedure. Eighteen (72%) patients had undergone definite surgery. Pre- and postoperative complications included enterocolitis (44.4%), perianal excoriation (77.7%), electrolyte imbalance (50%), and anastomotic leak (16.6%). Average duration of total parenteral nutrition before operation was 17.77 ± 12.54 days and after operation was 10.27 ± 5.23 days. Mean follow-up time was 27.6 ± 35.39 months. Two patients had 5 to 6 bowel movements per day. Seven had a frequency of stool ranging between 1 and 3 bowel movements per day. Their bowel movements returned to normal about 12 to 18 months after surgery. On follow-up, the height and weight development of the patients was found to be normal. Conclusions Gradual progress was observed in all the patients that took part in the study, and all patients had positive results eventually.

Changes in Quantitative Ultrasound in Infants Born at Less than 32 Weeks’ Gestation Over the First 2 Years of Life: Influence of Clinical and Biochemical Changes

Studies in preterm infants show reduced speed of sound (SOS) as measured by quantitative ultrasound (QUS) during the immediate neonatal period. There is a scarcity of data on SOS changes following hospital discharge. The aim of this study was to assess SOS over the first 2 years in preterm infants. Infants were recruited from a neonatal follow-up clinic. Tibial QUS was performed using the Omnisense 7000P scanner. Thirty-nine infants born at <32 weeks' gestation had a single SOS measurement (median 3,203 m/second, range 2,609-3,495) which correlated with corrected gestational age (CGA) (r = 0.8, P < 0.005). The majority of measurements were within the manufacturer's reference range for term infants. SOS standard deviation score (SDS) in infants aged 0-6 months CGA demonstrated a negative correlation with duration of total parenteral nutrition (r = 0.7, P < 0.05) and a positive correlation with serum phosphate (r = 0.6, P < 0.05.) Two groups of infants had serial measurements: eight had measurements performed at term CGA and early infancy (early) and seven had measurements in later infancy (late). In the early group SOS SDS increased (P < 0.005), and the greatest increase in SOS over time occurred in infants with the lowest SOS at term (r = 0.9). In the late group there was no significant change over time. SOS SDS change did not show any correlation to weight SDS change. Catch-up in SOS occurs postterm in most infants by 6 months and is independent of postnatal growth. Infants with the lowest SOS at term have the fastest rate of catch-up. The opportunity for catch-up may be greatest in early infancy.

Comparative study between window and conventional enterostomies in preterm neonates with small bowel perforations

Objectives Small bowel perforations in the neonatal period can be secondary to necrotizing enterocolitis (NEC), ischemic necrosis, or occlusive anomalies of the small bowel; furthermore, they may be of no discernible cause. Depending on the clinical condition of the infant and the extent of the disease, a number of surgical options are available; one of which is exteriorization. To reduce the morbidity of stoma among patients, we adopted a technique called window enterostomy (WEnt). The objectives of this study were to describe the technique and to compare WEnt with conventional enterostomy (CEnt) in preterm infants undergoing surgery for focal NEC or isolated small bowel perforation (ISBP). Methods We reviewed all cases of NEC and ISBP between January 1996 and March 2006 from our institution. Patients with focal NEC or ISBP who required a surgical intervention were included and categorized into the WEnt and the CEnt groups. We collected multiple data as study variables: demographics; site of perforation; operative time; need for a second operation; postoperative morbidity; duration of total parenteral nutrition; and postoperative weight gain. Results Twenty-four neonates met the criteria for study inclusion. Of these, 14 underwent CEnt and 10 underwent WEnt. The median gestational age and birth weight of the neonates were 25.4 weeks (SD = 1.4) and 814.4 g (SD = 195.1), respectively. In comparing the 2 groups, we found statistically significant differences in the operative time for the primary and secondary procedures, duration of total parenteral nutrition, time to full oral feeding, and weekly postoperative weight gain. The rate of postoperative complications was higher among the infants from the CEnt group. Conclusion Our results suggest that WEnt is a quick and workable technique with minimal morbidity for preterm neonates with focal NEC or ISBP.

Adding Palifermin in Allogeneic and Autologous Stem Cell Transplantation Resulted in Reduced Oral Mucositis and Enhanced Intestinal Mucosal Recovery Measured by Citrulline Serum Levels.

Background: In this ongoing prospective open label study we evaluate the effect of Palifermin on the development of oral and intestinal mucositis in 25 patients undergoing allogeneic or autologous hematopoietic stem cell transplantation (allo/auto-HSCT).Methods: Twenty-five patients, transplanted for acute or chronic leukemia (n=20) and non-Hodgkin's lymphoma (NHL, n=5) received 60 μg Palifermin per kilogram of body weight per day for three consecutive days before the initiation of conditioning therapy and immediately after HSCT. The control group comprised 9 patients diagnosed with acute leukaemia (n=6) and NHL (n=3). In the Palifermin group the distribution between allo- and auto-HSCT was 16 and 9 compared to 5 and 4 in the control group. Conditioning therapy consisted of fractionated total-body irradiation/Cyclophosphamide in case of leukemia and chemotherapy only based regimens in NHL patients. Oral mucositis was graded daily according to World Health Organisation (WHO) criteria. The intestinal mucosal barrier damage was assessed by analyzing Citrulline serum levels on HSCT days -12, -6, 0, +7, +14 and +21.Results: No severe side effects were observed in our patient cohort. Our preliminary analysis demonstrates a significant decrease in the incidence of oral mucositis WHO grade 3 or 4 with 24 percent in the Palifermin group as opposed to 78 percent in the control group (p=0,013). The median duration of mucositis was 4,7 days (range 0–19) in the Palifermin group compared to 9,3 days (range 0–19) in controls (p=0,037). Whereas 17 evaluable patients in both groups showed a similar decline in Citrulline serum concentrations until day +7 - reflecting a maximal intestinal mucosal barrier injury at this timepoint - a significantly faster recovery of Citrulline levels (18,5 vs 13,8 μM, p=0,04) in Palifermin recipients at day +21 could be found. The use of opioid analgesics as determined by morphine equivalents (median 105mg vs 112mg) was almost equal. However, there was a trend in the duration of total parenteral nutrition (14 vs 18 days, p=ns) in favor of the Palifermin group. Acute graft versus host disease grade I-IV was observed in 29%, grade III-IV in 21% of Palifermin treated patients after an allo-HSCT.Conclusions: Palifermin was generally well tolerated and reduces the incidence and duration of WHO grade 3 and 4 oral mucositis. Further, it promotes a faster recovery of intestinal mucosal damage in allogeneic and autologous HSCT recipients.

Oxidative injury and hepatocyte apoptosis in total parenteral nutrition–associated liver dysfunction

Purpose The aim of this study was to investigate the impact of oxidative injury and apoptosis on total parenteral nutrition (TPN)–associated hepatic dysfunction. Methods Fifty-nine New Zealand rabbits (6-8 days old) were divided into 4 groups: 12 in the control group (maternal fed), 15 in the PN-3 group (TPN for 3 days), 14 in the PN-7 group (TPN for 7 days), and 18 in the PN-10 group (TPN for 10 days). At the end of the experiment, blood biochemistry analysis and histologic examination of the liver were performed; the malondialdehyde content of liver tissues was determined and hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase–mediated nick-end labeling assay. Results We found that the serum level of direct bilirubin became higher as PN duration was extended. The light microscopy features in the PN-3 and PN-7 groups included inflammatory cells infiltrated in portal areas and some degeneration changes, whereas in the PN-10 group, cholestasis (proliferation of bile ducts and bile pigments in hepatocytes) or diffuse steatosis was shown. Electron microscopic manifestation in PN groups included reduced numbers of microvilli and some preapoptosis changes. Both the malondialdehyde content and apoptosis index were the highest in the PN-10 group; there were more apoptotic hepatocytes in the groups with longer PN duration. Conclusions The longer the TPN duration, the more severe the liver injury. Both oxidative injury and apoptosis may play important roles in the mechanism of TPN-associated hepatic dysfunction.

Does gastroschisis reduction require general anesthesia?: A comparative analysis

Background Outcome after gastroschisis repair without general anesthesia is controversial, and published conclusions are variable with no comparative studies. Aim The aim of this study was to present a comparative study evaluating outcome after gastroschisis repair with and without general anesthesia. Methods An ambispective nonrandomized study of a cohort of 51 neonates born with gastroschisis between July 1998 and December 2003 was performed. Twenty-four neonates (group 1) had conventional reduction under general anesthesia, and 27 (group 2) cotside minimal intervention reductions were without general anesthesia. Results Groups were comparable regarding gestational age, birth weight, and quality of eviscerated bowel. Statistical significance ( P < .05) was seen between groups 1 and 2 with regard to age at reduction of gastroschisis (5.6 ± 2.5 vs 3 ± 1 hours) and time taken for completion of gastroschisis reduction (58.1 ± 15 vs 49 ± 14 minutes). No statistical significance ( P > .05) was seen with respect to start of feeds (10.4 ± 3.6 vs 10.9 ± 4.1 days), duration of total parenteral nutrition (21.5 ± 7.3 vs 22.4 ± 6.8 days), and total hospital (stay 29 ± 10 vs 30 ± 13 days). Admission to the intensive care unit was required in 92% in group 1 for 1 to 6 days vs 7% in group 2 for 3 to 6 days. There was 1 death in group 1 (4%). Total hospital cost in group 1 was £12,283 ± £2438 vs £6208 ± £2120 in group 2 ( P = .013). Conclusions Neonates with gastroschisis, whose bowel was reduced without general anesthesia, have similar outcomes to those whose bowel was reduced under general anesthesia. Both approaches appear to be safe and effective, but reduction without general anesthesia was cost-effective.

Longitudinal changes in bone health as assessed by the speed of sound in very low birth weight preterm infants

To assess longitudinal changes in speed of sound (SOS) in very low birth weight (VLBW) infants and investigate the relationship with markers of osteopathy of prematurity (OP) and clinical illness. Twenty-five infants were recruited. Eighteen infants, median gestation 27 weeks (range 24-32), median birth weight 957 g (range 625-1500 g), had serial scans. SOS was measured at both tibiae weekly until 35 to 37 weeks corrected gestational age (CGA). Initial median SOS standard deviation score (SDS) (Z) score was -0.07 (range-1.3-1.3). SOS correlated with gestation (r, 0.8, P<.005), and birth weight (r, 0.67, P<.005.) SOS fell from a median of 2923 m/s (2672-3107) at birth to 2802 m/s (2502-2991) at 35 to 37 weeks CGA (P<.05). This fall was greater in the 24- to 27-week gestation cohort with a median reduction of 2.2 SDS (1.6, 4.0) compared with 1.3 SDS (0.8-2.2) in those>28 weeks (P<.05). There was a negative correlation between SOS, at the end of the study, peak serum alkaline phosphatase (ALP) (r, 0.6, P<.05), CRIB (Clinical Risk Index for Babies)/CRIB II scores (both r, 0.6, P<.05), and duration of total parenteral nutrition (TPN) (r, 0.58, P<.05.) Although tibial SOS was within the expected range at birth, there was a subsequent failure to gain SOS, and this was most marked in infants of a lower gestation.

Intestinal Failure–Associated Liver Disease: What Do We Know Today?

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.

Total parenteral nutrition–associated hyperglycemia correlates with prolonged mechanical ventilation and hospital stay in septic infants

Purpose We studied the effects of total parenteral nutrition (TPN)–associated hyperglycemia on the clinical outcome in premature septic infants in the neonatal intensive care unit. Methods The charts of all premature infants weighing less than 1500 g upon admission to the neonatal intensive care unit between January 1, 2002, and December 31, 2002, with sepsis, ventilator dependence, and feeding intolerance were studied. Maximum serum glucose concentrations were compared with duration of TPN, mechanical ventilation, hospital length of stay, and survival using Pearson regression analysis and Student's t test. Results Thirty-seven patients met the search criteria. The average caloric intake for all infants at the time of blood culture–proven sepsis was 83 ± 19 kcal/kg per day. The maximum serum glucose concentration (milligrams per deciliter) after having positive blood cultures (sepsis) was positively correlated with the duration of TPN ( r = 0.45, P = .005), length of dependence on mechanical ventilation ( r = 0.45, P = .006), and hospital length of stay ( r = 0.36, P = .03). The average maximum serum glucose level was significantly higher in the nonsurviving infants (241 ± 46 vs 141 ± 48, P < .0001). Conclusion Hyperglycemia correlated with prolonged ventilator dependency and increased hospital length of stay in premature septic infants. Avoidance of excessive nutrient delivery and tight glycemic control during periods of acute metabolic stress may improve outcome in this patient population.

Hepatic Copper in Patients Receiving Long-term Total Parenteral Nutrition

To assess the possibility of iatrogenic hepatic copper overload in adult patients on long-term total parenteral nutrition (TPN). TPN predisposes to hepatic copper accumulation through disturbances of the enterohepatic bile acid pool, but iatrogenic copper overload through TPN solutions may occur as well. Quantitative hepatic copper and multiple clinical, biochemical, and histopathologic parameters were compared between patients with long-term TPN associated liver disease (n = 28) and patients with drug-induced cholestatic liver disease (n = 10). Eighty-nine percent of TPN patients and all controls had mildly elevated hepatic tissue copper, but 29% of TPN patients had levels above the diagnostic threshold for Wilson's disease. Quantitative hepatic copper correlated positively with serum aspartate aminotransferase (P = 0.001, r = 0.59), total bilirubin (P < 0.001, r = 0.65), and direct bilirubin (P < 0.001, r = 0.63) in TPN patients, but not in controls. The amount of hepatic copper did not correlate with the duration of TPN (median, 1.9 years; range, 0.3-18.0 years) or serum copper levels. TPN patients with significant cholestasis accumulated more copper than patients with no or only minimal cholestasis (P = 0.002). Significant hepatic copper overload in TPN patients occurs through chronic cholestasis in TPN-associated liver disease and is independent from the total duration of TPN. Iatrogenic copper overload through trace elements in TPN solutions does not seem to be a significant factor.

Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease

Purpose Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN. Methods A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree. Results Neonates (38 studied) required a mean (±SD) of 33 ± 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis ( P = .56), birth weight ( P = .54), gestational age ( P = .18), and duration of TPN ( P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 ± 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology. Conclusions Total parenteral nutrition–associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.