RESUMEN
PURPOSE: To determine the presence of sickle cell retinopathy and maculopathy and to identify associations between markers of hemolysis and systemic and ocular manifestations in children affected by sickle cell disease. METHODS: Eighteen children with sickle cell disease, aged 5-16 years, underwent complete eye examination including best-corrected visual acuity, slit-lamp biomicroscopy, ophthalmoscopy after pharmacological mydriasis, spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA). Blood test results and clinical history information were collected for each child, including fetal hemoglobin (HbF), hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), reticulocytes percentage (%ret), lactic dehydrogenase (LDH), total and direct bilirubin, glomerular filtration rate, number of painful crises, acute chest syndromes, and splenic sequestration. Therapeutic regimen and transfusion therapy were also evaluated. RESULTS: Sixteen of 36 eyes (44.4%) had non-proliferative sickle cell retinopathy on ophthalmoscopic evaluation. No patients had proliferative sickle cell retinopathy. In 13 of 36 eyes (36.1%), SD-OCT and OCTA detected signs of sickle cell maculopathy. Nine eyes (25%) presented sickle cell retinopathy and maculopathy, 7 eyes (19.4%) sickle cell retinopathy alone, and 4 eyes (11.1%) sickle cell maculopathy alone. A statistically significant association was found between sickle cell retinopathy; lower levels of HbF, Hb, and Htc; and higher MCV and percentage of reticulocytes. Sickle cell maculopathy was associated with lower values of H and Htc and higher levels of reticulocytes and total bilirubin. CONCLUSIONS: We identified early signs of sickle cell retinopathy and maculopathy in a pediatric population with SD-OCT and OCTA. These two retinal complications were more frequent in children with higher hemolytic rates.
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Anemia de Células Falciformes , Degeneración Macular , Enfermedades de la Retina , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Niño , Angiografía con Fluoresceína , Humanos , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Factores de Riesgo , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
BACKGROUND: Non-invasive delivery of nebulized surfactant has been a neonatology long-pursued goal. Nevertheless, the clinical efficacy of nebulized surfactant remains inconclusive, in part, due to the great technical challenges of depositing nebulized drugs in the lungs of preterm infants. The aim of this study was to investigate the feasibility of delivering nebulized surfactant (poractant alfa) in vitro and in vivo with an adapted, neonate-tailored aerosol delivery strategy. METHODS: Particle size distribution of undiluted poractant alfa aerosols generated by a customized eFlow-Neos nebulizer system was determined by laser diffraction. The theoretical nebulized surfactant lung dose was estimated in vitro in a clinical setting replica including a neonatal continuous positive airway pressure (CPAP) circuit, a cast of the upper airways of a preterm neonate, and a breath simulator programmed with the tidal breathing pattern of an infant with mild respiratory distress syndrome (RDS). A dose-response study with nebulized surfactant covering the 100-600 mg/kg nominal dose-range was conducted in RDS-modelling, lung-lavaged spontaneously-breathing rabbits managed with nasal CPAP. The effects of nebulized poractant alfa on arterial gas exchange and lung mechanics were assessed. Exogenous alveolar disaturated-phosphatidylcholine (DSPC) in the lungs was measured as a proxy of surfactant deposition efficacy. RESULTS: Laser diffraction studies demonstrated suitable aerosol characteristics for inhalation (mass median diameter, MMD = 3 µm). The mean surfactant lung dose determined in vitro was 13.7% ± 4.0 of the 200 mg/kg nominal dose. Nebulized surfactant delivered to spontaneously-breathing rabbits during nasal CPAP significantly improved arterial oxygenation compared to animals receiving CPAP only. Particularly, the groups of animals treated with 200 mg/kg and 400 mg/kg of nebulized poractant alfa achieved an equivalent pulmonary response in terms of oxygenation and lung mechanics as the group of animals treated with instilled surfactant (200 mg/kg). CONCLUSIONS: The customized eFlow-Neos vibrating-membrane nebulizer system efficiently generated respirable aerosols of undiluted poractant alfa. Nebulized surfactant delivered at doses of 200 mg/kg and 400 mg/kg elicited a pulmonary response equivalent to that observed after treatment with an intratracheal surfactant bolus of 200 mg/kg. This bench-characterized nebulized surfactant delivery strategy is now under evaluation in Phase II clinical trial (EUDRACT No.:2016-004547-36).
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Productos Biológicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Modelos Biológicos , Nebulizadores y Vaporizadores , Fosfolípidos/administración & dosificación , Surfactantes Pulmonares/administración & dosificación , Animales , Productos Biológicos/metabolismo , Humanos , Recién Nacido , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Tamaño de la Partícula , Fosfolípidos/metabolismo , Surfactantes Pulmonares/metabolismo , ConejosRESUMEN
Fluid balance management in pediatric critically ill patients is a challenging task, since fluid overload (FO) in the pediatric ICU is considered a trigger of multiple organ dysfunction. Pediatric patients with congenital heart disease (CHD) have several pre, intra and postoperative risk factors of derangements in fluid management. In particular, the smallest patients with acute kidney injury are at highest risk of developing severe interstitial edema, capillary leak syndrome and FO. Several studies previously showed a significantly higher percentage of FO among children with severe renal dysfunction requiring RRT, strongly associated with poor outcomes. For this reason, in children, priority indication is currently given to the correction of water overload. The present review will discuss recent literature addressing the issue of fluid balance in critically ill children with CHD, dosages, benefits and drawbacks of diuretic therapy, alternative diuretic/nephroprotective drugs currently proposed in the pediatric cardiac surgery setting. Monitoring of fluid balance will be reviewed. Specific modalities of pediatric extracorporeal fluid removal will be presented.
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Fluidoterapia , Cardiopatías Congénitas/terapia , Niño , Enfermedad Crítica , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Humanos , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.
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Sistema Respiratorio/patología , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/metabolismo , Broncodilatadores/farmacología , Niño , Antagonistas Colinérgicos/metabolismo , Cuidados Críticos/métodos , Epinefrina/metabolismo , Medicina Basada en la Evidencia/métodos , Gases , Humanos , Cuidado Intensivo Neonatal/métodos , Óxido Nítrico/metabolismo , Prostaglandinas I/metabolismo , S-Nitrosotioles/química , Esteroides/química , Tensoactivos/farmacologíaRESUMEN
Mortality in pediatric cardiovascular failure is markedly improved with the advent of neonatal and pediatric intensive care and with the implementation of treatment guidelines. In 2002 the American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Shock reported mortality rates of 0%-5% in previously healthy and 10% in chronically ill children with septic shock associated with implementation of "best clinical practices". Early recognition of shock is the key to successful resuscitation in critically ill children. Often, shock results in or co-exists with myo-cardial dysfunction or acute lung injury. Recognition and appropriate management of these insults is crucial for successful outcomes. Resuscitation should be directed to restoration of tissue perfusion and normalization of cardiac and respiratory function. The underlying cause of shock should also be addressed urgently. The physiological response of individual children to shock resuscitation varies and is often unpredictable. Therefore, repeated assessments of vital parameters are needed for taking appropriate decisions. Global indices of tissue oxygen delivery help in targeting therapies more accurately. Isotonic fluids form the cornerstone of treatment and the amount required for resuscitation is based on etiologies and therapeutic response. After resuscitation has been initiated, targeted history and clinical evaluation must be performed to ascertain the cause of shock and management of co-morbidities should be implemented simultaneously. While the management of shock can be protocol based, the treatment needs to be individualized depending on the suspected etiology and therapeutic response particularly for children who suffer from congenital heart disease.
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Enfermedades del Prematuro/terapia , Resucitación/métodos , Choque/terapia , Lesión Pulmonar Aguda/complicaciones , Lesión Pulmonar Aguda/terapia , Factores de Edad , Manejo de la Vía Aérea , Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/terapia , Cardiotónicos/uso terapéutico , Niño , Preescolar , Terapia Combinada , Diuréticos/uso terapéutico , Fluidoterapia , Humanos , Hipnóticos y Sedantes/uso terapéutico , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Monitoreo Fisiológico , Oxígeno/metabolismo , Choque/tratamiento farmacológico , Choque/etiología , Choque Séptico/complicaciones , Choque Séptico/terapiaRESUMEN
AIM: To analyse the methods used to manage and monitor sedoanalgesia at Italian paediatric intensive care units (ICUs). METHODS: Data were collected by administering a questionnaire that aimed to investigate whether ICUs adopted a validated protocol to manage sedoanalgesia. RESULTS: The results revealed that a majority of the ICUs adopt a protocol for dealing with sedation and analgesia, but this protocol is implemented with difficulty or not at all in routine clinical practice. The most often used pharmacological combination, is midazolam and fentanyl. Several weaknesses remain in terms of the methods used to assess sedoanalgesia, which are generally not standardized, but rather based on recording the patient's physiological parameters. CONCLUSION: Sedation and analgesia are priority issues in the management of critically ill children. None of the numerous drugs available is ideal and the protocols currently used in clinical practice involve the combined use of different drugs. There is currently no shared and validated approach as to which is the most effective and safest sedoanalgesic regimen in critically ill children.
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Analgesia/métodos , Protocolos Clínicos , Cuidados Críticos/estadística & datos numéricos , Hipnóticos y Sedantes/uso terapéutico , Niño , Preescolar , Enfermedad Crítica/terapia , Encuestas de Atención de la Salud , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Italia , Dolor/prevención & control , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although hyperfibrinogenemia and insulin resistance are common in obesity and diabetes mellitus, the impact of obesity per se on fibrinogen turnover and the insulin effects on fibrinogen and protein kinetics is unknown. METHODS: We measured fibrinogen and albumin fractional (FSR) and absolute (ASR) synthesis rates, as well as protein turnover, in non-diabetic, obese and in control male subjects both before and following an euglycemic, euaminoacidemic, hyperinsulinemic clamp, using L-[(2)H(3)]-Leucine isotope infusion. RESULTS: In the obese, basal fibrinogen concentrations was approximately 25% greater (p < 0.035), and fibrinogen pool approximately 45% greater (p < 0.005), than in controls. Both FSR and ASR of fibrinogen were similar to control values. With hyperinsulinemia, although fibrinogen FSR and ASR were not significantly modified with respect to baseline in either group, fibrinogen ASR resulted to be approximately 50% greater in the obese than in controls (p < 0.015). Hyperinsulinemia equally stimulated albumin synthesis and suppressed leucine appearance from endogenous proteolysis in both groups. Amino acid clearance was also similar. In the obese, the insulin-mediated glucose disposal was approximately 50% lower (p < 0.03) than in controls, and it was inversely correlated with fibrinogen ASR during the clamp in both groups (r = - 0.58). CONCLUSIONS: In obese, non-diabetic males, post absorptive fibrinogen production is normal. Whole-body amino acid disposal, basal and insulin-responsive protein degradation, and albumin synthesis are also normal. However, the greater fibrinogen ASR in the obese with hyperinsulinemia, and the inverse relationship between insulin sensitivity and clamp fibrinogen production, suggest a role for hyperinsulinemia and/or insulin resistance on fibrinogen production in obesity.
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Fibrinógeno/metabolismo , Insulina/farmacología , Obesidad/metabolismo , Adulto , Aminoácidos/metabolismo , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Superficie Corporal , Proteína C-Reactiva/metabolismo , Colesterol/sangre , Fibrinógeno/efectos de los fármacos , Humanos , Insulina/sangre , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/fisiopatología , Valores de Referencia , Trombomodulina/sangre , Factor de Necrosis Tumoral alfa/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
Asthmatic airways are characterised by enhanced oxidative stress, which can be studied by measuring biomarkers, such as 8-isoprostane. The aims of the present study were: 1) to measure the concentrations of 8-isoprostane in exhaled breath condensate (EBC) and urine of children with problematic and well-controlled asthma; 2) to compare the concentrations of 8-isoprostane measured by gas chromatographic/negative ion chemical ionisation mass spectrometry (GC/NICI-MS) and by an enzymatic immunoassay (EIA). We recruited 20 asthmatic allergic children, 13 with well-controlled asthma and seven with problematic asthma. They underwent exhaled nitric oxide measurements and spirometry, and both EBC and urine samples were collected. 8-isoprostane was measured in EBC by GC/NICI-MS and EIA. 8-isoprostane concentrations in EBC were significantly higher in children with problematic asthma than in children with well-controlled asthma (p = 0.01). An acceptable reproducibility emerged between GC/NICI-MS and EIA (coefficient of reproducibility 11.5 pg x mL(-1)). 8-isoprostane levels measured in urine did not correlate with those measured in EBC. We showed that 8-isoprostane in EBC was significantly increased in children with problematic asthma, suggesting a role for oxidative stress in this asthma phenotype. In addition we found an acceptable reproducibility of EIA compared to GC/NICI-MS, even if the latter method had higher accuracy.
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Asma/diagnóstico , Asma/metabolismo , Biomarcadores/metabolismo , Pruebas Respiratorias/métodos , Dinoprost/análogos & derivados , Cromatografía de Gases y Espectrometría de Masas/métodos , Técnicas para Inmunoenzimas/métodos , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Niño , Dinoprost/metabolismo , Dinoprost/orina , Cromatografía de Gases y Espectrometría de Masas/normas , Humanos , Técnicas para Inmunoenzimas/normas , Óxido Nítrico/metabolismo , Estrés Oxidativo/fisiología , Reproducibilidad de los Resultados , EspirometríaRESUMEN
INTRODUCTION: The contribution of clinical neurophysiology in the neurological prognosis of hypoxic-ischemic coma has been well established in adults: the bilateral absence of cortical somatosensory evoked potentials (SEP) is considered the single best indicator of adverse outcome, while the presence of the auditory mismatch negativity (MMN) is thought to herald arousal. STUDY AIM: To use MMN combined with serial EEG recordings, somatosensory and brainstem auditory evoked potentials (BAEP) in a paediatric case of postanoxic coma managed with hypothermia, since they have not yet been described in children. METHODS: We report the case of a nine-year-old boy with hypoxic-ischemic encephalopathy due to cardiorespiratory arrest after accidental burial in sand, who was treated with therapeutic hypothermia for 72 hours. Serial EEG recordings, evoked potentials, brain CT scan and brain MRI were performed in the first few days after the event. RESULTS: SEP to median nerve stimulation showed bilateral absence of the N20 component, while the N13 and P14 peaks were preserved; BAEP showed normal I-V interpeak latency and normal hearing threshold. At the same time, the MMN component of auditory event related potentials, recorded in the classical oddball paradigm, was absent. Seventeen months after the accident, the patient is alive in persistent vegetative state. CONCLUSIONS: This case illustrates the particular significance of SEP and MMN together with EEG in gaining prognostic information, even in sedated and hypothermic patients, and encourages systematic study of these prognostic tools in paediatric postanoxic coma.
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Potenciales Evocados Auditivos del Tronco Encefálico , Potenciales Evocados Somatosensoriales , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/fisiopatología , Accidentes , Ritmo alfa , Asfixia/complicaciones , Niño , Paro Cardíaco/complicaciones , Humanos , Hipoxia-Isquemia Encefálica/etiología , Hipoxia-Isquemia Encefálica/terapia , Imagen por Resonancia Magnética , Masculino , Estado Vegetativo Persistente/diagnóstico , Estado Vegetativo Persistente/etiología , Estado Vegetativo Persistente/fisiopatología , Pronóstico , Estado Epiléptico/etiología , Estado Epiléptico/fisiopatología , Estado Epiléptico/terapia , Ritmo Teta , Tomografía Computarizada por Rayos XRESUMEN
Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely 'endogenous studies', which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely 'exogenous studies', which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.
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Surfactantes Pulmonares/farmacocinética , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Oxigenación por Membrana Extracorpórea , Hernia Diafragmática/tratamiento farmacológico , Hernia Diafragmática/fisiopatología , Hernias Diafragmáticas Congénitas , Humanos , Recién Nacido , Isótopos/farmacocinética , Síndrome de Aspiración de Meconio/tratamiento farmacológico , Síndrome de Aspiración de Meconio/fisiopatología , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/fisiopatología , Surfactantes Pulmonares/administración & dosificación , Surfactantes Pulmonares/efectos adversos , Surfactantes Pulmonares/química , Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológicoRESUMEN
Encephalitis can represent a complication of both Mycoplasma and Human Herpesvirus type 6 infections and, although uncommon, is associated with significant morbidity and mortality. We describe a 13-year-old girl with fever, headache and mental changes with a pattern of concomitant Mycoplasma and Human Herpesvirus-6 infection. The hypothetical relationship between this dual infection and the central nervous system disease is discussed.
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Meningoencefalitis/microbiología , Meningoencefalitis/virología , Infecciones por Mycoplasma/complicaciones , Infecciones por Roseolovirus/complicaciones , Aciclovir/uso terapéutico , Adolescente , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/líquido cefalorraquídeo , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Ceftriaxona/uso terapéutico , Electroencefalografía , Femenino , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/inmunología , Humanos , Inmunocompetencia , Imagen por Resonancia Magnética , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/tratamiento farmacológicoRESUMEN
Deficiency or dysfunction of pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases in the newborn. We describe the studies made by applying two recently developed methods to measure surfactant kinetics. The first allows the measurement of endogenous surfactant phosphatidylcholine (PC) synthesis and kinetics by a constant intravenous infusion of glucose or fatty acids labeled with stable isotope 13C. The second method consists of endotracheal administration of a tracer dose of 13C-labeled dipalmitoyl-phosphatidylcholine (DPPC) to measure disaturated-phosphatidylcholine (DSPC) half-life and apparent pool size. We present the results of surfactant kinetics in some of the respiratory diseases of the newborn infant.
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1,2-Dipalmitoilfosfatidilcolina/farmacocinética , Fosfatidilcolinas/biosíntesis , Surfactantes Pulmonares/farmacocinética , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , 1,2-Dipalmitoilfosfatidilcolina/uso terapéutico , Humanos , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Surfactantes Pulmonares/uso terapéuticoRESUMEN
We studied surfactant kinetics on Day 1 of life in 11 preterm infants on mechanical ventilation by infusing stable isotope labeled palmitic (PA) and linoleic acid (LLA). Six infants received exogenous surfactant for the treatment of respiratory distress syndrome (RDS) and five did not meet treatment criteria because of minimal or no disease. The isotopic enrichment of plasma free PA and LLA and of surfactant phosphatidylcholine PA (PC-PA) and LLA (PC-LLA) from tracheal aspirates was measured by mass spectrometry. Significant isotopic enrichment could be measured in PC-PA and PC-LLA from all patients. The fractional synthesis rate (FSR) of PC-LLA was higher than that of PC-PA (22.7 +/- 15.9 versus 12.1 +/- 7.7% per day, p = 0.018). Half-life (HL) of PC-PA was longer than that of PC-LLA (94.7 +/- 18.8 versus 46.6 +/- 32.6 h, p = 0.028). Patients who received exogenous surfactant had longer secretion times (ST) and delayed peak times (PK) but FSR and HL were unaffected. We concluded that: (1) surfactant kinetics can be measured in preterm infants with stable isotope labeled lipids; (2) surfactant FSR and HL calculated with PA and LLA gave different results; (3) patients treated with exogenous surfactant had similar FSRs compared with the nontreated subjects but had longer ST and delayed PK; (4) FSR from plasma free fatty acids (present study) was higher than that from plasma glucose in our previous work (Bunt JEH, Zimmermann LJI, Wattimena D, van Beek R, Sauer PJJ, Carnielli VP. Am J Respir Crit Care Med 1998;157:810-814) in a comparable population of preterm infants with RDS.
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Enfermedades del Prematuro/diagnóstico por imagen , Enfermedades del Prematuro/metabolismo , Surfactantes Pulmonares/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/metabolismo , Humanos , Recién Nacido , Recien Nacido Prematuro , Isótopos , Ácido Linoleico , Ácido Palmítico , CintigrafíaRESUMEN
Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.
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Productos Biológicos , Enfermedades del Prematuro/metabolismo , Fosfolípidos , Surfactantes Pulmonares/farmacocinética , Síndrome de Dificultad Respiratoria del Recién Nacido/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/farmacocinética , Isótopos de Carbono , Cromatografía de Gases y Espectrometría de Masas , Semivida , Humanos , Recién Nacido , Enfermedades del Prematuro/terapia , Surfactantes Pulmonares/uso terapéutico , Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Tráquea/químicaRESUMEN
A case of late recovery from anesthesia in a patient undergoing bronchoscopy for surgical removal of metastatic bronchial mass is presented. The patient was comatose and a CT scan revealed the presence of bleeding inside a tumor, probably a metastasis, located in the right cerebellum. This report demonstrates that undetected cerebral metastases might lead to late recovery from anesthesia and underlines that accurate neurologic examination is mandatory in patients affected by tumors potentially spreading to the brain.
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Anestesia General , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/secundario , Periodo de Recuperación de la Anestesia , Neoplasias Cerebelosas/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids. We infused albumin-bound [U-13C]palmitic acid (PA) and [U-13C]linoleic acid (LLA) for 24 h in eight critically ill infants (mean+/-SD: weight: 3.7+/-1.3 kg: age: 51.3+/-61.6 d) who required mechanical ventilation. The 13C enrichment of PA and LLA in surfactant phosphatidylcholine (PC), obtained from tracheal aspirates, was measured by gas chromatography combustion interface-isotope ratio mass spectrometry. We measured a significant incorporation of both 13C-PA and 13C-LLA into surfactant PC. PC-PA and PC-LLA became enriched after 8.7+/-4.9 h (range: 3.4-17.3) and 10.0+/-7.2 h (range: 3.0-22.4), respectively; the times at maximum enrichment were 49.2+/-8.9 and 45.6+/-19.3 h, respectively. The fractional synthesis rate of surfactant PC-PA ranged from 0.4 to 3.4% per h, whereas the fractional synthesis rate of PC-LLA ranged from 0.5 to 3.8% per h. The surfactant PC-PA and PC-LLA half-lives ranged from 16.8 to 177.7 and 23.8 to 144.4 h, respectively. This method provides new data on surfactant metabolism in infants requiring mechanical ventilation. We found that synthesis of surfactant from plasma PA and LLA is a slow process and that there were marked differences in PC kinetics among infants. This variability could be related to differences in lung disease and could affect the clinical course of the respiratory failure.
Asunto(s)
Enfermedad Crítica , Ácido Linoleico/metabolismo , Ácido Palmítico/metabolismo , Fosfatidilcolinas/metabolismo , Surfactantes Pulmonares/metabolismo , Isótopos de Carbono , Ingestión de Energía , Femenino , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Cinética , Ácido Linoleico/administración & dosificación , Masculino , Ácido Palmítico/administración & dosificación , Unión Proteica , Albúmina Sérica , Manejo de Especímenes/métodos , Factores de Tiempo , TráqueaRESUMEN
Lipolysis has been measured in humans by means of stable isotope techniques using labeled palmitic acid (PA) or glycerol as tracers. If other fatty acids (FA) such as linoleic acid (LLA) have the same rate of appearance (Ra) as PA and therefore contribute equally to oxidative and nonoxidative metabolism is unknown. We infused albumin-bound [U-13C]PA and [U-13C]LLA in seven critically ill infants (weight 3.6 +/- 1.3 kg, age 57 +/- 64 d) receiving 20.9 +/- 5.4 kcal. kg-1.d-1 of i.v. glucose only, and measured simultaneously the Ra of PA and LLA from the isotopic enrichment of plasma FFA by mass spectrometry. A needle biopsy of the s.c. adipose tissue was obtained for FA composition. PA in adipose tissue was higher than LLA (40 +/- 6.7 versus 5.4 +/- 3.2 mol %, p < 0.001). The Ra values of PA and LLA were 5.73 +/- 2.79 and 1.34 +/- 0.92 mumol.kg-1.min-1, respectively (p = 0.005). However, the ratio of the FA's Ra to their respective mol% values in adipose tissue was lower for PA than for LLA (0.15 +/- 0.06 versus 0.25 +/- 0.06, p = 0.02). The Ra of LLA acid was higher than could be expected from the FA composition of adipose tissue, thus indicating a preferential release of LLA during lipolysis. In critically ill infants receiving only i.v. glucose, the contribution of LLA to the oxidative and nonoxidative metabolism may be larger than what assumed from the FA composition of plasma and adipose tissue.
Asunto(s)
Enfermedad Crítica , Ácidos Grasos no Esterificados/sangre , Ácidos Linoleicos/sangre , Lipólisis/fisiología , Ácido Palmítico/sangre , Transporte Biológico/fisiología , Femenino , Humanos , Lactante , Recién Nacido , Ácido Linoleico , MasculinoRESUMEN
Pediatric intensive care units (PICUs) have been developed to provide intensive care for children between post-neonatal age and adolescence. These units have largely been developed in North America, mainly in tertiary hospitals. In Italy, critically ill children are still often nursed on adult ICU's, where medical and nursing staff often lack pediatric training. Here we report the first 5-year experience of the multidisciplinary PICU developed at the Department of Pediatrics, University of Padua, focusing on PICU and patients characteristics, as well as on the evaluation of outcome by means of the Pediatric Risk of Mortality (PRISM) score.
Asunto(s)
Cuidados Críticos/tendencias , Enfermedad Crítica/terapia , Adolescente , Niño , Preescolar , Cuidados Críticos/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Hospitales Universitarios/tendencias , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Unidades de Cuidado Intensivo Pediátrico/tendencias , ItaliaRESUMEN
Extracorporeal membrane oxygenation (ECMO) has become a nearly standard treatment for neonates with refractory hypoxemic respiratory failure due to various disease. Even though in the non-neonatal age the experience is less extensive, an increased widespread interest on the possible applications in children with severe life-threatening respiratory or cardiovascular insufficiency is well documented in the literature. General contraindications include presence of active bleeding, underlying lethal disease, congenital malformations, or severe brain damage. Whilst in the neonatal population common entry criteria have been widely accepted, the identification of precise parameters capable to predict mortality and thus indicating an ECMO support in older patients are still lacking. At present, nonetheless, more than 10.000 newborns and 1.000 children with severe respiratory insufficiency at high mortality risk have received an ECMO treatment, with a survival rate of more than 80% and 50%, respectively. The initial results of our ECMO program for both neonatal and pediatric patients with refractory respiratory failure are encouraging, both in terms of mortality and morbidity, and they will be briefly discussed.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Insuficiencia Respiratoria/terapia , Adolescente , Niño , Preescolar , Oxigenación por Membrana Extracorpórea/instrumentación , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Lactante , Recién Nacido , ItaliaRESUMEN
Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua.