Characterization of drug poisoning among adolescents seen at the municipal hospital of Bahía Blanca, Province of Buenos Aires, Argentina. / Caracterización de la consulta por intoxicación medicamentosa en los adolescentes en el Hospital Municipal de Bahía Blanca, Buenos Aires.

INTRODUCTION: Drug poisoning among children is a frequent reason for visits to the emergency department; among adolescents, it is intentional. OBJECTIVE: To describe the characteristics of drug poisoning among adolescents admitted to the municipal hospital of Bahía Blanca. Material and method. Descriptive study based on the review of medical records of patients aged 10-19 years seen for drug poisoning between 2012 and 2016. The following outcome measures were analyzed: age, sex, drug used, cause, clinical manifestations, and length of stay in days. RESULTS: Data from 72 patients were collected. Their mean age was 16 years, and the female:male ratio was 2.5:1. Anxiolytic poisoning (30%) predominated, followed by polydrug use (25%). Ninety-five percent of patients showed a suicidal intention; of these, 55% had a history of suicide attempt. CONCLUSION: Drug poisoning was observed predominantly among girls; it is worth noting the high percentage of youth who had a history of suicide attempt.

Introducción. La consulta por intoxicación medicamentosa en los niños se da con frecuencia en los servicios de emergencias médicas; en la adolescencia, es cuando ocurren de forma intencional. Objetivo. Caracterizar los patrones epidemiológicos de la intoxicación medicamentosa en adolescentes ingresados al Hospital Municipal de Bahía Blanca. Material y método. Estudio descriptivo, basado en la revisión de historias clínicas de pacientes de 10 a 19 años que consultaron por intoxicación medicamentosa, entre los años 2012 y 2016. Las variables analizadas fueron edad, sexo, fármaco consumido, causa, manifestaciones clínicas y días de internación. Resultados. Se recopilaron 72 pacientes. La edad media fue de 16 años, razón mujer-hombre de 2,5:1. Predominaron las intoxicaciones por ansiolíticos (30%), seguidas de las polimedicamentosas (25%). El 95% manifestaron intención suicida, de los cuales el 55% ya tenían antecedentes. Conclusión. La intoxicación medicamentosa ocurrió, predominantemente, en mujeres, y se destacó el gran porcentaje de adolescentes que presentaba episodios previos.

Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality.

The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005-2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48-18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01-16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97-24.41) and 12 (95% confidence interval 6.62-22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.

Unsuccessful Suicide Attempt With Tiapride.

To the best of our knowledge, no case has been published in the literature that reports an overdose of tiapride, either alone or in combination with other drugs. We report a self-poisoning case in an 18-year-old girl, with approximately 10 times the usual daily dose (ie, 2.5 g). Although the blood concentration was 20/30-fold higher than usually observed after therapeutic drug intakes (17,300 mcg/L), the patient remained almost asymptomatic.

Relapse of Takayasu arteritis as a cause of suicidal poisoning and subsequent major ischemic stroke successfully treated with thrombolytic therapy.

Introduction: Takayasu arteritis (TA) is a rare large vessel arteritis, affecting primarily aorta and its major branches. Its clinical manifestations can vary significantly - from asymptomatic to serious vascular events. Acute neurological complications are frequent at the onset of the disease and in relapses. Anxiety and depression are more frequent in TA patients than in general population as well as during relapses. Prevalence of transient ischemic attack or ischemic stroke in TA patients is approximately 10-20%. Case report: We presented a patient with TA that began with a depressive episode resulting in attempted suicide by bromazepame poisoning. This was subsequently followed by major ischemic stroke caused by thrombosis of the left middle cerebral artery (probably due to aortic arch embolism) successfully treated with intravenous thrombolysis. Conclusion: Intravenous thrombolysis appears to be safe and effective in patients with TA and stroke.

Assisted suicide by fentanyl intoxication due to excessive transdermal application.

Herein, we report a case of an assisted suicide committed by application of 34 matrix-based fentanyl-containing transdermal therapeutic systems (TTS) with different release rates. The TTS were supplied by the husband but administered by the deceased herself. Besides routine systematic toxicological analysis (STA), the concentrations of fentanyl and norfentanyl were determined in the blood (femoral and heart), urine, stomach content, brain, lung tissue, musculus iliopsoas, liver, kidney, bile and in some of the used TTS by LC-MS/MS. Blood levels of fentanyl were 60.6 µg/L in femoral blood and 94.1 µg/L in heart blood. These concentrations are in good concordance with levels described in cases with accidental or lethal suicidal fentanyl patch application. The organ distribution indicates an influence of post-mortem redistribution. The levels of residual fentanyl in the TTS were also determined. STA furthermore revealed supratherapeutic levels of bromazepam. Thus, the cause of death was a combination of fentanyl and bromazepam intoxication. However, considering the determined levels of fentanyl and norfentanyl in the entire set of specimens and the high toxicity in comparison to bromazepam, fentanyl was the leading toxic noxa.

Endoscopic removal of pharmacobezoar in case of intentional potassium overdose.

BACKGROUND: Hyperkalemia is a potentially life-threatening electrolyte abnormality commonly seen in the emergency department (ED). Intentional overdose of potassium supplements is an uncommon occurrence. OBJECTIVE: This case illustrates a novel approach to treatment of pharmacobezoar with esophagogastroduodenoscopy (EGD) and demonstrates its effectiveness in the setting of extended-release potassium chloride overdose. CASE REPORT: A 44-year-old female presented to the ED with intentional ingestion of an unknown amount of extended-release potassium chloride (K-Dur®) tablets and alprazolam (Xanax®). The patient's serum potassium was initially 7.3 mmol/L and she was treated with standard treatments, including albuterol, calcium gluconate, insulin, dextrose, and sodium bicarbonate. Radiographic investigation showed a pharmacobezoar in the gastric fundus. Treatment was then augmented with whole bowel irrigation (WBI) using polyethylene glycol solution via nasogastric tube. Patient did not tolerate the nasogastric tube, became combative with increasing alteration in her level of consciousness, and WBI therapy was stopped. After discussion with the gastroenterologist, the patient was treated with EGD to remove the pharmacobezoar. The EGD was successful in the removal of the pharmacobezoar and the patient's potassium normalized without complications. CONCLUSIONS: We recommend that in cases of suspected or confirmed potassium drug bezoar in the stomach, physicians consider EGD for removal. This allows for normalization of potassium level while preventing adverse sequelae.

Gabapentin overdose in a military beneficiary.

We report the case of a 59-year-old military beneficiary that presented to the emergency department after ingesting approximately 90 g of gabapentin immediate-release capsules during a deliberate self-harm attempt. Her serum gabapentin level was 72.8 mcg/mL approximately 3 hours after ingestion. Her renal function panel, complete blood count, and liver function panel were normal. Her urine drug screen, aspirin, ethanol, and acetaminophen level were negative. Her electrocardiogram was normal, including a normal QTc interval. Her only symptoms were nausea and mild sedation. She was admitted for observation with no sequelae noted. She was transferred to a psychiatric facility at that time for further evaluation and treatment. We report a case of gabapentin overdose that presented to the emergency department. Given the large volume ingestion with minimal morbidity, it appears that gabapentin has a wide therapeutic margin and may be safe in overdose.

UPLC-MS/MS determination in blood of a mixed-drug fatal intoxication: a case report.

Trends in forensic toxicology show the introduction of rapid analytical methods for the simultaneous quantitative analysis of drugs. The authors present a fatal case involving a 32-year-old male, found dead in bed by his mother, with several blue, white and orange pills next to the body. Empty tablets were found in the trash bin and a suicide note was on the desk. He was diagnosed with bipolar disorder and had been under psychiatric treatment, having repeatedly demonstrated intent to commit suicide. A rapid method was developed to determine 55 different medicines and 32 benzodiazepines in blood by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) with electrospray ionization source in positive and negative ion mode. Chromatographic analysis was preceded by an optimized solid-phase extraction procedure using Oasis(®) HLB (3 cc, 60 mg) extraction columns. The extracted analytes were separated by UPLC (Waters) with a reversed-phase Acquity UPLC(®) HSS T3 (2.1×100 mm id, 1.8 µm) column with acetonitrile and 0.1% formic acid in water as mobile phase, at 0.5 mL/min flow rate and a chromatographic run-time of 8 min. Analytes detection was achieved with a triple-quadrupole mass spectrometer in positive and negative electrospray ionization mode with multiple reaction monitoring (MRM). Two MRM transitions were monitored for each target-compound and one for each deuterated internal standards. Toxicological results showed high blood concentrations of antipsychotics (haloperidol, olanzapine and quetiapine), antidepressants (fluoxetine and paroxetine) and anxiolytics (bromazepam and lorazepam). Risperidone and other benzodiazepines were also present in therapeutic concentrations. Neither alcohol nor illicit drugs were present in the analyzed samples. The UPLC-MS-MS method showed to be appropriate for screening, identification and quantitation of antipsychotics, antidepressants, anxiolytics and antiepileptic drugs in blood after intake of therapeutic as well as toxic doses. The autopsy and toxicological results led the pathologist to rule that death was due to a mixed-drug intoxication. The manner of death was determined to be suicide.

Focal parietal necrosis of the sigmoid due to atypical neuroleptics: a case report.

We present the case of a 26-year-old man with schizoid personality disorder who suffered from a very focal and transparietal necrosis of the sigmoid after an overdose of atypical neuroleptics. This is a singular, rather unknown and potentially lethal side effect of these drugs. The physiopathology of this complication is multifactorial.

Bilateral femoral neuropathy after massive toxic ingestion in a suicide attempt.

INTRODUCTION: Bilateral femoral nerve injury can occur after various surgical and nonsurgical processes, but has rarely been reported. CASE REPORT: We describe a case of bilateral femoral neuropathy after a suicide attempt in a 41-year-old woman. We suggest a stretch mechanism to explain this observation. We also discuss the other causes of bilateral nerve palsy, usually secondary to a compressive injury, with a review of the medical literature. CONCLUSIONS: The patient reported is the first in the literature to have suffered from bilateral femoral nerve palsy after a suicide attempt. Half of the reported cases are secondary to a surgical process (particularly abdominopelvic surgery). If a compressive origin is most frequent, a stretch mechanism may at times explain a bilateral femoral neuropathy.

Acute intoxication caused by overdose of flunitrazepam and triazolam: high concentration of metabolites detected at autopsy examination.

A 52-year-old woman was found dead on the floor of the living room on the first floor of a house, which belonged to the man with whom she shared the house. On visiting the site, her clothes were found to be undisturbed. Packages of flunitrazepam (Silece, 2 mg/tablet) and triazolam (Halcion, 0.25 mg/tablet) were found strewn around the victim. Toxicological analysis was performed, and the concentrations of flunitrazepam, triazolam, and their metabolites in the victim's blood and urine were measured by high-performance liquid chromatography coupled with photodiode array and mass spectrometry. A high blood concentration of 7-aminoflunitrazepam was detected (1,270 ng/g), and further metabolites such as 7-acetamidoflunitrazepam, 7-acetamidodesmethylflunitrazepam, and 7-aminodesmethylflunitrazepam were detected in the blood and urine samples. In addition, 4-hydroxytriazolam and α-hydroxytriazolam were detected in her urine at a concentration of 950 and 12,100 ng/mL, respectively.On the basis of the autopsy findings and toxicology results of high concentrations of both flunitrazepam and triazolam derivatives, the cause of death was determined to be acute intoxication from flunitrazepam and triazolam.

Detection of amitriptyline, nortriptyline and bromazepam in liver, CSF and hair in the homicidal poisoning of a one-month-old girl autopsied 8 months after death.

We reported on the death by poisoning of a one-month-old baby that had followed the death of one of her sister (due to cyamemazine overdose). Exhumation of the corpse was done 8 months after burial and revealed the presence of amitriptyline. Parent drug and its metabolite were analysed by HPLC-MS/MS in positive ionisation mode on a C(18) analytical column using a gradient of acetonitrile and 2mM formate buffer at pH=3. Quantification is based on the main ion m/z=233, the common product ion of nortriptyline (MH(+), m/z 264), amitriptyline (MH(+), m/z 278) and nortriptyline D3 used as internal standard (MH(+), m/z 267). Amitriptyline and nortriptyline in the liver were measured at a concentration of 29.8 and 3.6 µg/g, respectively. Hair analyses revealed the presence of amitriptyline and nortriptyline at concentrations of 1811 and 43 pg/mg, respectively, while complementary analyses showed the presence of bromazepam in the hair at a concentration of 740 pg/mg, thus documenting previous administrations. The mother confessed later having used the drinkable form of the pharmaceutical LAROXYL(®) by pouring the content of a 20 ml bottle (at 40 mg/ml) into the feeding-bottle of her child. The milk was sweet but still bitter and following the testimony of a close relative, the whole family helped to feed the crying baby.

Toxicokinetics of a dipyridamole (Persantin) intoxication: case report.

We report a case of a 51-year-old woman who was admitted to the hospital after ingestion of large doses of dipyridamole (12 g), temazepam (1 g) and oxazepam (0.2 g) with suicidal intent. The highest dipyridamole concentration that was measured in serum was 9.2 mg/L, which was paralleled by impaired platelet activation. For temazepam and oxazepam, peak serum concentrations were 8.5 and 1.3 mg/L, respectively. The patient was treated with activated charcoal, magnesium sulfate and aminophylline and could be discharged in good physical condition within 17 hours. This is the first report that provides toxicokinetic data and a corresponding pharmacodynamic effect after an intoxication with dipyridamole.

A case of torsades de pointes induced by severe QT prolongation after an overdose of eperisone and triazolam in a patient receiving nifedipine.

INTRODUCTION: Eperisone hydrochloride is a centrally acting muscle relaxant, and triazolam is a short-acting benzodiazepine. Although commonly prescribed, cardiotoxicity induced by a single overdose of either drug is comparatively rare. A patient receiving nifedipine developed torsades de pointes (TdP) because of prolongation of the corrected QT (QTc) interval after an overdose of eperisone hydrochloride and triazolam. CASE REPORT: A 60-year-old man receiving nifedipine was admitted in a comatose condition 3 h after ingesting 5,000 mg of eperisone and 2.5 mg of triazolam. Electrocardiogram showed sinus rhythm with prolongation of the QTc interval (820 ms). The serum electrolyte levels were as follows: potassium, 3.8 mEq/L; magnesium, 2.4 mg/dL. The serum drug concentrations were high: eperisone, 15,360 ng/mL; triazolam, 110.8 ng/mL. A temporary cardiac pacemaker was implanted immediately after the development of TdP, 11 h after the ingestion. The serum triazolam concentration normalized on day 2. The QTc interval and eperisone concentration normalized on day 6. CONCLUSION: Eperisone and triazolam overdose can cause life-threatening cardiotoxicity. Electrocardiographic monitoring and serial determination of QTc interval are likely the best way to observe these patients and evaluate the risk of cardiotoxicity.

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.

Protracted deep coma after bromazepam poisoning.

BACKGROUND: Bromazepam intoxication is very common but surprisingly rarely reported. CASE DESCRIPTION: We describe the case of a 73-year-old woman who suffered from a prolonged coma after acute self poisoning with bromazepam (serum concentration of 2,000 ng/ml at admission, 2 - 10 hours after ingestion of up to 180 mg) and zolpidem (900 ng/ml at admission). Only the former lasted at toxic concentrations. Recovery of consciousness allowed extubation on Day 16. Repeat-dose activated charcoal (25 g every 6 h from Day 14 to 16) resulted in minimal effects on bromazepam grossly estimated kinetics. CONCLUSION: Despite its relatively low theoretic half-life, bromazepam may induce a prolonged life-threatening coma, even in the absence of renal or hepatic failure.