Congenital abnormalities in children of 43 pregnant women who attempted suicide with large doses of nitrazepam.

OBJECTIVE: To evaluate the teratogenic effect of very large doses of nitrazepam in children born to pregnant women who attempted suicide and to check the feasibility of self-poisoning pregnant women model. DESIGN AND SETTING: Comparative analysis of exposed children and their unexposed sibs born to the same mothers who attempted suicide during the study pregnancy and admitted to the toxicological inpatients clinic, Budapest, 1960-1993. STUDY PARTICIPANTS: Of 1044 pregnant women who attempted suicide, 107 (10.3%) used large doses of nitrazepam alone or combination with other drugs, and 43 delivered live-born babies, these exposed children were evaluated. MAIN OUTCOMES MEASURES: Structural birth defects, i.e., congenital abnormalities (CAs), pregnancy age at delivery, and birth weight. RESULTS: The mean dose of nitrazepam used for suicide attempt was 204 mg. Of 43 exposed children, 13 (30.2%) were affected with CAs, while of their 29 sib controls, 3 (10.3%) (OR with 95%CI: 3.8, 1.0-14.6). Most CAs in exposed children were mild and belonged to the deformation type. The mean pregnancy age was shorter. CONCLUSIONS: The very large doses of nitrazepam used for suicide attempt during pregnancy resulted in a high rate of CAs which may be connected with the disruption of protein metabolism in fetal mesenchyma. The self-poisoning pregnant women model is feasible for the evaluation of teratogenic effect of drugs.

[Time limits for gastrointestinal decontamination in poisoning]. / Tidsgraenser for gastrointestinal dekontaminering ved forgiftning.

A 70-year-old man was admitted to hospital within 5 hours after an intended overdose of benzodiazepines and morphine. He was treated with flumazenil and naloxone but GID was considered unsafe. 24 hours after admission the patient had a GCS at 5 and significant respiratory insufficiency. After intubation, large amounts of tablets were aspirated and activated charcoal instilled. Respirator treatment was required for 24 hours and the course was complicated by aspiration pneumonia. The case challenges strict time limits and a restricted attitude towards gastric emptying in massive overdose.

Tissue distribution of nitrazepam and 7-aminonitrazepam in a case of nitrazepam intoxication.

We report a case of nitrazepam poisoning in which the distribution of nitrazepam and 7-aminonitrazepam was determined in body fluids and tissues. A 52-year-old woman was found dead in a shallow ditch (approximately 5 cm in depth), in the winter. Ambient temperature was 2-8 degrees C. The postmortem interval was estimated to be approximately 1 day and no putrefaction was observed. The cause of death was thought to be drowning due to nitrazepam overdose and cold exposure. Blood concentrations of nitrazepam and 7-aminonitrazepam were very site dependent (0.400-0.973 microg/ml and 0.418-1.82 microg/ml). In addition, the concentration of the same analytes in the bile were 4.08 and 1.67 microg/ml, respectively, and in the urine: 0.580 and 1.09 microg/ml, respectively. A high accumulation of both substances was observed in various types of brain tissue (2.17-6.22 microg/g and 2.49-5.11 microg/g). Only small amounts of nitrazepam and 7-aminonitrazepam were detected in the liver (0.059 and 0.113 microg/g, respectively). Large differences in the observed concentrations of nitrazepam and 7-aminonitrazepam among arterial and venous blood samples were thought to be mainly due to dilution of arterial blood by water entering the circulation through lungs at the time of death. Bacterial metabolism of nitrazepam may also have contributed to the observed differences.

Citalopram in fatal poisoning cases.

Citalopram, a selective serotonin reuptake inhibitor, is the most frequently prescribed antidepressant in Sweden. To investigate the extent to which citalopram in overdose is found in fatal poisoning cases compared with other drugs, all fatal poisonings in one forensic medicine district in Sweden during the years 1994-1999 were examined. Drugs found in overdose in more than 10 cases were included. The ratio between number of cases with each included drug and prescription of defined daily dose/1,000 inhabitants/day (DDD) was determined. Citalopram was the fourth most frequently found drug in overdose, occurring in 22 (6%) of the 358 fatal poisoning cases, after dextropropoxyphene (DXP), flunitrazepam and nitrazepam, which were present in 111 (31%), 56 (16%) and 31 (9%) cases, respectively. When related to the prescription rate, citalopram was significantly less represented than five of the other seven included drugs, namely DXP, flunitrazepam, nitrazepam, amitriptyline and clomipramine. Propiomazine and zopiclone occurred to the same extent as citalopram. According to the assessments of the forensic physicians, citalopram was the cause of death in five cases (1.4%) and contributed to death in another nine cases (2.5%). It is concluded that citalopram, in spite of its high prescription rate, has not become a drug of importance in fatal poisoning cases. Since, this result may not be generalisable to non-fatal poisoning cases, it is recommended that the prevalence of citalopram in these cases be examined separately.

Two cases of lethal nitrazepam poisoning.

This case report describes two cases of lethal poisoning caused by a combination of advanced chronic disease and an overdose of nitrazepam. In both cases, a relatively small blood concentration of nitrazepam was found postmortem.

[Drug poisoning in the 39th week of pregnancy--a case report]. / Tablettenintoxikation in der 39. Schwangerschaftswoche--Eine Kasuistik.

It is reported on an intoxication with nitrazepam at the end of pregnancy. The fetal cardiotachogram showed a silent oscillation type for more than 20 hours. A cesarean section could not be performed, therefore the pregnancy was terminated by spontaneous delivery 20 hours later after the beginning of labour. Although a fetal endangering by a silent oscillation type could not be excluded, due to the metabolism of nitrazepam in the mother the newborn baby did not show major intoxication symptoms.

A fatality involving secobarbital, nitrazepam, and codeine.

A fatal case involving the suicidal ingestion of secobarbital, nitrazepam, and codeine is presented. The drugs were quantified using gas chromatography for codeine and high-performance liquid chromatography for the two other drugs. The blood concentrations of secobarbital, nitrazepam, and codeine were found to be 11.48, 1.72, and 0.036 microgram/ml, respectively. Results are discussed in the light of the existing literature.

Pulmonary oedema following carbamazepine overdose.

The successful management of a case of pulmonary oedema is described after the late recognition of an overdose of carbamazepine which complicated recognised benzodiazepine overdosage. The presentation and management are described and the possible mechanism of this rare complication discussed.

Rhabdomyolysis and acute renal failure following an overdose of doxepine and nitrazepam.

A 50-year-old woman developed rhabdomyolysis and myoglobinuric renal impairment after an oral dose of 250 mg nitrazepam and 1,250 mg doxepin. Serum creatinine increased from 70 mumol/l to 472 mumol/l in two days. Serum creatine phosphokinase reached a maximal level of 391 mu kat/l (reference range less than 2.5 mu kat/l) on the third day and serum myoglobin was maximally 910 nmol/l (reference range less than 4.5 nmol/l) on the fourth day after the overdose. Passive and active movements of the knees and ankles became increasingly restricted, but the patient felt no muscle pain. Diuresis decreased to 20-22 ml/hour in spite of repetitive doses of furosemide, but was enforced to greater than 100 ml/hour by vigorous infusion of saline. Haemodialysis was avoided on this regimen. It is suggested that in patients intoxicated with nitrazepam and/or doxepin, rhabdomyolysis should be suspected when a rapidly increasing serum concentration of creatinine is found, even in the absence of muscle pain.

[Therapy of the anticholinergic syndrome in poisonings]. / Die Therapie des anticholinergen Syndroms bei Intoxikationen.

Underlying literature and taking into consideration own experiences in the anticholinergic syndrome the following view is taken: Physostigmine salicylate is the remedy of choice for the treatment of the anticholinergic syndrome and altogether causes only slight side effects. While for differential-diagnostic reasons the application is recommended under hospital conditions, the pre-hospital application is to be estimated as problematical. The improvement of the clinical symptoms under the influence of physostigmine salicylate must not lead to the neglect of the control of the patient. A differentiated use of physostigmine salicylate is necessary, and it cannot be regarded as "universal antidote" in intoxications caused by central-nervous effective substances.

Lack of evidence of teratogenicity of benzodiazepine drugs in Hungary.

In order to investigate possible teratogenic effects of commonly used benzodiazepines (diazepam, chlordiazepoxide, nitrazepam) in Hungary, four approaches were used: 1. A retrospective case-control study of 630 cases with isolated cleft lip +/- cleft palate, 179 cases with isolated cleft palate, 392 cases of multiple congenital anomalies including cleft lip and/or cleft palate, and their matched control cases; 2. The Case-Control Surveillance System of Congenital Anomalies in Hungary, 1980 to 1984, involving 355 cases with isolated cleft palate, 417 cases with multiple congenital anomalies, and 186 cases with Down's syndrome (as positive controls). Benzodiazepines were taken by 14.9% of 11,073 control pregnant women studied; 3. A prospective study of 33 pregnant women attending the Counselling Clinic following ingestion of benzodiazepines during the first trimester of pregnancy; 4. An observational study involving 12 pregnant women who attempted suicide and one with accidental overdosage with benzodiazepines during pregnancy. None of these four approaches gave any indication of an association between facial clefting and in utero exposure to these substances.

Incidence of self poisoning in patients prescribed psychotropic drugs.

The drugs most commonly used in self poisoning are the psychotropics, but the proportion of patients given these drugs who take overdoses is unknown. In a prospective study of 43117 people in Oxfordshire, prescriptions issued by general practitioners were linked with records of hospital admissions and deaths. During two years there were 79 episodes of deliberate self poisoning leading to hospital admission or death. The number of patients who took overdoses of psychotropic drugs was small in relation to the total number prescribed such drugs. Of 5600 people aged 10 or older who received psychotropic drugs during one year, 17 (3.0 per 1000) poisoned themselves with these drugs within 12 months. The rate of self poisoning with psychotropic drugs declined significantly with increasing age (p less than 0.001). Almost three quarters of the patients who took overdoses of prescribed psychotropics received further psychotropic drugs during the three months after their admission to hospital.