The Impact of Opioid Receptor Gene Polymorphism on Fentanyl and Alfentanil's Analgesic Effects in the Pediatric Perioperative Period.

Introduction: The polymorphism of the gene coding mu-opioid receptor (OPRM1) is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages. Methods: This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil. Postoperative pain was rated using Numerical Rating Scale (0-10). All the patients were genotyped forOPRM1 118A>G (rs1799971) gene polymorphism. Results: School children under the age of 11 with the OPRM1 AA genotype were shown to have a higher BMI (p<0.05). Children over the age of 12 carrying G allele OPRM1, had increased postoperative pain sensitivity and intensity (3.28±1.95 vs 4.91±2.17; p<0.05), as compared to AA allele carriers. Discussion: OPRM1 118A>G polymorphism may explain the variation in the perception of postoperative pain in children over the age of 12 and may be a useful predictor for adjusting the dose of analgesics, but the dose is relative to the patient's needs regardless of his genetic characteristics. In younger children, carriers of polymorphic OPRM1 118G allele may be protected from obesity, due to diminished MOP expression.

Neglected Monteggia Fractures in Children-A Retrospective Study.

(1) Background: A Monteggia fracture is an infrequent injury in children. It can be missed during an initial consultation in 20-50% of patients. Chronic radial head dislocation may lead to several complications. Thus, surgical reconstruction of chronic Monteggia injuries is justified. The aim of this study is to analyze the single tertiary center experience in the treatment of neglected Monteggia fractures. (2) Methods: A retrospective study of patients treated for missed Monteggia fractures was conducted. Hospital records, operative charts, follow-up records and a set of X-rays were analyzed for each patient. Radiographic results were graded as good, moderate or poor. The functional status of elbows was estimated using the Mayo Elbow Performance Index. (3) Results: A total of 13 patients (8 boys and 5 girls) aged 4-12 years (mean 7.15) were treated during the study period. An angulation osteotomy of the ulna was performed in ten patients and a radial shortening osteotomy in three patients. A Bell-Tawse annular ligament reconstruction was performed in five patients, and a direct repair was performed in two patients. Eight patients had radiocapitellar trans-fixation. There were nine good radiographic results, three moderate and one poor. The functional result was excellent in nine patients, good in three and poor in one. (4) Conclusions: Our work has many limitations (only 13 patients and different types of operations), and conclusions should be drawn very carefully from such a small and diverse group. The surgical reconstruction of neglected Monteggia fractures in children should be attempted in all patients. Angulation and elongation osteotomies of the ulna are suitable for most patients. If there is a marked overgrowth of the radius, gradual ulnar lengthening and radial head reduction using the Ilizarov method may be a better option. Annular ligament reconstruction is not mandatory.

Consequences of Transplacental Transmission of the SARS-CoV-2 Virus: A Single-Center Experience.

The issues of vertical viral transmission from mother to fetus and the potential complications caused by SARS-CoV-2 coagulopathy are still unclear. There are few literature data about the vertical transmission of SARS-CoV-2 and health outcomes in neonates born to mothers with symptomatic or asymptomatic coronavirus disease, with the existing data based on small sample sizes. This case series study consists of two newborn children (one pre-term and one term) who were born to SARS-CoV-2-positive mothers and admitted to the neonatal intensive care unit a few hours after birth. One child had cyanotic changes that affected the entire left leg and the left forearm, with multiple livid changes on the front of the chest and abdomen, the right upper arm, right thigh, neck, and face, and one child had an altered umbilical cord. The first child was treated conservatively, and the second child was treated surgically.

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.

Perioperative respiratory adverse events during ambulatory anesthesia in obese children.

Obesity is one of the most common clinical conditions in the pediatric population with an increasing prevalence ranging from 20 to 30% worldwide. It is well known that during ambulatory anesthesia, obese children are more prone to develop perioperative respiratory adverse events (PRAEs) associated with obesity. To avoid or at least minimize these adverse effects, a thorough preoperative assessment should be undertaken as well as consideration of specific anesthetic approaches such as preoxygenation before induction of anesthesia and optimizing drug dosing. The use of short-acting opioid and nonopioid analgesics and the frequent implementation of regional anesthesia should also be included. Noninvasive airway management, protective mechanical ventilation, and complete reversion of neuromuscular blockade and awake extubation also proved to be beneficial in preventing PRAEs. During the postoperative period, continuous monitoring of oxygenation and ventilation is mandatory in obese children. In the current review, we sought to provide recommendations that might help to reduce the severity of perioperative respiratory adverse events in obese children, which could be of particular importance for reducing the rate of unplanned hospitalizations and ultimately improving the overall postoperative recovery.

Importance of a Follow-Up Ultrasound Protocol in Monitoring Posttraumatic Spleen Complications in Children Treated with a Non-Operative Management.

Background and objectives: For the last three decades, non-operative management (NOM) has been the standard in the treatment of clinically stable patients with blunt spleen injury, with a success rate of up to 95%. However, there are no prospective issues in the literature dealing with the incidence and type of splenic complications after NOM. Materials and methods: This study analyzed 76 pediatric patients, up to the age of 18, with blunt splenic injury who were treated non-operatively. All patients were included in a posttraumatic follow-up protocol with ultrasound examinations 4 and 12 weeks after injury. Results: The mean age of the children was 9.58 ± 3.97 years (range 1.98 to 17.75 years), with no statistically significant difference between the genders. The severity of the injury was determined according to the American Association for Surgery of Trauma (AAST) classification: 7 patients had grade I injuries (89.21%), 21 patients had grade II injuries (27.63%), 33 patients had grade III injuries (43.42%), and 15 patients had grade IV injuries (19.73%). The majority of the injuries were so-called high-energy ones, which were recorded in 45 patients (59.21%). According to a previously created posttraumatic follow-up protocol, complications were detected in 16 patients (21.05%). Hematomas had the highest incidence and were detected in 11 patients (14.47%), while pseudocysts were detected in 3 (3.94%), and a splenic abscess and pseudoaneurysm were detected in 1 patient (1.31%), respectively. The complications were in a direct correlation with injury grade: seven occurred in patients with grade IV injuries (9.21%), five occurred in children with grade III injuries (6.57%), three occurred in patients with grade II injuries (3.94%), and one occurred in a patient with a grade I injury (1.31%). Conclusion: Based on the severity of the spleen injury, it is difficult to predict the further course of developing complications, but complications are more common in high-grade injuries. The implementation of a follow-up ultrasound protocol is mandatory in all patients with NOM of spleen injuries for the early detection of potentially dangerous and fatal complications.

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.

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.

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.

Therapeutic role of methotrexate in pediatric Crohn's disease.

The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in CD include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX). Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines only or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of MTX in children suffering from CD. This review summarizes the literature on the therapeutic role of MTX in children with CD. MTX is often administered as a second-line immunomodulator, and 1-year clinical remission was reported in 25-69% of children with CD after excluding for the use of thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first-line immunomodulator in pediatric patients with CD, are promising. A definite conclusion, however, may only be made on the basis of additional research with a larger number of subjects.

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.

Management of Anesthesia in a Child with a Large Neck Rhabdoid Tumor.

OBJECTIVE: The aim of this paper was to report the management of anesthesia of a child with a large neck rhabdoid tumor. CLINICAL PRESENTATION AND INTERVENTION: A 9-month- old female patient underwent urgent neck tumor excision due to intratumoral bleeding from a large tumor that compressed and dislocated the trachea; therefore, intubation was expected to be difficult. Sevoflurane inhalation induction was utilized to maintain spontaneous respiration. Oral laryngoscopy revealed Cormack-Lehane grade 3 laryngeal view. The trachea was intubated using a reinforced tube on the third attempt. Fiberoptic bronchoscope-assisted intubation was planned as an alternative in case of conventional intubation failure. Anticipation of massive blood loss necessitated central venous catheterization. CONCLUSION: Establishing a safe airway, intubation during spontaneous breathing and invasive hemodynamic monitoring are crucial factors in the anesthetic management of pediatric patients with a large neck tumor.

Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children's age: impact of anesthetic chemical structure.

OBJECTIVES: The aim of this study was to determine the relationship between the antioxidant profile of anesthetics and its relation to total antioxidant capacity (TAC) of plasma in children who underwent tourniquet-induced ischemia-reperfusion (IR) injury during extremity operations. METHODS: Children were randomized into three groups: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia (TIVA) with propofol (group T), and regional anesthesia (group R). Venous blood samples were obtained before peripheral nerve block and induction of general anesthesia (baseline), 1 minute before tourniquet release (BTR), and 5 and 20 minutes after tourniquet release (ATR). Plasma TAC as well as antioxidant potential of propofol, thiopental, and bupivacaine were measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: Plasma TAC in group T was increased significantly at 20 minutes ATR in comparison with basal and BTR values, and also was significantly higher in comparison with plasma TAC in groups S and R measured at the same time point. The radical scavenging activity of anesthetics in vitro indicated that only propofol possessed a significant antioxidative activity in the reaction with DPPH radical in comparison with thiopental and bupivacaine. DISCUSSION: These data confirm that TIVA with propofol attenuates oxidative stress related to tourniquet-induced ischaemia-reperfusion injury in children.

[Anaesthesia for noncardiac surgery in children with congenital heart disease].

Children with Congenital Heart Disease (CHD) presenting for non-cardiac surgery have various physiological and functional abnormalities and thus pose great challenges to the anaesthesiologist. The principles of anaesthesia are to minimize pathophysiological changes which may upset the complex interaction between systemic and pulmonary vascular resistance. Knowledge of the specific cardiac anatomy, familiarity with the modifications of the cardiorespiratory physiology, the awareness of the potential risks of complications for each individual case are mandatory for the choice of the anaesthesia strategy for each patient. During the preoperative assessment, the risk-benefit ratio should be estimated and preoperative plan established in order to optimize the preoperative status. An anaesthesiologist must also understand pharmacology of drugs being used and should tailor anaesthetic management to the type of surgery. An interdisciplinary team approach is the cornerstone for the safe delivery of anaesthesia to this paediatric patient population. The team should comprise an anesthesiologist, a paediatric cardiologist, a surgeon, a cardio-surgeon and a neonatologist. This review is meant to explain the classification of congenital heart diseases and to equip the anaesthesiologist with the necessary information about preoperative assessment, anaesthesiology management, monitoring tools important for the safe non-cardiac surgery procedures as well as therapeutic strategies during the postoperative period.

The effects of different anesthesia techniques on free radical production after tourniquet-induced ischemia-reperfusion injury at children's age.

BACKGROUND/AIM: Reperfusion of previously ischemic tissue leads to injuries mediated by reactive oxygen species. The aim of the study was to investigate the effects of different anesthesia techniques on oxidative stress caused by tourniquet-induced ischemia-reperfusion (IR) injury during extremity operations at children's age. METHODS: The study included 45 patients American Society of Anesthesiologists (ASA) classification I or II, 8 to 17 years of age, undergoing orthopedic procedures that required bloodless limb surgery. The children were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release (BTR), 5 and 20 min after tourniquet release (ATR). Postischemic reperfusion injury was estimated by measurement of concentration of malondialdehyde (MDA) in plasma and erythrocytes as well as catalase (CAT) activity. RESULTS: Plasma MDA concentration in the group S was significantly higher at 20 min ATR in comparison with the groups T and R (6.78 +/- 0.33 micromolL-1(-1) vs. 4.07 +/- 1.53 and 3.22 +/- 0.9. micromolL-1(-1), respectively). There was a significant difference in MDA concentration in erytrocythes between the groups S and T after 5 min of reperfusion (5.88 +/- 0.88 vs. 4.27 +/- 1.04 nmol/mlEr, p < 0.05). Although not statistically significant, CAT activity was slightly increased as compared to baseline in both groups S and R. In the group T, CAT activity decreased at all time points when compared with baseline, but the observed decrease was only statistically significant at BTR (34.70 +/- 9.27 vs. 39.69 +/- 12.91 UL-1, p < 0.05). CONCLUSION: Continuous propofol infusion and regional anesthesia techniques attenuate lipid peroxidation and IR injury connected with tourniquet application in pediatric extremity surgery.

[Anaesthesia in children with inherited neuromuscular diseases].

Children with inherited neuromuscular diseases often require anaesthesia for diagnostic or therapy procedures. These patients have an increased risk of perioperative complications due to the nature of the disease and medications administered during anaesthesia. Many anaesthetics and muscle relaxants can aggravate the underlying disease and trigger life-threatening reactions (cardiorespiratory complications, malignant hyperthermia). Besides, the neuromuscular disorders are associated with atypical and undesirable responses to drugs used during anaesthesia and the perioperative period. The paper presents pathophysiological basis of inherited/genetic neuromuscular diseases and specific anaesthesiological problems. The recommendations are suggested with the aim to make the perioperative course in children optimally safe.