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.

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.

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.

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.

[Peripheral nerve blocks in paediatric anaesthesia].

INTRODUCTION: Most children undergoing surgery can benefit from regional anaesthetic techniques, either as the sole anaesthetic regimen or, as usual in paediatric practice, in combination with general anaesthesia. The use of peripheral nerve blocks (PNBs) in paediatric anaesthesia is an effective way to decrease the side-effects and complications associated with central blocks. In spite of their many advantages, including easy performance end efficacy, peripheral nerve blocks are still underused. OBJECTIVE: This article discusses a general approach to PNBs in children and provides data concerning the practice of this regional technique in different age groups. METHODS: Data from 1,650 procedures were prospectively collected during the period from March 1, 2007 to February 29, 2008. The type of PNB, if any, as well as the patient age were noted. Our patients were divided into four groups: 0-3 years, 4-7 years, 8-12 years and 13-18 years. RESULTS: During the investigated period, PNBs as a sole technique or in anaesthetized children were performed in 7.45% of cases. Ilioinguinal/iliohypogastric nerve block and penile block were the most common (70% of all PNBs) distributed mainly among the children between 4-7 years of age (p < 0.05). In older children, extremity PNBs predominate in regard to other types of blocks. PNBs are most frequently performed under general anaesthesia (85%), so the perineural approach requires a safe technique to avoid nerve damage. CONCLUSION: The observed differences in PNB usage seem to be related to patient age and correlate with common pathology and also with technical availability of PNB performance.

[Myocarditis exacerbation in a child undergoing inguinal herniopasty after viral infection].

INTRODUCTION: Immunosuppressive effects of general anaesthesia and surgery could have unexpected consequences in a child with recent infection. The incidence of myocarditis in childhood is unknown. CASE OUTLINE: During general anaesthesia for inguinal hernia repair, a seven-year-old boy suddenly developed heart failure. Clinical presentation included hypotension, pulmonary oedema, drop in haemoglobin oxygen saturation, ST segment elevation and premature ventricular contractions. Haemodynamic stability and adequate oxygenation were achieved with dopamine and furosemide. Preoperative history, physical examination and complete blood count were unremarkable. Moderate cardiomegaly and pulmonary oedema were present on chest radiography. Diminished left ventricular contractility found on echocardiography increased troponin I and CK-MB levels suggested myocardial injury. Increased C-reactive protein with lymphocytosis suggested inflammation as its cause. Parents failed to report rubella 10 days before the operation. A clinical diagnosis of myocarditis as a complication of rubella was based on increased titer of IgM to rubella. With intravenous immunoglobulin, corticosteroids and symptomatic treatment for heart failure, his condition improved and ejection fraction reached 68% one month after operation. CONCLUSION: In future, we need protocols with instructions for paediatric patients undergoing elective surgery and anaesthesia after viral infections.