Journal of The Korean Society of Clinical Toxicology

Volume 17(2); December 2019

Discrepancies and Validation of Ethanol Level Determination with Osmolar Gap Formula in Patients with Suspected Acute Poisoning: Haewon Jung, Mi Jin Lee, Jae Wan Cho, Jae Yun Ahn, Changho Kim; J Korean Soc Clin Toxicol. 2019;17(2):47-57. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.47

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Abstract PDF: Purpose: Osmolar gap (OG) has been used for decades to screen for toxic alcohol levels. However, its reliability may vary due to several reasons. We validated the estimated ethanol concentration formula for patients with suspected poisoning and who visited the emergency department. We examined discrepancies in the ethanol level and patient characteristics by applying this formula when it was used to screen for intoxication due to toxic levels of alcohol. Methods: We retrospectively reviewed 153 emergency department cases to determine the measured levels of toxic ethanol ingestion and we calculated alcohol ingestion using a formula based on serum osmolality. Those patients who were subjected to simultaneous measurements of osmolality, sodium, urea, glucose, and ethanol were included in this study. Patients with exposure to other toxic alcohols (methanol, ethylene glycol, or isopropanol) or poisons that affect osmolality were excluded. OG (the measured-calculated serum osmolality) was used to determine the calculated ethanol concentration. Results: Among the 153 included cases, 114 had normal OGs (OG≤14 mOsm/kg), and 39 cases had elevated OGs (OG>14). The mean difference between the measured and estimated (calculated ethanol using OG) ethanol concentration was -9.8 mg/dL. The 95% limits of agreement were -121.1 and 101.5 mg/dL, and the correlation coefficient R was 0.7037. For the four subgroups stratified by comorbidities and poisoning, the correlation coefficients R were 0.692, 0.588, 0.835, and 0.412, respectively, and the mean differences in measurement between the measured and calculated ethanol levels were -2.4 mg/dL, -48.8 mg/dL, 9.4 mg/dL, and -4.7 mg/dL, respectively. The equation plots had wide limits of agreement. Conclusion: We found that there were some discrepancies between OGs and the calculated ethanol concentrations. Addition of a correction factor for unmeasured osmoles to the equation of the calculated serum osmolality would help mitigate these discrepancies.

The Protective Effect of Green Tea Extract on Alpha-amanitin Induced Hepatotoxicity: Su Hwan An, Kyung Hoon Sun, Ran Hong, Byoung Rai Lee, Yongjin Park; J Korean Soc Clin Toxicol. 2019;17(2):58-65. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.58

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Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

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Effects of herbal and mushroom formulations used in Traditional Chinese Medicine on in vitro human cancer cell lines at the preclinical level: An empirical review of the cell killing mechanisms
Qiulan Wu, Tingting Dai, Jie Song, Xiaorong Liu, Shaomin Song, Lili Li, Jingbing Liu, Arivalagan Pugazhendhi, Joe Antony Jacob
Process Biochemistry.2020; 94: 136. CrossRef

Application of Thallium Autometallography for Observation of Changes in Excitability of Rodent Brain following Acute Carbon Monoxide Intoxication: Min Soo Lee, Seung Bum Yang, Jun Ho Heo; J Korean Soc Clin Toxicol. 2019;17(2):66-78. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.66

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Abstract PDF: Purpose: Thallium (TI+) autometallography is often used for the imaging of neuronal metabolic activity in the rodent brain under various pathophysiologic conditions. The purpose of this study was to apply a thallium autometallographic technique to observe changes in neuronal activity in the forebrain of rats following acute carbon monoxide (CO) intoxication. Methods: In order to induce acute CO intoxication, adult Sprague-Dawley rats were exposed to 1100 ppm of CO for 40 minutes, followed by 3000 ppm of CO for 20 minutes. Animals were sacrificed at 30 minutes and 5 days after induction of acute CO intoxication for thallium autometallography. Immunohistochemical staining and toluidine blue staining were performed to observe cellular damage in the forebrain following intoxication. Results: Acute CO intoxication resulted in significant reduction of TI+ uptake in major forebrain structures, including the cortex, hippocampus, thalamus, and striatum. In the cortex and hippocampal CA1 area, marked reduction of TI+ uptake was observed in the cell bodies and dendrites of pyramidal neurons at 30 minutes following acute CO intoxication. There was also strong uptake of TI+ in astrocytes in the hippocampal CA3 area following acute CO intoxication. However, there were no significant histological findings of cell death and no reduction of NeuN (+) neuronal populations in the cortex and hippocampus at 5 days after acute CO intoxication. Conclusion: The results of this study suggest that thallium autometallography can be a new and useful technique for imaging functional changes in neural activity of the forebrain structure following mild to moderate CO intoxication.

Systematic Review of Vitamin B12 Regimen for Patient with Subacute Combined Degeneration of the Spinal Cord Following Nitrous Oxide Abuse: Jin Seok Chung, Min Hong Choa, Sung Phil Chung, In Cheol Park; J Korean Soc Clin Toxicol. 2019;17(2):79-85. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.79

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Abstract PDF: Purpose: The purpose of this study is to evaluate the effectiveness of vitamin B12 treatment in subacute combined degeneration (SCD) caused by nitrous oxide (N2O) abuse. Methods: Relevant literature was accessed through PubMed, EMBASE, Scopus, and KoreaMed. All the literature that was relevant to human use of vitamin B12 treatment for SCD caused by N2O abuse was included. Case reports were excluded if the treatment regimens were not precisely described. The literature search was conducted by two investigators during September 2019 for the final publication period. The languages of the publications were restricted to English and Korean. Results: Twenty-three published articles that contained 24 cases were included. Sixteen cases among them were treated with intramuscular vitamin B12 of 1 mg/day and the rest received different doses or routes. Although most cases described significant clinical improvements, one case showed no beneficial effect due to the patient's noncooperation. Another case showed adverse events, including spinal myoclonus, following vitamin B12 therapy. Conclusion: Vitamin B12 has been broadly used for the treatment of SCD caused by N2O abuse. However, most of the relevant studies were case reports that reported various regimens of vitamin B12 administration. Further studies are needed to establish a standard regimen of vitamin B12 because the incidence of N2O abuse may increase in South Korea.

PaCO2 at Early Stage is Associated with Adverse Cardiovascular Events in Acute Carbon Monoxide Poisoning: Keun Mo Yang, Byeong Jo Chun, Jeong Mi Moon, Young Soo Cho; J Korean Soc Clin Toxicol. 2019;17(2):86-93. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.86

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Abstract PDF: Purpose: The objective was to determine the association between PaCO2 and adverse cardiovascular events (ACVEs) in carbon monoxide (CO)-poisoned patients. Methods: This retrospective study included 194 self-breathing patients after CO poisoning with an indication for hyperbaric oxygen therapy and available arterial blood gas analysis at presentation and 6 hours later. The baseline characteristics and clinical course during hospitalization were collected and compared. The mean PaCO2 during the first 6 hours after presentation was calculated. Results: The incidence rates of moderate (30 mmHg< PaCO2 <35 mmHg) or severe (PaCO2 ≤30 mmHg) hypocapnia at presentation after acute CO poisoning were 40.7% and 26.8%, respectively. The mean PaCO2 during the first 6 hours was 33 (31-36.7) mmHg. The incidence of ACVEs during hospitalization was 50.5%. A significant linear trend in the incidence of ACVEs was observed across the total ranges of PaCO2 variables. In multivariate regression analysis, mean PaCO2 was independently associated with ACVEs (OR 0.798 (95% CI 0.641-0.997)). Conclusion: Mean PaCO2 during the first 6 hours was associated with increased ACVEs. Given the high incidence of ACVEs and PaCO2 derangement and the observed association between PaCO2 and ACVEs, this study suggests that 1) PaCO2 should be monitored at the acute stage to predict and/or prevent ACVEs; and 2) further study is needed to validate this result and investigate early manipulation of PaCO2 as treatment.

Severity Predictors of Elderly Poisoning Patients Admitted to an Emergency Medical Center: Chang Yong Park, Kyung Man Cha, Byung Hak So, Won Jung Jeong; J Korean Soc Clin Toxicol. 2019;17(2):94-101. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.94

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Purpose: This study examined the clinical characteristics of severe elderly poisoning patients to determine the factors that can prevent them. Methods: Data were collected from patients over 65 years of age presenting to the emergency center with poisoning from 2013 to 2018. Their medical records were analyzed retrospectively, and patients with a poisoning severity score of three or more were defined as the severe poisoning group. The risk factors were evaluated by univariate and multivariate analysis. Results: This study analyzed 292 patients, of whom 37 (12.7%) belonged to the severe poisoning group. The severe poisoning group showed a significantly higher association with pesticide poisoning and intentional suicide attempts. Loneliness and somatization were the cause of the suicidal ideas. No significant differences in age, sex, drinking, ingestion time, poisonous materials other than pesticides, and neuropsychological consultation were observed between the two groups. Conclusion: The severe elderly poisoning patients were the result of intentional poisoning for suicide. Loneliness and somatization were the most influential causes of suicidal poisoning. Therefore, psychiatric screening and frequent medical treatment for elderly people are required to prevent severe poisoning in elderly patients.

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The 2022 Annual Report on Toxicology Surveillance and Severe Poisoning Cases at Emergency Departments in Korea
Eun Sun Lee, Su Jin Kim, Gyu Chong Cho, Mi Jin Lee, Byung Hak So, Kyung Su Kim, Juhyun Song, Sung Woo Lee
Journal of The Korean Society of Clinical Toxicology.2023; 21(1): 1. CrossRef

A Preliminary Study for Effect of High Flow Oxygen through Nasal Cannula Therapy in Carbon Monoxide Poisoning: Young-Min Kim, Sang-Chul Kim, Kwan-Jin Park, Seok-Woo Lee, Ji-Han Lee, Hoon Kim; J Korean Soc Clin Toxicol. 2019;17(2):102-107. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.102

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Abstract PDF: Purpose: Acute carbon monoxide (CO) poisoning is one of the most common types of poisoning and a major health problem worldwide. Treatment options are limited to normobaric oxygen therapy, administered using a non-rebreather face mask or hyperbaric oxygen. Compared to conventional oxygen therapy, high-flow nasal cannula oxygen (HFNC) creates a positive pressure effect through high-flow rates. The purpose of this human pilot study is to determine the effects of HFNC on the rate of CO clearance from the blood, in patients with mild to moderate CO poisoning. Methods: CO-poisoned patients were administered 100% oxygen from HFNC (flow of 60 L/min). The fraction of COHb (fCOHb) was measured at 30-min intervals until it decreased to under 10%, and the half-life time of fCOHb (fCOHb t1/2) was subsequently determined. Results: At the time of ED arrival, a total of 10 patients had fCOHb levels ≥10%, with 4 patients ranging between 10% and 50%. The mean rate of fCOHb elimination patterns exhibits logarithmic growth curves that initially increase quickly with time (HFNC equation, Y=0.3388*X+11.67). The mean fCOHbt1/2 in the HFNC group was determined to be 48.5±12.4 minutes. Conclusion: In patients with mild to moderate CO poisoning, oxygen delivered via high flow nasal cannula is a safe and comfortable method to treat acute CO toxicity, and is effective in reducing the COHb half-life. Our results indicate HFNC to be a promising alternative method of delivering oxygen for CO toxicity. Validating the effectiveness of this method will require larger studies with clinical outcomes.

Characteristics of Korean Poisoning Patients: Retrospective Analysis by National Emergency Department Information System: Woongki Kim, Kyung Hwan Kim, Dong Wun Shin, Junseok Park, Hoon Kim, Woochan Jeon, Joon Min Park, Jung Eon Kim, Hyunjong Kim; J Korean Soc Clin Toxicol. 2019;17(2):108-117. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.108

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Purpose: The study examined the poisoned patients' characteristics nationwide in Korea by using data from the National Emergency Department Information System (NEDIS). Methods: Among the patients' information sent to NEDIS from January 1, 2013 to December 31, 2015, the included subjects' main diagnosis in ED showed poisoning according to the 7th edition of the Korean Standard Disease Classification (KCD-7). We analyzed the patients' gender, age, initial vital signs, visit time, stay time of staying in ED, results of ED care, main diagnosis in ED, length of hospitalization, and results of hospitalization. Results: A total of 106,779 ED visits were included in the analysis. There were 55,878 males (52.3%), which was more than the number of females. The number of intentional poisoning was 49,805 (59.6%). 75,499 cases (70.8%) were discharged, and 25,858 cases (24.2%) were hospitalized. The numbers of poisoning patients per 1,000 ED visits were 14 in Chungnam and 11.9 in Jeonbuk. The most common cause of poisoning, according to the main diagnosis, was venomous animals. It was the same for hospitalized patients, and pesticide was next. Pesticide was the most common cause of mortality in ED (228 cases, 46.1%) and after hospitalization (584 cases, 54.9%). The incidence of poisoning by age group was frequent for patients in their 30s to 50s, and mortality in ED and post-hospitalization were frequent for patients in their 60s to 80s. Conclusion: This study investigated the characteristics of poisoning patients reported in the past 3 years. Pesticide poisoning had a high mortality rate for patients in ED and in-hospital. For mortality, there was a high proportion of elderly people over 60. Thus, policy and medical measures are needed to reduce this problem. Since it is difficult to identify the poison substance in detail due to nature of this study, it is necessary to build a database and monitoring system for monitoring the causative substance and enacting countermeasures.

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응급실 기반 중독 심층 실태조사 1차년도 결과 보고
성우 이, 수진 김, 규종 조, 미진 이, 병학 소, 경수 김, 주현 송
Public Health Weekly Report.2024; 17(14): 535. CrossRef
The 2022 Annual Report on Toxicology Surveillance and Severe Poisoning Cases at Emergency Departments in Korea
Eun Sun Lee, Su Jin Kim, Gyu Chong Cho, Mi Jin Lee, Byung Hak So, Kyung Su Kim, Juhyun Song, Sung Woo Lee
Journal of The Korean Society of Clinical Toxicology.2023; 21(1): 1. CrossRef
Demographic characteristics of patients admitted to the emergency department for intoxication and a time series analysis during the COVID-19 period
Bongmin Son, Nayoon Kang, Eunah Han, Gina Yu, Junho Cho, Jaiwoog Ko, Taeyoung Kong, Sung Phil Chung, Minhong Choa
Journal of The Korean Society of Clinical Toxicology.2023; 21(2): 92. CrossRef
Prioritising Risk Factors for Prescription Drug Overdose among Older Adults in South Korea: A Multi-Method Study
Eun-Hae Lee, Ju-Ok Park, Joon-Pil Cho, Choung-Ah Lee
International Journal of Environmental Research and Public Health.2021; 18(11): 5948. CrossRef
Changes in Diagnosis of Poisoning in Patients in the Emergency Room Using Systematic Toxicological Analysis with the National Forensic Service
Je Seop Lee, Yong Sung Cha, Seonghoon Yeon, Tae Youn Kim, Yoonsuk Lee, Jin-Geul Choi, Kyoung-Chul Cha, Kang Hyun Lee, Hyun Kim
Journal of Korean Medical Science.2021;[Epub] CrossRef

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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Abstract PDF: 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.

Characteristics of Acute Herbicide Poisoning: Focused on Chlorophenoxy Herbicide: Hakyoon Song, Sangchun Choi, Yoon Seok Jung, Eunjung Park, Hyukhoon Kim; J Korean Soc Clin Toxicol. 2019;17(2):126-131. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.126

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Purpose: Herbicide-related mortality has decreased since the complete ban of paraquat product sales in 2012, but there still have been other herbicides intoxications with relatively severe complications. Glyphosate and glufosinate herbicides are used widely, and considerable research has been conducted. Chlorophenoxy herbicide is another major herbicide that has shown poor outcomes and mortality without proper management, but research in this area is lacking. Therefore, this study compared the clinical features of chlorophenoxy herbicide with those of other herbicides. Methods: The medical records of patients exposed to herbicides at a tertiary academic university hospital in Korea from May 2014 to April 2019 were reviewed retrospectively. The demographic and clinical data of 135 patients were then analyzed to identify the recent herbicides intoxication trends after the paraquat sales ban, focusing mainly on chlorophenoxy herbicide poisoning. Results: Of the 135 patients, 13 patients (9.6%) had chlorophenoxy herbicide poisoning. No significant differences in all the variables were observed between the chlorophenoxy herbicide poisoning group and non-chlorophenoxy herbicides poisoning groups. Toxic symptoms after poisoning varied from nothing noticeable to confusion; none of the patients had severe complications after their treatments. Conclusion: Acute chlorophenoxy poisoning is relatively less severe, with lower mortality rates than glyphosate and glufosinate poisoning.

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Association between continuous renal replacement therapy and mortality after acute herbicide (glyphosate and/or glufosinate) intoxication: propensity score matching approach
Seung Woo Lee, Won-joon Jeong, Seung Ryu, Yongchul Cho, Yeonho You, Jung Soo Park, Changshin Kang, Hong Joon Ahn, So Young Jeon, Jinwoong Lee
Journal of The Korean Society of Clinical Toxicology.2023; 21(1): 17. CrossRef

A Case of Green Tobacco Sickness (GTS) in Elderly Patient: Dong Kil Jeong, Doh-Eui Kim; J Korean Soc Clin Toxicol. 2019;17(2):132-134. Published online December 31, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.2.132

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Abstract PDF: Green tobacco sickness is an illness caused by dermal exposure to nicotine. The common symptoms of the disease include dizziness, headache, nausea, vomiting, severe general weakness, fluctuations of blood pressure or heartbeat, abdominal cramping, chills, increased sweating, salivation, and difficulty breathing. A 79-year-old female arrived at the emergency room for an evaluation of sudden onset dizziness. Magnetic resonance imaging and angiography of the brain did not show any relevant abnormal findings. Four days later, with supportive care, she said that she had harvested green tobacco for six hours on the day of admission and the tobacco harvest was the first time in her life. She sweated excessively during the hot and humid weather and the tobacco leaves were wet from rain the night before. The serum cotinine tested at five days of admission was 16ng/ml. She was diagnosed with acute nicotine poisoning by her clinical symptoms and the half-life of cotinine in the blood.

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