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Sedative-hypnotic agent overdose [keywords]
- Double, suicidal intoxication with hydroxycarbamide--a case report. [Case Reports, Journal Article]
- Przegl Lek 2012; 69(8):587-8.
Hydroxycarbamide (HCB), also known as hydroxyurea, is an urea derivative used mainly as antineoplastic and antisickling agent. We described a 31 yrs. female, with essential thrombocythemia, who was admitted to our clinic because of double suicidal ingestion of hydroxycarbamide. First time it was 7.5 g of HCB with coingestion of 50 mg of diazepam, and several glasses of wine, second time it was 10 g of HCB, with coingestion of 100 mg paroxetine and few glasses of vodka. Both suicidal attempts were triggered by multiple reactive factors. At the time of admissions the patient was conscious, restless, with decreased mood. Transient decrease of total leukocyte count was noted on fourth day of first overdose. The second overdose led to no significant changes in blood count. There were no other abnormalities in biochemical results. According to the best of our knowledge this is the first report of acute suicidal intoxication with hydroxy-carbamide in an adult.
- Acetaminophen/diphenhydramine overdose in profound hypothermia. [Case Reports, Journal Article]
- Clin Toxicol (Phila) 2013 Jan; 51(1):50-3.
There are few reports of acetaminophen overdose in hypothermic patients and even fewer reports describing profound hypothermia. The kinetics, risk of hepatotoxicity, and the possible dose adjustments to N-acetylcysteine (NAC) therapy are not known in this setting.A 37-year-old female was found unconscious outside in December and was brought by ambulance to a tertiary care Emergency Department (ED) following a presumed overdose of acetaminophen and diphenhydramine. She later confirmed the ingestion and reported the ingestion had occurred approximately 18 hours prior to being found. On arrival, she was profoundly hypothermic, with a core rectal temperature of 17°C. Her initial serum acetaminophen concentration was 232 mcg/mL 19 hours post ingestion of a reported dose of approximately 50 grams of acetaminophen and 2.5 grams of diphenhydramine. Active rewarming was started immediately and IV NAC was initiated using the standard treatment protocol. The patient did not develop serious signs of hepatic injury or NAC toxicity. The patient's AST and ALT peaked 12 hours after admission at 84 IU/L (ref 10-37 U/L) and 104 IU/L (ref 12-78 U/L), respectively. Her INR peaked 2 hours after admission at 1.46 (ref < 1.2).Despite the significant ingestion of acetaminophen, delayed presentation, prolonged period of decreased responsiveness, and profound hypothermia, the patient did not develop any signs/symptoms of liver injury. NAC was administered in a standard dose during her rewarming period without apparent toxicity. The patient's absorption and/or metabolism of acetaminophen were likely slowed by her hypothermia and possibly by the anticholinergic coingestant. Initiation of IV NAC at a standard dose was apparently safe and effective in preventing hepatotoxicity as the patient was rewarmed.Profound hypothermia may be protective of hepatic injury in acetaminophen overdose. Delayed absorption from the coingestant, diphenhydramine, may also have played a role. IV NAC was given in a standard dose without apparent toxicity in the setting of profound hypothermia. Lastly, IV NAC, in standard dosing, appeared to be effective in preventing hepatotoxicity during rewarming in a patient with a potentially hepatotoxic concentration of acetaminophen with a coingestion of the anticholinergic agent, diphenhydramine.
- Evaluation of the first immunoassay for the semi-quantitative measurement of meprobamate in human whole blood or plasma using biochip array technology. [Journal Article]
- Clin Chim Acta 2012 Jan 18; 413(1-2):273-7.
Meprobamate is a carbamate, and the main metabolite of carisoprodol. It is used as an anxiolytic agent. Overdose of both drugs produces intoxication that is often serious and sometimes life threatening. However there was until now no immunoassay for the diagnosis of this intoxication.A chemiluminescent immunoassay for the semi-quantitative measurement of meprobamate in human blood and plasma has recently been developed, using the Evidence Investigator system (Randox®). In this study, the immunoassay was evaluated by testing drug-free (n=10) or spiked whole blood and plasma samples (n=70), and authentic post mortem whole blood samples from deceased patients in which meprobamate was present (n=38) or not (n=10). A previously validated gas chromatography-mass spectrometry (GC-MS) method was used for confirmation and quantification. 97 psychoactive drugs including carisoprodol were analyzed for possible interference.With a cut-off at 0.5 mg/L, specificity, sensitivity and accuracy were 100%, 97.2% and 97.6%, respectively. All the untreated patients presented results under the cut-off. Meprobamate was not detected in three whole blood samples spiked with concentrations under the therapeutic range. In the authentic patients (n=48), there were no false-negative results. A good correlation was found between the immunoassay and GC-MS (r=0.90). Quantitative results of the immunoassay are approximately two-fold lower than GC-MS results. Only carisoprodol presented a cross-reactivity, 38±6.6% at 10 mg/L, and 26±4.8% at 100mg/L.The first meprobamate immunoassay has shown very good specificity, selectivity and accuracy, which allow its use in hospital clinical laboratories for rapid diagnosis of meprobamate (or carisoprodol) intoxications.
- Suicide with cisatracurium and thiopental: forensic and analytical aspects. [Case Reports, Journal Article]
- J Anal Toxicol 2011; 35(6):375-80.
The suicide of a 43-year-old male by intravenous injection of cisatracurium, a non-depolarizing neuromuscular blocking agent, and thiopental, an ultra-short-acting barbiturate, is presented. Systematic toxicological screening by gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-diode-array detection, and LC-MS-MS confirmed the presence of thiopental. A large peak in the GC-MS chromatogram was matched by the Pfleger-Maurer library as corlumine, but neither atracurium neither its metabolite, laudanosine, were detected. To confirm the absence or the presence of laudanosine in the blood sample, an ultra-performance liquid chromatography-MS-MS method for cisatracurium and laudanosine quantification was developed. The calibration range was 2.5-500 ng/mL for laudanosine and 10-500 ng/mL for cisatracurium. The biases were lower than 12.3%. Intraday and interday precisions, expressed as coefficient of variation, were lower than 13.3%. This method allowed to confirm the presence of laudanosine and measurement of laudanosine in all samples. The femoral blood concentration was therapeutic (0.46 μg/mL). This case report documents a possible analytical pitfall and describes a simple and fast method for cisatracurium determination. Moreover, the purpose of this case report was to document the postmortem redistribution of cisatracurium and laudanosine, which could help make it possible to interpret tissue or cardiac blood concentrations in forensic cases where femoral blood is not available.
- Clinical effects and lethal and forensic aspects of propofol. [Journal Article, Research Support, N.I.H., Extramural, Review]
- J Forensic Sci 2011 Jan.:S142-7.
Propofol is a potent intravenous anesthetic agent that rapidly induces sedation and unconsciousness. The potential for propofol dependency, recreational use, and abuse has only recently been recognized, and several cases of accidental overdose and suicide have emerged. In addition, the first documented case of murder using propofol was reported a few months ago, and a high profile case of suspected homicide with propofol is currently under investigation. A number of analytical methods have been employed to detect and quantify propofol concentrations in biological specimens. The reported propofol-related deaths and postmortem blood and tissue levels are reviewed. Importantly, limitations of propofol detection are discussed, and future considerations are presented. Because propofol has the potential for diversion with lethal consequences, the forensic scientist must have a basic understanding of its clinical indications and uses, pharmacologic properties, and detection methods. In addition, medical institutions should develop systems to prevent and detect diversion of this potential drug of abuse.
- Pattern of acute food, drug, and chemical poisoning in Sari City, Northern Iran. [Journal Article, Research Support, Non-U.S. Gov't]
- Hum Exp Toxicol 2010 Sep; 29(9):731-8.
This descriptive and retrospective study was conducted at the poisoning ward of Imam teaching hospital, Sari, Iran, with the aim of evaluating the pattern of poisoning. Hence, the medical profiles of 2057 patients, who were admitted, were carefully reviewed during the period from April 2006 to March 2008 for 2 years. During this period, 2057 cases, 53.9% female and 46.1% male, were admitted with the indication of acute poisoning. The greatest proportion of poisoning occurred between the ages of 18 and 29 years, with suicidal intentions. Most cases of poisoning were intentional (85%). The most common agents involved in acute poisoning were drugs (77.7%), especially sedatives/hypnotics such as benzodiazepines, followed by opioid analgesics. Organophosphate and carbamate insecticides were the third major agent that induced poisoning. Twenty-seven patients (1.3%) who were mostly females and young adults died. Death mostly occurred due to organophosphate and carbamate insecticides (19 cases) poisoning, followed by sedatives/hypnotics like benzodiazepines (3 cases). High prevalence of intentional overdose and mortality among young adults requires considerable attention and further studies to find out the underlying causes. In addition, strict rules must be followed regarding the sale of central nervous system drugs and pesticides, particularly organophosphate and carbamate insecticides. Establishing poison information centers in different parts of the country, preparing national treatment guidelines, training healthcare providers, and ensuring easy availability of the antidotes are also recommended.
- Evaluation of a fatal propofol intoxication due to self administration. [Case Reports, Journal Article]
- J Forensic Leg Med 2009 Jul; 16(5):287-9.
Propofol is a short acting intravenous anaesthetic, active agent of Diprivan. The abuse potential of propofol has not completely defined, but there are anecdotal case reports in the literature about propofol abuse and dependency. This report presents a fatal case of a middle age female victim who died of self-administered propofol intoxication. The propofol level of the blood sample was measured with gas chromatography-mass spectrometry after liquid-liquid extraction. The results of toxicological investigation suggested that death was not directly caused by propofol intoxication, however, based on the pathomorphological changes detected during the medico-legal autopsy we supposed that the fatal outcome was resulted by respiratory depression after rapid injection.
- A series of hospital homicides. [Journal Article]
- Leg Med (Tokyo) 2009 Apr.:S100-2.
Patient deaths in hospitals due to medical staff are very rare. In the autumn of 2006, preliminary proceedings were initiated against a nurse on account of an overdose of medication leading to death, administered during her care of the patient. In the course of these proceedings, exhibits relating to the deaths of a total of 13 patients who had died due to chemical-toxicological causes were reviewed. Nine of them were exhumed. On average, death had occurred 22 months prior to exhumation (range of 1-34 months). The average age of the deceased was 76 years (range of 65-92 years). In five of the cases, analysis results and an evaluation of the medical records confirmed that a final, undocumented dose of sodium nitroprusside or midazolam was administered. After administration of sodium nitroprusside, the active agent rapidly releases nitrogen monoxide, itself undetectable. Another indicator that can be detected, however, is the cyanide that is also released. In one of the exhumed patients, cyanide could still be detected 18 months after death. The nurse stated that her motive was sympathy towards seriously ill patients. She was sentenced res judicata to life imprisonment on five counts of causing the death of a patient.
- Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine. [Case Reports, Journal Article]
- J Med Toxicol 2009 Mar; 5(1):27-31.
Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses.
CASE REPORT:We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state.
CONCLUSION:To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.
- Hemoperfusion in the treatment of acute clozapine intoxication in China. [Journal Article]
- J Clin Psychopharmacol 2007 Dec; 27(6):667-71.
No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP).In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered.One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP.A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.