Journal of The Korean Society of Clinical Toxicology

Original Article

Predicting serum acetaminophen concentrations in acute poisoning for safe termination of N-acetylcysteine in a resource-limited environment: Dahae Kim, Kyungman Cha, Byung Hak So; J Korean Soc Clin Toxicol. 2023;21(2):128-134. Published online December 29, 2023; DOI: https://doi.org/10.22537/jksct.2023.00013

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Abstract PDF: Purpose: The Prescott nomogram has been utilized to forecast hepatotoxicity from acute acetaminophen poisoning. In developing countries, emergency medical centers lack the resources to report acetaminophen concentrations; thus, the commencement and cessation of treatment are based on the reported dose. This study investigated risk factors that can predict acetaminophen detection after 15 hours for safe treatment termination.
Methods
Data were collected from an urban emergency medical center from 2010 to 2020. The study included patients ≥14 years of age with acute acetaminophen poisoning within 15 hours. The correlation between risk factors and detection of acetaminophen 15 hours after ingestion was evaluated using logistic regression, and the area under the curve (AUC) was calculated.
Results
In total, 181 patients were included in the primary analysis; the median dose was 150.9 mg/kg and 35 patients (19.3%) had acetaminophen detected 15 hours after ingestion. The dose per weight and the time to visit were significant predictors for acetaminophen detection after 15 hours (odds ratio, 1.020 and 1.030, respectively). The AUCs were 0.628 for a 135 mg/kg cut-off value and 0.658 for a cut-off 450 minutes, and that of the combined model was 0.714 (sensitivity: 45.7%, specificity: 91.8%).
Conclusion
Where acetaminophen concentrations are not reported during treatment following the UK guidelines, it is safe to start N-acetylcysteine immediately for patients who are ≥14 years old, visit within 15 hours after acute poisoning, and report having ingested ≥135 mg/kg. Additional N-acetylcysteine doses should be considered for patients visiting after 8 hours.

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

Extracorporeal Life Support in Acute Poisoning: Si Jin Lee, Gap Su Han, Eui Jung Lee, Do Hyun Kim, Kyoung Yae Park, Ji Young Lee, Su Jin Kim, Sung Woo Lee; J Korean Soc Clin Toxicol. 2018;16(2):86-92. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.86

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Abstract PDF: Purpose: Cardiovascular or respiratory complications of acute intoxication are the most common causes of mortality. Advanced cardiac life support (ACLS) or specific antidotes help manage these cardiac or respiratory complications in acute intoxication. On the other hand, some cases do not respond to ACLS or antidotes and they require some special treatment, such as extracorporeal life support (ECLS). ECLS will provide the chance of recovery from acute intoxication. This study examined the optimal timing of ECLS in acute intoxication cases. Methods: This paper is a brief report of a case series about ECLS in acute poisoning. The cases of ECLS were reviewed and the effects of ECLS on the blood pressure and serum lactate level of the patients were analyzed. Results: A total of four cases were reviewed; three of them were antihypertensive agent-induced shock, and one was respiratory failure after the inhalation of acid. The time range of ECLS application was 4.8-23.5 hours after toxic exposure. The causes of ECLS implementation were one for recurrent cardiac arrest, two for shock that did not respond to ACLS, and one for respiratory failure that did not respond to mechanical ventilator support. Three patients showed an improvement in blood pressure and serum lactate level and were discharged alive. In case 1, ECLS was stared at 23.5 hours post toxic exposure; the patient died due to refractory shock and multiple organ failure. Conclusion: The specific management of ECLS should be considered when a patient with acute intoxication does not recovery from shock or respiratory failure despite ACLS, antidote therapies, or mechanical ventilator support. ECLS improved the hemodynamic and ventilator condition in complicated poisoned patients. The early application of ECLS may improve the tissue perfusion state and outcomes of these patients before the toxic damage becomes irreversible.

Antidotes Stocking and Delivery for Acute Poisoning Patients at 20 Emergency Departments in Korea 2015-2017: Seungmin Lee, Han Deok Youn, Hanseok Chang, Sinae Won, Kyung Hwan Kim, Bum Jin Oh; J Korean Soc Clin Toxicol. 2018;16(2):131-140. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.131

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Abstract PDF: Purpose: The National Emergency Medical Center has been running a project for the storage and delivery of antidotes for acute poisoning patients of the Department of Health and Welfare, Korea. This study analyzed the results of this project over the past two years. Methods: The requests received by the National Emergency Medical Center and the data on the delivery process were analyzed. Results: This study analyzed a total of 121 patients with acute poisoning, who were requested to receive an antidote reserved at 20 key hospitals in 2015-2017, and whose age was $52.3{pm}23.5;years$; old; 54 were women. Intentional poisoning were 58.7%, and the home was the most common place of exposure (66.9%). The toxic substances were chemicals (32.2%), pesticides (27.3%), medicines (24.8%), and snake venom (4.1%). The patient's poison severity score was $2.4{pm}0.7$ (median 3) indicating moderate-to-severe toxicity. Antidote administration was the cases treated in key hospitals 67.8% (82/121), in which transferred patients accounted for 57.3% (47/82). After receiving an antidote request from a hospital other than the key hospitals, the median was 75.5 minutes (range 10 to 242 minutes) until the antidote reached the patient, and an average of 81.5 minutes was required. The results of emergency care were intensive care unit (70.3%), general wards (13.2%), death (10.7%), and discharge from emergency department (5.0%). Conclusion: This study showed that the characteristics of acute poisoning patients treated with an antidote were different from previous reports of poisoned patients in the emergency department, and basic data on the time required for delivery from key hospitals was different.

The Effect of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity in a Murine Model: Chang Yeon Ryu, Kyung Hoon Sun, Ran Hong, Yongjin Park; J Korean Soc Clin Toxicol. 2018;16(2):108-115. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.108

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Abstract PDF: Purpose: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on${alpha}$-amanitin-induced hepatotoxicity have been published. ${alpha}$-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that ${alpha}$-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on ${alpha}$-amanitin-induced hepatotoxicity in a murine model. Methods: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving ${alpha}$-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. Results: GLEA significantly improved the beneficial functional parameters in ${alpha}$-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with ${alpha}$-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. Conclusion: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after ${alpha}$-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.

Pneumatosis Cystoides Intestinales and Portomesenteric Venous Gas following Anticholinesterase Pesticide Poisoning: Suk Hee Lee, Kyung-Woo Lee, Jin Hee Jung; J Korean Soc Clin Toxicol. 2017;15(1):56-59. Published online June 30, 2017; DOI: https://doi.org/10.22537/jksct.2017.15.1.56

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Abstract PDF: Pneumatosis cystoides intestinalis and portomesenteric venous gas are uncommon radiological findings, but are found commonly in cases of bowel ischemia, or as a result of various non-ischemic conditions. A 72-year-old man visited an emergency center with altered mental status 2 hours after ingestion of an unknown pesticide. On physical examination, he showed the characteristic hydrocarbon or garlic-like odor, miotic pupils with no response to light, rhinorrhea, shallow respiration, bronchorrhea, and sweating over his face, chest and abdomen. Laboratory results revealed decreased serum cholinesterase, as well as elevated amylase and lipase level. We made the clinical diagnosis of organophosphate poisoning in this patient based on the clinical features, duration of symptoms and signs, and level of serum cholinesterase. Activated charcoal, fluid, and antidotes were administered after gastric lavage. A computerized tomography scan of the abdomen with intravenous contrast showed acute pancreatitis, poor enhancement of the small bowel, pneumatosis cystoides intestinalis, portomesenteric venous gas and ascites. Emergent laparotomy could not be performed because of his poor physical condition and refusal of treatment by his family. The possible mechanisms were believed to be direct intestinal mucosal damage by pancreatic enzymes and secondary mucosal disruption due to bowel ischemia caused by shock and the use of inotropics. Physicians should be warned about the possibility of pneumatosis cystoides intestinalis and portomesenteric venous gas as a complication of pancreatitis following anticholinesterase poisoning.

A Case of Aconite Poisoning Successfully Recovered after Intravenous Fat Emulsion Therapy: Hee Jun Shin, Hoon Lim; J Korean Soc Clin Toxicol. 2016;14(1):60-65. Published online June 30, 2016

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Abstract PDF: Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.

A Clinical Analysis of Patients Who Visited Emergency Department due to Chemical Incident Occurred at Industrial Place: A Retrospective Study: Hee Jun Shin, Se Kwang Oh, Byeong Dai Yoo, Duck Ho Jun, Dong Ha Lee, Kuck Hyeun Woo, Seong Yong Yoon, Sung Yong Choi; J Korean Soc Clin Toxicol. 2015;13(2):78-86. Published online December 31, 2015

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Abstract PDF: Purpose: The purpose of this study is to understand what kinds of chemical substances have been used annually and to investigate incidents that occurred due to chemical hazard release and to analyze statistically clinically chemical injury patients who visited one regional emergency medical center in Gumi city with documented references review. Methods: Annual chemical waste emission quantity (Kg/Year) (Cwep) was reproduced using national web site data governed by the Ministry of Environment and 5 years (from 1 .Jan. 2010 to 31. Dec. 2014) of medical records of chemical injury patients who visited our emergency department were reviewed retrospectively. By applying exclusion criteria, 446 patients of 460 patients were selected. Results: Dichloromethane, Toluene, Trichloroethylene, and Xylene were always included within Top 5 of Cweq. Six cases of chemical incidents were reported and in 3 of 6 cases involving Hydrogen fluoride were included during the study period. Male gender and twenties were the most prevalent group. Injury evoking chemicals were Hydrogen fluoride, unknown, complex chemicals (over 2 substances) in sequence. The most frequent site of wounds and injuries was the respiratory tract. Gas among status, intoxication among diagnosis, and discharge among disposition was most numerous in each group. Conclusion: There have been no uniform clinical protocols for chemical wounds and injuries due to various kinds of chemicophysical properties and ignorance of antidotes. Therefore conduct of a multicenter cohort study and experiments for ruling out chemicals according to chemicophysical priority as well as development of antidotes and clinical protocols for chemical injury patients is needed.

The Experiences of the Emergency Antidote Stock and Delivery Service by the Korean Poison Information Center: So Young Park, Bum Jin Oh, Chang Hwan Sohn, Ru Bi Jeong, Kyoung Soo Lim, Won Kim, Seung Mok Ryoo; J Korean Soc Clin Toxicol. 2013;11(1):9-18. Published online June 30, 2013

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Abstract PDF: Purpose: Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide stocking and delivery system for emergency antidotes in Korea. We report on a two-year experience of a nationwide stocking and delivery trial for emergency antidotes at emergency departments in Korea. Methods: An expert panel of clinical toxicologists reviewed and made a list of 15 stocked antidote. These antidotes were purchased or imported from other countries and delivered from 14 antidote stocking hospitals nationwide 24 hours per day, seven days per week. Results: From August 1, 2011 to April 30, 2013, 177 patients with acute poisoning, with a median age of 48.5 years, were administered emergency antidotes. The causes of poisoning were intentional in 52.0% and 88.0% were intentional as a suicide attempt. Regarding clinical severity, using the poisoning severity score, 40.7% of patients had severe to fatal poisoning and 39.0% had moderate poisoning according to clinical severity. The most frequent presenting symptom was neurologic deficit, such as altered mentality (62.7%). alerted mentality (62.7%). Emergency antidotes were administered as follows: methylene blue (49 cases), flumazenil (31), N-acetylcysteine (25), glucagon (17), 100% ethanol (15), cyanide antidote kit (12), anti-venin immunoglobulin (5), pyridoxine (4), hydroxocobalamine (2), and deferoxamine (1). The median time interval from antidote request to delivery at the patient's bedside was 95 minutes (interquartile range 58.8-125.8). Conclusion: Findings of this study demonstrated the possibility of successful operation of the nationwide system of emergency antidotes stocking and delivery in Korea.

Acute Organophosphorus Pesticide Poisoning: Mi-Jin Lee, Joon-Seok Park, Tai-Yong Hong, Sung-Soo Park, Yeon-Ho You; J Korean Soc Clin Toxicol. 2008;6(2):83-90. Published online December 31, 2008

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Abstract PDF: Organophosphate (OP) pesticides are the most common source of human toxicity globally, causing high mortality and morbidity despite the availability of atropine as a specific antidote and oximes to reactivate acetylcholinesterase. The primary toxicity mechanism is inhibition of acetylcholinesterase (AchE), resulting in accumulation of the neurotransmitter, acetylcholine, and abnormal stimulation of acetylcholine receptors. Thus, the symptoms (muscarinic, nicotinic, and central nervous system) result from cholinergic overactivity because of AchE inhibition. OP can also cause rhabdomyolysis, pancreatitis, parotitis, and hepatitis. OP therapy includes decontamination, supportive therapy, and the use of specific antidotes such as atropine and oximes. However, there has been a paucity of controlled trials in humans. Here we evaluated the literature for advances in therapeutic strategies for acute OP poisoning over the last 10 years.

Survey of the Antidote Stocking in the Emergency Medical Centers in Korea: Je-Sung You, Eui-Chung Kim, Hahn-Shick Lee, Seung-Ho Kim, Sung-Pil Chung; J Korean Soc Clin Toxicol. 2007;5(2):106-111. Published online December 31, 2007

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Abstract PDF: Purpose: Inadequate hospital stocking and unavailability of essential antidotes is a worldwide problem. The purpose of this study was to determine the adequacy of antidote stocks in Korean hospitals based on a modified version of US antidote stocking guidelines. Methods: Both written and telephone surveys to collect information on hospital demographics and antidote stocking were given to the emergency departments or hospital pharmacies of 117 hospitals with emergency medical centers. The twenty antidotes included in the survey were taken from year 2000 US antidote stocking guidelines, except for activated charcoal and black widow spider antivenin. Antidote stocks were compared by hospital size, geographic location, and type of emergency medical center. Results: Complete responses were received from all hospitals. A mean of $12.4{pm}2.9$ antidotes were adequately stocked per hospital. All hospitals stocked atropine, $CaCl_2$ naloxone, and sodium bicarbonate. However, digoxin Fab fragment (16%), cyanide kits (15%), EDTA (10%), BAL (9%), and fomepizole (1%) were not uniformly stocked. Large and teaching hospitals were significantly more likely to stock greater numbers of antidotes. Conclusions: Korean hospitals as a group do not have adequate antidote stocks. Korean stocking guidelines and an antidote management system are recommended in order to correct these deficiencies.

Research on Poisoning Data Collection using Toxic Exposure Surveillance System: Retrospective Preliminary Survey: Bum-Jin Oh, Won Kim, Gyu-Chong Cho, Hui-Dong Kang, Yoo-Dong Shon, Jae-Ho Lee, Kyoung-Soo Lim; J Korean Soc Clin Toxicol. 2006;4(1):32-43. Published online June 30, 2006

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Abstract PDF: Purpose: Toxic Exposure Surveillance System (TESS) is widely used for poisoning data collection and making a counterplan. But, there were few reports about poisoning data collection using TESS in Korea. The aim was to collect poisoning data using TESS report form and investigate the recognition of emergency physician about the necessity of TESS as preliminary survey. Methods: Retrospectively, we gathered data from hospital records about the patient who admitted hospital emergency room due to poisoning. Date were gathered by paper and/or web client system report form in patients recruited by ICD-10 codes Results: From Jun 2004 to May 2005,3,203 patients were enrolled in 30 hospitals and their mean age was $44.9{pm}20.3years$ old(male: female = 1,565: 1,638). The most frequent site of exposure was their own residence (73.2%, 2,345/3,203) and most of reported patients were older than 20 years(89.7%, 2,871/3,203). Frequent substances involved in poisoning were medication(41.9%) and pesticide(33.3%). Intentional poisoning was 60.7%(1,954). In fatality, overall frequency was 5.1%(162/3,203) and the most frequent route of exposure was ingestion(96.3%, 156/162) and the most frequent substance was pesticide(85.2%, 138/ 162). Antidotes were administered in 202 patients(2-PAM, atropine, antivenin, N-acetylcystein, vitamin K, flumazenil, ethanol, methylene blue, naloxone, calcium compound). 19 of 20 emergency physicians agreed with necessity of TESS. Conclusion: Data collection using TESS report form showed preliminary poisoning events in Korea. Frequent poisoning substance were medication and pesticide. The fatality was mainly related with pesticide ingestion. Many doctors in emergency room recognized the necessity of TESS.

Chemical Asphyxiants - Cyanides and Hydrogen Sulfides: Yang Ho Kim, Young Hee Choi, Choong Ryeol Lee, Ji Ho Lee, Cheolln Yoo, Hun Lee; J Korean Soc Clin Toxicol. 2003;1(1):12-20. Published online June 30, 2003

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Abstract PDF: Cyanides and hydrogen sulfide ($H_2S$) are major chemical asphyxiants. They have common mechanism of action which inhibit cellular respiration and induce histotoxic hypoxia. They do not generate ATP, and all processes dependent on ATP are stopped. No extraction of $O_2$ from blood decreases AV $O_2$ differences, and the shift to anaerobic glycolysis brings about lactic acidosis with high anion gap. The mainstay of the treatment is rapid treatment with appropriate use of antidotes. However, there are several differences between cyanides and $H_2S$. First, $H_2S$ is not metabolized by enzymes such as thiosulfate. Thus thiosulfate does not play any role in treatment of $H_2S$. Second, $H_2S$ is a more potent inhibitor of cytochrome aa3 than cyanide. Third, $H_2S$ induces more divergent neurologic sequele than cyanide. Finally, $H_2S$ is not absorbed via skin.

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