Cell Population Data (CPD) for Early Recognition of Sepsis and Septic Shock in Children: A Pilot Study.

Objectives: Innovative Cell Population Data (CPD) have been used as early biomarkers for diagnosing sepsis in adults. We assessed the usefulness of CPD in pediatric patients with sepsis/septic shock, in terms of early recognition and outcome prediction. We revised 54 patients (0-15 y) admitted to our Pediatric Intensive Care Unit (PICU) for sepsis/septic shock during a 4-year period. Twenty-eight patients were excluded, 26 septic patients were enrolled (G1). Forty children admitted for elective surgery served as controls (G2). Data on five selected CPD parameters, namely neutrophils fluorescence intensity (NE-SFL), monocytes cells complexity (MO-X), monocytes fluorescence intensity (MO-Y), monocytes complexity and width of dispersion of events measured (MO-WX), and monocytes cells size and width dispersion (MO-WZ), were obtained at time of PICU admission (t0) by a hematological analyzer (Sysmex XN 9000®). As the primary outcome we evaluated the relevance of CPD for diagnosing sepsis/septic shock on PICU admission. Furthermore, we investigated if CPD at t0 were correlated with C-reactive protein (CRP), patient survival, or complicated sepsis course. Results: On PICU admission (t0), NE-SFL, MO-WX, and MO-Y were higher in sepsis/septic shock patients compared to controls. NE-SFL values were correlated with CRP values in G1 patients (r = 0.83). None of the five CPD parameters was correlated with survival or complicated sepsis course. Conclusion: We found higher values of NE-SFL, MO-WX, and MO-Y in children with sepsis/septic shock upon PICU admission. These parameters may be a promising adjunct for early sepsis diagnosis in pediatric populations. Larger, prospective studies are needed to confirm our preliminary observations.

Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): protocol for a multicentre, randomised, double-blind, controlled, non-profit trial.

INTRODUCTION: Some evidence indicates that exogenous surfactant therapy may be effective in infants with acute viral bronchiolitis, even though more confirmatory data are needed. To date, no large multicentre trials have evaluated the effectiveness and safety of exogenous surfactant in severe cases of bronchiolitis requiring invasive mechanical ventilation (IMV). METHODS AND ANALYSIS: This is a multicentre randomised, placebo-controlled, double-blind study, performed in 19 Italian paediatric intensive care units (PICUs). Eligible participants are infants under the age of 12 months hospitalised in a PICU, suffering from severe acute hypoxaemic bronchiolitis, requiring IMV. We adopted a more restrictive definition of bronchiolitis, including only infants below 12 months of age, to maintain the population as much homogeneous as possible. The primary outcome is to evaluate whether exogenous surfactant therapy (Curosurf, Chiesi Pharmaceuticals, Italy) is effective compared with placebo (air) in reducing the duration of IMV in the first 14 days of hospitalisation, in infants suffering from acute hypoxaemic viral bronchiolitis. Secondary outcomes are duration of non-invasive mechanical ventilation in the post-extubation phase, number of cases requiring new intubation after previous extubation within 14 days from randomisation, PICU and hospital length of stay (LOS), duration of oxygen dependency, effects on oxygenation and ventilatory parameters during invasive mechanical respiratory support, need for repeating treatment within 24 hours of first treatment, use of other interventions (eg, high-frequency oscillatory ventilation, nitric oxide, extracorporeal membrane oxygenation), mortality within the first 14 days of PICU stay and before hospital discharge, side effects and serious adverse events. ETHICS AND DISSEMINATION: The trial design and protocol have received approval by the Italian National Agency for Drugs (AIFA) and by the Regional Ethical Committee of Verona University Hospital (1494CESC). Findings will be disseminated through publication in peer-reviewed journals, conference/meeting presentations and media. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, issue date 22 May 2019. NCT03959384.

A shared protocol for porcine surfactant use in pediatric acute respiratory distress syndrome: a feasibility study.

BACKGROUND: Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. METHODS: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. RESULTS: Sixty-nine children, age 0-24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. CONCLUSION: The use of porcine Surfactant improves oxygenation, P/F ratio, OI and pH in a population of children with moderate or severe pARDS caused by multiple diseases. A shared protocol seems to be a good option to obtain the same criteria of enrollment among different PICUs and define a unique way of use and administration of the drug for future studies.

The Importance of Mortality Risk Assessment: Validation of the Pediatric Index of Mortality 3 Score.

OBJECTIVE: To evaluate the performance of the newest version of the Pediatric Index of Mortality 3 score and compare it with the Pediatric Index of Mortality 2 in a multicenter national cohort of children admitted to PICU. DESIGN: Retrospective, prospective cohort study. SETTING: Seventeen Italian PICUs. PATIENTS: All children 0 to 15 years old admitted in PICU from January 2010 to October 2014. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Eleven thousand one hundred nine children were enrolled in the study. The mean Pediatric Index of Mortality 2 and 3 values of 4.9 and 3.9, respectively, differed significantly (p < 0.05). Overall mortality rate was 3.9%, and the standardized mortality ratio was 0.80 for Pediatric Index of Mortality 2 and 0.98 for Pediatric Index of Mortality 3 (p < 0.05). The area under the curve of the receiver operating characteristic curves was similar for Pediatric Index of Mortality 2 and Pediatric Index of Mortality 3. The Hosmer-Lemeshow test was not significant for Pediatric Index of Mortality 3 (p = 0.21) but was highly significant for Pediatric Index of Mortality 2 (p < 0.001), which overestimated death mainly in high-risk categories. CONCLUSIONS: Mortality indices require validation in each country where it is used. The new Pediatric Index of Mortality 3 score performed well in an Italian population. Both calibration and discrimination were appropriate, and the score more accurately predicted the mortality risk than Pediatric Index of Mortality 2.

Exogenous surfactant replacement: how to deliver it?

Exogenous surfactant is a therapeutic option for newborns, children and adults with acute respiratory distress disorders. Although tracheal instillation is still reputed as the classical method of surfactant delivery, alternative techniques have been investigated. Surfactant administration by using thin intra-tracheal catheters, bronchoscopy, laryngeal mask airway, or nebulisation, although variably effective, appear to be less invasive when compared to tracheal intubation. However, further research is still needed to better clarify this matter. (www.actabiomedica.it).

Early recognition and management of septic shock in children.

Septic shock remains a major cause of morbidity and mortality among children, mainly due to acute hemodynamic compromise and multiple organ failures. In the last decade, international guidelines for the management of septic shock, as well as clinical practice parameters for hemodynamic support of pediatric patients, have been published. Early recognition and aggressive therapy of septic shock, by means of abundant fluid resuscitation, use of catecholamines and other adjuvant drugs, are widely considered of pivotal importance to improve the short and long-term outcome of these patients. The aim of this paper is to summarize the modern approach to septic shock in children, particularly in its very initial phase, when pediatric healthcare providers may be required to intervene in the pre-intensive care unit setting or just on admission in the pediatric intensive care unit.

Daily practice of mechanical ventilation in Italian pediatric intensive care units: a prospective survey.

OBJECTIVES: To assess how children requiring endotracheal intubation are mechanically ventilated in Italian pediatric intensive care units (PICUs). DESIGN: A prospective, national, observational, multicenter, 6-month study. SETTING: Eighteen medical-surgical PICUs. PATIENTS: A total of 1943 consecutive children, aged 0-16 yrs, admitted between November 1, 2006 and April 30, 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on cause of respiratory failure, length of mechanical ventilation (MV), mode of ventilation, use of specific interventions were recorded for all children requiring endotracheal intubation for >24 hrs. Children were stratified for age, type of patient, and cause of respiratory failure. A total of 956 (49.2%) patients required MV via an endotracheal tube; 673 (34.6%) were ventilated for >24 hrs. The median length of MV was 4.5 days for all patients. If postoperative patients were excluded, the median time was 5 days. Bronchiolitis (6.7%), pneumonia (6.7%), and upper airway obstruction (5.3%) were the most frequent causes of acute respiratory failure, and altered mental status (9.2%) was the most frequent reason for MV. The overall mortality was 6.7% with highest rates for heart disease (nonoperative), sepsis, and acute respiratory distress syndrome (26.1%, 22.2%, and 16.7% respectively). Length of stay, associated chronic disease, severity score on admission, and PICU mortality were significantly higher in children who received MV (p < .05) than in children who did not. Controlled MV and pressure support ventilation + synchronized intermittent mandatory ventilation were the most frequently used modes of ventilatory assistance during PICU stay. CONCLUSIONS: Mechanical ventilation is frequently used in Italian PICUs with almost one child of two requiring endotracheal intubation. Children treated with MV represent a more severe category of patients than children who are breathing spontaneously. Describing the standard care and how MV is performed in children can be useful for future clinical studies.

Neurally adjusted ventilatory assist: a new approach to mechanically ventilated infants.

Neurally adjusted ventilator assist (NAVA) is a new mode of partial ventilatory support, in which neural inspiratory activity is monitored through the continuous esophageal recording of the electrical activity of the diaphragm. Assistance is triggered and cycled off in according to this signal and is delivered in proportion to its intensity. NAVA can improve patient-ventilator synchrony while maintaining spontaneous breathing. Small preliminary studies have shown that NAVA can be successfully used also in term and preterm infants, being safe and well tolerated. However, much additional work is still needed before NAVA can be recommended in the everyday practice of the neonatologist.

Neonatal resuscitation in the ward: the role of nurses.

Cardiopulmonary resuscitation (CPR) is necessary in about 1-2% of all newly born infants in their first minutes of life. However, CPR may also be needed in newborns beyond the time of birth, particularly in high risk categories of infants admitted in the NICU or in other less specialised units. In all these scenarios, the role of nurses is essential for several aspects, including early recognition of a deteriorating infant, with the aim to prevent cardiac arrest, as well as the starting of immediate basic life support manoeuvres at the bedside, whenever needed. Furthermore, nurses have a special part in family care during cardiopulmonary resuscitation.

Procalcitonin for the diagnosis of early-onset neonatal sepsis: a multilevel probabilistic approach.

OBJECTIVES: To compare the accuracy of procalcitonin (PCT) in early-onset neonatal sepsis (EOS) using standard cut-off values and a multilevel probabilistic approach. DESIGN AND METHODS: A retrospective study of PCT was performed in 149 newborns at risk of EOS, including preterm or prolonged rupture of membranes, chorioamnionitis or maternal infection, GBS colonization and signs of fetal distress. PCT values were analysed according to time of assay, i.e. at birth and at 24 and 48 h. We estimated sensitivity, specificity, positive (LR+) and negative likelihood ratio (LR-), diagnostic odds ratio (DOR) and number needed to diagnose (NND) using traditional and optimal (derived from ROC analysis) PCT cut-off values. RESULTS: Using optimal cut-off, the LR+, DOR and NND at birth were 10, 18.9 and 2.2, at 24 h they were 5.3, 11.2 and 2.1, and at 48 h they were 5.6, 18.1 and 1.7, respectively. The multilevel analysis generated three post-test probabilities for each time of assay. At 24 h post-test probabilities of EOS were 78% for PCT >90, 11% for PCT 10.1-90 and 3% for PCT <10.1 mg/L, respectively. Similar results were found in the other time points, with a wide range of intermediate PCT concentrations that did not change the post-test probability. CONCLUSIONS: The multilevel probabilistic approach was more effective in assessing the diagnostic power of PCT in EOS, showing that a wide range of intermediate PCT values was not able to discriminate between presence and absence of infection.

Transient phrenic nerve paralysis associated with status asthmaticus.

Phrenic nerve paralysis is a condition typically occurring after invasive procedures in the chest and neck. Here we describe a case of transient unilateral diaphragmatic paralysis in a child with status asthmaticus complicated by complete right lung atelectasis. Common causes of this disorder and possible implications for our case are discussed.