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.

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.

Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial.

BACKGROUND: Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. METHODS: In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. FINDINGS: Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean [SD]) was 98.6 (14.2) in the awake-regional group and 98.2 (14.7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0.169, 95% CI -2.30 to 2.64). The median duration of anaesthesia in the general anaesthesia group was 54 min. INTERPRETATION: For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. FUNDING: Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study--Comparing Apnea and Neurodevelopmental Outcomes, a Randomized Controlled Trial.

BACKGROUND: Postoperative apnea is a complication in young infants. Awake regional anesthesia (RA) may reduce the risk; however, the evidence is weak. The General Anesthesia compared to Spinal anesthesia study is a randomized, controlled trial designed to assess the influence of general anesthesia (GA) on neurodevelopment. A secondary aim is to compare rates of apnea after anesthesia. METHODS: Infants aged 60 weeks or younger, postmenstrual age scheduled for inguinal herniorrhaphy, were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born less than 26 weeks gestation. The primary outcome of this analysis was any observed apnea up to 12 h postoperatively. Apnea assessment was unblinded. RESULTS: Three hundred sixty-three patients were assigned to RA and 359 to GA. Overall, the incidence of apnea (0 to 12 h) was similar between arms (3% in RA and 4% in GA arms; odds ratio [OR], 0.63; 95% CI, 0.31 to 1.30, P = 0.2133); however, the incidence of early apnea (0 to 30 min) was lower in the RA arm (1 vs. 3%; OR, 0.20; 95% CI, 0.05 to 0.91; P = 0.0367). The incidence of late apnea (30 min to 12 h) was 2% in both RA and GA arms (OR, 1.17; 95% CI, 0.41 to 3.33; P = 0.7688). The strongest predictor of apnea was prematurity (OR, 21.87; 95% CI, 4.38 to 109.24), and 96% of infants with apnea were premature. CONCLUSIONS: RA in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.

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.

Anesthesia and the developing brain: a way forward for clinical research.

It is now well established that many general anesthetics have a variety of effects on the developing brain in animal models. In contrast, human cohort studies show mixed evidence for any association between neurobehavioural outcome and anesthesia exposure in early childhood. In spite of large volumes of research, it remains very unclear if the animal studies have any clinical relevance; or indeed how, or if, clinical practice needs to be altered. Answering these questions is of great importance given the huge numbers of young children exposed to general anesthetics. A recent meeting in Genoa brought together researchers and clinicians to map a path forward for future clinical studies. This paper describes these discussions and conclusions. It was agreed that there is a need for large, detailed, prospective, observational studies, and for carefully designed trials. It may be impossible to design or conduct a single study to completely exclude the possibility that anesthetics can, under certain circumstances, produce long-term neurobehavioural changes in humans; however , observational studies will improve our understanding of which children are at greatest risk, and may also suggest potential underlying etiologies, and clinical trials will provide the strongest evidence to test the effectiveness of different strategies or anesthetic regimens with respect to better neurobehavioral outcome.

Continuous positive airway pressure with helmet versus mask in infants with bronchiolitis: an RCT.

BACKGROUND: Noninvasive continuous positive airway pressure (CPAP) is usually applied with a nasal or facial mask to treat mild acute respiratory failure (ARF) in infants. A pediatric helmet has now been introduced in clinical practice to deliver CPAP. This study compared treatment failure rates during CPAP delivered by helmet or facial mask in infants with respiratory syncytial virus-induced ARF. METHODS: In this multicenter randomized controlled trial, 30 infants with respiratory syncytial virus-induced ARF were randomized to receive CPAP by helmet (n = 17) or facial mask (n = 13). The primary endpoint was treatment failure rate (defined as due to intolerance or need for intubation). Secondary outcomes were CPAP application time, number of patients requiring sedation, and complications with each interface. RESULTS: Compared with the facial mask, CPAP by helmet had a lower treatment failure rate due to intolerance (3/17 [17%] vs 7/13 [54%], P = .009), and fewer infants required sedation (6/17 [35%] vs 13/13 [100%], P = .023); the intubation rates were similar. In successfully treated patients, CPAP resulted in better gas exchange and breathing pattern with both interfaces. No major complications due to the interfaces occurred, but CPAP by mask had higher rates of cutaneous sores and leaks. CONCLUSIONS: These findings confirm that CPAP delivered by helmet is better tolerated than CPAP delivered by facial mask and requires less sedation. In addition, it is safe to use and free from adverse events, even in a prolonged clinical setting.

Use and reimbursement of off-label drugs in pediatric anesthesia: the Italian experience.

BACKGROUND: Most of the drugs used in anesthesia are off-label in children even if they present solid clinical evidence in adults. This lack of authorization is caused by multiple factors including the difficulty in conducting research in this area (due to the ethical concerns and/or the low number of available participants, the high variability of the outcome measures) and the lack of economic interest of the pharmaceutical companies (due to the limited market). OBJECTIVE: Define a list of medicinal products commonly used off-label in pediatrics anesthesia to be reimbursed by Italian National Health System. METHODS AND RESULTS: We hereby describe the methodological framework used to allow reimbursed use of a list of medicinal products, widely used off-label in pediatric patients, ensuring the best therapeutic results with the lowest possible risk for children. A task force of pediatric anesthesiologists from Italy petitioned the Italian Medicines Agency (AIFA) to allow a number of commonly utilized but off-label drugs for pediatric anesthesia to be reimbursed for specific indications. For each drug, both the supporting literature and expert opinion were used, and the resulting list of drugs allowed to be used/reimbursed officially by AIFA was significantly expanded. This paper documents one approach to the problem of off-label use of drugs for pediatric patients that can be a model for future efforts. CONCLUSION: Continuous efforts are needed from government institutions and sponsors on drug development and on drug approval process in pediatrics, as research on drug effectiveness and safety is mandatory in children as in adults. At the same time, clinicians must become more familiar with the drug-approval process, participate to sponsored trials, and perform ztrials themselves.

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.

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.

Does the Italian pediatric anesthesia training program adequately prepare residents for future clinical practice? What should be done?

BACKGROUND: Pediatric anesthesia should be considered a subspecialty addressing the complete pediatric population (from preterm to teenager) and requiring particular anatomical, pathophysiological, pharmacological and anesthesiological knowledge. A survey was conducted to evaluate the training in pediatric anesthesia performed by Medical Schools of Anesthesia in Italy and to assess if the European Federation of Associations of Pediatric Anesthesia (FEAPA) guidelines for training in pediatric anesthesia had been adopted. METHODS: The survey was addressed to the Directors of the Departments of Anesthesia and Intensive Care of the Medical Schools throughout Italy using a questionnaire. RESULTS: We contacted all 37 Schools of Anesthesia, but only 26 of these (70 %) answered all the questions. A specific training program exists in 24 (92%). The duration of the training is variable: in 40% of the schools it lasts 2 months, in 27% 3 months and in 33% more than 3 months (3-6 months). Only 29% of the Schools required a minimum number of procedures to be performed during the training period. A final test is performed in 46% of the Schools. A dedicated staff for pediatric anesthesia exists in 70% of the Italian Schools. CONCLUSIONS: In Italy, the FEAPA guidelines have not yet been completely adopted. The experience of a dedicated unit for pediatric anesthesia will be invaluable to define operative guidelines, courses and to establish the minimum equipment necessary for pediatric management in nonspecialist hospitals.

Pediatric Index of Mortality 2 score in Italy: a multicenter, prospective, observational study.

OBJECTIVES: To assess the performance of the Pediatric Index of Mortality (PIM) 2 score in Italian pediatric intensive care units (PICUs). DESIGN: Prospective, observational, multicenter, 1-year study. SETTING: Eighteen medical-surgical PICUs. PATIENTS: Consecutive patients (3266) aged 0-16 years admitted between 1 March 2004 and 28 February 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To assess the performance of the PIM2 score, discrimination and calibration measures were applied to all children admitted to the 18 PICUs, in the entire population and in different groups divided for deciles of risk, age and admission diagnosis. There was good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.89 (95% CI 0.86-0.91) and good calibration of the scoring system [non-significant differences between observed and predicted deaths when the population was stratified according to deciles of risk (chi2 9.86; 8 df, p = 0.26) for the whole population]. CONCLUSIONS: The PIM2 score performed well in this sample of the Italian pediatric intensive care population. It may need to be reassessed in the injury and postoperative groups in larger studies.

A case of severe diazoxide toxicity.

Hyperinsulism is a rare cause of persistent hypoglycemia in the neonatal period. Therapy can be accomplished either surgically or pharmacologically. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several adverse effects of this drug have been described. A case of severe diazoxide intoxication with fluid retention, congestive heart failure, and respiratory failure is reported. The patient was a 43-day-old infant, affected by persistent and severe hypoglycemia. After the diagnosis, hyperinsulinism was established he was treated with diazoxide (17 mg x kg(-1) daily) and octreotide (12 microg x kg(-1) daily). A few days later he presented with hepatomegaly, severe fluid retention, diffuse edema, congestive heart failure, and respiratory failure requiring mechanical ventilation. After introduction of ACE inhibitors he developed acute renal failure. The clinical condition worsened and he developed pulmonary hypertension requiring high-frequency oscillatory ventilation. Diazoxide was stopped on the 12th day in spite of poor control of blood sugar. During the next 5 days his hemodynamic status dramatically improved and he was weaned from catecholamines: he lost weight, had a negative fluid balance, and the edema disappeared, a normal diuresis resumed and renal function improved. Improvement of respiratory patterns and gas exchange made it possible to switch back to conventional ventilation and then to extubate the patient. Echocardiography demonstrated reduction of the PA pressure to normal and resolution of atrial enlargement. The patient was scheduled for elective subtotal pancreatectomy. Diagnosis and management of diazoxide intoxication are discussed.