Pediatric anesthesia in Europe: Variations within uniformity.

Organization of healthcare strongly differs between European countries and results in country-specific requirements in postgraduate medical training. Within the European Union (EU), the European Board of Anaesthesiology has set recommendations of training for the Specialty of Anaesthesiology including standards for Postgraduate Medical Specialist training including a description for providing service in pediatric anesthesia. However, these standards are advisory and not mandatory. Here we aimed to review the current state and associated challenges of pediatric anesthesia training in Europe. We report an important country-specific variability both in training and regulations of practice of pediatric anesthesia in the EU and in the United Kingdom. The requirements for training in pediatric anesthesia varies between nothing specified (Belgium) or providing anesthesia with direct supervision to a minimum of 50 cases below 5 years of age (Germany) to 3-6 month clinical practice in a specialized pediatric hospital (France). Likewise, the regulations for providing anesthesia to children varies from no regulations at all (Belgium) to age specific requirements and centralization of all children below 4 years of age to specified centers (United Kingdom). Officially recognized pediatric anesthesia fellowship programs are not available in most countries of Europe. It remains unclear if and how country-specific differences in pediatric anesthesia training are associated with clinical outcomes in pediatric perioperative care. There is converging interest and support for the establishment of a European pediatric anesthesia curriculum.

Clinical Importance of Potential Genetic Determinants Affecting Propofol Pharmacokinetics and Pharmacodynamics.

Interindividual variability in response to drugs used in anesthesia has long been considered the rule, not the exception. It is important to mention that in anesthesiology, the variability in response to drugs is multifactorial, i.e., genetic and environmental factors interact with each other and thus affect the metabolism, efficacy, and side effects of drugs. Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. Individual differences in genetic factors [single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular transporters, and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The objective of this review (through the analysis of published research) was to systematize the influence of gene polymorphisms on the pharmacokinetics and pharmacodynamics of propofol, to explain whether and to what extent the gene profile has an impact on variations observed in the clinical response to propofol, and to estimate the benefit of genotyping in anesthesiology. Despite the fact that there has been a considerable advance in this type of research in recent years, which has been largely limited to one or a group of genes, interindividual differences in propofol pharmacokinetics and pharmacodynamics may be best explained by the contribution of multiple pathways and need to be further investigated.

ERECTOR SPINAE PLANE BLOCK AND PLACEMENT OF PERINEURAL CATHETER FOR DEVELOPMENTAL HIP DISORDER SURGERY IN CHILDREN.

The ultrasound-guided erector spinae plane (ESP) block is a novel interfascial plane block technique providing analgesic effects in different localizations of the body, in accordance with the level of administration. Although ESP block is usually performed in the thoracic region in pediatric patients, it is possible to achieve ESP block in the lumbar region as well. Postoperative pain management is essential in patients undergoing operative hip treatment, one of the most common procedures in pediatric orthopedic surgery. We report on a case of effective intraoperative analgesia achieved by ultrasound-guided lumbar ESP block and another case of effective intra- and postoperative analgesia accomplished with perineural catheter placement in addition to lumbar ESP block, both performed in children surgically treated for developmental hip disorders.

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE).

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants. CLINICAL TRIAL REGISTRATION: NCT02350348.

The Effect of UGT1A9, CYP2B6 and CYP2C9 Genes Polymorphism on Propofol Pharmacokinetics in Children.

PURPOSE: This study was conducted to determine the effect of UGT1A9 98T>C, CYP2B6 516G>T and CYP2C9 430C>T genetic polymorphisms on the pharmacokinetics of propofol in children of different sexes and ages who undergone total intravenous anesthesia (ТIVA) and deep sedation during diagnostic and therapeutic procedures. PATIENTS AND METHODS: The prospective study included 94 children, ASA I-II status, 1 to 17 years of age, who undergone standard anesthetic protocol for TIVA, which implied the continuous use of propofol. Before the administration of propofol, venous blood was sampled to determine the presence of genetic variations in UGT1A9, CYP2B6 and CYP2C9 gene using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). From each patient included in the study blood samples were taken: 10 mins after the induction of anesthesia, immediately before the discontinuation of the propofol infusion, 10 mins after discontinuation of the propofol infusion and 20 mins after discontinuation of the propofol infusion to determine the pharmacokinetics of the drug in the plasma of the subjects The plasma propofol concentration was determined by HPLC analytical technique. RESULTS: UGT1A9 genotype is an independent predictor of the propofol concentration in children immediately after the end of the continuous infusion and 10 mins afterwards. In the carriers of the polymorphic UGT1A9 C allele, the propofol distribution constant was higher. The carriers of the polymorphic CYP2B6 T allele received a significantly lower overall and initial dose of propofol. Unlike polymorphism of the UGT1A9 gene, the tested CYP2C9 and CYP2B6 gene polymorphisms are not independent predictors of the pharmacokinetics of propofol. CONCLUSION: Further investigations of UGT1A9, CYP2B6 and CYP2C9 and other genes that participate in propofol metabolism as well as detailed analyses of the general conditions, administered therapies and associated diseases could explain the large interindividual variability of propofol metabolism in children.

POSTOPERATIVE PAIN AND STRESS RESPONSE: DOES CHILD'S GENDER HAVE AN INFLUENCE?

Surgical procedure causes multisystem stress response reactions. The aim of this study was to assess whether gender has an impact on the level of neuroendocrine response to surgical stress and intensity of postoperative pain in children undergoing inguinal hernia repair surgery, as well as satisfaction of their parents with preoperative and postoperative care. The study included 60 children aged 3-6 years, all of them the only child in the family. All children included in the study were categorized as American Society of Anesthesiologists PS Class I, and divided into two groups: group 1 composed of 30 boys and group 2 composed of 30 girls. After oral premedication with midazolam, general anesthesia with endotracheal intubation was performed in all patients. Ketorolac, 1 mg.kg-1, was administered for postoperative analgesia. Serum cortisol was measured in all children preoperatively and postoperatively. The quality of postoperative analgesia was evaluated by Wong-Baker (FACES) scale, along with parental satisfaction. Male children who were the only child in the family had stronger neuroendocrine response to surgical stress and stronger intensity of postoperative pain. The parents of the girls expressed greater satisfaction with preoperative and postoperative care.

Topical anesthetics for pediatric laser treatment.

Topical anesthetic agent causes transient insensibility to pain in a limited area of skin, and provides effective anesthesia in a short onset time, short duration, with seldom local or systemic side effects on intact skin and is simple to use. Topical formulations may offer significant benefits for prevention of procedural pain. Currently, they are considered to be the most effective anesthesia for laser treatments. Unfortunately, there is no standard anesthetic technique for this procedure. Lasers are being widely used in numerous dermatological and esthetics treatments in childhood. The advancement of new knowledge in laser technology have contributed to the development of new lasers that are commonly used in a pediatric population, such as Pulsed Dye, Carbon-dioxide and Nd:YAG laser. The most commonly used topical anesthetics in young patients for minimally or moderately painful laser cutaneous procedures are Lidocaine, Prilocaine, Tetracaine gel and combinations thereof.

Caudal block with analgosedation - a superior anaesthesia technique for lower abdominal surgery in paediatric population.

Aim To compare intraoperative hemodynamic and respiratory stability and postoperative emergence delirium between two anaesthesia regimens in children (caudal block with intravenous continuous analgosedation versus general endotracheal anaesthesia) and intensity of postoperative pain and quality of postoperative analgesia. Method Forty children aged 2-6 years who underwent lower abdominal surgery were randomized depending on performed anaesthesia into two groups: caudal block with analgosedation (group CB) and general endotracheal anaesthesia (group GA). Intraoperative hemodynamic and respiratory stability were evaluated measuring systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR) and arterial oxygen saturation (SaO2) in preinduction (t0), at the moment of surgical incision (t1), 10 minutes after surgical incision (t2) and at the time of skin suturing (t3). Postoperative emergence delirium was evaluated using Paediatric Anaesthesia Emergence Delirium score (PAED). Postoperative pain was evaluated by Children's and Infants' Postoperative Pain score (CHIPPS). Both scores were recorded every 5 minutes during first half hour postoperatively, additionally after 60 minutes postoperatively for CHIPPS score. Results SBP, DBP and MAP were lower at t1 (p<0.0001), t2 (p<0.05) and t3 (p<0.001) in the group CB. HR was lower at all studied time points (p<0.005) in the group CB. SaO2 was lower in the CB group but comparable with the GA group. PAED and CHIPPS scores were lower at 5, 10, 15, 20 and 25 minutes postoperatively (p<0.001) in the CB group. Conclusion Caudal block with analgosedation provides better control of intraoperative hemodynamic conditions, postoperative emergence delirium and postoperative pain than general endotracheal anaesthesia.

Safe pediatric procedural sedation and analgesia by anesthesiologists for elective procedures: A clinical practice statement from the European Society for Paediatric Anaesthesiology.

The growing number of medical procedures performed in children that require cooperation of patients, lack of movement, anxiolysis or/and analgesia triggers the increased need for procedural sedation. This document presents the consensus statement of the European Society for Paediatric Anaesthesiology about the principles connected with the safe management of procedural sedation and analgesia (PSA) by anaesthesiologists for elective procedures in children. It does not aim to provide a legal statement on how and by whom PSA should be performed. The document highlights that any staff taking part in sedation of children must be appropriately trained with the required competencies and must be able to demonstrate regularly that they have maintained their knowledge, skills and clinical experience. The main goal of creating this document was to reflect the opinions of the community of the paediatric anaesthesiologists in Europe regarding how PSA for paediatric patients should be organized to make it safe.

Evaluation of factors for poor outcome in preterm newborns with posthemorrhagic hydrocephalus associated with late-onset neonatal sepsis.

PURPOSE: Preterm newborns, due to many factors, are at increased risk for poor neural development, intraventricular hemorrhages, infections, and higher rate of mortality. The aim of this study was to evaluate the risk factors associated with poor outcome in preterm neonates with late-onset neonatal sepsis (LONS) who had posthemorrhagic hydrocephalus and underwent neurosurgical procedures for treatment of the hydrocephalus. PATIENTS AND METHODS: Preterm neonates who had undergone insertion of ventriculoperitoneal shunt or Ommaya reservoir, during the 10-year period at University Children's Hospital, were retrospectively analyzed. According to the presence or absence of LONS, patients were divided into LONS group and non-LONS group. In both groups, we analyzed demographic and clinical data as well as nondependent factors. Additionally, we evaluated the patients who had lethal outcome in respect to all the analyzed factors. RESULTS: A total of 74 patients were included in the study, 35 in LONS group and 39 in control group. Patients in LONS group were born significantly earlier with lower birth weight, needed significantly higher O2 inspiratory concentration, and had longer duration of mechanical ventilation when compared to the nonseptic group. Five patients in LONS group had lethal outcome, and for these patients we identified a grade American Society of Anaesthesiologists score of 4 (P=0.000), ductus arteriosus persistens (P=0.000), bronchopulmonary dysplasia (P=0.003), and pneumothorax (P=0.003) as independent preoperative risk factors for lethal outcome. CONCLUSION: Neurosurgical procedures are relatively safe in neonates with posthemorrhagic hydrocephalus without LONS after birth. However, if LONS is present, various conditions such as preoperative high grade American Society of Anaesthesiologists score, ductus arteriosus persistens, bronchopulmonary dysplasia, and pneumothorax markedly increase the risk for a lethal outcome after the operation.

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative).

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice.

The Safety and Efficacy of the Continuous Peripheral Nerve Block in Postoperative Analgesia of Pediatric Patients.

Postoperative analgesia is imperative in the youngest patients. Pain, especially if experienced during childhood, has numerous adverse effects-from psychological, through complications of the underlying disease (prolonged treatment, hospital stay, and increased costs of the treatment) to an increase in the incidence of death due to the onset of the systemic inflammatory response. Peripheral blocks provide analgesia for 12-16 h, and are safer due to rare side effects that are easier to treat. The continuous peripheral block (CPNB) has been increasingly used in recent years for complete and prolonged analgesia of pediatric patients, as well as a part of multidisciplinary treatment of complex regional pain syndrome. It has been shown that outpatient CPNB reduces the need for parenteral administration of opioid analgetics. It has also been proved that this technique can be used in pediatric patients in home conditions. Safety of CPNB is based on the increasing use of ultrasound as well as on the introduction of single enantiomers local anesthetics (ropivacaine and levobupivacaine) in lower concentrations. It is possible to discharge patient home with catheter, but it is necessary to provide adequate education for staff, patients, and parents, as well as to have dedicated anesthesiology team. Postoperative period without major pain raises the morale of the child, parents. and medical staff.

Comparison of ketamine and ketofol for deep sedation and analgesia in children undergoing laser procedure.

The aim of our study was to research and evaluate cardiovascular and respiratory stability, clinical efficacy, and safety of two different anesthetic agents in pediatric patients who underwent Pulse dye (wavelength 595 nm, pulse duration 0-40 ms, power 0-40 J) and CO2 (wavelength 10,600 nm, intensity-fraxel mod with SX index 4 to 8, power 0-30 W) laser procedure. This prospective non-blinded study included 203 pediatric patients ASA I-II, aged between 1 month and 12 years who underwent short-term procedural sedation and analgesia for the laser procedure. After oral premedication with midazolam, 103 children were analgo-sedated with ketamine and fentanyl (K group) and 100 with ketofol and fentanyl (KT group). Vital signs, applied drug doses, pulse oximetry, and parental satisfaction questionnaire were used to compare these two groups. Statistical differences were tested using Student's t test, Mann-Whitney U test, chi-square test, and Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was used to assess the cut-off value of the duration of anesthesia predicting apnea. Tachycardia was recorded in a significantly higher number of patients who received ketamine as the anesthetic agent (35.9 vs. 3% respectively). Hypertension was also significantly more frequent in patients who received ketamine in comparison with patients who received ketofol (25.2 vs. 3%). Laryngospasm was not observed in both examined groups. There was no statistically significant difference between groups in satisfaction of parents and doctors. Apnea and respiratory depression occurred significantly more frequent in ketofol than in ketamine group (12 vs. 0.97% and 13 vs. 0%). Based on ROC analysis for apnea, we found a significantly higher number of patients with apnea in the ketofol group when duration of anesthesia was longer than 17 min. Our study has shown that ketofol is more comfortable than ketamine in short-term laser procedures in children, causing less hemodynamic alteration with mild respiratory depression and less post-procedural adverse events.

A Comparison of Three Different Volumes of Levobupivacaine for Caudal Block in Children Undergoing Orchidopexy and Inguinal Hernia Repair.

OBJECTIVE: The aim of this study was to compare the efficacy of 3 different volumes of 0.25% levobupivacaine caudally administered on the effect of intra- and postoperative analgesia in children undergoing orchidopexy and inguinal hernia repair. SUBJECTS AND METHODS: Forty children, aged 1-7 years, American Society of Anesthesiologists (ASA) physical status I and II, were randomized into 3 different groups according to the applied volumes of 0.25% levobupivacaine: group 1 (n = 13): 0.6 mL∙kg-1; group 2 (n = 10): 0.8 mL∙kg-1; and group 3 (n = 17): 1.0 mL∙kg-1. The age, weight, duration of anesthesia, onset time of intraoperative analgesic, dosage, and addition of intraoperative fentanyl were compared among the groups. The time to first use of the analgesic and the number of patients who required analgesic 24 h after surgery in the time intervals within 6 h, between 6 and 12 h, and between 12 and 24 h postoperatively were evaluated among the groups. Statistical analyses were performed with a Dunnett t test, ANOVA, or Kruskal-Wallis test and χ2 test. Logistic regression analysis was used in order to examine predictive factors on duration of postoperative analgesia. RESULTS: Age, weight, duration of anesthesia, onset time of intraoperative analgesic, dosage, and addition of intraoperative fentanyl were similar among the groups. The time to first analgesic use did not differ among the groups, and logistic regression modelling showed that using the 3 different volumes of levobupivacaine had no predictive influence on duration of postoperative analgesia. The numbers of patients who required analgesics within 6 h (3/2/3), between 6 and 12 h (3/1/3), and between 12 and 24 h (1/0/2) after surgery were similar among the groups. CONCLUSION: The 3 different volumes of 0.25% levobupivacaine provided the same quality of intra- and postoperative pain relief in pediatric patients undergoing orchidopexy and inguinal hernia repair.

MOEBIUS SYNDROME: CHALLENGES OF AIRWAY MANAGEMENT.

Moebius syndrome is a rare nonprogressive congenital neurological disorder with a wide range of severity and variability of symptoms. This diversity is a consequence of dysfunction of different cranial nerves (most often facial and abducens nerves), accompanying orofacial abnormalities, musculoskeletal malformations, congenital cardiac diseases, as well as specific associations of Moebius and other syndromes. The authors present anesthesia and airway management during the multiple tooth extraction surgery in a 10-year-old girl with Moebius syndrome associated with Poland and trigeminal trophic syndromes.

Food allergy in children.

Food allergy represents a highly up-to-date and continually increasing problem of modern man. Although being present in all ages, it most often occures in children aged up to three years. Sensitization most often occurs by a direct way, but it is also possible to be caused by mother's milk, and even transplacentally. Predisposition of inadequate immune response to antigen stimulation, reaginic or nonreaginic, is of non-selective character so that food allergy is often multiple and to a high rate associated with inhalation and/or contact hypersensitivity. Also, due to antigen closeness of some kinds of food, cross-reactive allergic reaction is also frequent, as is the case with peanuts, legumes and tree nuts or cow's, sheep's and goat's milk. Most frequent nutritive allergens responsible for over 90% of adverse reactions of this type are proteins of cow's milk, eggs, peanuts, tree nuts, wheat, soy, fish, shellfish, crustaceans, and cephalopods. Allergy intolerance of food antigens is characterized by a very wide spectrum of clinical manifestations. Highly severe systemic reactions, sometimes fatal, are also possible.The diagnosis of food allergy is based on a detailed personal and family medical history, complete clinical examination, and corresponding laboratory and other examinations adapted to the type of hypersensitivity and the character of patient's complaints, and therapy on the elimination diet. A positive effect of elimination diet also significantly contributes to the diagnosis. Although most children "outgrow" their allergies, allergy to peanuts, tree nuts, fish, shellfish, crustaceans, and cephalopods are generally life-long allergies.

Congenital diaphragmatic hernia - a Belgrade single center experience.

OBJECTIVE: Though the outcome for children with congenital diaphragmal hernia (CDH) is improving, management of seriously compromised respiratory and cardiovascular function remains a great challenge. The aim of this study was to review a tertiary center experience in treating children with CDH. DESIGN: Retrospective observational study from January 2005 to December 2014. SETTING: Neonatal Intensive Care Unit (NICU) of University Children Hospital (UCH), Belgrade, Serbia. PATIENTS: Children with CDH. RESULTS: The CDH was diagnosed prenatally in 23% patients. An overall survival rate was 62%. Among those patients who underwent surgical repair 29 (90%) survived. There was statistically significant difference in survival rate between operated patients and total examined population (P=0.020). Prenatally diagnosed neonates with CDH had significantly lower survival rate comparing to those who were postnatally diagnosed (20% vs. 75%; P=0.002). Fatal outcome was more frequent in patients with small birth weight comparing to those with normal birth weight (67% vs. 30%; P=0.046). CONCLUSIONS: Our center survival rate for CDH is in accordance with other reported studies. Based on our experience there are potential points for further improvement. First, further increase of prenatal detection, planning for delivery, and coordinated transfer to tertiary institution, in order to avoid transfer of near death patients. Second, preoperative management in the NICU. This could be done by more uniform implementation of current consensual guidelines in monitoring, mechanical ventilation and circulatory support of these delicate patients, together with rationale use of newer therapeutic resources.