Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score-Weighted Analysis.

OBJECTIVES: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality. DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING: Seventeen PICUs in Italy. PATIENTS: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

Unplanned and medical admissions to pediatric intensive care units significantly decreased during COVID-19 outbreak in Northern Italy.

Northern Italy has been the first European area affected by the COVID-19 pandemic and related social restrictive measures. We sought to evaluate the impact of the COVID-19 outbreak on PICU admissions in Northern Italy, using data from the Italian Network of Pediatric Intensive Care Units Registry. We included all patients admitted to 4 PICUs from 8-weeks-before to 8-weeks-after February 24th, 2020, and those admitted in the same period in 2019. Incidence rate ratios (IRR) evaluating incidence rate differences between pre- and post-COVID-19 periods in 2020 (IRR-1), as well as between the post-COVID-19-period with the same period in 2019 (IRR-2), were computed using zero-inflated negative binomial or Poisson regression modeling. A total of 1001 admissions were included. The number of PICU admissions significantly decreased during the COVID-19 outbreak compared to pre-COVID-19 and compared to the same period in 2020 (IRR-1 0.63 [95%CI 0.50-0.79]; IRR-2 0.70 [CI 0.57-0.91]). Unplanned and medical admissions significantly decreased (IRR-1 0.60 [CI 0.46-0.70]; IRR-2 0.67 [CI 0.51-0.89]; and IRR-1 0.52, [CI 0.40-0.67]; IRR-2 0.77 [CI 0.58-1.00], respectively). Intra-hospital, planned (potentially delayed by at least 12 h), and surgical admissions did not significantly change. Patients admitted for respiratory failure significantly decreased (IRR-1 0.55 [CI 0.37-0.77]; IRR-2 0.48 [CI 0.33-0.69]).Conclusions: Unplanned and medical PICU admissions significantly decreased during COVID-19 outbreak, especially those for respiratory failure. What is Known: • Northern Italy has been the first European area affected by the COVID-19 pandemic. • Although children are relatively spared from the severe COVID-19 disease, the pediatric care system has been affected by social restrictive measures, with a reported 73-88% reduction in pediatric emergency department admissions. What is New: • Unplanned and medical PICU admissions significantly decreased during the COVID-19 outbreak compared to pre-COVID-19 and to the same period in 2019, especially those for respiratory failure. Further studies are needed to identify associated factors and new prevention strategies.

Perioperative management of children with neuromuscular disorders based on a common protocol: A prospective, national study in Italy.

BACKGROUND: Children with neuromuscular diseases (NMDs) often display respiratory muscle weakness which increases the risk of postoperative pulmonary complications (PPCs) after general anaesthesia. Non-invasive ventilation (NIV) associated with mechanical insufflation-exsufflation (MI-E) can reduce the incidence and severity of PPCs. The aim of this study was to report our experience with a shared perioperative protocol that consists in using NIV combined with MI-E to improve the postoperative outcome of NMD children (IT-NEUMA-Ped). METHOD: We conducted a multicentre, observational study on 167 consecutive paediatric patients with NMDs undergoing anaesthesia from December 2015 to December 2018 in a network of 13 Italian hospitals. RESULTS: We found that 89% of the 167 children (mean age 8 years old) were at high risk of PPCs, due to the presence of at least one respiratory risk factor. In particular, 51% of them had preoperative ventilatory support dependence. Only 14 (8%) patients developed PPCs, and only two patients needed tracheostomy. Average hospital length of stay (LOS) was 6 (2-14) days. The study population was stratified according to preoperative respiratory devices dependency and invasiveness of the procedure. Patients with preoperative ventilatory support dependence showed significantly higher intensive care unit (ICU) admission rate and longer hospital LOS. CONCLUSION: Disease severity seems to be more related to the outcome of this population than invasiveness of procedures. NIV combined with MI-E can help in preventing and resolve PPCs.

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 infant with severe bronchiolitis: from high flow nasal cannula to continuous positive airway pressure and mechanical ventilation.

Bronchiolitis is one of the most frequent reasons for Pediatric Intensive Care Unit (PICU) admission in children less than 1 year of age. It causes a wide spectrum of clinical scenarios from mild to severe respiratory failure and supportive therapy range from high flow nasal cannula (HFNC) to nonconventional ventilation and extra corporeal membrane oxygenation (ECMO) in the most severe forms. Aim of this article is to review the available ventilation mode in children with bronchiolitis and the scientific evidence. The main medical databases were explored to search for clinical trials that address management strategies for respiratory support of infants with respiratory syncytial virus (RSV) infection. HFNC use is increasing and it seems to be useful as first line therapy in the emergency room and in the pediatric ward to prevent PICU admission but it is not clear yet if it is equivalent to noninvasive ventilation (NIV). NIV use in bronchiolitis is well established, mainly in continuous positive airway pressure mode in moderate and severe bronchiolitis. A mild evidence towards use of NIV to prevent endotracheal intubation is raising from few studies. Finally, for patients who failed a NIV trial, endotracheal intubation should be considered as the best option to support ventilation with conventional, nonconventional mode and ECMO in the most severe acute respiratory distress syndromes. There is a lack of quality studies for the use of any of the proposed ventilatory support in infants with bronchiolitis, especially in the severe forms. Nevertheless, in the last two decades daily use of noninvasive positive pressure supports have reached a large consensus based on clinical judgement and weak published evidence. We need specific and clear guidelines on which is the optimal management of these patients, and more robust randomized clinical trials to best evaluate timing and efficacy of HFNC and NIV use.

EMpowerment of PArents in THe Intensive Care Questionnaire: Translation and Validation in Italian PICUs.

OBJECTIVES: To translate and validate the EMpowerment of PArents in THe Intensive Care questionnaire to measure parent satisfaction and experiences in Italian PICUs. DESIGN: Prospective, multicenter study. SETTING: Four medical/surgical Italian PICUs in three tertiary hospitals. PATIENTS: Families of children, 0-16 years old, admitted to the PICUs were invited to participate. Inclusion criteria were PICU length of stay greater than 24 hours and good comprehension of Italian language by parents/guardians. Exclusion criteria were readmission within 6 months and parents of a child who died in the PICU. INTERVENTIONS: Distribution, at PICU discharge, of the EMpowerment of PArents in THe Intensive Care questionnaire with 65 items divided into five domains and a six-point rating scale: 1 " certainly no" to 6 "certainly yes." MEASUREMENTS AND MAIN RESULTS: Back and forward translations of the EMpowerment of PArents in THe Intensive Care questionnaire between Dutch (original version) and Italian languages were deployed. Cultural adaptation of the instrument was confirmed by a consultation with a representative parent group (n = 10). Totally, 150 of 190 parents (79%) participated in the study. On item level, 12 statements scored a mean below 5.0. The Cronbach's α, measured for internal consistency, on domain level was between 0.67 and 0.96. Congruent validity was measured by correlating the five domains with four gold standard satisfaction measures and showed adequate correlations (rs, 0.41-0.71; p < 0.05). No significant differences occurred in the nondifferential validity testing between three children's characteristics and the domains; excepting parents with a child for a surgical and planned admission were more satisfied on information and organization issues. CONCLUSIONS: The Italian version of the EMpowerment of PArents in THe Intensive Care questionnaire has satisfactory reliability and validity estimates and seems to be appropriate for Italian PICU setting. It is an important instrument providing benchmark data to be used in the process of quality improvement toward the development of a family-centered care philosophy within Italian PICUs.

Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome.

OBJECTIVES: Withdrawal syndrome is an adverse reaction of analgesic and sedative therapy, with a reported occurrence rate between 17% and 57% in critically ill children. Although some factors related to the development of withdrawal syndrome have been identified, there is weak evidence for the effectiveness of preventive and therapeutic strategies. The main aim of this study was to evaluate the frequency of withdrawal syndrome in Italian PICUs, using a validated instrument. We also analyzed differences in patient characteristics, analgesic and sedative treatment, and patients' outcome between patients with and without withdrawal syndrome. DESIGN: Observational multicenter prospective study. SETTING: Eight Italian PICUs belonging to the national PICU network Italian PICU network. PATIENTS: One hundred thirteen patients, less than 18 years old, mechanically ventilated and treated with analgesic and sedative therapy for five or more days. They were admitted in PICU from November 2012 to May 2014. INTERVENTIONS: Symptoms of withdrawal syndrome were monitored with Withdrawal Assessment Tool-1 scale. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of withdrawal syndrome was 64.6%. The following variables were significantly different between the patients who developed withdrawal syndrome and those who did not: type, duration, and cumulative dose of analgesic therapy; duration and cumulative dose of sedative therapy; clinical team judgment about analgesia and sedation's difficulty; and duration of analgesic weaning, mechanical ventilation, and PICU stay. Multivariate logistic regression analysis revealed that patients receiving morphine as their primary analgesic were 83% less likely to develop withdrawal syndrome than those receiving fentanyl or remifentanil. CONCLUSIONS: Withdrawal syndrome was frequent in PICU patients, and patients with withdrawal syndrome had prolonged hospital treatment. We suggest adopting the lowest effective dose of analgesic and sedative drugs and frequent reevaluation of the need for continued use. Further studies are necessary to define common preventive and therapeutic strategies.

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.

Predictors of Failure of Awake Regional Anesthesia for Neonatal Hernia Repair: Data from the General Anesthesia Compared to Spinal Anesthesia Study--Comparing Apnea and Neurodevelopmental Outcomes.

BACKGROUND: Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive outcomes. The General Anesthesia compared to Spinal anesthesia study compares neurodevelopmental outcomes after awake RA or GA in otherwise healthy infants. The aim of the study is to describe success and failure rates of RA and report factors associated with failure. METHODS: This was a nested cohort study within a prospective, randomized, controlled, observer-blind, equivalence trial. Seven hundred twenty-two infants 60 weeks or less postmenstrual age scheduled for herniorrhaphy under anesthesia were randomly assigned to receive RA (spinal, caudal epidural, or combined spinal caudal anesthetic) or GA with sevoflurane. The data of 339 infants, where spinal or combined spinal caudal anesthetic was attempted, were analyzed. Possible predictors of failure were assessed including patient factors, technique, experience of site and anesthetist, and type of local anesthetic. RESULTS: RA was sufficient for the completion of surgery in 83.2% of patients. Spinal anesthesia was successful in 86.9% of cases and combined spinal caudal anesthetic in 76.1%. Thirty-four patients required conversion to GA, and an additional 23 patients (6.8%) required brief sedation. Bloody tap on the first attempt at lumbar puncture was the only risk factor significantly associated with block failure (odds ratio = 2.46). CONCLUSIONS: The failure rate of spinal anesthesia was low. Variability in application of combined spinal caudal anesthetic limited attempts to compare the success of this technique to spinal alone.

Evolution of Noninvasive Mechanical Ventilation Use: A Cohort Study Among Italian PICUs.

OBJECTIVE: To assess how clinical practice of noninvasive ventilation has evolved in the Italian PICUs. DESIGN: National, multicentre, retrospective, observational cohort. SETTING: Thirteen Italian medical/surgical PICUs that participated in the Italian PICU Network. PATIENTS: Seven thousand one-hundred eleven admissions of children with 0-16 years old admitted from January 1, 2011, to December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cause of respiratory failure, length and mode of noninvasive ventilation, type of interfaces, incidence of treatment failure, and outcome were recorded. Data were compared with an historical cohort of children enrolled along 6 months from November 1, 2006, to April 30, 2007, over the viral respiratory season. Seven thousand one-hundred eleven PICU admissions were analyzed, and an overall noninvasive ventilation use of 8.8% (n = 630) was observed. Among children who were admitted in the PICU without mechanical ventilation (n = 3,819), noninvasive ventilation was used in 585 patients (15.3%) with a significant increment among the three study years (from 11.6% in 2006 to 18.2% in 2012). In the endotracheally intubated group, 17.2% children received noninvasive ventilation at the end of the weaning process to avoid reintubation: 11.9% in 2006, 15.3% in 2011, and 21.6% in 2012. Noninvasive ventilation failure rate raised from 10% in 2006 to 16.1% in 2012. CONCLUSIONS: Noninvasive ventilation is increasingly and successfully used as first respiratory approach in several, but not all, Italian PICUs. The current study shows that noninvasive ventilation represents a feasible and safe technique of ventilatory assistance for the treatment of mild acute respiratory failure. Noninvasive ventilation was used as primary mode of ventilation in children with low respiratory tract infection (mainly in bronchiolitis and pneumonia), in acute on chronic respiratory failure or to prevent reintubation.

Emergencies cards for neuromuscular disorders 1st Consensus Meeting from UILDM - Italian Muscular Dystrophy Association Workshop report.

Acute hospitalisation may be required to support patients with Neuromuscular disorders (NMDs) mainly experiencing respiratory complications, swallowing difficulties, heart failure, urgent surgical procedures. As NMDs may need specific treatments, they should be ideally managed in specialized hospitals. Nevertheless, if urgent treatment is required, patients with NMD should be managed at the closest hospital site, which may not be a specialized centre where local emergency physicians have the adequate experience to manage these patients. Although NMDs are a group of conditions that can differ in terms of disease onset, progression, severity and involvement of other systems, many recommendations are transversal and apply to the most frequent NMDs. Emergency Cards (EC), which report the most common recommendations on respiratory and cardiac issues and provide indications for drugs/treatments to be used with caution, are actively used in some countries by patients with NMDs. In Italy, there is no consensus on the use of any EC, and a minority of patients adopt it regularly in case of emergency. In April 2022, 50 participants from different centres in Italy met in Milan, Italy, to agree on a minimum set of recommendations for urgent care management which can be extended to the vast majority of NMDs. The aim of the workshop was to agree on the most relevant information and recommendations regarding the main topics related to emergency care of patients with NMD in order to produce specific ECs for the 13 most frequent NMDs.

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.

Predicting Hemodynamic Failure Development in PICU Using Machine Learning Techniques.

The present work aims to identify the predictors of hemodynamic failure (HF) developed during pediatric intensive care unit (PICU) stay testing a set of machine learning techniques (MLTs), comparing their ability to predict the outcome of interest. The study involved patients admitted to PICUs between 2010 and 2020. Data were extracted from the Italian Network of Pediatric Intensive Care Units (TIPNet) registry. The algorithms considered were generalized linear model (GLM), recursive partition tree (RPART), random forest (RF), neural networks models, and extreme gradient boosting (XGB). Since the outcome is rare, upsampling and downsampling algorithms have been applied for imbalance control. For each approach, the main performance measures were reported. Among an overall sample of 29,494 subjects, only 399 developed HF during the PICU stay. The median age was about two years, and the male gender was the most prevalent. The XGB algorithm outperformed other MLTs in predicting HF development, with a median ROC measure of 0.780 (IQR 0.770-0.793). PIM 3, age, and base excess were found to be the strongest predictors of outcome. The present work provides insights for the prediction of HF development during PICU stay using machine-learning algorithms.

Working as a team in airway surgery: History, present and perspectives.

Teamwork is one of the most important trend in modern medicine. Airway team were created in many places to respond in a multidisciplinary and coordinated way to challenging clinical problems which were beyond the possibility of an individual management. In this chapter, we illustrate the historical steps leading to the development of an airway team in a pediatric referral hospital, describe the present teamwork activity defining the key points for the creation of a team and discussing different organization models; finally we delineate possible future directions for the airway teams in the globalized world.

Pediatric anesthesia practice in Italy: a multicenter national prospective observational study derived from the APRICOT Trial.

BACKGROUND: Pediatric anesthesia nowadays requires specific knowledge and expertise. The Anesthesia PRactice In Children Observational Trial (APRICOT) was a European multicenter study designed for the identification of perioperative severe critical events and management. We aimed at analyzing the Italian database in an attempt to determine the practice of anesthesia and the incidence of severe critical events in Italy. METHODS: Secondary analyses of the database consisted in extracting the raw data from the 25 Italian centers that participated to APRICOT. Descriptive statistics and comparison with the reference data were made for all the variables collected. RESULTS: The study analyzed 2087 children. The Italian cohort represents 6.7% of the overall study population. Most of the children were ASA 1-2 (90.6%) and underwent a surgical procedure (62.8%). In more than 84% of the cases, anesthesia management was performed by an expert with main or frequent activity in pediatric anesthesia with on an average 15 years of experience. The overall incidence of severe critical events was 3% (95% CI: 2.2-3.8). The most frequently reported severe critical incidents were of respiratory (2%; CI: 1.4-2.6) and cardiovascular origin (0.7%; CI. 0.3-1), while drug error, anaphylaxis and bronchial aspiration were very rare. There were no reports of perioperative cardiac arrest or patients with neurological damage. CONCLUSIONS: This secondary analysis demonstrates that the incidence of severe critical incidence was lower in Italy in comparison to that reported for Europe. This low rate of critical events may be related to the high expertise and experience of the anesthesiologists in charge of the children in the Italian centres that participated to APRICOT.

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.

Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016-2017 epidemic season: a systematic review of seven Italian reports.

BACKGROUND: The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016-2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis. METHODS: Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29-36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016-2017, versus 2 seasons before (2014-2015 and 2015-2016) and one season after (2017-2018) the AIFA limitation. RESULTS: During the 2016-2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016-2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk. CONCLUSIONS: The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29-36 wGA) infants aged < 6 months at the beginning of the RSV season.

Miliary tuberculosis leading to acute respiratory distress syndrome: Clinical experience in pediatric intensive care.

Acute respiratory distress syndrome (ARDS) represents a rare complication of miliary tuberculosis (TB) in the adult setting, and it is even less common in the pediatric population. The presence of comorbidities and the possibility of a delayed diagnosis may further impair the clinical prognosis of critically ill patients with disseminated TB and acute respiratory failure. In this report, we present a case series of five pediatric patients with miliary TB and ARDS, where rescue and multimodal respiratory support strategies have been applied with a favorable outcome in more than half of them. The burden of miliary TB over time on a general pediatric intensive care unit-including two ARDS patients-is also illustrated.

Incidence of and mortality due to sepsis, severe sepsis and septic shock in Italian Pediatric Intensive Care Units: a prospective national survey.

OBJECTIVES: The objective was to assess the incidence of sepsis, severe sepsis and septic shock and their mortality in Italian Pediatric Intensive Care Units (PICUs). DESIGN: This is a prospective, observational, multi-center, 1-year study. SETTING: Fifteen medical-surgical PICUs participated in this study. PATIENTS: Two-thousand and seven hundred and forty-one children (2,741), aged 0-16 years, who were consecutively admitted in the participating PICUs, from 1 March 2004 to 28 February 2005, were enrolled in the study. INTERVENTIONS: There were no interventions in this study. MEASUREMENTS AND MAIN RESULTS: Data on infection, systemic inflammatory response syndrome (SIRS), severe sepsis and septic shock were collected using criteria defined by Proulx in 1996. Sepsis-related diagnosis was stratified for five age groups (neonates, infant, preschool, school, adolescent) and type of admission (medical, surgical, trauma). The presence of existing comorbidities has been considered for children with and without sepsis diagnosis. The results showed a lower overall incidence of sepsis, severe sepsis and septic shock (7.9, 1.6 and 2.1%, respectively) if compared with other studies. Children with sepsis diagnosis had a higher morbidity and higher mortality than those without sepsis. Severe sepsis and septic shock had a mortality rate of 17.7 and 50.8%, respectively. Mortality is significantly higher for children with existing comorbidities than those without existing comorbidities. CONCLUSIONS: Septic shock mortality is still high in Italian PICUs and attempts to improve medical treatment are necessary. We suggest that application of the new definitions for sepsis diagnosis and diffusion of guidelines for early recognition and aggressive treatment of severe sepsis and septic shock in Italy represent a high priority to reduce mortality. DESCRIPTOR: The descriptor is pediatrics.