Journal of The Korean Society of Clinical Toxicology

Review Article

Diagnosis and treatment of serotonin syndrome: Je Sung You, Sung Phil Chung; J Korean Soc Clin Toxicol. 2024;22(2):11-17. Published online December 31, 2024; DOI: https://doi.org/10.22537/jksct.2024.00008

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Abstract PDF: Serotonin syndrome is a drug-induced clinical syndrome caused by increased serotonin activity in the central nervous system. It occurs when starting a serotonergic drug, increasing its dose (including overdoses) or using a serotonergic drug in combination with other drugs. It manifests along a broad spectrum, ranging from mild side effects to life-threatening conditions. This condition should be suspected if patients have altered mental states, autonomic dysfunction, or neuromuscular symptoms such as clonus and tremor after using serotonergic drugs. Although the Hunter criteria have been widely used, new diagnostic criteria have recently been proposed to screen severe serotonin toxicity. It is necessary to differentiate it from neuroleptic malignant syndrome, which is associated with taking antipsychotic drugs that exert dopamine-antagonistic effects. If serotonin syndrome is suspected, the relevant drug should be stopped, and the patient should be treated with benzodiazepines. Severely ill patients with hyperthermia or neuromuscular symptoms require aggressive treatment. Serotonin receptor antagonists such as cyproheptadine or chlorpromazine have been tried as antidotes, but the level of evidence for their therapeutic effectiveness is very low.

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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Abstract PDF: 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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Abstract PDF: 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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Abstract PDF: 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.

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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Abstract PDF: 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.

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