Biomedical subjects
Publications and source records attributed to L Desfrere.
Oxygen weaning is a controversial problem which can be summarized in three questions: what do we expect from oxygen supplementation? what are the optimal targets? with what sort of monitoring? We shall try to evaluate these different questions assuming the uncertainty of the proposed answers and the short-lived character of them.
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.
The resuscitation of extremely preterm infants presents complex medical, social and ethical issues for the families and the health professionals. The principle of a systematic resuscitation "temporary intensive care" does not prohibit the question of a limit in terms of gestational age and birth weight. In France, a do not resuscitate order (comfort care alone) is appropriate for newborns weighing less than 500g and/or with a gestational age of less than 24 weeks' since the mortality is nearly 100%. The survival of infants born at 24 weeks' gestational age remains low with significant risks of chronic medical problems and neurodevelopmental disabilities. The decisions regarding the extent of resuscitative efforts depend on antenatal factors, condition of the neonate at birth and the parental opinion. Before the delivery, parents should receive appropriate information about survival and risks of adverse long-term outcome. The physician should follow the parents' desires whenever the parents' decision would not obviously violate the infants' best interests. However, they must be informed that decisions about neonatal management made before the delivery can have to be changed in the delivery room, depending on the condition of the neonate at birth. At 25 weeks of gestational age, the prognosis is better and the resuscitation should be more intensive.
Chylothorax is defined as an accumulation of chyle in the pleural space. This condition usually occurs after an operation, the congenital idiopathic form being rare (1/15 000 births). Recovery is observed within four to six weeks of diagnosis in most cases. Treatment is either conservative or surgical. Four cases are reported of congenital chylothorax (three idiopathic, one accompanied by diffuse lymphangectasia) managed by chemical pleurodesis (intrapleural injection of povidone-iodine). Tolerance was satisfactory: unaltered thyroid function in the three cases explored; one case of transient generalised oedema. Treatment was deemed successful in three of the four cases. One child died from renal failure (unrelated to the chemical pleurodesis). Pleurodesis by povidone-iodine appears to be well tolerated and may represent a good alternative to mechanical abrasion or surgery for congenital idiopathic chylothorax. Its use for refractory chylothorax may also decrease the morbidity related to prolonged hospital stay.
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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.
Endotracheal tubes (ETTs) constitute a resistive extra load for intubated patients. The ETT pressure drop (DeltaP(ETT)) is usually described by empirical equations that are specific to one ETT only. Our laboratory previously showed that, in adult ETTs, DeltaP(ETT) is given by the Blasius formula (F. Lofaso, B. Louis, L. Brochard, A. Harf, and D. Isabey. Am. Rev. Respir. Dis. 146: 974-979, 1992). Here, we also propose a general formulation for neonatal and pediatric ETTs on the basis of adimensional analysis of the pressure-flow relationship. Pressure and flow were directly measured in seven ETTs (internal diameter: 2.5-7.0 mm). The measured pressure drop was compared with the predicted drop given by general laws for a curved tube. In neonatal ETTs (2.5-3.5 mm) the flow regime is laminar. The DeltaP(ETT) can be estimated by the Ito formula, which replaces Poiseuille's law for curved tubes. For pediatric ETTs (4.0-7.0 mm), DeltaP(ETT) depends on the following flow regime: for laminar flow, it must be calculated by the Ito formula, and for turbulent flow, by the Blasius formula. Both formulas allow for ETT geometry and gas properties.