Italian pediatric intensive care units admitting critically ill cancer children: results from a national survey.

BACKGROUND: Pediatric patients affected by oncologic disease have a significant risk of clinical deterioration that requires admission to the intensive care unit. This study reported the results of a national survey describing the characteristics of Italian onco-hematological units (OHUs) and pediatric intensive care units (PICUs) that admit pediatric patients, focusing on the high-complexity treatments available before PICU admission, and evaluating the approach to the end-of-life (EOL) when cared in a PICU setting. METHODS: A web-based electronic survey has been performed in April 2021, involving all Italian PICUs admitting pediatric patients with cancer participating in the study. RESULTS: Eighteen PICUs participated, with a median number of admissions per year of 350 (IQR 248-495). Availability of Extracorporeal Membrane Oxygenation therapy and the presence of intermediate care unit are the only statistically different characteristics between large or small PICUs. Different high-level treatments and protocols are performed in OHUs, non depending on the volume of PICU. Palliative sedation is mainly performed in the OHUs (78%), however, in 72% it is also performed in the PICU. In most centers protocols that address EOL comfort care and treatment algorithms are missing, non depending on PICU or OHU volume. CONCLUSIONS: A non-homogeneous availability of high-level treatments and in OHUs is described. Moreover, protocols addressing EOL comfort care and treatment algorithms in palliative care are lacking in many centers.

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.

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.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.

BACKGROUND AND OBJECTIVES: Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. METHODS: Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. RESULTS: Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. CONCLUSIONS: High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.

Persistent pain following common outpatient surgeries in children: A multicenter study in Italy.

INTRODUCTION: The prevalence of persistent postsurgical pain in children is over 20% after major surgeries; however, data are scarce on the prevalence, character, and risk factors among children undergoing common ambulatory surgeries. The primary aim of this study was to evaluate the prevalence of persistent pain following pediatric ambulatory surgery at 1, 3, and 6 months. Secondary aims were to identify risk factors and characterize the pain and consequences of persistent postsurgical pain. METHODS: ASA I-II, ages 1 month to 16 years old, undergoing elective hypospadias repair, herniorraphy, orchiopexy, and orthopedic surgery were enrolled in a prospective, longitudinal, observational study at 3 pediatric centers in Italy. All patients received general plus regional anesthesia. Postoperative pain was evaluated using age appropriate pain scales at 1 and 3 hours. At 1, 3, and 6 months, pain scores were obtained and Parent's Postoperative Pain Measures (<8 yo) and Child Activity Limitations Interview (>8 yo) surveys were administered. RESULTS: About 350 patients completed the study. The prevalence of pain at 1, 3, and 6 months was 24% (84/350), 6.0% (21/350), and 4.0% (14/350), respectively. Inguinal herniorraphy patients experienced significantly higher pain at all 3-time points; 35.6%, 14.9%, and 9.2%. There was no significant association between mean pain scores >4 in PACU and persistent pain. Pain persisting at 6 months had neuropathic characteristics and frequently interfered with daily activities and sleep. CONCLUSION: Our data support the presence of persistent pain in pediatric patients after common surgeries. Most patients who developed persistent pain at 6 months had pain at 1 month. We recommend questioning at follow-up visit about persistent pain and functional impairment with follow-up until resolution.

The European society of regional anesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us?

PURPOSE OF REVIEW: To summarize the two recent sets of European and American Societies of Regional Anesthesia (ESRA-ASRA) Practice Advisory Guidelines for the performance of pediatric regional anesthesia (PRA). RECENT FINDINGS: Owing to the still ongoing debate regarding crucial issues concerning the effective and safe conduct of PRA and because of the lack of any generally accepted guidelines regarding PRA the (ESRA-ASRA) have addressed these in two topical publications. SUMMARY: Following an extensive literature search and an evidence-based approach the ESRA-ASRA task force have now provided a practice advisory on the following hot topics in PRA: the safety and appropriateness of placing block during general anesthesia or deep sedation, the use of test dosing, whether to use air or saline when performing loss-of-resistance, the risk of masking an acute compartment syndrome by use of PRA, dosing of local anesthetics for neuroaxial nerve blocks as well as peripheral nerve blocks, and finally the use of various drugs as adjuncts to local anesthetics.

The European Society of Regional Anaesthesia and Pain Therapy and the American Society of Regional Anesthesia and Pain Medicine Joint Committee Practice Advisory on Controversial Topics in Pediatric Regional Anesthesia.

BACKGROUND AND OBJECTIVES: Some topics in the clinical management of regional anesthesia in children remain controversial. To evaluate and come to a consensus regarding some of these topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a joint committee practice advisory on pediatric regional anesthesia (PRA). METHODS: Representatives from both ASRA and ESRA comprised the joint committee practice advisory on PRA. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Experts selected controversial topics in PRA. RESULTS: The performance of PRA under general anesthesia or deep sedation is associated with acceptable safety and should be viewed as the standard of care (Evidence B2 and Evidence B3). Because of the difficulty interpreting a negative test dose, the use of test dosing should remain discretionary (Evidence B4). The use of either air-loss of resistance or saline-loss of resistance techniques is supported by expert opinion, but the literature supporting one technique over the other is sparse and controversial; when used appropriately, each technique may be safely used in children. There are no current evidence-based data that the use of RA increases the risk for acute compartment syndrome or delays its diagnosis in children. CONCLUSIONS: High-level evidence is not yet available for the topics evaluated, and most recommendations are based on Evidence B studies. The ESRA/ASRA recommendations intend to provide guidance for the safe practice of regional anesthesia in children.

Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study.

BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

Safe perioperative pediatric care around the world.

Pediatric anesthesia is no longer a small subspecialty, but an important sector where developments in the new century have brought effective and safe management to children in the perioperative period. Unfortunately, what is common daily practice in the high-income countries with all the guidelines, checklists, instruments, and dedicated pediatric anesthesiologists is often only a dream in the low- and middle-income countries where the basic anesthesia services for improving the high rate of morbidity and mortality still are lacking. Anesthesia given by nonphysicians, with no monitoring, lack of elementary supplies, poor control of infections and hemorrhage, and no water or electricity are very often the 'usual' conditions. The World Health Organization is working hard to offer teams, basic equipments, and teaching and what is needed to offer children of these countries the same opportunities given in the industrialized countries. Other projects such as the Lifebox Project have a similar aim. This paper outlines some of what organizations are doing around the world, with different strategies all having the same target: safe pediatric anesthesia.

Everyday regional anesthesia in children.

Regional anesthesia in children is an evolving technique with many advantages in perioperative management. Although most regional anesthesia techniques are sufficiently described in the literature, the implementation of these techniques into daily clinical practice is still lacking. The main problems associated with pediatric regional anesthesia (PRA) include the appropriate selection of blockade, the management around the block, and how to teach these techniques in an optimal manner. This review article provides an overview of these 'hot' topics in PRA.

Local anesthetis and adjuvants in pediatric regional anesthesia.

The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. The clinical practice has shown that in pediatric population, effective analgesia is obtained by 1% mepivacaine, 1% lidocaine and 0.25% bupivacaine or better 0.2% ropivacaine, 0.2-0.25% levobupivacaine. In addition, levobupivacaine and ropivacaine have a better profile in terms of safety in comparison to bupivacaine and are the local anesthetics of choice for the daily clinical practice also in children as in adults. Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.

Controversial issues in pediatric regional anesthesia.

Regional anesthesia in children has reached in the last decades a widespread approval and today is a valid and effective technique used in the daily activity in many pediatric centres. Data from surveys and studies show the very low rate of complications and suggest that the use of regional techniques in children is at least as safe as general anesthesia alone. Despite these evidences there are aspects still creating discussions on the best approach to avoid or prevent risks and on the way to make this techniques more and more reliable and safe. Compartment syndrome, test dose, loss-of-resistance technique and blocks performed under general anesthesia are examples of, sometimes, never-ending stories; this review without the presumption to solve every problem shows the more recent data to offer, if possible, the best updated-answer on these topics.

Continuous central and perineural infusions for postoperative pain control in children.

PURPOSE OF REVIEW: Continuous infusion remains the technique of choice when there is a prolonged operation or intense postoperative pain is anticipated. Supplementing a general anesthesia with a nerve block can result in a pain-free awakening and postoperative analgesia without the potentially deleterious effects associated with parenteral opioids. The literature confirms the very low rate of complications and adverse effects of regional anesthesia in children. RECENT FINDINGS: Clinicians need to be aware of the key points for performing a block and placing a catheter in children: good knowledge of anatomic and physiologic differences between adults and children is necessary; the use of newer local anesthetics, such as ropivacaine and levobupivacaine, increases the therapeutic window; and moreover it is mandatory to work with dedicated pediatric equipment. SUMMARY: The introduction of high-resolution portable ultrasound brought a great advance for the pediatric anesthesiologists; ultrasound-guided visualization of anatomic structures, in fact, allows greater precision of needle and catheter placement, and confirmation that the drug is deposited in the site of choice. This article reviews the safety and efficacy of central and perineural continuous infusions for postoperative pain control in children.

The American Society of Regional Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and Pain Therapy joint committee recommendations for education and training in ultrasound-guided regional anesthesia.

Ultrasound-guided regional anesthesia (UGRA) is a growing area of both clinical and research interest. The following document contains the work produced by a joint committee from ASRA and the European Society of Regional Anesthesia and Pain Therapy. This joint committee was established to recommend to members and institutions the scope of practice, the teaching curriculum, and the options for implementing the medical practice of UGRA.This document specifically defines the following:1. 10 common tasks used when performing an ultrasound-guided nerve block,2. The core competencies and skill sets associated with UGRA,3. A training practice pathway for postgraduate anesthesiologists, and4. A residency-based training pathway.In both the residency and postgraduate pathways, training, competency, and proficiency requirements include both didactic and experiential components. The Joint Committee recommends that the decision to grant UGRA privileges be based at the individual institution level. Each institution that conducts UGRA is encouraged to support a productive quality improvement process.

The American Society of Regional Anesthesia and Pain Medicine and the European Society Of Regional Anaesthesia and Pain Therapy Joint Committee recommendations for education and training in ultrasound-guided regional anesthesia.

Ultrasound-guided regional anesthesia (UGRA) is a growing area of both clinical and research interest. The following document contains the work produced by a joint committee from ASRA and the European Society of Regional Anesthesia and Pain Therapy. This joint committee was established to recommend to members and institutions the scope of practice, the teaching curriculum, and the options for implementing the medical practice of UGRA.This document specifically defines the following:In both the residency and postgraduate pathways, training, competency, and proficiency requirements include both didactic and experiential components. The Joint Committee recommends that the decision to grant UGRA privileges be based at the individual institution level. Each institution that conducts UGRA is encouraged to support a productive quality improvement process.