Kadir Serafettin Tekgunduz

Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis

Objectives We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure. Data source MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles. Study selection Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA. Data extraction Data regarding efficacy and safety were collected and analysed. Results Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel–Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar. Conclusions Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far.

Intravenous Paracetamol for Patent Ductus Arteriosus in Premature Infants - A Lower Dose Is Also Effective

babies with hsPDA. The first patient was a 29-week premature infant (birth weight 1,045 g, postnatal age 3 days). Oral ibupro-fen was contraindicated in this patient due to suspected necrotizing enterocolitis (NEC). We started IV paracetamol with the dose regimen suggested by Oncel et al. [1] . After the first 4 doses, transaminase levels were checked and a significant increase was detected compared to pretreatment levels (aspartate aminotransferase (AST) 43 vs. 260 U/l, alanine aminotransferase (ALT) 11 vs. 180 U/l). The drug was ceased and transaminase levels normalized over the following 4 days. After this experience, we decreased each dose to 10 mg/kg (3 doses/day). An echocardiographic study was per-formed after each of the 3 doses. If the duc-tal shunt had disappeared, treatment was stopped, but if it persisted, an additional 3 doses were given, for a maximum of 4 days. In 6 additional patients, IV paracetamol was used with this dosing regimen. All were very low birth weight infants. The gesta-tional ages were <28 weeks (1 patient) and 28–31 weeks (5 patients). Oral ibuprofen could not be given to 2 patients due to Dear Sir, We read with great interest the recent article by Oncel et al. [1] entitled ‘Intrave-nous paracetamol treatment in the man-agement of patent ductus arteriosus in ex-tremely low birth weight infants’. It is the first study to report the results of intrave-nous (IV) paracetamol in premature in-fants where a 3-day treatment (15 mg/kg dose, 4 doses/day) is offered. In the case of treatment failure at the end of the third day, a second course is administered. Palmer et al. [2] reported the following dose regimen for IV acetaminophen to be safe in premature infants: 28–32 weeks, 10 mg/kg; 32–36 weeks, 12.5 mg/kg, and 36 weeks, 15 mg/kg. Although the gestational ages of the patients in the study of Oncel et al. [1] were low, they used a higher dose; no side effect related to IV paracetamol was re-ported. In our clinical practice, prematures with hemodynamically significant patent ductus arteriosus (hsPDA) and contraindi-cations for oral ibuprofen present a great challenge. For these patients, IV para ce ta-mol seems to be a good alternative. We ad-ministered IV paracetamol in 7 preterm

Clinical experience with recombinant tissue plasminogen activator in the management of intracardiac and arterial thrombosis in children.

Thrombotic events may complicate the clinical course of many pediatric diseases. Drugs for therapeutic thrombolysis include streptokinase, urokinase and tissue plasminogen activator (t-PA). There is less experience with recombinant t-PA (rt-PA) in children. We aimed to present our experiences with rt-PA in children with intracardiac or peripheral arterial thrombus. We retrospectively reviewed the children who received rt-PA for thrombus. Twenty-two children (13 boys, 9 girls; age range: 1 day–17 years) with intracardiac (n = 5), prosthetic heart valve (n = 2) and peripheral arterial (n = 15) thrombus were evaluated. Twelve (54%) had congenital heart disease, two (9%) had rheumatic heart disease, three (14%) had leukemia and five (23%) had documented sepsis, prematurity or meconium aspiration syndrome. Ten of the 15 peripheral arterial thromboses were observed following cardiac catheterization. Three of the five intracardiac thrombi were detected in children with leukemia. All children received low-molecular-weight heparin. rt-PA (alteplase) infusion (at a dose of 0.01–0.5 mg/kg per h) was administered for different time periods (3–66 h). Ten of 11 patients with peripheral arterial occlusion and three of five patients with intracardiac thrombus showed full recovery. However, there was no response in two patients with intracardiac thrombus and in two patients with heart valve thrombus. Nose bleeding, melena and decreased serum fibrinogen concentration were observed in seven patients during the rt-PA infusion. All bleedings stopped after cessation of rt-PA infusion, and no blood transfusion was required in any patient. We conclude that rt-PA infusion seems effective and well tolerated in children for the treatment of peripheral arterial and intracardiac thrombus.

Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene.

Abstract Mutations in the KCNJ11 gene are responsible for the majority of permanent neonatal diabetes mellitus (PNDM) cases. Some mutations in this gene, including p.Q52R, are associated with the developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. We describe a patient with PNDM who had no neurological finding although she was determined to have a novel mutation (p.Q52L) in the same residue of the KCNJ11 as in the previously reported cases with DEND syndrome. This case suggests that not all Q52 mutations in the KCNJ11 gene are necessarily related to DEND syndrome.

A Comparison of Different Methods of Temperature Measurement by Mothers and Physicians in Healthy Newborns

ObjectiveTo compare the accuracy of digital axillary thermometer (DAT), rectal glass mercury thermometer (RGMT) and infrared forehead skin thermometer (IFST) measurements made by mothers and physicians in healthy newborns.MethodsThe body temperature measurements of 120 healthy newborns were made on their 2nd day of life using DAT, RGMT and IFST, first by mothers followed by a designated physician. Correlation analysis was performed for the measurements obtained by mothers and the physician. The presence of a former child or children at home, the educational level of the mother and maternal age were also recorded.ResultsNo correlation was observed between the measurements made by mothers and the physician using RGMT (R2 = 0.096). The temperatures measured by mothers and the physician showed a significant correlation when a DAT and IFST were used (R2 = 0.923, p < 0.001; R2 = 0.916, p < 0.001, respectively).ConclusionsDifficulty of use and interpretation make RGMTs less practical than DATs and IFST for use by mothers. Measurements with an IFST are obtained from a newborn’s forehead in a shorter length of time compared to DATs, which makes it a more practical option.

Safety and Efficacy of Intravenous Colistin in Neonates With Culture Proven Sepsis.

Background: Although it is well described among adults, intravenous colistin use and its associated toxicities in newborns are poorly understood. Objectives: We present our experience of efficacy and safety of intravenous colistin in the treatment of sepsis in term and preterm neonates. Patients and Methods: The records of neonates who received colistin between January 2013 and February 2014 were retrospectively reviewed. All neonates with culture proven nosocomial infections due to multidrug resistant organisms and treated continuously with colistin for more than 72 hours were included in the study. Results: Patients were evaluated for clinical and microbiological response to the drug and its and side effects. Twelve newborn infants with mean 31.8 ± 3.5 weeks gestational age and median 1482 (810 - 3200) gram birth weight were included. 11/12 (91.7%) patients showed microbiological clearance with intravenous colistin. One patient who had recurrent cerebrospinal fluid positive culture was treated with intraventricular colistin. The major side effects observed was hyponatremia and hypokalemia in 2 (16.6%) patients, all infants required magnesium supplementation. Conclusions: Intravenous colistin administration appears to be safe and efficacious for multidrug-resistant gram-negative infections in neonates, including preterm infants. However, we believe that large prospective controlled studies are needed to confirm its efficacy and safety in neonates.

Evaluation of Premature Infants Hospitalized in Neonatal Intensive Care Unit between 2010-2012.

OBJECTIVE With continuing developments in the field of neonatology, survival rates of low birth weight and small for gestational age infants have increased, which in turn has brought important prematurity-related problems. The aim of this study was to evaluate retrospectively the prematurity problems that are the significant causes of morbidity and mortality. MATERIALS AND METHODS 613 premature infants hospitalized in the neonatal intensive care unit of Ataturk University Medical Faculty Hospital between January 2010 and January 2012 were included in this study. Infants were divided into groups according to their birth weight and gestational age. RESULTS 323 infants were male (52.6%) and 290 were female (47.4%). 63.9% of infants weighed ≥1500 grams, and 58.5% had a gestational age of ≥33 weeks. Respiratory distress syndrome (RDS) was detected in 249 (40.6%), bronchopulmonary dysplasia (BPD) in 124 (20.2%), necrotizing enterocolitis (NEC) in 41 (6.6%), retinopathy of prematurity (ROP) in 202 (32.9%), and intracranial hemorrhage (ICH) in 15 (2.4%). RDS, BPD, NEC, ROP, and ICH rates were inversely proportional to decreases in gestational age and birth weight, and were found to be statistically significant. CONCLUSION Mortality and morbidity rates were similar to the other data published from our country, but the rates were above those reported in developed countries. We believe that our morbidity and mortality rates can reach levels comparable to those of developed countries with improved antenatal care, regular follow-up of pregnancy and increased numbers of physicians and health care personnel per patient.

Cow’s Milk Allergy in Preterm Infant with Bronchopulmonary Dysplasia

Cows milk allergy is frequent in the first year of life. The symptoms may start during the first weeks of life, and may be cutaneous (50-60%), gastrointestinal (50-60%) or respiratory (20-30%), often involving more than one organ system. In this report, we describe a case of cows milk allergy in a preterm infant in whom rectal bleeding and respiratory symptoms resolved with the introduction of an extensively hydrolyzed formula. Occurrence of the respiratory symptoms of this disorder in a preterm infant with bronchopulmonary dysplasia may cause re-hospitalization after discharge.

Intraventricular Colistin Use in a Premature Infant with Cerebral Abscess and Ventriculitis

The treatment of multidrug-resistant Acinetobacter baumannii infections is a serious problem in neonatal Intensive Care Units. Colistin has been used successfully in the treatment of these infections. Due to the limited penetration of colistin into the cerebrospinal fluid, central nervous system infection due to A. baumannii necessitates intrathecal or intraventricular application. Here, we describe our experience with intravenous and intraventricular colistin administration in a premature infant (33 gestational weeks) with shunt infection and brain abscess. No side-effects related to the drug were observed. To the best of our knowledge, our patient is the first premature infant to undergo intraventricular colistin administration. Although the central nervous system infection in our patient was treated successfully, it is obvious that detailed prospective studies are required regarding colistin usage in neonates and especially in premature infants.

Hyperlipidemia Due to Rectal Phenobarbital Use: Case Report

Treatment with hepatic enzyme-inducing antiepileptic drugs leads to increases in the levels of total cholesterol (TC) and triglyceride (TG). We report a case of a 10-monthold infant with hyperlipidemia due to use of rectal phenobarbital-paracetamol combination during echovirus infection. To the best of our knowledge, this is the first case reported in the literature of hyperlipidemia due to rectal phenobarbital use.