Fetal risks with dextrans during delivery.

Epidural analgesia for caesarean section is increasingly used and is gradually replacing general anaesthesia. Hypotension is one of the main risks: preloading of the maternal circulation is used to prevent maternal hypotension and its consequences. For this, various colloid and crystalloid solutions are used. We report a case of maternal anaphylactoid reaction with apparent death in a neonate after dextran administration to the mother. After 100ml of a dextran 40 solution administered intravenously, immediately before an epidural blockade, the mother fainted and developed urticaria and mild respiratory disturbances, without hypotension. At that point dextran infusion was stopped. An apparently dead neonate was rapidly delivered. Immediate and vigorous cardiopulmonary resuscitation was successful. Clonismus appeared 12h later, followed by 3 general epileptic fits treated by phenytoin infusion and subsequently oral phenobarbital. No aetiology was found. After 2 months of treatment, barbiturates were stopped following clinical and electroencephalogram (EEG) improvement. Several similar cases of neonatal disorders resulting from preventive dextran administration during delivery were studied in a national pharmacovigilance survey in France. There were 32 cases reported with moderate maternal anaphylactoid reaction associated with severe acute fetal distress; it is probably advisable to take a cautious approach and avoid preventive fluid preload by dextran administration. Gelatins or crystalloid solutions should be preferred, with intravenous vasopressive amine administered promptly and repeated if necessary should significant maternal hypotension occur during epidural anaesthesia.

[Adverse effects of oxybutynin chloride (Ditropan). Evaluation of the official survey of Regional Pharmacovigilance Centers]. / Effets indésirables du chlorure d'oxybutynine (Ditropan). Bilan de l'enquête officielle des Centres Régionaux de Pharmacovigilance.

We analyzed the 200 reported cases of adverse reactions to Ditropan (209 side-effects) collated by the Centres Régionaux de Pharmacovigilance and Laboratoire Debat since the drug was first marketed. The frequency of such side-effects was of the order of 1 per 20,917 treatment months. Children were affected four times more frequently than adults. The manifestations resembled atropine overdose in 103 cases (52 children, 51 adults), and were mainly neurological (59%) and ocular (22%). Two cases of erythema multiform and 33 of miscellaneous allergic skin reactions occurred. The fact that atropine overdose was more frequent in children can be explained by the proportionately higher dosage. Dose adjustment based on pediatric pharmacokinetic studies appears to be essential. In children, the drug is prescribed most frequently (56%) for conditions outside the licensed indications, particularly nocturnal enuresis, a condition for which the efficacy of Ditropan has not been established. We consider that this calls for a specific contraindication in isolated nocturnal enuresis and in children aged less than five years.

[Pulmonary toxicity of nilutamide (Anandron). Cooperative evaluation of French Regional Pharmacovigilance Centers]. / Toxicité pulmonaire du nilutamide (Anandron). Bilan coopératif des centres français de pharmacovigilance.

We have studied 12 reports of pneumonitis associated with nilutamide (Anandron) and notified to the French regional ADR monitoring centers between November 1987 and June 1990. The mean age of the patients was 71.5 +/- 9.5 years, and 35% (5/12) had a history of lung disease. All 12 patients developed dyspnea, cough and fever, 4.7 +/- 6 months after starting nilutamide. Ten patients (83%) required admission to hospital. The symptoms revolved in 11 cases when the drug was withdrawn. In the other case, they disappeared when another drug was stopped and the dose of nilutamide was reduced. Six patients were treated with glucocorticoids. The severity of nilutamide-associated pneumonitis appears to be related to the time between the onset of dyspnea and consultation.

[Does the placebo effect exist in newborn infants?]. / L'effet placebo existe-t-il chez le nouveau-né?

Although comparison with a placebo is necessary to demonstrate the "true" effect of a drug, neonatologists are usually reluctant to use a placebo. The reason given is the lack of placebo effect in neonates. We studied heart and respiration rates and behaviour in normal neonates during heelstick for diagnosis of phenylketonuria. In this open randomized study we compared no treatment with an "analgesic" treatment consisting of water and sucrose. There was no difference in heart and respiration rates and behaviour between the two groups. These results do not demonstrate a "suggested" placebo effect and can in part be explained by the model and tools used to measure pain. The results do not support the non-use of placebo in drug evaluation trials in children.

[Comparison of plasma concentration and tolerance of a single dose of human calcitonin by intradermal and subcutaneous administration]. / Comparaison des concentrations plasmatiques et de la tolérance d'une dose unique de calcitonine humaine administrée par voie intradermique et sous-cutanée.

UNLABELLED: The aim of the study was to compare plasmatic levels of calcitonin obtained after intradermic (ID) and usual subcutaneous (SC) route of administration. METHOD: 6 volunteers between 18 and 40 years old received calcitonin 0.5 mg (Cibacalcin, Ciba-Geigy Laboratory) by ID and SC routes in a random order but at the same site of injection. Each administration was spaced by 8 days. Plasmatic levels were measured by R.I.A. before administration then 2 (M2), 7 (M7), 15 (M15), 30 (M30) minutes and 1 (H1), 2 (H2), 4 (H4), 8 (H8), 12 (H12) hours after each administration. RESULTS: Tmax were at 23.6 +/- 10 min and 16.2 +/- 7.5 min for SC and ID routes respectively. With ID route, Tmax was reached simultaneously or earlier (3 times). Cmax is significantly higher with ID route. Neither mean plasmatic levels at each plasmatic dosage nor mean areas under the curve between 0 to 1,440 min or between 0 to 480 min (this latest AUC calculate to minimize the importance of calcitonin basal level) were significantly different with ID and SC routes. 16 mild side effects (8 with each administration) were observed in 4 subjects. They appeared before 5 min. and were transient (1 hour) for cutaneous manifestations, and later between hours 3 and 7 for nausea and vomiting or asthenia. The mean lowering of calcemia was 0.29 +/- 0.21 and 0.18 +/- 0.11 mmol/l respectively for SC and ID route. In this study ID and SC routes for calcitonin administration are not different with regard to plasma levels and side effects.

[Are theophylline determinations useful to the clinician during treatment with a sustained-release form of theophylline?]. / Les dosages de théophylline sont-ils utiles au clinicien au cours des traitements par théophylline à libération continue?

The aims of the study were the correlation between dosage and plasmatic levels of slow release theophylline and the reason for dosage adjustment. 64 pharmacokinetic studies were performed in 58 asthmatic children between 17 months and 16 years. Plasmatic levels of theophylline were performed by fluoroimmunology technique at H0 (before the dose) 2 (H2), 4 (H4), 6 (H6) and 8 (H8) hours after the dose of slow release theophylline. The best correlation between dose and plasmatic levels were observed at H4 and H6 for Armophylline and Euphylline respectively. Dosage adjustment were based both upon clinical state and plasmatic levels in 55 cases. In 9 cases the modification of dose were decided only because of plasmatic levels out the therapeutic range. The authors proposed a schema of dosage modifications based upon clinical state; plasmatic levels must be used as a guide for dose adjustment in patients clinically uncontrolled.

[Drug utilization at the end of pregnancy]. / Consommation médicamenteuse en fin de grossesse.

To evaluate drug utilization during the last 15 days of pregnancy, one hundred six women were interviewed post-delivery in the CHU Bretonneau in Tours. Eighty-three percent received at least one drug during the 15 days preceding delivery and 27% more than 3 different drugs. Treatments for venous disorders (31% of patients), iron (31%), analgesics (25%), antacids (11%), magnesium (11%) and laxatives (11%) were most frequently used. In 92% of cases the drug was prescribed. Five women received a drug with potential risk for the neonate. However only one infant developed and adverse effect, possibly due to benzodiazepine (hypotonia).

[Aplasia cutis after exposure to carbimazole in utero]. / Aplasia cutis après exposition in utero au carbimazole.

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.

[Pleural effusion induced by bromocriptine]. / Epanchements pleuraux induits par la bromocriptine.

Bromocriptine, a derivative of ergot of rye, is used in high doses for the treatment of Parkinson's disease and may be responsible for pleuro-pulmonary complications. We report a case of a 72 year old patient treated for 2 years for Parkinson's disease with a daily dose of 30 mgms. of bromocriptine and in whom a pleural effusion, initially unilateral then bilateral, was discovered with a deterioration in the general physical state. The effusion was a transudate and examination did not give any clues as to aetiology, there was a rapidly favourable outcome following the cessation of treatment. Amongst the respiratory complications of bromocriptine it is the pleuro-pulmonary fibrosis which is most frequently reported. The cases of isolated pleural effusions are rare and are generally exudates. Several hypotheses have been put forward to explain the pathogenesis of these disorders: there is a theory that the molecule induces a toxic fibrogenesis, there is a vascular theory analogous with the secondary effects of methysergide and finally immunological theory. The frequency of the disorder is probably underestimated and these drug reactions justify a close follow up for any respiratory problems in patients who are subjected to treatment with bromocriptine.

[Pediatric pharmacologic surveillance]. / Pharmacovigilance pédiatrique.

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.

[Local catastrophe and C.A.P.: apropos of 1 plant in Touraine]. / Catastrophe locale et C.A.P.: à propos d'une usine en Touraine.

Drinking water supply to a 200,000 inhabitant urban area had to be interrupted owing the pollution of the Loire river due to fire in a chemical plant in the vicinity of Tours. This event showed a regretful lack of information diffusion making the role of the Poison Control Center more difficult. Consequences related to acute toxicity were negligible but the evaluation of long-term risk is still pending.

[Adverse effects of oxybutynin chloride (Ditropan) in pediatrics]. / Effets indésirables du chlorure d'oxybutynine (Ditropan) en pédiatrie.

BACKGROUND: The side effects of oxybutynin chloride (Ditropan) often include atropinic and allergic reactions. Their relative frequency in children merits a nationwide investigation. METHODS: All the side effects of Ditropan reported to the French Regional ADR monitoring centers and to the pharmaceutical firm Debat between January 1985 and June 1990 were analysed. Only 87 effects of the 286 side effects reported in adults and children occurred with sufficient frequency in 84 children to warrant study. RESULTS: The 84 children (38 males, 43 females, 3 of unknown sex) were 30 months to 15 years old (mean: 6.5 years); 13 of them were less than 5 years. The mean dose of Ditropan prescribed was 0.5 +/- 0.12 mg/kg/day. 52 children developed atropinic symptoms, 20 skin and/or allergic reactions and 15 various other manifestations. These side effects required admission to hospital in 14% of cases. The side effects were 4 times more frequent in children (1/4,000 regulations) than in adults. CONCLUSIONS: The higher frequency of atropinic reactions in children may be due to the higher dosage of the drug used and/or to differences in hydroxylation metabolism, that is genetically determined in adults. New recommendations for use of this drug are proposed.

Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen syrup in children with pyrexia associated with infectious diseases and treated with antibiotics.

A double-blind, randomised, parallel group study has been done comparing the efficacy and tolerability of 7.5 mg/kg ibuprofen syrup (n = 77) and 10 mg.kg-1 acetaminophen syrup (n = 77) in 154 children (6 months to 5 years) with fever (> or = 38 degrees C) associated with infectious diseases and treated with antibiotic therapy. The area under the percentage reduction in temperature curve captured the net effect of each drug and provided the best estimate for comparison of efficacy during a defined period. Temperature evolution over time was not significantly different between the two groups. Nevertheless, the temperature reduction over the first 4 h of treatment (H0-H4) was significantly higher after ibuprofen (60%) than acetaminophen (45%). Both ibuprofen and acetaminophen were well tolerated. In conclusion, significant antipyretic activity, good tolerability and its availability as a syrup make ibuprofen an effective means of fever control in children.

Oxidative polymorphism of dextromethorphan in a Burundi population.

The wide availability, metabolism by the same cytochrome P450 as debrisoquine and, above all, the inocuity of dextromethorphan (DMP) favour the frequent choice of this drug as the test substance in determining oxidation phenotypes. 100 healthy Burundian volunteers (94 m and 6 f) in this study ingested 50 mg DMP bromhydrate, i.e. 38.5 mg of DMP base. Urine was collected for 8 h following the dose and TLC was used to analyse it. The method was particularly useful in view of its low cost, speed and the ease of applying it to a large study group. 5% of the Burundian subjects were poor metabolizers.