A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose.

BACKGROUND: The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy. METHODS: Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and 1993. Congenital abnormalities, intrauterine development based on birth weight and post-conceptional age, mental retardation, cognitive-behavioral status were compared in exposed children born to mothers who had attempted suicide by means of a drug overdose during pregnancy with their siblings, born either before or after the affected pregnancy, as sib controls. RESULTS: Of a total of 1 044 pregnant women, 74 used the combination of amobarbital, glutethimide and promethazine (Tardyl®, one of the most popular drugs for treatment of insomnia in Hungary) for suicide attempt. Of these 74 women, 27 delivered live-born babies. The mean dose of Tardyl® used for suicide attempts was 24 times the usually prescribed clinical dose. The rate of congenital abnormalities and intrauterine retardation was not higher in exposed children than in their sib controls. However, of the 27 exposed children, eight (29.6%) were mentally retarded (X²1=79.7, p= Sig) while mental retardation did not occur among 46 sib controls. These exposed children were born to mothers who attempted suicide with Tardyl® between the 14th and 20th post-conceptional weeks. The components of Tardyl® used separately for a suicide attempt during pregnancy were not associated with a higher risk of mental retardation. Therefore the high doses of Tardyl® associated with the high risk for mental retardation may be due to the interaction of its three drug components. CONCLUSIONS: The findings of the study showed that the high doses of a drug containing three components may be associated with a significantly increased risk for mental retardation without any structural defects, whereas each of these three component drugs taken alone was not associated with this adverse effect.

A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses.

Animal investigations showed some embryolethal and teratogenic effects of glutethimide, a piperidindion derivative non-barbital hypnotic drug. Thus, the objective of this study was to evaluate the effects of very large doses of glutethimide that were used for a suicide attempt during pregnancy on the embryo-fetal development of exposed children. Self-poisoned pregnant women were identified from the population of female patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest who had been admitted from the 3 million people of Budapest and its surrounding region. The rates of congenital abnormalities, intrauterine fetal development (based on birth weight and pregnancy age at delivery) and cognitive-behavioral status of exposed children born to mothers who attempted suicide with glutethimide alone or in combination with other drugs during pregnancy were compared with their sib controls. Of 1044 pregnant women with self-poisoning during pregnancy between 1960 and 1993, 33 used glutethimide for a suicide attempt sixteen of these women delivered live-born infants. The dose of glutethimide ranged between 1000 and 15,000 mg with a mean of 4234 mg. Of the 16 exposed children, five were male and 11 were female. Three exposed children were affected with congenital abnormalities (atrial septal defect type II, pectus carinatum, fetal alcohol syndrome). Of their 16 matched unexposed sib pairs, two had congenital abnormalities. The mean birth weight of the exposed children was somewhat larger due to somewhat longer pregnancy age at delivery. Cognitive status and behavioral scale of the exposed children did not indicate a fetotoxic (including neurotoxic) effect of large doses of glutethimide. Very large doses of glutethimide used for a suicide attempt by 16 pregnant women did not produce teratogenic or fetotoxic (including neurotoxic) effects in their children.

[Suicidal attempts with old (currently unused) drug]. / Zatrucie samobójcze lekiem z przeszlosci.

Suicidal attempt with old (currently unused) drug is described. The suicidal attempts are usually performed with the use of contemporary pharmacotherapeutics. In the report a case of suicidal attempt with old drug Tardyl is presented. Tardyl (Glutethimid) was prescribed to the patient and has been stored for 20 years. The patient was previously treated for depression and many suicidal attempts. In the course of intoxication: balance disturbances, psychomotor retardation, changes in consciousness with temporary excitation were observed. The concentration of glutethimid in the urine was 1.1 mg% and 0.5 mg% in the blood. Patient was treated according to the general rules of intensive care. After 4 days of therapy the patient improved and was transferred to psychiatric unit in Koscian.

Fatalities associated with an acute overdose of glutethimide (Doriden) and codeine.

Abuse of the oral combination of glutethimide (DORIDEN) and codeine, commonly referred to as "sets", in the northwest Pennsylvania area is reviewed. Nine fatalities have been reported in the Erie area from 1985-87 due to acute toxicity with this combination. The glutethimide/codeine combination reportedly produces a euphoric effect comparable to intravenous heroin but is longer lasting. Age of the victims ranged from 18 to 37 years. In all cases there was a history of chronic intentional "sets" abuse by the victims prior to death. The 9 fatalities due to this combination of prescription drugs is unusually high for this area considering the population and rural nature of the Erie community. Although the use of "sets" has been reported occasionally in other localized areas of the country, no other significant use has been reported in Pennsylvania.

Lack of correlation between plasma 4-hydroxyglutethimide and severity of coma in acute glutethimide poisoning. A case report and brief review of the literature.

Glutethimide poisoning is characterised by coma, anticholinergic poisoning syndrome, hypotension, and other complications. Previous studies have shown that the severity of intoxication does not correlate with plasma glutethimide concentrations in individual patients. Glutethimide is partly converted to 4-hydroxyglutethimide, a metabolite which accumulates in the plasma of humans, and which has been thought to contribute to coma after plasma glutethimide concentrations have fallen. We followed plasma concentrations of glutethimide and 4-hydroxyglutethimide in a man who overdosed with glutethimide. Plasma 4-hydroxyglutethimide concentrations did not correlate with the degree of coma in our patient, and actually rose as the patient awakened. Other studies also indicate that 4-hydroxyglutethimide may not play an important role in glutethimide poisoning.

Resin hemoperfusion for drug intoxication--an update.

Hemoperfusion through Amberlite XAD-4 resin column has been shown to effectively remove sedative-hypnotics, analgesics and other drugs causing acute intoxication. There is no appreciable clinical toxicity and dramatic shortening of coma time and possible decrease in mortality may be achieved. Thrombocytopenia and clotting may be diminished by pre-perfusion coating with 2.5% albumin. Albumin coating may facilitate the repeated use of hemoperfusion without any complications. More recently, resin hemoperfusion has been used for procainamide, N-acetylprocainamide and theophylline intoxication achieving exceptionally high clearance rates.

Barbiturate and nonbarbiturate sedative hypnotic intoxication in children.

This article reviews the pharmacology, toxicology, and treatment of both barbiturate and nonbarbiturate sedative hypnotic overdose. Although poisoning with these agents has declined over recent years, intoxication with them can still result in a life-threatening situation requiring immediate assessment and treatment.

Toxicological analysis of amobarbital and glutethimide from bone tissue.

Author examined cadaver organs and bone samples (sternum, rib) of drug poisoning cases. Following suitable procedures, active drug components (amobarbital, glutethimide, and so forth) were identified by gas chromatography/mass spectrometry (GC/MS). Based on results of quantitative GC analysis, relationships were sought between the active agent concentrations measured in the organs and the bone samples.

Clinical experience with the use of charcoal haemoperfusion: is prostacyclin required?

Twenty patients have undergone a total of 47 charcoal haemoperfusions without the use of prostacyclin. A fall in platelet numbers and evidence of platelet activation have been found during haemoperfusion but few clinical complications have been observed. Therefore, we believe that the clinical value of the addition of prostacyclin during charcoal haemoperfusion has not been proven. Nevertheless, its apparent protective effect on platelet numbers and activation indicates that further controlled trials of the use of prostacyclin during charcoal haemoperfusion are required.

Blood concentrations and clinical findings in nonfatal and fatal intoxications involving glutethimide and codeine.

Blood concentrations and clinical findings were evaluated in twenty-six nonfatal and twelve fatal intoxications involving the combination of glutethimide and codeine ("loads"). The mean glutethimide concentration was 10 +/- 5 mg/L for nonfatal cases (range 2-18 mg/L) and 13.9 +/- 6.6 mg/L for fatal cases (range 4.6-26.4 mg/L). The mean codeine concentration for fatal intoxications was 1.21 +/- 1.17 mg/L (range 0.13-4.32 mg/L). Codeine concentrations were not measured in cases of nonfatal intoxication. Nine nonfatal cases required hospitalization on a medical ward (mean length of stay 3 +/- 3 days). Depressed level of consciousness was the most common abnormal physical finding (24 cases); 18 patients were lethargic but arousable with nonpainful stimulation and 6 patients with serum glutethimide concentrations of 10 mg/L or greater were comatose. The level of consciousness showed statistically significant correlation with the glutethimide concentration (P less than 0.01). Twenty-four nonfatal intoxications involved at least one other drug in addition to glutethimide and codeine (salicylates in 12 and acetaminophen in 4), while only 7 fatal cases involved at least one additional drug (acetaminophen and diazepam in 3 each). The finding of glutethimide should prompt a search for codeine and vice versa, especially when the presence of either does not in and of itself explain the clinical condition of the patient.