High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study.

PURPOSE: Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible. METHODS: We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year. RESULTS: 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group. CONCLUSION: It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic. TRIAL REGISTRATION NUMBER: NCT02219165.

Predictive Value of Optic Nerve Sheath Diameter for Diagnosis of Intracranial Hypertension in Children With Severe Brain Injury.

Background and Aims: Intracranial Hypertension (ICH) is a life-threatening complication of brain injury. The invasive measurement of intracranial pressure (ICP) remains the gold standard to diagnose ICH. Measurement of Optic Nerve Sheath Diameter (ONSD) using ultrasonography is a non-invasive method for detecting ICH. However, data on paediatric brain injury are scarce. The aim of the study was to determine the performance of the initial ONSD measurement to predict ICH occurring in children with severe brain injury and to describe the ONSD values in a control group. Methods: In this cross-sectional study, ONSD was measured in children aged 2 months-17 years old with invasive ICP monitoring: before placement of ICP probe and within the 60 min after, and then daily during 3 days. ONSD was also measured in a control group. Results: Ninety-nine patients were included, of whom 97 were analysed, with a median (IQR) age of 8.7 [2.3-13.6] years. The median (IQR) PIM 2 score was 6.6 [4.4-9.7] and the median (IQR) PELOD score was 21 [12-22]. Aetiologies of brain injury were trauma (n = 72), infection (n = 17) and stroke (n = 8). ICH occurred in 65 children. The median (IQR) ONSD was 5.58 mm [5.05-5.85]. ONSD performed poorly when it came to predicting ICH occurrence within the first 24 h (area under the curve, 0.58). There was no significant difference between the ONSD of children who presented with ICH within the first 24 h and the other children, with a median (IQR) of 5.6 mm [5.1-5.9] and 5.4 mm [4.9-5.8], respectively. Infants aged less than 2 years had a median (IQR) ONSD of 4.9 mm [4.5-5.2], significantly different from children aged more than 2 years, whose median ONSD was 5.6 mm [5.2-5.9]. Age, aetiology or ICP levels did not change the results. Thirty-one controls were included, with a median age of 3.7 (1.2-8.8) years. The median (IQR) of their ONSD measurement was 4.5 mm [4.1-4.8], significantly lower than the patient group. Conclusion: In a paediatric severe brain injury population, ONSD measurement could not predict the 24 h occurrence of ICH. Severity of patients, timing and conditions of measurements may possibly explain these results.

Decreased Human Leukocyte Antigen DR on Circulating Monocytes Expression After Severe Pediatric Trauma: An Exploratory Report.

OBJECTIVES: Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes. DESIGN: Prospective observational study. SETTING: PICU and trauma unit at a tertiary-care university hospital in South Africa. PATIENTS: Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02). CONCLUSIONS: Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes.

Nutritional Status Deterioration Occurs Frequently During Children's ICU Stay.

OBJECTIVES: Malnutrition and faltering growth at PICU admission have been related to suboptimal outcomes. However, little is known about nutritional status deterioration during PICU stay, as critical illness is characterized by a profound and complex metabolism shift, which affects energy requirements and protein turnover. We aim to describe faltering growth occurrence during PICU stay. DESIGN: Single-center prospective observational study. SETTING: Twenty-three-bed general PICU, Lyon, France. PATIENTS: All critically ill children 0-18 years old with length of stay longer than 5 days were included (September 2013-December 2015). INTERVENTIONS: Weight and height/length were measured at admission, and weight was monitored during PICU stay, in order to calculate body mass index for age z score. Faltering growth was defined as body mass index z score decline over PICU stay. Children admitted during the first year of the study and who presented with faltering growth were followed after PICU discharge for 3 months. MEASUREMENTS AND MAIN RESULTS: We analyzed 579 admissions. Of them, 10.2% presented a body mass index z score decline greater than 1 SD and 27.8% greater than 0.5. Admission severity risk scores and prolonged PICU stay accounted for 4% of the variability in nutritional status deterioration. Follow-up of post-PICU discharge nutritional status showed recovery within 3 months in most patients. CONCLUSIONS: Nutritional deterioration is frequent and often intense in critically ill children with length of stay greater than 5 days. Future research should focus on how targeted nutritional therapies can minimize PICU faltering growth and improve post-PICU rehabilitation.

Faltering growth in the critically ill child: prevalence, risk factors, and impaired outcome.

Low body mass index (BMI) z score is commonly used to define undernutrition, but faltering growth allows for a complementary dynamic assessment of nutritional status. We studied the prevalence of undernutrition and faltering growth at admission in the pediatric intensive care (PICU) setting and their impacts on outcome. All (685) consecutive children (aged 0 to 18 years old) admitted in a single-center PICU over a 1-year period were prospectively enrolled. Nutritional status assessment was based on anthropometric measurements performed at admission and collected from medical files. Undernutrition was considered when z score BMI for age was < - 2SD. Faltering growth was considered when the weight for age curve presented a deceleration of > - 1 z score in the previous 3 months. Undernutrition was diagnosed in 13% of children enrolled, and faltering growth in 13.7% mostly in children with a normal BMI. Faltering growth was significantly associated with a history of underlying chronic disease, and independently with extended length of PICU stay in a multivariate analysis. CONCLUSION: Assessment of nutritional status in critically ill children should include both undernutrition and faltering growth. This study highlights that faltering growth is independently associated with suboptimal outcome in PICU. What is Known: • Malnutrition, defined according to BMI-for-age z score, is correlated with poor outcome in the critically ill child. • In this setting, nutritional assessment should consist not only of a static assessment based on BMI-for-age z score but also of a dynamic assessment to identify recent faltering growth. What is New: • Critically ill children frequently present with faltering growth at admission. • Faltering growth is a newly identified independent associated factor of suboptimal outcome in this setting (extended length of stay).

Different treatment benefits were estimated by clinical trials performed in adults compared with those performed in children.

OBJECTIVE: Our main objective was to see whether the therapeutic benefit observed in placebo controlled randomized controlled trials (RCTs) is different between adults and children. STUDY DESIGN AND SETTING: We searched three electronic databases for meta-analyses that included double-blind, placebo-controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs). RESULTS: We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect for 13 drugs, indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations. CONCLUSION: We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 of 124 drugs. Data on dose adjustment and child age groups from RCTs were not adequately reported to investigate their influence on the treatment benefit dissimilarities.

Neurally adjusted ventilator assist (NAVA) reduces asynchrony during non-invasive ventilation for severe bronchiolitis.

BACKGROUND: To determine the prevalence of main inspiratory asynchrony events during non-invasive intermittent positive-pressure ventilation (NIV) for severe bronchiolitis. Ventilator response time and asynchrony were compared in neurally adjusted ventilator assist (NAVA) and in pressure assist/control (PAC) modes. METHODS: This prospective physiological study was performed in a university hospital's paediatric intensive care unit and included 11 children (aged 35.2 ± 23 days) with respiratory syncytial virus bronchiolitis with failure of nCPAP. Patients received NIV for 2 hr in PAC mode followed by 2 hr in NAVA mode. Electrical activity of the diaphragm and pressure curves were recorded for 10 min. Trigger delay, main asynchronies (auto-triggering, double triggering, or non-triggered breaths) were analyzed, and the asynchrony index was calculated for each period. RESULTS: The asynchrony index was lower during NAVA than during PAC (3 ± 3% vs. 38 ± 21%, P < 0.0001), and the trigger delay was shorter (43.9 ± 7.2 vs. 116.0 ± 38.9 ms, P < 0.0001). Ineffective efforts were significantly less frequent in NAVA mode (0.54 ± 1.5 vs. 21.8 ± 16.5 events/min, P = 0.01). Patient respiratory rates were similar, but the ventilator rate was higher in NAVA than in PAC mode (59.5 ± 17.9 vs. 49.8 ± 8.5/min, P = 0.03). The TcPCO2 baselines values (64 ± 12 mmHg vs. 62 ± 9 mmHg during NAVA, P = 0.30) were the same and their evolution over the 2 hr study period (-6 ± 10 mmHg vs. -12 ± 17 mmHg during NAVA, P = 0.36) did not differ. CONCLUSION: Patient-ventilator inspiratory asynchronies and trigger delay were dramatically lower in NAVA mode than in PAC mode during NIV in infants with severe bronchiolitis.

Effect of molecular adsorbents recirculating system treatment in children with acute liver failure caused by Wilson disease.

OBJECTIVES: Because fulminant Wilson disease (WD) has an extremely poor prognosis, the use of liver support that can bridge patients to liver transplantation is lifesaving. We report the experience of albumin dialysis in acute liver failure (ALF) caused by WD in children. METHODS: Chart review of children admitted for ALF secondary to acute WD and treated by the molecular adsorbents and recirculating system. Measures of copper level in blood and within the circuit during molecular adsorbents recirculating system (MARS) sessions were performed. Clinical and biological assessments after MARS session were reported. RESULTS: Four children, with a median age of 12.3 years, were treated from 2004 to 2009 for a severe ALF associated with acute renal failure, haemolysis, and severe cholestasis. All of the children had a new Wilson index >12. A total of 14 MARS sessions were performed, for a median duration of 7.5 hours. Tolerance was good, except for 1 child who experienced haemorrhage because of vascular injury following insertion of the dialysis catheter. A neurological improvement or stabilisation was noted in all of the children along with an improvement in the Fisher index and ammonia level after MARS treatment. MARS was able to remove copper, to decrease the serum copper level of 28% in mean, and to decrease the bilirubin and creatinin levels >25%. All of the children were subsequently underwent liver transplants with a good outcome without disability. CONCLUSIONS: MARS is able to remove copper and to stabilise children with ALF secondary to WD, allowing bridging to LT.

Multifaceted intervention to enhance the screening and care of hospitalised malnourished children: study protocol for the PREDIRE cluster randomized controlled trial.

BACKGROUND: Hospital malnutrition is an underestimated problem and as many as half of malnourished patients do not receive appropriate treatment. In order to extend the management of malnutrition in health care facilities, multidisciplinary teams focusing on clinical nutrition were established in France. The establishment of such teams within hospital facilities remains nonetheless difficult. We have consequently developed a multifaceted intervention coordinated by a Nutritional Support Team (NST). Our study aims to evaluate the impact of this multifaceted intervention coordinated by a NST, in adherence to recommended practices for the care of malnourished children, among health care workers of a paediatric university hospital. METHODS/DESIGN: We carried out 1) a six-month observational phase focusing on the medical care procedures relative to malnourished children followed by 2) a cluster randomised controlled trial phase to evaluate the impact of a multidisciplinary nutrition team over an 18 month time frame.Based on power analyses and assuming a conservative intracluster correlation coefficient, 1289 children were needed to detect a 25% difference in rates between the two groups of the cluster trial.The implementation of our intervention was coordinated by the NST and had three major components: a) access to a computerised malnutrition screening system associated with an automatic alert system, b) an awareness campaign directed toward the health care workers and c) a leadership based strategy.Main outcomes included the number of daily weighings during hospitalisation, the investigation of malnutrition etiology and the management of malnutrition by a dietician and/or the NST.Due to the clustered nature of the data with children nested in departments, a generalized estimated equations approach will be used to analyse the impact of the multifaceted intervention on primary and secondary outcomes. DISCUSSION: Our results will provide an overall response regarding the effectiveness of our multifaceted intervention and we should be able to suggest an organization and mode of operation of NST. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01081587.

[Pediatric nutrition: Severe deficiency complications by using vegetable beverages, four cases report]. / Complications carentielles suite à l'utilisation de « laits ¼ végétaux, chez des nourrissons de deux mois et demi à 14 mois (quatre cas).

INTRODUCTION: The use of vegetable beverages improperly called « vegetable milk ¼ is promoted by food faddism to replace dairy products, even in infant diet whereas it is totally inadequate. CASE REPORTS: Case 1: a 9 month-old infant fed by a rice beverage for 2 months presented hypoalbuminemia (7 g/L) with kwashiorkor syndrome complicated by severe sepsis. Case 2: a 14 month-old infant fed by a rice beverage for 2 months had iron and vitamin B12 deficiency with deep anemia (Hb 35 g/L) and tissue hypoxia (hyperlactacidemia). Case 3: a 13 month-old infant fed by an almond beverage during 3 weeks presented metabolic alkalosis with hypochloremia due to sodium and chloride deficiency and revealed by hypoventilation. Case 4: a 2,5 month-old infant with epileptic encephalopathy was fed by several vegetable beverages (almond, nut, chestnut and soy) for a month and a half and presented deep hyponatremia (96 mmol/L) with coma and respiratory acidosis caused by aspiration pneumonia. He died secondarily. DISCUSSION: Deficiencies promote infections and severe metabolic disorders. Clinical polymorphism lead to diagnosis wandering that can be noxious. The reasons of these diet changes can be nutritional ignorance, perceived milk intolerance or food faddism, sometimes on the advice of an alternative medicine physician. Parental restricted diet or infant immunization recommendations negligence should warn about associated nutritional errors in young infants. CONCLUSION: These avoidable pathologies frequently caused by well-intending but misinformed parents must be reported to Nutrivigilance. This behaviour can be life threatening and must lead, in the most severe cases, to prosecution.