The Effect of Glutamine Supplementation on Microbial Invasion in Surgical Infants Requiring Parenteral Nutrition: Results of a Randomized Controlled Trial.

BACKGROUND: To determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN). METHODS: An prospective double-blind randomized controlled trial studying surgical infants receiving PN for at least 5 days for congenital or acquired intestinal anomalies (2009-2012) was used. Infants were randomized to receive either glutamine supplementation (parenteral plus enteral; total 400 mg/kg/d) or isonitrogenous control. The primary end point was microbial invasion evaluated after 5 days of supplementation and defined as: (i) positive conventional blood culture, (ii) evidence of microbial DNA in blood (polymerase chain reaction), (iii) plasma endotoxin level ≥50 pg/mL, or (iv) plasma level of lipopolysaccharide binding protein ≥50 ng/mL. Data are given as median (range) and compared by logistic regression. RESULTS: Sixty infants were randomized and reached the primary end point. Twenty-five patients had intestinal obstruction, 19 had abdominal wall defects, and 13 had necrotizing enterocolitis. Thirty-six infants showed evidence of microbial invasion during the study, and 17 of these were not detected by conventional blood culture. There was no significant difference between the 2 groups in the primary outcome; evidence of microbial invasion after 5 days was found in 9/31 (control group) and 8/29 (glutamine group) (odds ratio 0.83 [0.24-2.86; P = 0.77]). CONCLUSION: More than half of surgical infants requiring PN showed evidence of microbial invasion. Approximately half of this was not detectable by conventional blood cultures. Parenteral plus enteral glutamine supplementation had no effect on incidence of microbial invasion.

Hypercapnia and acidosis during open and thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized controlled trial.

OBJECTIVE: We aimed to evaluate the effect of thoracoscopy in neonates on intraoperative arterial blood gases, compared with open surgery. BACKGROUND: Congenital diaphragmatic hernia (CDH) and esophageal atresia with tracheoesophageal fistula (EA/TEF) can be repaired thoracoscopically, but this may cause hypercapnia and acidosis, which are potentially harmful. METHODS: This was a pilot randomized controlled trial. The target number of 20 neonates (weight > 1.6 kg) were randomized to either open (5 CDH, 5 EA/TEF) or thoracoscopic (5 CDH, 5 EA/TEF) repair. Arterial blood gases were measured every 30 minutes intraoperatively, and compared by multilevel modeling, presented as mean and difference (95% confidence interval) from these predictions. RESULTS: Overall, the intraoperative PaCO2 was 61 mm Hg in open and 83 mm Hg [difference 22 mm Hg (2 to 42); P = 0.036] in thoracoscopy and the pH was 7.24 in open and 7.13 [difference -0.11 (-0.20 to -0.01); P = 0.025] in thoracoscopy. The duration of hypercapnia and acidosis was longer in thoracoscopy compared with that in open. For patients with CDH, thoracoscopy was associated with a significant increase in intraoperative hypercapnia [open 68 mm Hg; thoracoscopy 96 mm Hg; difference 28 mm Hg (8 to 48); P = 0.008] and severe acidosis [open 7.21; thoracoscopy 7.08; difference -0.13 (-0.24 to -0.02); P = 0.018]. No significant difference in PaCO2, pH, or PaO2 was observed in patients undergoing thoracoscopic repair of EA/TEF. CONCLUSIONS: This pilot randomized controlled trial shows that thoracoscopic repair of CDH is associated with prolonged and severe intraoperative hypercapnia and acidosis, compared with open surgery. These findings do not support the use of thoracoscopy with CO2 insufflation and conventional ventilation for the repair of CDH, calling into question the safety of this practice. The effect of thoracoscopy on blood gases during repair of EA/TEF in neonates requires further evaluation. (ClinicalTrials.gov Identifier: NCT01467245).

Recurrence rate of Morgagni diaphragmatic hernia following laparoscopic repair.

PURPOSE: Morgagni diaphragmatic hernia can be repaired laparoscopically. The aim of this study is to evaluate the outcome of this minimally invasive approach. METHODS: A retrospective review was conducted on all consecutive children who underwent repair of Morgagni hernia from January 2002 to December 2011 in our hospital. Data are expressed as median (range). RESULTS: There were 12 children with Morgagni hernia. Age at surgery was 7.5 months (2-125). Associated malformations were present in 7 children (58 %). All children underwent initial laparoscopic approach. Two children (16 %) underwent conversion to open surgery. The hernia was closed primarily in 11 children (92 %), using a polyester patch in 1 (8 %). There were no intraoperative or immediate postoperative complications. Five children (42 %), all repaired initially without a patch, had a recurrence of the Morgagni hernia. The repair of the recurrent hernia was performed laparoscopically in four out of the five children, and a patch was used in two patients with no further recurrences or complications. CONCLUSIONS: There is a high rate of recurrence after laparoscopic Morgagni hernia repair. This is exclusively associated with laparoscopic repair without patch, and it is in contrast with the low recurrence rate reported previously. More frequent use of patch may be beneficial.

Trends in the treatment and outcome of congenital diaphragmatic hernia over the last decade.

PURPOSE: Congenital diaphragmatic hernia (CDH) remains a challenging and life-threatening congenital anomaly. The aim was to evaluate whether treatment and survival has changed during the last decade. METHODS: We retrospectively analysed all consecutive infants with CDH referred to two European tertiary paediatric surgical centres over 11 years (January 1999 to December 2009). Minimum follow-up was 1 year. χ(2) test for trend was used to evaluate significance. RESULTS: There were 234 infants. There was no significant variation over time in the proportion of infants receiving high frequency oscillatory ventilation (HFOV) (p = 0.89), inhaled nitric oxide (iNO) (p = 0.90) or extracorporeal membrane oxygenation (ECMO) (p = 0.22). 205 infants (88 %) were stabilised and underwent surgical repair; of these, 186 (79 %) survived after surgery. Over time there was a significant increase in the proportion of infants undergoing surgical repair (p = 0.018) without a concomitant significant improvement in survival (p = 0.099). CONCLUSION: This multicentre analysis indicates that the survival rate of infants with CDH referred to two European paediatric surgical centres is high (79 %). The use of HFOV, iNO and ECMO has not changed in recent years. We observed a significant increase in the proportion of infants who undergo surgery but this has not resulted in a significant increase in the overall survival rate.

Intestinal failure-associated liver disease in surgical infants requiring long-term parenteral nutrition.

PURPOSE: Our aim was to determine incidence, severity, and outcome, as well as predisposing factors and underlying diagnoses, of intestinal failure-associated liver disease (IFALD) in surgical infants requiring long-term parenteral nutrition (PN). METHODS: We retrospectively studied surgical infants receiving PN for at least 28 days for congenital or acquired intestinal anomalies over a 5-year period (January 2006 to December 2010). Intestinal failure-associated liver disease was defined as type 1 (early)--persistent elevation of alkaline phosphatase for 6 weeks or longer; type 2 (established)--additional elevated total bilirubin (≥ 50 µmol/L); and type 3 (late)--additional clinical signs of end-stage liver disease. RESULTS: Eighty-seven infants required PN for at least 28 days. Intestinal failure-associated liver disease occurred in 29 infants (33%). Intestinal failure-associated liver disease was managed medically in all but 2 patients who underwent intestinal elongation. None were referred for intestinal or liver transplant. Intestinal failure-associated liver disease has been reversed in 17 (59%) of cases to date. Sixty-one children receiving long-term PN (70%) have achieved enteral autonomy, whereas 12 (14%) require home PN. Severity of IFALD was significantly associated with duration of PN and female sex. CONCLUSION: Intestinal failure-associated liver disease remains a fairly common but rarely life-threatening complication of intestinal failure in surgical infants. Intestinal failure-associated liver disease can be reversed in more than half of these children, and enteral autonomy was achieved in more than two thirds, even with minimal use of intestinal elongation. This is the first study to demonstrate an association between the severity of IFALD in surgical infants and female sex.

Chlorhexidine antisepsis significantly reduces the incidence of sepsis and septicemia during parenteral nutrition in surgical infants.

BACKGROUND/PURPOSE: After a change in national policy, central venous catheter (CVC) antisepsis with chlorhexidine was introduced in our hospital. Our aim was to evaluate whether this change reduced the rate of infection seen during parenteral nutrition (PN) in infants requiring gastrointestinal surgery. METHODS: Two groups of consecutive infants were compared: control, 98 infants who had CVC antisepsis with 70% isopropanol alone, and chlorhexidine, 112 infants who had CVC antisepsis with 2% chlorhexidine in 70% isopropanol. Incidence rates of sepsis (blood cultures taken) and septicemia (blood cultures positive) were compared by Poisson regression. RESULTS: Seventy-one percent of infants experienced clinically suspected sepsis. The incidence of septicemia was 32%. The incidence rate ratio for sepsis was 0.72 (95% confidence interval, 0.61-0.84) for the chlorhexidine group vs control (P < .0005). The incidence rate ratio for septicemia was 0.49 (95% confidence interval, 0.36-0.67; P < .0005); that is, over a given period of PN, patients had half the rate of positive blood cultures after the introduction of chlorhexidine antisepsis compared with before. CONCLUSION: (1) The incidence of sepsis and septicemia among surgical infants on PN for gastrointestinal anomalies is high. (2) Chlorhexidine CVC antisepsis has significantly reduced this incidence, and we advocate its use in this group of patients.

Brain lipid-binding protein: a marker of differentiation in neuroblastic tumors.

PURPOSE: Neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN) are neuroblastic tumours (NT) of sympathetic nervous system origin. Brain lipid-binding protein (BLBP) has potential morphogenic activity during nervous system development but has not been studied in these tumours. We analyzed the expression of BLBP in NT according to histological subtypes and extent of differentiation. METHODS: Thirty cases of NT (10 each of NB, intermixed GNB, and GN) were identified from the histopathology archive of a single center. Tissue sections were obtained from representative paraffin blocks and immunohistochemistry for BLBP performed. RESULTS: Brain lipid-binding protein was not expressed in any NB case. In all cases of GN, BLBP was strongly expressed in the cytoplasm of mature ganglion cells but negative in Schwannian stroma. In the intermixed GNB, there was similar strong BLBP immunoreactivity in the cytoplasm of fully differentiated and differentiating ganglion cells but no BLBP expression in immature neuroblasts. CONCLUSION: Brain lipid-binding protein is strongly expressed in mature and maturing ganglion cells in NT (GN and GNB), whereas it is absent in poorly differentiated neuroblasts of GNB and NB. Cytoplasmic expression of BLBP in NT increases as the cells undergo neural differentiation and is therefore associated with the extent of tumour differentiation and favorable histology.

Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) and esophageal atresia with tracheoesophageal fistula (EA/TOF) can be repaired thoracoscopically, but this may cause hypercapnia, acidosis, and reduced cerebral oxygenation. We evaluated the effect of thoracoscopy in infants on cerebral oxygen saturation (cSO(2)), arterial blood gases, and carbon dioxide (CO(2)) absorption. METHODS: Eight infants underwent thoracoscopy (6 CDH and 2 EA/TOF). Serial arterial blood gases were taken. Regional cSO(2) was measured using near-infrared spectroscopy. Absorption of insufflated CO(2) was calculated from exhaled (13)CO(2)/(12)CO(2) ratio measured by mass spectrometry. RESULTS: CO(2) absorption increased during thoracoscopy with a maximum 29% ± 6% of exhaled CO(2) originating from the pneumothorax. Paco(2) increased from 9.4 ± 1.3 kPa at the start to 12.4 ± 1.0 intraoperatively and then decreased to 7.6 ± 1.2 kPa at end of operation. Arterial pH decreased from 7.19 ± 0.04 at the start to 7.05 ± 0.04 intraoperatively and then recovered to 7.28 ± 0.06 at end of operation. Cerebral hemoglobin oxygen saturation decreased from 87% ± 4% at the start to 75% ± 5% at end of operation. This had not recovered by 12 (74% ± 4%) or 24 hours (73% ± 3%) postoperatively. CONCLUSIONS: This preliminary study suggests that thoracoscopic repair of CDH and EA/TOF may be associated with acidosis and decreased cSO(2). The effects of these phenomena on future brain development are unknown.

Efficacy of video-assisted thoracoscopic surgery in managing childhood empyema: a large single-centre study.

BACKGROUND/PURPOSE: A randomised controlled trial evaluating the role of video-assisted thoracoscopic surgery (VATS) in childhood empyema reported a failure rate of 16.6%. Our aim is to determine the outcome of VATS in a large series of children managed by 3 paediatric surgeons experienced in endoscopic surgery. METHOD: A retrospective study of all children with empyema admitted under the care of the 3 surgeons between February 2004 and February 2008 was undertaken. Recorded details included demographic data, mode of presentation, preoperative investigations, operative details, antibiotic usage, microbiological data, postoperative course, follow-up data and complications. RESULTS: 114 children (69 boys, 45 girls) had VATS for empyema. Their median age was 5 (0.2-15) years. The pleural cavity was drained for a median of 4 (2-13) days. Median postoperative hospital stay was 7 (4-36) days. Median follow-up was 8 (1-24) months. There were 8 (7%) treatment failures: 5 conversions to thoracotomy and 3 recurrent empyemas. There were 7 complications (6%): air leak (n = 6) and lung injury (n = 1). 104 (91%) children had full resolution of symptoms. There were no deaths. CONCLUSION: Video-assisted thoracoscopic surgery has a better outcome in childhood empyema than reported in a recent randomised trial and it has an important role in the management of this condition.

Carbon dioxide absorption and elimination in breath during minimally invasive surgery.

Carbon dioxide (CO(2)) is the gas most commonly used to inflate the body cavities during 'keyhole' surgery (e.g. laparoscopy and thoracoscopy). However, CO(2) can be absorbed, leading to increased arterial CO(2) and increased CO(2) elimination from the lungs. These increases in CO(2) are observed following a wide variety of procedures both in adults and in infants and children. Although it is usually assumed that increases in arterial or end-tidal CO(2) directly reflect absorption of CO(2) from body cavities, this is not necessarily true, as either increases in metabolically produced CO(2) or respiratory compromise making it more difficult to eliminate CO(2) could also be responsible for these changes. Recently, a new technique has been introduced which enables absorbed CO(2) to be distinguished from metabolic CO(2).

Influence of endogenous nitric oxide on sympathetic vasoconstriction in normoxia, acute and chronic systemic hypoxia in the rat.

We studied the role of nitric oxide (NO) in blunting sympathetically evoked muscle vasoconstriction during acute and chronic systemic hypoxia. Experiments were performed on anaesthetized normoxic (N) and chronically hypoxic (CH) rats that had been acclimated to 12% O(2) for 3-4 weeks. The lumbar sympathetic chain was stimulated for 1 min with bursts at 20 or 40 Hz and continuously at 2 Hz. In N rats, acute hypoxia (breathing 8% O(2)) reduced baseline femoral vascular resistance (FVR) and depressed increases in FVR evoked by all three patterns of stimulation, but infusion of the NO donor sodium nitroprusside (SNP), so as to similarly reduce baseline FVR, did not affect sympathetically evoked responses. Blockade of NO synthase (NOS) with L-NAME increased baseline FVR and facilitated the sympathetically evoked increases in FVR, but when baseline FVR was restored by SNP infusion, these evoked responses were restored. Acute hypoxia after L-NAME still reduced baseline FVR and depressed evoked responses. In CH rats breathing 12% O(2), baseline FVR was lower than in N rats breathing air, but L-NAME had qualitatively similar effects on baseline FVR and sympathetically evoked increases in FVR. SNP similarly restored baseline FVR and evoked responses. Inhibition of neuronal NOS or inducible NOS did not affect baselines, or evoked responses. We propose that in N and CH rats sympathetically evoked muscle vasoconstriction is modulated by tonically released NO, but not depressed by additional NO released on sympathetic activation. The present results suggest that hypoxia-induced blunting of sympathetic vasoconstriction in skeletal muscle is not mediated by NO.

The assessment of fatigue in primary Sjögren's syndrome.

OBJECTIVE: Disabling fatigue is a prominent feature of primary Sjögren's syndrome (PSS). We evaluated a number of questionnaires for their ability to discriminate fatigue in PSS from that in other rheumatic disorders and healthy controls. METHODS: 33 female caucasian patients with PSS, 45 with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 30 controls completed self-administered questionnaires including; Visual Analogue Scales (VAS), the Chalder Fatigue Scale (CFS), the Nottingham Health Profile (NHP) and the Medical Outcomes Short Form 36 Questionnaire (SF-36). RESULTS: All patient groups scored significantly worse than controls on the 'Energy' dimension of the NHP, the fatigue VAS and the 'Vitality' domain of the SF-36. No significant differences were observed between PSS patients and controls using the CFS. CONCLUSIONS: The NHP. VAS and SF-36 are useful in identifying fatigue in these rheumatic disorders. Further work is required to identify the characteristic features of fatigue in these conditions.