Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity

Abstract : We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. As exogenous adenosine infusion mimics the haemodynamic changes that characterize acute renal failure (ARF), we wanted to know whether adenosine was a mediator in this model and whether an adenosine receptor blocker could prevent the CsA-induced ARF. Group 1 were untreated controls. Group 2 received CsA (25 mg/kg per day) for 5 days. Renal function parameters were measured, showing ARF in all animals compared to controls. Theophylline (1 mg/kg i.v. bolus) was then administered and renal function was reassessed. Theophylline significantly reduced renal vascular resistance (-8%) and increased renal blood flow (RBF) (+20%), glomerular filtration rate (GFR) (+50%), filtration fraction (+24%) and diuresis (+73%), suggesting that adenosine was involved in the CsA-induced ARF. In group 3, theophylline (30 mg/kg per day) was given concomitantly with CsA for 5 days. GFR was normalized, but theophylline did not hinder the drop in RBF seen with CsA alone in group 2. Microscopy observation of the kidneys showed that chronic theophylline administration aggravated the morphological changes induced by CsA alone. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with an adenosine-mediated afferent arteriolar constriction which cannot be prevented by concomitant theophylline administratio

Respiratory support by neurally adjusted ventilatory assist (NAVA) in severe RSV-related bronchiolitis: a case series report

<p>Abstract</p> <p>Background</p> <p>Neurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation controlled by diaphragmatic electrical signals. The electrical signals allow synchronization of ventilation to spontaneous breathing efforts of a child, as well as permitting pressure assistance proportional to the electrical signal. NAVA provides equally fine synchronization of respiratory support and pressure assistance varying with the needs of the child. NAVA has mainly been studied in children who underwent cardiac surgery during the period of weaning from a respirator.</p> <p>Case presentation</p> <p>We report here a series of 3 children (1 month, 3 years, and 28 days old) with severe respiratory distress due to RSV-related bronchiolitis requiring invasive mechanical ventilation with a high level of oxygen (FiO₂≥50%) for whom NAVA facilitated respiratory support. One of these children had diagnosis criteria for acute lung injury, another for acute respiratory distress syndrome.</p> <p>Establishment of NAVA provided synchronization of mechanical ventilatory support with the breathing efforts of the children. Respiratory rate and inspiratory pressure became extremely variable, varying at each cycle, while children were breathing easily and smoothly. All three children demonstrated less oxygen requirements after introducing NAVA (57 ± 6% to 42 ± 18%). This improvement was observed while peak airway pressure decreased (28 ± 3 to 15 ± 5 cm H₂O). In one child, NAVA facilitated the management of acute respiratory distress syndrome with extensive subcutaneous emphysema.</p> <p>Conclusions</p> <p>Our findings highlight the feasibility and benefit of NAVA in children with severe RSV-related bronchiolitis. NAVA provides a less aggressive ventilation requiring lower inspiratory pressures with good results for oxygenation and more comfort for the children.</p

Continuous Monitoring of Cerebral Autoregulation in Children Supported by Extracorporeal Membrane Oxygenation: A Pilot Study.

OBJECTIVE: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome. DESIGN: Observational prospective study. PATIENTS AND SETTING: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy. MEASUREMENTS: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx-MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start. RESULTS: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3-93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02-0.15) vs. 0.01 (- 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE- patients [0.09 (0.01-0.23) vs. 0.04 (- 0.02 to 0.06), p = 0.04 and 33.3% (24.8-62.1) vs. 20.8% (17.3-23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5-32.9) vs. 5.6% (3.6-9.9), p = 0.02] and above ULA [13% (5.3-38.4) vs. 4.2% (2.7-7.4), p = 0.004], respectively. CONCLUSION: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE

Hémodynamique non invasive et approche thérapeutique du choc septique chez l'enfant

Nous avons exploré un hydroxy-éthylamidon comme soluté de remplissage en étudiant par échocardiographie-Doppler son retentissement sur le débit cardiaque. Notre étude ne démontre pas que ce produit serait plus efficace que le sérum salé isotonique. Nous avons également analysé les conséquences d'un traitement par dopamine, sur les pressions artérielles pulmonaires du nouveau-né, particulièrement à risque d'une hypertension artérielle pulmonaire. La dopamine entraîne une fois sur deux une augmentation plus importante des pressions pulmonaires que des pressions systémiques. Enfin, nous avons évalué par thermodilution transpulmonaire les effets de la milrinone, un inhibiteur de la phospho-diestérase type 3, sur l'hémodynamique d'un modèle expérimental de choc septique. Il en découle que cette molécule pourrait faire l'objet d'études cliniques ultérieures pour améliorer la prise en charge thérapeutique du choc septique de l'enfant.We test one hydroxyethyl starch as a plasma volume expander with an appraisal of its effects on cardiac output by Doppler echocardiographic evaluation. Our study did not provide evidence that hydroxyethyl starch is more efficient than isotonic saline. We also analysed repercussion of a vasopressor therapy by dopamine on pulmonary arterial pressures of newborns prone to the development of persistent pulmonary hypertension. Dopamine has variable effects on pulmonary/systemic arterial ratio, with half the neonates showing an increase in pulmonary pressure relative to systemic pressure. Finally, we used by transpulmonary thermodilution to assess the effects of milrinone, a type III phosphodiesterase inhibitor, on hemodynamics in an experimental septic shock model. Our results show that this agent could be tested in further clinical trials to improve the management of pediatric septic shock.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

LEUCEMIES AIGUES CONGENITALES (A PROPOS DE TROIS CAS (DES PEDIATRIE))

NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Évaluation de la prise en charge des enfants en insuffisance rénale aigüe traités par hémodiafiltration en réanimation pédiatrique au CHU de Nantes

Au CHU de Nantes, une dizaine d'enfants par an sont traités en réanimation pédiatrique par hémodiafiltration veino-veineuse continue pour une insuffisance rénale aigue. L'objectif de ce travail était d'évaluer les pratiques du service selon une démarche d'évaluation des pratiques professionnelles définie par des sociétés savantes. Les résultats montrent que certains aspects sont maitrisés par l'équipe tels que l'anticoagulation, l'abandon des solutés à base d'acétate, le branchement isovolémique ou la manipulation de néphrotoxiques. D'autres peuvent faire l'objet d'amélioration, tels que l'évaluation optimale de l'état hémodynamique et les apports hydroélectrolytiques adaptés. En complément du protocole d'hémodiafiltration déjà existant, une fiche d'aide à la prescription pourrait être mise en place pour faciliter la prise en charge en urgence de ces patients.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF