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13 "Benzodiazepine"
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Comparative Analysis of decreased Mental state Patients after Overdose with Sedative-hypnotics
Seung Jae Oh, Soo Hyung Cho, So Yeon Ryu
J Korean Soc Clin Toxicol. 2022;20(1):8-14.   Published online June 30, 2022
DOI: https://doi.org/10.22537/jksct.2022.20.1.8
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Purpose: This study was undertaken to investigate how sedative-hypnotics affect the occurrence and severity of the patient's symptoms. In addition, we conducted a study to determine the type of patients who reacted severely and required hospitalization; patients were accordingly classified as hospitalized patients and patients discharged from the emergency room. Methods: From January 2017 to December 2019, we investigated the demographics, drug information, history, laboratory tests, and severity of patients who visited our emergency department and were diagnosed with benzodiazepine, zolpidem, and doxylamine succinate overdose. We further compared details of hospitalized patients and discharged patients. Results: Subjects who had overdosed and visited the ED included 120 for benzodiazepine, 147 for zolpidem, and 27 for doxylamine succinate. Comparisons between the three groups revealed differences in their early diagnosis, psychiatric history, and sleep disturbance. Differences between groups were also determined for mental state, poisoning history, treatment received in the intensive care unit, and intubation and ventilator support. In cases of benzodiazepine overdose, we obtained a high hospitalization rate (40.0%), admission to the intensive care unit (24.2%), and intubation rate (18.3%). Comparisons between hospitalized patients and discharged groups showed differences in transferred patients, early diagnosis, and mental state. Conclusion: Patients poisoned by sedative-hypnotics are increasing every year. In cases of benzodiazepine and zolpidem, the hospitalization rates were high, and benzodiazepine overdose resulted in hospitalization, intensive care unit admission, and pneumonia in a majority of cases. Therefore, active treatment and quick decisions in the emergency room are greatly required.
Zolpidem Detection and Blood Level in Acute Poisoning-suspected Patients in Emergency Departments: Review of 229 Cases
Jaehyung Yu, Hanseok Chang, Sinae Won, Jeonghun Yeom, Arum Lee, Na-Youn Park, Bum Jin Oh
J Korean Soc Clin Toxicol. 2019;17(2):118-125.   Published online December 31, 2019
DOI: https://doi.org/10.22537/jksct.2019.17.2.118
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Purpose: Non-benzodiazepine hypnotic drugs (including zolpidem) are associated with an increased risk of suicide and suicidal ideation. Considering the wide usage of zolpidem, this drug should be considered a possible etiology for stupor or coma in any patient exposed to this drug. However, there are no reports on zolpidem blood levels in emergency department patients in Korea. We therefore reviewed the analyzed data of a toxicology laboratory at one university affiliated hospital. Methods: The sex, age, chief symptoms, suspiciousness of poisoning, and presumption of poison were analyzed from January 2018 to June 2019. The detection frequency and level of zolpidem in the patient blood were compared to the mental changes presented, which is the main consequence of zolpidem. Results: A total of 229 toxicological analyses, requested to a toxicological laboratory at one university affiliated hospital, were reviewed. Among 229 patients, the mean age was 54.3±20.7 years old with 113 women and 116 men. 8.7% of patients have psychiatric illness and 39.7% were poisoned intentionally. The chief symptoms detected were: mental change 55.0%, gastrointestinal 14.4%, cardiovascular 10.5%, focal neurological 7.4%, respiratory 3.5%, none 8.7%, and unknown 0.4%. A request for detailed reports revealed that causative poisons were specified only in 20.1% cases. Zolpidem was detected in 22.3% cases (51/229), with median blood level 1.26 mg/L (interquartile 0.1, 5.06 mg/L) and urine 0.90 mg/L (interquartile 0.11, 5.6 mg/L). Furthermore, zolpidem was more frequently detected in toxicology analysis of patients where mental change was the primary symptom, as compared to other symptoms (32.5% vs. 9.7%, p<0.01). Conclusion: This study reported the blood level of zolpidem in suspected poisoning patients admitted to the emergency department.
Flumazenil administration in suspected patients with acute hypnotics and sedatives poisoning: risk-benefit re-evaluation
Jae Hong Huh, Sang Chun Choi, Yong Gyun Lim, Samsun Lampotang, Eung Jung Park
J Korean Soc Clin Toxicol. 2016;14(2):92-99.   Published online December 31, 2016
DOI: https://doi.org/10.22537/jksct.2016.14.2.92
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Purpose: The use of flumazenil administration in the emergency department is still controversial because of concerns about adverse effects. The present study was conducted to re-evaluate the risk-benefit ratio associated with flumazenil administration to patients suspected of having acute hypnotics and sedatives poisoning in the emergency department. Methods: A retrospective chart review study was conducted for patients whose final diagnoses were "poisoning" and "benzodiazepine" or "sedatives-hypnotics" from Mar. 2006 to Feb. 2015. The basal characteristics of the patients, including past medical history, ingredients and dose of ingested drug and co-ingested drugs were investigated. For patients administered flumazenil, responsiveness and time from admission to flumazenil administration were investigated with supplement. All collected data were analyzed in aspect terms of risk/benefit. Results: A total of 678 patients were included in our study. Benzodiazepine was the most common sedative/hypnotic drug prescribed, and the frequency of prescription continuously increased. The proportion of TCA as co-ingestion decreased from 13.1% to 3.9% in patients with acute sedative/hypnotic poisoning. Flumazenil was administered to 55 patients (8.1%), of which 29 patients (52.7%) were applied to contraindications. Fifty-three patients (96.4%) showed positive responsiveness, including partial responsiveness after flumazenil administration. No severe adverse events were identified. Conclusion: Based on the current trends in prescription patterns for sedative/hypnotic drugs, increased use of non-TCA antidepressants, and responsiveness to administration of flumazenil, benefit seemed weighted more in this study, although the observed benefits were based on limited results. Further prospective multicenter studies will be needed to optimize benefit-risk ratio.
Risk Factors for Aspiration Pneumonia in Acute Benzodiazepine Overdose
Won Sik Chung, Kyung Man Cha, Hyung Min Kim, Won Jung Jeong, Byung Hak So
J Korean Soc Clin Toxicol. 2016;14(1):26-32.   Published online June 30, 2016
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Purpose: Aspiration pneumonia is an important complication of drug intoxication with decreased mental status. The purpose of the study is to investigate the risk factors of aspiration pneumonia in the patients of benzodiazepine overdose with or without co-ingestion of other drugs. Methods: A retrospective chart review of patients who visited the emergency department between January 2012 and December 2014 was conducted. Demographic data, time from ingestion to visit, initial vital signs, symptoms, mental status, medical history, laboratory results, chest radiological findings and co-ingested medications were recorded. Multiple logistic analyses were performed to verify the association between variables and the development of aspiration pneumonia. Results: A total of 249 patients presented to the emergency department with benzodiazepine overdose. Aspiration pneumonia had developed in 24 patients (9.6%). Univariate analysis revealed time from ingestion to visit was longer, Glasgow coma scale score was lower, hypoxia was presented, leukocytosis was shown, types of ingested drugs was high, less activated charcoal was applied and tricyclic antidepressants was taken in patients that developed aspiration pneumonia. Time from ingestion to visit (odds ratio (OR) 1.121, 95% confidence interval (CI), 1.057-1.189, p=0.000), GCS score (OR 0.724. 95% CI, 0.624-0.839, p=0.000), oxygen saturation (OR 0.895, 95% CI, 0.835-0.959, p=0.002), and co-ingestion of TCA (OR 4.595, 95% CI, 1.169-18.063, p=0.029) were identified as risk factors of morbidity of aspiration pneumonia upon multiple logistic regression analysis. Conclusion: Time from ingestion to visit, low GCS score, low oxygen saturation and co-ingestion of TCA were risk factors of the development of aspiration pneumonia in benzodiazepine overdose patients.
Comparison of Prescription Patterns and Clinical Features according to Clinical Departments in Sedative-hypnotic Intoxication
Do Min Kim, Won Bin Park, Yong Su Lim, Jin Joo Kim, Jae Ho Jang, Jee Yong Jang, Hyuk Jun Yang, Geun Lee
J Korean Soc Clin Toxicol. 2014;12(2):54-62.   Published online December 31, 2014
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Purpose: The purpose of this study was to compare prescription patterns and clinical features according to clinical departments in sedative-hypnotic intoxication. Methods: This was a retrospective study of histories, substances of poisoning, acquisition routes, clinical courses, and outcomes of patients treated for acute intoxication in a single emergency medical center from January, 2011 to December, 2013. Results: A total of 769 patients were treated for acute intoxication, 281 patients ingested sedative hypnotics during the study period. Among 281 patients, 155 patients were prescribed by psychiatric department and 80 patients were prescribed by non-psychiatric department. Benzodiazepines were more likely to be prescribed by psychiatrists, and zolpidem was preferred by non-psychiatrists (p<0.001). Non-psychiatrists were more likely to prescribe short acting benzodiazepines than psychiatrists (p<0.001). However, there was no statistically significant difference in the clinical outcomes, including prevalence of admission to ICU, ventilator care, and length of stay in ICU. In patients prescribed by non-psychiatrists, there were more patients prescribed without psychiatric diagnosis and diagnosed as major depression disorder after hospitalization. Conclusion: To promote rational prescribing of sedative hypnotics, proper psychiatric evaluation should be performed before prescribing, and educational programs including the contents of interactions and side effects of sedative hypnotics are needed.
A Case of Seizures after Zolpidem Withdrawal
Hyung Jun Moon, Jung Won Lee, Byeong Dae Yoo
J Korean Soc Clin Toxicol. 2013;11(2):127-129.   Published online December 31, 2013
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The imidazopyridine, zolpidem, a non-benzodiazepine hypnotic drug, is widely-prescribed for insomnia. It is regarded as a good alternative to benzodiazepine because of the reduced possibility for abuse and development of dependence. However, more recently, due to the reduced possibility for abuse and development of dependence, it is regarded as a good alternative to benzodiazepine. adverse effects of zolpidem have been recognized. The objective of this report is to provide information on the potential for occurrence of benzodiazepine-like withdrawal seizure in patients who chronically take zolpidem continually. We present and discuss a case of seizure after sudden interruption of the protracted use of an abusively high dose of zolpidem. Zolpidem may not be the ideal drug for longterm pharmacotherapeutic management of insomnia. Clinicians should administer zolpidem at a low-dose for a short period of time for prevention of drug abuse and dependence and the potential for occurrence of benzodiazepine- like withdrawal seizure.
A Case of Mental Change in a Patient Who Received a Zoletil Injection
Yeong Ki Lee, In Gu Kang, Cheol Sang Park, Seok Jin Heo, Youn Seok Chai, Seong Soo Park, Jae Kwang Lee, Hyun Jin Kim, Won Joon Jeong
J Korean Soc Clin Toxicol. 2013;11(1):23-27.   Published online June 30, 2013
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Zoletil is a non-opioid, non-barbiturate animal anesthetic and proprietary combination of two drugs, a dissociative anesthetic drug, tiletamine, with the benzodiazepine anxiolytic drug, zolazepam. Zoletil has greater potency than ketamine. Zoletil is abused for recreational purposes, especially by people with easy access to medicine. However, in Korea, it is available over-the-counter. Here we report on a case of an 83-year-old woman who received injection of seven vials of "Zoletil 50" by her daughter and presented with an altered mental change. Her mental state was stupor and vital sign was hypotension, bradycardia. Her blood tests indicated metabolic and respiratory acidosis and hyperkalemia. She was treated with intravenous naloxone and flumazenil but was not responsive. She was admitted to the ICU and treated with supportive therapy. Her mental state showed transient recovery, however, her clinical manifestation worsened and she expired.
Availability of Toxicologic Screening Tests in the Emergency Department
In-Kyung Um, Jong-Su Park, Kap-Su Han, Han-Jin Cho, Sung-Hyuck Choi, Sung-Woo Lee, Yun-Sik Hong
J Korean Soc Clin Toxicol. 2011;9(1):26-29.   Published online June 30, 2011
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Purpose: The role of a point of care test (POCT) is currently becoming important when treating patients and making decisions in the emergency department. It also plays a role for managing patients presenting with drug intoxication. But the availability of the test has not yet been studied in Korea. Therefore, we investigated the utility and the availability of POCT for drug screening used in the emergency department. Methods: This was a retrospective study for those patients with drug intoxication between January 2007 and December 2010 in an urban emergency department. Results: Between the study period, 543 patients were examined with a Triage$^{(R)}$-TOX Drug Screen. Among those, 248 (45.7%) patients showed negative results and 295 (54.3%) patients showed positive results. The sensitivity of the test for benzodiazepine, acetaminophen and tricyclic antidepressants were 85.9%, 100%, 79.2%, respectively. Conclusion: POCT of drug screening in emergency department showed good accuracy especially in patient with benzodiazepine, acetaminophen and tricyclic antidepressant intoxication. Therefore, it can be useful diagnostic tool for the management of intoxicated patients.
Characteristics of elderly patients with acute poisoning
Bo-Kyeong Kim, Si-Young Jung, Koo-Young Jung
J Korean Soc Clin Toxicol. 2010;8(2):61-68.   Published online December 31, 2010
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Purpose: Poisoning is a major health problem for the elderly, and poisoning can cause fatal side effects. However, the characteristics and clinical features of elderly patients with acute poisoning have not been well studied in the previous domestic research. So, we tried to analyze the clinical characteristics and toxic substances of the patients who were 65 years old or older and who were admitted to the regional emergency medical center due to acute poisoning. Methods: We retrospectively reviewed the medical records and poisoning protocols of the patients who were 65 years of age or older and who had with acute poisoning and who visited the ED in our emergency center from January 2005 to December 2009. We collected the demographic information, the gender, the underlying diseases, the causes and toxic substances, the initial presentation, the treatment and the outcomes. Results: A total of 2179 poisoned patients visited the hospital during 5 years, and among them 244 were 65 years of age or older (11.2%). The mean age was $75.6{pm}6.9$ years and the male:female ratio was 1:1.7. The most common cause of poisoning was suicide (73.4%) and the most common source of poisonous substances was their own drugs. Of the substances used for poisoning, benzodiazepine was the most common drug (25.8%), followed by sedatives other than benzodiazepine (25.4%), insecticide (12.7%), chemical agents (12.3%) and herbicides (8.2%). The most common initial presentation was mental change (64.8%). When comparing the factors between the three elderly groups, there was no difference in gender, the cause, the substances and the underlying disease. The outcomes of treatment included ICU admission (56.1%), a good condition at discharge (12.7%) and admission to a general ward (12.7%). The overall mortality rate was 10.2% for the elderly patients. Conclusion: In this Korean study, unlike the foreign studies, the most common cause of poisoning in elderly patients was intentional poisoning. The admission rate was 68.8% and mortality rate was 10.2%.
A Case of Acute Psychosis after Sibutramine Ingestion
Hyung-Min Kim, Seon-Hee Woo, Se-Min Choi, Byung-Hak So
J Korean Soc Clin Toxicol. 2009;7(2):176-179.   Published online December 31, 2009
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A 38-year-old woman was admitted to our hospital due to agitation, nausea, chest discomfort, tachycardia and hypertension 6h after ingesting approximately 60 capsules of sibutramine. The woman developed the clinical features of acute psychosis, including auditory hallucination, agitation and paranoid ideation, on day 2. No relevant changes were detected on the laboratory examinations or on the electrocardiogram throughout the period of hospitalization. She was treated with risperidone and benzodiazepine. The symptoms subsequently resolved completely with cessation of the provoking agent. The patient was discharged on day 7 and the follow-up revealed no sequelae for 5 months.
Clinical Characteristics of Acute Zolpidem Intoxication
Joo-Hyun Suh, Hyung-Keun Roh, Eun-Kyung Eo, Young-Jin Cheon, Koo-Young Jung
J Korean Soc Clin Toxicol. 2008;6(2):91-98.   Published online December 31, 2008
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Purpose: The hypnotic effect of zolpidem is comparable to benzodiazepines, but has less abuse and addiction potential than benzodiazepines, so is one of the most commonly prescribed hypnotics. The frequency of acute zolpidem overdose has increased, but clinical analysis and severity predictors are not known in Korea. Methods: A retrospective evaluation of histories, clinical courses, and laboratory findings of each patient treated from June, 2000, to May, 2006, in a university hospital for acute zolpidem intoxication. Results: We evaluated 30 patients, including 16 co-intoxication cases. Twenty-five patients presented mental alterations but became alert within 2 days. All patients recovered completely. The median zolpidem concentration was 0.9 mg/L (range: $0.2{sim}7.4;mg/L$). There was a weak correlation between the amount ingested and zolpidem concentration (r=0.25). None of them presented severe laboratory abnormalities, and these abnormalities did not relate to zolpidem concentration. Conclusion: The clinical progress of acute zolpidem intoxication is mild. We could not predict zolpidem concentration or clinical severity from the amount ingested and could not predict the clinical course from laboratory findings in the emergency department.
Status Epilepticus as a Benzodiazepine withdrawal syndrome
Young-Min Oh, Kyoung-Ho Choi
J Korean Soc Clin Toxicol. 2008;6(1):45-48.   Published online June 30, 2008
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A 57-year-old man was transferred to our emergency department with decreased mental status after organophosphate intoxication. He had a four year history of benzodiazepine and hypnotic medication use for chronic insomnia and a depressive mood disorder. He had no previous history of seizures, diabetes mellitus, and hypertension. By hospital day 5, the patient was noted to be awake and to have repetitive jerking movements involving the left upper extremity, and appeared apathetic, depressed and less responsive to external stimuli. A benzodiazepine withdrawal syndrome was subsequently apparent when he developed several generalized tonic clonic seizures and status epilepticus. Using a continuous midazolam intravenous infusion, we successfully controlled the refractory seizure without complications. We present a rare case of status epilepticus from a benzodiazepine withdrawal that developed during the treatment for organophosphate intoxication.
A Case of Rhabdomyolysis after Alprazolam Overdose
Sung-Ho Ki, Hyun-Joo Park, Woong-Gil Choi, Hyung-Keun Roh
J Korean Soc Clin Toxicol. 2004;2(2):151-153.   Published online December 31, 2004
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Causes of rhabdomyolysis can be divided into traumatic and nontraumatic, Among the nontraumatic rhabdomyolysis, it is known that ingestion of drugs is one of the common causes. However, there have been few reports that benzodiazepine overdose causes rhabdomyolysis, moreover there was no report about rhabdomyolysis after alprazolam overdose. We experienced a case of rhabdomyolysis after alprazolam overdose. A 51-year-old woman was brought to the emergency room 11 hours after ingestion of 30 tablets (15 mg) of alprazolam in a suicidal attempt. On admission she was comatose and her CK level was 8,290 lUlL. The CK level increased up to 25,598 IU/L 10 hours after admission, but she became alert on the third day. Subsequently the CK level decreased gradually with supportive care without renal impairment and she discharged from the hospital on the $10^{th}$ day. Although a pressure effect on the dependent portion of the body due to mental alteration before admission might have caused the rhabdomyolysis, the alprazolam, per se, cannat be ruled out for the cause.

JKSCT : Journal of The Korean Society of Clinical Toxicology