Çağlar Ödek

The use of colistin in critically ill children in a pediatric intensive care unit.

Background: Colistin is active against most multidrug-resistant, aerobic Gram-negative bacteria. Because of the reported nephrotoxicity during the first years of use of colistin, there were concerns of its use in pediatrics where there was limited experience The aim of this study is to document the clinical characteristics and outcomes of use of colistin in pediatric patients at a pediatric intensive care unit in Turkey. Methods: We reviewed the medical and laboratory records of 29 critically ill children who were treated with colistin for 38 courses between January 2011 and December 2011 at the Department of Pediatric Intensive Care Unit in Ankara University Medical School, Turkey. Results: The median age was 17 months (range 3–217 months). Male-to-female ratio was 1:1.37. Ventilator-associated pneumonia (21 courses) was the leading diagnosis followed by catheter-related blood stream infection (6 courses), bacteremia (4 courses), ventriculoperitoneal shunt infection, peritonitis and pneumonia (1 course). The most commonly isolated microorganisms were Acinetobacter baumanni, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, and Enterobacter cloacae. Two colistin formulations were used. Colimycin (Kocak Farma) was used in 21 colistin treatment episodes. The median dosage of colistin in this group was 5.0 mg/kg/d (2.3–5.6 mg/kg/d). Colomycin (Forest Laboratories) was used in 17 colistin treatment episodes. The median dosage of colistin in the second group was 75,000 International Unit/kg/d (50,000–80,000 International Unit/kg/d). Thirty colistin treatment episodes (79%) had a good or partial clinical response and 8 (21%) had a poor clinical response. Of the 8 colistin treatment episodes with poor clinical response, 3 were in the Colimycin group and 5 were in the Colomycin group. Ten patients died. There was no evidence of neurotoxicity in this study. Nephrotoxicity was observed in 1 patient but was not attributed to colistin because the patient had multiorgan failure at the same time. Conclusions: This study in a small cohort of patients suggests that the use of colistin in severe nosocomial infections caused by multidrug-resistant Gram-negative bacteria is well-tolerated and efficacious.

Efficacy of noninvasive mechanical ventilation in prevention of intubation and reintubation in the pediatric intensive care unit.

PURPOSE To determine the efficiency of noninvasive mechanical ventilation (NIV) both in protection from intubation and in preventing reintubation of postextubation in patients in the pediatric intensive care unit (PICU). METHODS A prospective observational study was conducted in a multidisciplinary 10-bed tertiary PICU of a university hospital. All patients were admitted to our unit from June 2012 to May 2014 and deemed to be candidates to receive continuous positive airway pressure or bilevel positive airway pressure. MEASUREMENTS AND RESULTS We performed 160 NIV episodes in 137 patients. Their median age was 9 months (range, 1-240 months), and their median weight was 7.5 kg (range, 2.5-65 kg). Fifty-seven percent of patients were male. Noninvasive mechanical ventilation was successful in 70% (112 episodes) of patients. There was an underlying illness in 83.8% (134 episodes) of the patients. Bilevel positive airway pressure support was given to 57.5% (92 episodes) of the patients, whereas the remaining 42.5% (68 episodes) received continuous positive airway pressure support. Among the causes of respiratory failure in our patients, the most frequent were postextubation, pneumonia, bronchiolitis, atelectasia, and cardiogenic pulmonary edema. Sedation was applied in 43.1% of the episodes. Complications were detected in 29 episodes (18.1 %). The NIV failure group showed higher Pediatric Risk of Mortality III-24 score, shorter NIV duration, more frequent underlying disease, lower number fed, longer length of PICU stay, and hospital stay, and mortality was higher. CONCLUSIONS Noninvasive mechanical ventilation effectively and reliably reduced endotracheal intubation in the treatment of respiratory failure due to different clinical situations. Our results suggest that NIV can play an important role in PICUs in helping to avoid intubation and prevent reintubation. Although there were serious underlying diseases in most of our patients, such as immunosuppression, 70% avoided intubation with use of NIV.

Valproic acid-induced acute pancreatitis and multiorgan failure in a child.

Valproic acid (VPA) is still an important antiepileptic drug, with the broadest spectrum used in all types of seizures and syndromes. It has serious adverse effects such as hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. The incidence of VPA-associated pancreatitis has been estimated to be 1:40,000. We present a 6-year-old boy who developed acute pancreatitis (AP) and multiple-organ failure after 3 months of VPA therapy. The patients laboratory values showed that his kidney and hepatic function had impaired and thrombocytopenia, and coagulopathy had developed. The patients abdominal tomography showed a suspected appearance, which was consistent with pancreatitis. Because amylase and lipase levels were found to be high, AP was considered. The patient improved after cessation of VPA treatment. Ten days later, the patient recovered both clinically and laboratorial. Consequently, the patient was discharged with cure. In conclusion, AP is a rare, severe adverse reaction to VPA treatment. If a child, who is receiving VPA, develops abdominal pain and vomits, VPA-associated pancreatitis must be considered.

Oxcarbazepine and valproic acid‐induced lupus in a 7‐year‐old boy

Sir, Various drugs have been reported to cause symptoms and laboratory findings that closely resemble lupus. The disorder is known as drug-induced lupus erythematosus (DILE) and it is generally seen in adults. Among different drugs, anticonvulsants—most commonly carbamezepine, ethosuximide and diphenylhydantoin—have been implicated to cause DILE (1,2). In this report, we present an oxcarbazepine and valproic acid-induced DILE in a small boy and we aimed to draw attention to this rare disorder in childhood. A 7-year-old boy was admitted to our hospital with the complaints of fever, loss of appetite, diffuse arthralgias, myalgias, weight loss, swelling of the finger and toe joints. He had experienced recurrent seizures since 4 years of age and had used multiple antiepileptic agents. Six months ago—while on single oxcarbazepine therapy—he began to complain about diffuse arthralgias and morning stiffness. In another centre, elevated erythrocyte sedimentation rate (ESR) (50 mm/h), C-reactive protein (CRP) (1 mg/dL) and antinuclear antibody (ANA) positivity (1/160) were detected. Naproxen was commenced for his pain. However, intermittent arthralgias and arthritic episodes persisted during the follow-up. Three months ago, valproic acid was added due to ongoing seizures and 2 months ago levetiracetam was started and oxcarbazepine was reduced. One week after the drug alteration, corresponding to 45 days after the onset of valproic acid treatment (while on tripple therapy), his current complaints began and continued for about 1 month. Physical examination revealed generalized lymphadenopathy, hepatosplenomegaly, arthritis in his proximal interphalangial joints of the hands, wrists and ankles. Laboratory tests were as follows; urinalysis: normal, Hb: 10.7 g/dL, WBC: 2800/mm3, Plt: 284 000/mm3, ESR: 87 mm/hr, CRP: 7.6 mg/dL (0–0.8), C3: 92.6 mg/dL and C4: 15 mg/dL, urea: 11 mg/dL, creatinine: 0.4 mg/dL, protein: 6.85 g/dL, albumin: 3.2 g/dL, D. Coombs: +++, ANA: ++++ (1/1000), anti-histone ab: +, anti nucleosome ab: +. Anti-ds DNA, ANCA, anticardiolipin, anti-Sm antibodies and bone marrow aspiration findings were normal. Drug-induced lupus was diagnosed together with the clinical and laboratory findings. Oxcarbazepine was stopped, valproic acid was gradually reduced and stopped, steroid treatment was started for persistent severe symptoms. Clinical findings vanished on the second day of steroid therapy. Laboratory tests were as follows 2 weeks later; Hb: 12.3 g/dL, WBC: 13 300/mm3, Plt: 325 000/mm3, ESR: 10 mm/h, CRP: 0.79 mg/dL, protein: 7.6 g/dL, albumin: 4.2 g/dL. Anti-histone ab returned to normal at the end of the first month and ANA was + (1/80) on the seventh month. The differential diagnosis of a patient with persistent fever, weight loss, arthralgias, myalgias and generalized malaise encompass serious conditions including malignancies, systemic infections and connective tissue diseases. Drug-induced complications should also be recalled in such patients; however, they are usually overlooked in the paediatric population. Overall, approximately 10% of SLE cases have been reported to occur secondary to drugs (3); whereas the exact incidence of DILE in childhood is unknown. Any symptom regarding the broad spectrum of manifestations seen in lupus can be present in DILE, however, arthralgias, myalgias, fever and serositis are common characteristic presenting symptoms (1,2). Presence of anti-histone antibodies in the absence of the other specific antinuclear antibodies is a typical finding of DILE. Herein, we draw attention of paediatricians to this rare but important disorder, in this case due to a new generation antiepileptic, oxcarbazepine. Oxcarbazepine is structurally a derivative of carbamazepine, with an extra oxygen atom on the dibenzazepine ring. This difference helps to reduce its impact on liver and also its side effects. The mechanism of oxcarbazepine is same as carbamazepine—sodium channel blockageand it is usually used to treat similar conditions (4,5). Carbamazepine is metabolized to reactive intermediates by activated leukocytes and such metabolites could be responsible for some

A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation.

Abstract Niemann-Pick disease type C (NPC) is a fatal autosomal recessive lipid storage disease associated with impaired trafficking of unesterified cholesterol and glycolipids in lysosomes and late endosomes. This disease is commonly characterized by hepatosplenomegaly and severe progressive neurological dysfunction. There are two defective genes that cause this illness. One of these genes is NPC1 gene which is the cause of illness in 95% of the patients. The other gene is the rare type NPC2 which is the cause of illness in 5% of the patients. Patients with NPC2 usually present with respiratory distress in early infancy, which is rather unusual with NPC1. This article discusses about a patient who died at an early age from pulmonary involvement and who subsequently was found to have a novel homozygous mutation of NPC2 gene.

Cyclosporine-associated thrombotic microangiopathy and thrombocytopenia-associated multiple organ failure: a case successfully treated with therapeutic plasma exchange.

Introduction: Thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis, thrombocytopenia, and microangiopathic hemolytic anemia. Previous studies have shown that cyclosporine (CsA) is associated with TMA but the number of reported cases is very limited. We describe a 13-year-old girl with CsA-associated TMA and thrombocytopenia-associated multiple organ failure (TAMOF). Case Report: The patient was diagnosed with polyglandular deficiency syndrome and had a history of celiac disease, autoimmune thyroiditis, and diabetes mellitus type I. CsA was started 7 months before her admission to our pediatric intensive care unit for persistent diarrhea associated with celiac disease. At the time of her admission to our pediatric intensive care unit, she was thrombocytopenic and anemic with multiple organ failure. Laboratory and clinical findings were consistent with TMA and TAMOF. CsA was discontinued and therapeutic plasma exchange was performed daily for 5 days. The patient improved clinically, laboratory findings normalized, and TMA and multiple organ failure dissolved. Conclusion: This case report indicates that therapeutic plasma exchange may be effective in the treatment of CsA-associated TMA and TAMOF, especially in the presence of systemic findings.

Pressure-induced angioedema associated with endotracheal tube: successful treatment with epinephrine in two cases.

Pressure-induced urticaria is a non-immunoglobulin E-mediated type of urticaria. Some patients only have angioedema, and the term pressure-induced angioedema (PIA) is more appropriate for them. PIA has not previously been reported in association with endotracheal tube. Here we describe two patients who developed PIA after endotracheal intubation. There were no histories of angioedema, drug and food allergy in both patients. Tests for specific aero-allergens and latex were negative. Serum total immunoglobulin E and C4 levels were in normal ranges. Antihistamines and intravenous steroid therapy were ineffective. Angioedema regressed with intravenous epinephrine infusion and did not relapse after extubation. Conclusion: We suggest that endotracheal tubes can cause PIA. Epinephrine therapy should be used early at treatment, especially in the patients who are at great risk for life-threatening airway problems.

Acute reversible cardiomyopathy and heart failure in a child with acute adrenal crisis.

Acute adrenal crisis is a life-threatening disorder. Cardiovascular complications of the condition are usually limited to hypovolaemic hypotension and shock. An acute reversible cardiomyopathy and heart failure in association with acute adrenal crisis is rarely reported, particularly in children. A 6-year-old girl with adrenal crisis which was complicated by acute reversible cardiomyopathy is reported. Inotropic and ventilatory support in addition to intravenous hydrocortisone and furosemide therapy were required to achieve cardiovascular stability. The cardiomyopathy resolved over 5 days and she was discharged with normal cardiac and intellectual functions. Cardiomyopathy should be considered in patients with acute adrenal crisis demonstrating any symptoms or signs of heart failure.