Role of fluid status markers as risk factors for suboptimal vancomycin concentration during continuous infusion in neonates: an observational study.

Vancomycin is widely used in neonatal sepsis but proportion of newborn reaching recommended concentration is variable. Fluid status impact on vancomycin level remains understudied. We aimed to study fluid factors impacting vancomycin concentration at 24 h of treatment. We performed a prospective and retrospective observational monocentric study of NICU patients requiring a vancomycin treatment. We used a continuous infusion protocol, with age-appropriate loading and maintenance doses. Vancomycin target serum concentration after 24 h (C24h) was above 20 mg/L. Demographic, infections, and organ failure variables were analyzed as potential predictors of C24h. Over the study period, 70 infective episodes in 52 patients were included. At treatment initiation, the median post-natal age was 12.5 days (IQR 7-23), post menstrual age 30 weeks (IQR 28-35), and median weight 1140 g (IQR 835-1722). Germs isolated were mainly gram-positive with 73.5% being coagulase-negative Staphylococci. Median C24h was 18.7 mg/L (IQR 15.4-22.4). Overall, 41 (58.6%) treatments had a C24h < 20 mg/L. After multivariate analysis, higher creatinine level (OR 1.03 (95% CI 1.002-1.06)) was associated with C24h ≥ 20 mg/L; weight gain the day before infection (OR 0.21 (95% CI 0.05-0.79)) and positive biomarkers of inflammation (OR 0.22 (0.05-0.94)) were associated with C24h < 20 mg/L. CONCLUSION: Vancomycin C24h was underdosed in 60% of patients and factors linked to changes in vancomycin pharmacokinetic such as volume of distribution and clearance, linked to creatinine level, inflammation, or weight gain, were identified. WHAT IS KNOWN: • Adjustment of vancomycin regimen remains difficult due to inter- and intra-individual variability of vancomycin pharmacokinetics. • Impact of fluid status on vancomycin concentration in critically ill neonates is incompletely studied. WHAT IS NEW: • Proportion of patients with adequate vancomycin concentration using a target adapted to nosocomial gram-positive bacteria MIC is low. • We confirmed the role of creatinine level and report two new factors associated with low vancomycin concentration: presence of systemic inflammation and weight gain.

[Can a simple lung ultrasound score predict length of ventilation for infants with severe acute viral bronchiolitis?] / Un score échographique pulmonaire simple peut-il prédire la durée de ventilation des nourrissons atteints de bronchiolite aiguë sévère ?

BACKGROUND: Lung ultrasound (LU) is a bedside point-of-care technique in critical care and emergency medicine. LU is quick and non-irradiating, and provides accurate diagnostic information when compared with chest radiographs. Specific LU signs have been described for bronchiolitis. This study aimed to evaluate the correlation between severity of LU-diagnosed lung lesions, using a quantitative LU score, and the length of non-invasive ventilation (LOV) for infants diagnosed with severe viral bronchiolitis. METHODS: This was a prospective observational single-center study conducted at a level 3 pediatric intensive care unit. A LU score was calculated for 47 infants under 6 months of age with severe acute viral bronchiolitis during the 2015-2016 epidemic, and the number of intercostal spaces with consolidation or interstitial syndrome was counted for each lung. The LU score is based on the presence of A lines or B-line artifacts and consolidation (0-2 points). The modified Wood score (mWCAS) was used to define clinical severity. Other parameters such as gestational age at birth, age, supplemental oxygen (LOS), and length of stay were recorded. All LU scans were later reviewed by two trained ultrasonographers to assess the score's inter-rater reproducibility. RESULTS: The LU score on admission (3.5±2.6) did not correlate with LOV (69±68.6), mWCAS score (4±1.6), LOS (3±3.4), or length of stay (4±3.4). However, there was a significant correlation between the number of affected intercostal spaces on the right and LOS (Spearman's Rho 0.318; P=0.037). CONCLUSION: This is the first study to evaluate the use of LU in infants needing PICU admission for severe acute bronchiolitis. The LU score does not correlate with LOV, mWCAS, LOS, or length of stay, but the number of pathological intercostal spaces on the right side correlates significantly with LOS. Although LU scores have been validated for the newborn and the adult, this has been in the setting of restrictive lung diseases. Bronchiolitis is a predominantly obstructive lung disease and this may explain the lack of performance observed.

Surfactant from neonatal to pediatric ICU: bench and bedside evidence.

Surfactant is a cornerstone of neonatal critical care for the treatment of respiratory distress syndrome of preterm babies. However, other indications have been studied for various clinical conditions both in term neonates and in children beyond neonatal age. A high degree of evidence is not yet available in some cases and this is due to the complex and not yet totally understood physiopathology of the different types of pediatric and neonatal lung injury. We here summarise the state of the art of the bench and bedside knowledge about surfactant use for the respiratory conditions usually cared for in neonatal and pediatric intensive care units. Future research direction will also be presented. On the whole, surfactant is able to improve oxygenation in infection related respiratory failure, pulmonary hemorrhage and meconium aspiration syndrome. Bronchoalveolar lavage with surfactant solution is currently the only means to reduce mortality or need for extracorporeal life support in neonates with meconium aspiration. While surfactant bolus or lavage only improves the oxygenation and ventilatory requirements in other types of postneonatal acute respiratory distress syndrome (ARDS), there seems to be a reduction in the mortality of small infants with RSV-related ARDS.

[Medical care of brain malformative vascular diseases discovered during the pre- or neonatal period]. / Prise en charge des malformations vasculaires cérébrales découvertes en période ante- ou néonatale.

Three types of brain arteriovenous vascular malformations can be found during the neonatal period, according to their anatomical location. Vein of Galen malformations are the most common. The others are pial arteriovenous malformations or dural arteriovenous malformations, which include dural sinus malformations. They can be asymptomatic, but most often they are associated with different symptoms, related to their angioarchitecture or their effect on the brain. High-flow arteriovenous malformations can thus be responsible for heart failure. Local or regional venous hyperpressure exposes the patient to subacute or chronic brain lesions, or to hydrovenous disorders such as hydrocephalus. Some types of venous reflux can expose patients to brain hemorrhage. The treatment chosen for these vascular malformations and their consequences is transarterial or transvenous embolization, depending on the angioarchitecture and type of lesion. The schedule for the treatment will be determined according to the malformation type and its local or general effects on the brain. The aim of this article is to present the recommendations of the French National Referral Center for neurovascular malformations in children, in order to help clinicians and radiologists treat these patients during pre- or neonatal period.

Increase of fungal endocarditis in children.

BACKGROUND: Infective endocarditis (IE) is a rare and feared infection that mainly occurs in patients with underlying cardiac disease or altered function of the immune system. Recent epidemiological data on both sepsis and nosocomial infections indicate a rise in gram-negative bacterial and fungal infection, particularly in patients requiring critical care support. This study sought to characterize the change in the spectrum of IE encountered in a single pediatric tertiary care center during the last 18 years, to evaluate emergence of fungal IE and to identify contributing factors. PATIENTS AND METHODS: Review of all cases of IE diagnosed between January 1986 and August 2003 at a single university children's hospital. Patients were distributed between two equal time periods and compared according to the era of IE diagnosis. RESULTS: In 43 patients, 44 episodes of IE were identified with most cases occurring in children with congenital or acquired heart disease. The annual number of diagnosed cases fluctuated during the study (mean 2.4 cases/year). Blood or specimen cultures were positive in 34 cases (77%) with gram-positive organisms most frequently observed (n=20, 44.4%). Fungal IE cases (n=9, 20%) occurred preferentially during the second period (p<0.03), and were more common in children with noncardiac diseases (p=0.023). Factors associated with fungal IE were the use of broad-spectrum antibiotics (p<0.001) and the presence of an infected central venous catheter (p=0.01). Overall mortality did not differ between the two eras. CONCLUSION: The incidence of fungal IE seems to have significantly increased in more recent years. Use of broadspectrum antibiotics for prolonged time or/and central venous catheters were identified as predisposing factors to fungal infective endocarditis.

Fulminant liver failure in a child with invasive group A streptococcal infection.

UNLABELLED: Liver involvement is mentioned in streptococcal toxic shock syndrome, but never as fulminant liver failure (FLF). We report the case of a 2-year-old child who developed isolated FLF secondary to invasive group A streptococcal infection without shock due to a M1T1-type strain expressing speA, speB and speC toxin genes. On antibiotics, he recovered rapidly without liver transplantation. CONCLUSION: A streptococcal pyrogenic exotoxin likely constituted the initial insult leading to FLF. This etiology can be included in the differential diagnosis of FLF and would support early introduction of antibiotics.

Postshunt encephalopathy in liver transplanted children with portal vein thrombosis.

BACKGROUND: Surgical portosystemic shunting has been reported to alleviate successfully portal hypertension in liver transplanted recipients with portal vein thrombosis. METHODS: We report two liver transplanted children with portal vein thrombosis who developed post-shunt acute encephalopathy. In one child, a mesocaval H-type shunt was created surgically because of bleeding related to Roux-en-Y loop varices at 3 months posttransplantation; in the other, a large spontaneous splenorenal shunt was discovered at the time of diagnosis of portal vein thrombosis on day 34 posttransplantation and was preserved. RESULTS: Post-shunt encephalopathy developed 6 months and 2.7 years after transplantation, causing death in one child. CONCLUSIONS: This report illustrates the risk and the possible dismal outcome of post-shunt encephalopathy in liver transplanted children. Therapeutic procedures other than portosystemic shunting that will restore an hepatopetal portal flow to the liver graft should be considered in liver-transplanted children with portal vein thrombosis.

Bioresorbable microspheres by spinning disk atomization as injectable cell carrier: from preparation to in vitro evaluation.

Vesico-ureteral reflux, a common pathology in children, can be treated cystoscopically by injection of a bulking material underneath the most distal, intramural ureter, which forces the latter to do a detour, increasing its submucosal path. This increase of the length of the submucosal path of the ureter within the bladder is directly responsible for the anti-reflux effect. So far Teflon and collagen paste have been commonly used as bulking materials. We suggest replacing these materials by living tissue consisting of bladder smooth muscle, normally present at this location. The aim of this work is to provide a long-term effective treatment by producing bioresorbable microspheres which can act as a support matrix and an entrapment substance for bladder smooth muscle cells, with the goal of an in vivo transfer of the in vitro cultured cells with a minimal surgical procedure. By the use of Spinning Disk Atomization, which has specifically been developed for this purpose, we have shown two methods for the preparation of porous poly(lactic acid) microspheres with tunable sizes from 160 to 320 microm. The controlled solvent burst method has shown the advantage over the crystal leaching method in the direct creation of microspheres with large closed pores, by atomizing the polymer solution in controlled temperature conditions. Microspheres with various closed pore structures have thus been prepared. The innovation of this work is in the direct and rapid formation of porous microspheres with a pore morphology which is designed to create cavities suitable for adherence and growth of cells by adapting the temperature conditions of atomization. Injection tests have shown promising results in using these cell-loaded microspheres for future non-invasive tissue engineering.

Acute pancreatitis after orthotopic liver transplantation in children: incidence, contributing factors, and outcome.

BACKGROUND: Acute pancreatitis after orthotopic liver transplantation is a well-known complication in adults that has never been described in children. In adults, end-stage liver disease related to hepatitis B, intraoperative pancreatic injury caused by extensive peripancreatic dissection, the type of biliary anastomosis performed, and numerous drugs, have all been described as predisposing factors in acute pancreatitis after liver transplantation. The current retrospective review was undertaken to identify the incidence, the contributing factors, and the outcome of acute pancreatitis after liver transplantation in children. METHODS: During a 10-year period, 375 children underwent 434 liver transplantations in the authors' institution. In seven patients (1.9%), clinical acute pancreatitis developed after orthotopic liver transplantation. Indication for initial liver transplantation was biliary atresia (n = 3), acute liver failure (n = 3), and type 1 Crigler-Najjar syndrome. In all seven patients, liver graft function was initially adequate. The diagnosis of acute pancreatitis was based on clinical, biochemical, ultrasonographic, and surgical signs. RESULTS: In six patients, acute pancreatitis appeared within the first week after transplantation. The diagnosis was confirmed by abdominal laparotomy in five children. In the current series, emergency liver transplantation (p < 0.001), retransplantations (p < 0.001), and infectious peritonitis (p < 0.001) were contributing factors. Despite supportive measures, three patients died (43%) because of multiple organ dysfunction syndrome. CONCLUSIONS: Acute pancreatitis is an uncommon but life-threatening complication after liver transplantation in children. Early diagnosis and aggressive treatment of infectious complications are major elements in the management of acute pancreatitis after liver transplantation.