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Biomedical subjects

A Brunhes

Publications and source records attributed to A Brunhes.

7 recordsLinked to original sources
PubMed2005

Dose-finding study of ibuprofen in patent ductus arteriosus using the continual reassessment method.

OBJECTIVE: Intravenous ibuprofen (IBU) has been found to be as effective as indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm infants and has been associated with fewer adverse effects in comparative phase III studies. The dose regimen used (10-5-5 mg/kg/day) was based on limited pharmacokinetic data and no phase II study was available to determine the optimal dose of IBU for this indication. The present study was designed to determine the minimum effective dose regimen (MEDR) of IBU (one course) required to close ductus arteriosus in preterm infants. METHOD: A double-blind dose-finding study was conducted using the continual reassessment method, a Bayesian sequential design. Two distinct target closure rates were initially chosen according to postmenstrual age (PMA) at birth: 80% in infants with a PMA of 27-29 weeks, and 50% in infants with a PMA < 27 weeks. Forty neonates (20 in each PMA group) with PDA were treated between days 3 and 5 of life. Four different dose regimens were tested: loading doses of 5, 10, 15 or 20 mg/kg, followed by two doses (1/2 loading dose) at 24-h intervals. Efficacy was evaluated by echocardiography 24 h after the third infusion. RESULTS: In infants with a PMA of 27-29 weeks, the estimated MEDR was 10-5-5 mg/kg with a final estimated probability of success of 77% (95% credibility interval: 56-92%). The 15-7.5-7.5 mg/kg dose regimen had a better estimated probability of success (88%, 95% credibility interval: 68-97%), but resulted in more minor renal adverse effects. In contrast, in infants with a PMA < 27 weeks, the estimated MEDR was 20-10-10 mg/kg with an estimated probability of success of 54.8% (95% credibility interval: 22-84%), whereas the conventional dose regimen resulted in a low estimated probability of success (30.6%, 95% credibility interval: 13-56%). In these infants, compared with those with a PMA of 27-29 weeks, minor renal adverse effects were more frequent from the 10-5-5 mg/kg/day dose regimen and did not appear to be clearly dose related. CONCLUSION: This study confirms that the currently recommended dose regimen (10-5-5 mg/kg) of IBU is associated with a high closure rate (80%) and few adverse effects in premature infants with a PMA of 27-29 weeks. The failure rate was much higher below 27 weeks. A higher dose regimen (20-10-10 mg/kg) might achieve a higher closure rate. However, tolerability and safety of this dose regimen should be assessed in a larger population before considering the use of these doses for ductus arteriosus closure.

Bayes Theorem↗
PubMed2003

Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome.

OBJECTIVES: To investigate if systemic hypertension occurs in fetuses with twin-to-twin transfusion syndrome (TTTS). METHODS: We conducted an observational cohort study in a tertiary care centre in 23 pregnant women with TTTS. Polyhydramnios stuck twin sequence occurred at a median gestational age of 22 weeks (range 15-27). Biventricular myocardial hypertrophy was diagnosed in 22/23 recipient fetuses. In cases with atrioventricular valve regurgitation (AVR), it was possible to estimate the fetal systolic systemic blood pressure by ultrasound, on the basis of the simplified Bernouilli equation. The diagnosis of fetal hypertension (FHT) was made when the estimated systolic arterial pressure was equal to or above 1.6-fold the expected value. RESULTS: In 10 pregnancies (group A), fetal blood pressure could be assessed in recipients with AVR. The maximum velocities ranged from 2.9 to 5 m/s, leading to estimates of systemic fetal arterial pressure from 37 to 104 mmHg, that is, 1.6- to 2.8-fold the expected values. In 13 pregnancies (group B), fetal blood pressure could not be assessed in the absence of AVR. In group A, perinatal death (16/20) and hydrops (7/20) were significantly more frequent than in group B (8/26 and 1/26 respectively). CONCLUSION: Fetal systemic hypertension may occur in recipient twins and could play a role in the pathophysiology of TTTS.

Cohort Studies↗
PubMed2002

Stability and biological activity of epoietin beta in parenteral nutrition solutions.

The aim of this in vitro study was to determine stability and biological activity of epoietin (Epo) beta in a parenteral nutrition solution over 24 h. Epo beta was added to the parenteral nutrition solution which was administered through intravenous tubing and a Posidyne Neo filter. Samples were collected after 0, 4, 12, and 24 h. The Epo concentrations were measured before and after filter passage by an ELISA assay. The Epo biological activity was determined in the UT7/Epo cell line. The Epo concentration in the parenteral nutrition solution remained stable for 24 h. However, 35% of the Epo was adsorbed by the filter. The samples collected induced proliferation of UT7/Epo cells. These results suggest that Epo can be administered in parenteral nutrition solutions, but the dosage would need to be increased when a filter is used.

Drug Stability↗
PubMed2000

Impact of delayed repair and elective high-frequency oscillatory ventilation on survival of antenatally diagnosed congenital diaphragmatic hernia: first application of these strategies in the more "severe" subgroup of antenatally diagnosed newborns.

OBJECTIVE: a) To analyze the influence of a new management strategy on the outcome of neonates with antenatally diagnosed congenital diaphragmatic hernia (CDH); b) to determine early prognosis respiratory factors with the new strategy. DESIGN: Retrospective study. SETTING: Level III perinatal center. PATIENTS AND METHOD: Between 1985 and 1997, 51 consecutive neonates with antenatally diagnosed CDH were admitted to our level III neonatal intensive care unit. Before 1992 (period 1; n = 19), we used conventional mechanical ventilation and early surgery requiring transfer. Since 1992 (period 2; n = 32), we prospectively tested a new approach including (a) systematically use of high-frequency oscillatory ventilation (HFOV) regardless of the initial clinical severity, (b) delayed surgery following stabilization requiring transfer to a different surgical unit, but (c) no transfer of unstable patients with surgery under HFOV in our neonatal intensive care unit (n = 10). The two cohorts were comparable in terms of potential ante and postnatal prognostic indicators. RESULTS: Survival was improved with the new strategy: 21/32 (66%) vs. 5/19 (26%); P < 0.02. This improvement between periods 1 and 2 was due to a decrease in both preoperative and postoperative deaths in the later period. The better survival during period 2 was associated with the appearance of very late deaths, frequent pleural effusions, and the survival of more severe forms having evolved to a chronic respiratory insufficiency. Survivors were ventilated for longer time with longer duration of oxygen supplementation. The best oxygenation index (OI), alveolar arterial difference and oscillation amplitude (P/P) during the first 24 h, but not the best PaCO2, were the most reliable prognostic indicators during period 2. An OI < or = 10 with a P/P < or = 55 cmH2O was associated with a very good prognosis (94% survival). CONCLUSIONS: The prognosis of antenatally diagnosed CDH was improved by systematic HFOV on admission, no systematic transfer, and delayed surgery. This improvement is associated with modification of postnatal outcome.

Female↗
PubMed2000

High-frequency oscillatory ventilation in the management of respiratory distress syndrome.

Early use of high-frequency oscillatory ventilation with a high volume strategy (HFOV-HVS) has been proposed to decrease the incidence of chronic lung disease following respiratory distress syndrome (RDS) in extremely immature infants. Despite encouraging results of animal experiments, clinical trials have provided discordant results. Our own multicenter trial showed that using HFOV-HVS, compared with conventional ventilation, decreased exogenous surfactant requirements, but did not modify pulmonary outcome, and increased the risk of severe intraventricular hemorrhage. This prompted us to change our management of RDS, by switching from elective use of HFOV to an 'early rescue' approach.

Animals↗