Biomedical subjects
Publications and source records attributed to E Autret.
A 42-year-old woman had an accidental overdose of chloral hydrate due to repeated absorption of a therapeutic dose of chloral syrup for insomnia. The total ingestion was estimated at 8 g. Overnight slight loss of consciousness associated with severe cardiac arrhythmia (bigeminia ventricular extra-systole) needed admission to the intensive care unit and intravenous lignocaine for two days. The evolution was satisfactory.
The evaluation of a drug used in neuroanesthesia is based upon controlled trials. The main principles of such trials are not different from trials of other drugs but some characteristics should be emphasized. The first phase of the development of a drug is an evaluation in healthy volunteers of its tolerance and kinetics, which must combine rapid and short action without residual effect. The second phase is a study of the tolerance and kinetics but also of its efficacy because only patients are involved. Action upon cerebral circulation is of great importance. During the third phase, trials have to prove that the new drug has "something more" than the drug usually prescribed for the same indication to obtain approval for marketing. The next phase is the best period for the evaluation of safety by recording the adverse effects observed when many patients are exposed to the new drug. The french system of post marketing surveillance is based upon spontaneous reports of adverse effects by prescribers To be correctly performed a trial needs the collaboration of a neuroanesthetist, a pharmacologist and a statistician. The trial needs to be controlled which means a comparison of two groups of patients, one with the drug and the other one without the drug. The treatment has to be randomized and blind to be sure that any difference between the two groups is in fact due to the drug. The clinician has to define the evaluation criteria and the tool of measurement to calculate the number of patients needed for the purpose of the trial.
Modifications in the pharmacokinetics of aminoglycosides have been reported among patients with cystic fibrosis. We obtained suction blister fluid (SBF) to study the tissue diffusion of amikacin in cystic fibrosis in 2 children (a 9-year-old boy and a 7-year-old girl) over the course of bronchopulmonary infection. Amikacin was administered intravenously using a single dose of 5 mg/kg. The peak plasma concentrations were 24.5 and 11.2 mg/l, and the peak SBF concentrations were 8.3 and 3.2 mg/l. The ratio of the area under the curve in SBF and plasma was 58 and 60%, respectively. These results suggest a good penetration of amikacin through SBF and a good tissue diffusion of amikacin. The preliminary data suggest that the suction blister method may be useful to assess the tissue diffusion of drugs.
A severe chloroquine poisoning, featuring indicators of bad prognosis, has been treated by a diazepam-type therapy. The outcome was favourable in a dramatic way. A toxicokinetic study showed very high chloroquine plasmatic levels, consistent with the severity of the poisoning.
The authors report a case of a skin defect in the scalp of a child whose mother took carbimazole during her pregnancy. Including our case there are now 15 congenital scalp defects reported: however, these rare cases do not show that carbimazole should not be used during pregnancy.
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The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself.
A one month old child inadvertently received an intravenous bolus injection of 50 mg of lidocaine instead of contrast iodine. The clinical picture comprised collapse, respiratory arrest, convulsions and coma. The calculated maximum level of lidocaine was 5.39 mg/l. The recovery was complete. The toxicity of lidocaine is discussed.
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A retrospective study was undertaken to evaluate the relevance of benzodiazepine detection in 42 children with accidental poisoning. Immunoenzymatic assay for benzodiazepine in serum and colorimetric method in urines were positive respectively in 3 and 4 patients only. Several reasons could explain these results: the high detection threshold, the different drug reactivity according to the molecular structure and the great delay between intoxication and toxicology analysis. An advised physician should not prescribe a toxicological analysis after a small quantity of benzodiazepine ingestion.
Pharmacovigilance consists of collection, analysis and management of adverse drug reactions. It is mainly based on spontaneous reports of side-effects made by physicians. The pediatric character of pharmacovigilance is determined by the consequences of drug administration in a growing organism, and the risks incurred by incorrect use of drugs. Observation and notification of side effects by pediatricians constitute the basis for the prevention of adverse drug reactions in children.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Thirty-two neonates were treated with netilmicin 3 mg/kg every 12 h by IV infusion for 30 min for suspected infections, colonization, or proven infections. Pharmacokinetic studies were performed in order to define the situations in which monitoring of plasma levels would be appropriate. Mean plasma levels were within the therapeutic range and did not differ in fullterms and preterms. In the 4 children who had 2 successive pharmacokinetic studies, plasma levels were increased between H1 and H5 at the second evaluation due to netilmicin accumulation. Plasma half-life was longer in proven infections and seemed to decrease in preterms with increased gestational age. These results suggest that the dosage schedule should be left inchanged, but that administration time should be reduced from 30 to 20 min and that peak and trough plasma levels should be measured only in proven infections, in very premature babies (gestational age less than 33 wk), and during netilmicin treatment longer than 5 d.
A continuous-wave form Doppler monitor was used to examine the effect of caffeine on cerebral blood flow velocity (CBFV) in 7 clinically stable preterm neonates suffering from apnea. Caffeine, in the form of caffeine citrate, or saline were given intravenously at loading doses of 20 mg/kg. Every subject was his own control. Placebo (saline) was systematically injected prior to caffeine citrate. Simultaneous recording of heart rate, arterial blood pressure, respiratory rate, TcPO2, TcPCO2 were made before, then at the end of the injection, and 30, 60 and 120 min after the end of each administration of either placebo or caffeine. Compared with placebo, caffeine injection was not associated with significant changes in CBFV. An increase was found in both heart-rate and respiratory rate (p less than 0.05). Mean arterial blood pressure, TcPCO2 and TcPO2 did not change significantly. Our data suggest that a caffeine citrate loading dose of 20 mg/kg as currently used at the beginning of treatment of apnea in preterm neonates has no effect on CBFV.
Continuous wave Doppler monitor was used to examine the effect on cerebral blood flow velocity (CBFV) of caffeine in 7 clinically stable preterm neonates suffering from apnea. Caffeine, as caffeine citrate at a loading dose of 20 mg.kg-1 BW, or saline were given intravenously. Every subject was his own control. Placebo (saline) was systematically injected prior to caffeine citrate. Simultaneous recording of heart rate, arterial blood pressure, respiratory rate, Tc PO2, and Tc PCO2 were made before, at the end of the injection, and 30, 60 and 120 min after the end of each administration of either placebo or caffeine. Compared with placebo, caffeine injection was not associated with significant changes in CBFV. An increase was found in both heart rate and respiratory rate (p less than 0.05). Mean arterial blood pressure, Tc PCO2 and Tc PO2 did not change significantly. Our data suggest that a caffeine citrate loading dose of 20 mg.kg-1 BW as currently used at the beginning of treatment of apnea in preterm neonates has no effect on CBFV.
Nestosyl is usually used for dental pain in children. We report a methemoglobinemia after accidental ingestion of 10 ml in a 2 year-old girl. Cyanosis was cleared and O2 saturation and PaO2 were normalized 15 mn after methylene blue (1 mg/kg) administered intravenously. Nestosyl contains butoform, benzocaine, resorcine and 8-hydroxyquinoleine: the 3 latest can induce methemoglobinemia. The benefit of the drug is not demonstrated and this potentially severe side effect justifies its delivery only after medical prescription and information about its dangers.