Complications of Mechanical Ventilation in Pediatric Patients in Serbia

Background. Mechanical ventilation is a frequently applied therapy in critically ill children and can be lifesaving in many cases. Clinical use of this technique has well documented benefits, but can be associated with different complications and adverse physiologic effects. Objectives. The aim of this study was to investigate the complications and clinical outcome of mechanical ventilation in Serbian pediatric patients. Material and Methods. The study encompassed 42 children with respiratory insufficiency that underwent mechanical ventilation during hospitalization over a period of 12 consecutive months. The influence of clinical and mechanical parameters on the occurrence of complications and clinical outcome were analyzed. Results. The patients were ventilated for a total of 432 days and a total of 61 complications were observed in 42 patients (97 complications per 1000 ventilation days). The most common complications associated with mechanical ventilation in Serbian pediatric patients with respiratory insufficiency were cardiovascular insufficiency (52.4%) and multiple organ failure (35.7%). High values of applied PIP ( gt 26 cm H2O), PEEP ( gt 6 cm H2O) and Tv ( gt 6 mL/kg) were associated with the occurrence of complications and negative clinical outcome. Conclusions. Complications of mechanical ventilation in the pediatric population occur frequently, but lower volumes/pressures of ventilation contribute to a decrease in incidence. Further studies are needed to examine associated risk factors and strategies to reduce the occurrence of complications and improve clinical outcome

Perioperativna anafilaksa kod dece u Srbiji

INTRODUCTION: Several studies have identified neuromuscular blocking agents as the most common cause of anaphylaxis during general anesthesia. The reported data vary considerably between countries. AIM: In this study we have investigated anaphylactic reactions to neuromuscular blocking agents, general anaesthetics and latex in children from Serbia. METHODS: This case series study has encompassed hypersensitivity testing in 78 children over a period of twelve consecutive months. The diagnostic protocol consisted of a case history, immunoglobulin E (IgE) testing and skin tests for hypersensitivity to neuromuscular blocking agents, general anesthetics and latex. RESULTS: Of 78 children, 63% were hypersensitive to neuromuscular blocking agents, 28% to latex, 13% to hypnotics, 10% to opioids and 15% to coloids. Sixty cases (77%) of anaphylaxis were IgE-mediated. Among children who underwent more than one intervention, the presence of cross-sensibilisation for neuromuscular blocking agents commercially available in Serbia was identified in 77% of cases. CONCLUSION: Neuromuscular blocking agents were the most frequent causal agents of anaphylaxis in Serbian children, as verified by skin tests and specific IgE tests. High frequencies of allergies to neuromuscular blocking agents and latex obtained in this study underscore the importance of carrying out an allergy study to detect an allergic cause in perioperative reactionsUVOD: Nekoliko studija je identifikovalo neuromuskularne blokatore kao najčešći uzrok anafilakse tokom opšte anestezije, ali prijavljeni podaci znatno variraju između zemalja. CILJ: U ovoj studiji ispitivane su anafilaktičke reakcije na neuromuskularne blokatore, opšte anestetike i lateks kod dece iz Srbije. METODE: Ova studija serije slučajeva obuhvatila je testiranje preosetljivosti kod 78 dece tokom perioda od dvanaest uzastopnih meseci. Dijagnostički protokol se sastojao od istorije slučajeva, testiranja imunoglobulina E (IgE) i kožnih testova za preosetljivost na neuromuskularne blokatore, opšte anestetike i lateks. REZULTATI: Od 78 ispitivane dece, 63% je preosetljivo na neuromuskularne blokatore, 28% na lateks, 13% na hipnotike, 10% na opioide i 15% na koloide. U 60 slučajeva (77%) anafilaksija je posredovana IgE-om. Među decom koja su prošla više od jedne intervencije, prisustvo unakrsne senzibilizacije za neuromuskularne bokatore komercijalno dostupne u Srbiji identifikovano je u 77% slučajeva. ZAKLJUČAK: Neuromuskularni blokatori najčešći su uzročni agensi anafilaksije kod srpske dece, što je potvrđeno testovima kože i specifičnim IgE testovima. Visoke učestalosti alergija na neuromuskularne blokatore i lateks dobijene u ovoj studiji naglašavaju važnost sprovođenja studija alergije kako bi se otkrili alergijski uzroci u perioperativnim reakcijama

Analysis of CFTR Gene Variants in Idiopathic Bronchiectasis in Serbian Children

This study has investigated a potential role of common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variants in the etiology of noncystic fibrosis bronchiectasis in Serbian children. The study has encompassed 48 patients (19 male and 29 female, aged between 5 and 18 years, median age 10.6 +/- 3.3), diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of thorax and pathologic examination of lobectomy materials. The CFTR gene analysis was performed on genomic DNA extracted from peripheral blood samples of patients by polymerase chain reaction (PCR)-Mediated Site-Directed Mutagenesis method, Denaturing Gradient Gel Electrophoresis method, and DNA sequencing. Mutation c.1521_1523delCTT (F508del) was detected with an allelic frequency of 1.0%, and c.224G gt A (R75Q) variant. Carriers of c.1210-12T[5] (IVS8-5T) allele were significantly more common than in the general population (10.4% vs. 5.0%, P = 0.0302). The frequency of homozygotes for Met 470 allele was higher in patients than in the general population (33% vs. 20%), while heterozygotes for p. Met470Val were less frequent (31% vs. 50%), and this difference was statistically significant (P = 0.0222). The results obtained in this study indicate involvement of 2 common CFTR variants, c. 1210-12T[5] and c. 1408A, in idiopathic bronchiectasis in children, but this observation should be further confirmed by more extensive analysis of the CFTR gene in a larger group of patients

Presentation of an infant with nutritional deficiency dermatitis as the initial manifestation of cystic fibrosis

Introduction. Cystic fibrosis (CF) is a multisystemic autosomal recessive disease most frequently recognized by characteristic respiratory and/or digestive manifestations. Exceptionally rare, as is the case with the infant we are presenting, the initial sign of the disease can be nutritional deficiency dermatitis (NDD). Case Outline. A three-month-old male infant of young and healthy non-consanguineous parents, born at term after the first uneventful pregnancy, was hospitalized due to atopic dermatitis (AD)-like skin changes, failure to thrive and normochromic anemia (Hb 60 g/L). As exclusively breast-fed, failure to thrive was attributed to hypogalactia and skin changes to nutritional allergy, so that, besides exclusion of cow’s milk protein and other highly allergenic foods in mother’s diet, hypoallergenic milk formula was added to the child’s diet. However, dietetic measures were without effect, and the child was re-hospitalized at age 4.5 months, this time in the condition of severe malnutrition with hypoproteinemic edemas, extensive dermatitis, moderate hepatosplenomegaly and recurrent normochromic anemia (Hb 57 g/L). After plasma-free erythrocyte transfusion, correction of hypoalbuminemia and two-week parenteral and semi-elementary nutrition resulted in gradual recovery of the child, also including the resolution of skin changes. Having in mind the clinical course of the disease, as well as the response to applied therapeutic measures, CF was suspected as the cause of the child’s problems, which was also confirmed by a high level of sweat chlorine (92 mmol/L) and DNA analysis (∆F508/∆F508). Conclusion. Our experience indicates that NDD, as the initial manifestation of CF, should be also kept in mind in differential diagnosis of the infant’s AD-like changes

Desensitization with DTP (diphtheria, tetanus and pertussis) vaccine

Immunization with DTP vaccine (diphtheria, tetanus and pertussis) is a part of the vaccination calendar offered in childhood. Adverse allergic reactions vary from minimal urticarial reactions to life-threatening anaphylaxis. In infancy these reactions usually interrupt the vaccination calendar, but immunization in these children should be done. At the University Children's Hospital of Belgrade, a group of 137 children with suspected allergic anaphylactic reaction to DTP, DT, TT and monopertussis vaccine was studied for the last six years. Skin (prick and intradermal) tests were performed with corresponding vaccine. If both tests were negative, the vaccine could be given as a single dose of 0.5 ml. If one of these tests were positive desensitization with vaccine could be done (according to the protocol described by Carey and Meltzer). In one group of 52 children three days before desensitization, premedication with antihistamines, was done, whereas in the other group of 52 children premedication was not done. Two (3.8%) children in a group of 52 children with premedication had a minor (local) reaction after vaccination and 50 children (96.2%) had no reaction after vaccination, whereas no children (0%) had systemic reaction after desensitization

Allergy to cephalosporin antibiotics in children

A particular problem is the safety of administering cephalosporins to penicillin-allergic children, because cephalosporin allergenic determinants have not been properly identified. Cephalosporin antibiotics are widely used to treat common infections and are often the first-line prophylaxis before many types of surgery. So the arm of this study is to determine the frequency of allergic reactions of anaphylactic type to cephalosporins and their cross-reactivity with penicillins. At University Children’s Hospital in Belgrade a group of 1,170 children with suspected anaphylactic allergic reaction to penicillins and/or cephalosporins were tested for the last eight years. Skin tests were performed with standard concentration of penicillins and cephalosporins. In children where skin tests were negative single-blind placebo-controlled challenges were performed. In case of positive skin tests further examinations were interrupted and the children were considered allergic to that drug. The frequency of anaphylactic allergic reactions to cephalosporins is 0.2 % to 17 %, and depends on cephalosporins generation. The cross-reactivity between cephalosporins and penicillins is 0.1 % to 14.5 %, and among cephalosporins is 0 % to 11.7 %

Influence of the Polymorphism C-509T in the TGFB1 Gene Promoter on the Response to Montelukast

Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine with a key role in asthma airway inflammation and remodeling. Since elevated levels of this cytokine in airways might be associated with response to asthma therapy, the aim of this study was to investigate whether the presence of the polymorphism C-509T in the promoter of the TGFB1 gene is associated with response to montelukast. A group of 102 asthmatic patients was genotyped for the presence of the C-509T polymorphism by DNA sequencing and subjected to induced sputum sampling. Cells from sputum samples and BEAS 2B cells were treated with montelukast and endogenous TGFB1 expression was measured by quantitative real-time polymerase chain reaction. The promoter activity was analyzed by luciferase assays in BEAS 2B cells transfected with constructs carrying variants -509C and -509T of the TGFB1 gene promoter. After treatment with montelukast, the decrease in TGFB1 gene expression was greater for the -509TT genotype (58.9%) than for the -509CC and -509CT genotypes (49.6% and 31.8%, respectively) (P=0.071). In BEAS 2B cells, expression of endogenous TGFB1 was reduced by about 27% after montelukast treatment, while luciferase activity of both promoter variants was increased after montelukast treatment (-509C allele: 48.3%, P=0.060; and -509T allele: 100.5%, P=0.062). A more intensive response was registered in the promoter containing the -509T allele, which had 135% higher activity than the -509C variant (P=0.035). This study showed that the presence of the -509T allele in the TGFB1 promoter might modulate effects of montelukast on TGFB1 gene expression, but future studies are necessary, taking into consideration other genetic and nongenetic factors. It is of potential importance for clinical management of asthma to clarify the influence of the C-509T polymorphism on the response to treatment with montelukast

Response to salbutamol in children with acute asthma exacerbations

The aim of this study was to investigate response to salbutamol in children with acute asthma exacerbations in order to estimate the efficiency and safety of its administration in pediatric population. The study included 56 children with asthma (age range 5-12) who were diagnosed and treated over a period of two years. In all children, salbutamol was administered via nebulization, in doses of 1.25 mg in children aged 5-6 and 2.5 mg in children aged 7-12. Respiratory and blood parameters were monitored before and 30 minutes after salbutamol administration. In children with acute asthma exacerbations, respiratory frequency, potassium level, sodium level and PaCO, decreased significantly after salbutamol administration, while PEF, PEF%, glycemia, PaO2 and SatO(2) significantly increased. Hypokalemia due to salbutanzol effect occurred in 15 (26.8%) children. Most significant improvement in oxygenation, with increase of PEF, PEF%, PaO2 and SatO(2), after salbutamol administration was achieved in patients with mild acute exacerbations. Salbulanzol administered via nebulization leads to the occurrence of adverse metabolic elfe cts, hypokalemia and hyperglycemia. Howevez; it can be safely used in the treatment of acute asthma exacerbations and demonstrates high clinical efficacy in the management of acute bronchospasm. The most effective salbutamol treatment is achieved in patients with mild exacerbations

Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis?

The aim of this study was to investigate polymorphisms in the promoter region of the neutrophil elastase (ELANE) gene as potential modulators of the therapeutic response in children with idiopathic bronchiectasis. The study included 48 children between 5 and 17 years old who were diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of the thorax. In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants, and postural drainage. Response to therapy was evaluated by the change in FeNO levels before and after administration of therapy. The ELANE promoter region polymorphisms were analyzed by PCR-direct DNA sequencing. According to the predicted activity of ELANE genotypes, subjects were divided into two groups: low/intermediate activity (n = 18) and high activity (n = 30). Subjects in the group with high-activity genotype had higher initial FeNO levels and this difference was statistically significant (t = 2.906; p = 0.006). The difference between FeNO levels before and after therapy was also statistically significantly higher in children with high-activity genotype (t = 3.329; p = 0.002). Statistically significant correlation was observed between the change in FeNO levels and ELANE genotypes (r = 0.350; p = 0.015). Children with high-activity genotype had higher initial FeNO levels and showed better response to therapy than children with low/intermediate-activity genotypes

Anaphylaxis followed by unilateral lung opacity and hypocomplementemia in a young female

A 36-year-old woman was stung in the right wrist by a bee, suffered typical anaphylaxis, and was transferred to a local hospital. After a few hours, which corresponded to late-onset reaction, she developed shortness of breath and weakness and was transferred to the emergency department, where the diagnosis of anaphylaxis was confirmed. Serum complement levels, components C3 and C4, were undetectable. Flexible bronchoscopy excluded lung hemorrhage. She was on the ventilator for 4 days and was fully awake during that time. After the treatment, her improvement was rapid, and she fully recovered. Three weeks after she had been stung by a bee, skin prick tests to bee, wasp, and yellow jacket venom were done, and all tests came back negative as well as IgE and IgG4 antibodies to the same venoms. Coagulation factors and the complement, including C1q inhibitor, were normal. Occurrence of complement activation and consumption could point to the immune complexes as basis of pathophysiological mechanism. It remains unclear why such a reaction would involve only the right lung and why no detectable immune complexes were discovered. The clinical picture in the presented case resembled acute respiratory distress syndrome, but the exact nature of lung consolidation remains puzzling. The most likely explanation is a very rare case of airway obstruction. To our knowledge, this is the only reported case of anaphylaxis associated with undetectable serum complement levels. The potential role and diagnostic significance of hypocomplementemia in cases of anaphylaxis should be further investigated