Journal of The Korean Society of Clinical Toxicology

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.

Different Clinical Courses for Poisoning with WHO Hazard Class Ia Organophosphates EPN, Phosphamidon, and Terbufos in Humans: Jong Gu Mun, Jeong Mi Moon, Mi Jin Lee, Byeong Jo Chun; J Korean Soc Clin Toxicol. 2018;16(1):1-8. Published online June 30, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.1.1

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Abstract PDF: Purpose: Extremely hazardous pesticides are classified as World Health Organization (WHO) hazard class Ia. However, data describing the clinical course of WHO class Ia OP (organophosphate) poisonings in humans are very scarce. Here, we compare the clinical features of patients who ingested hazard class Ia OPs. Methods: This retrospective observational case study included 75 patients with a history of ingesting ethyl p-nitrophenol thio-benzene phosphonate (EPN), phosphamidon, or terbufos. The patients were divided according to the chemical formulation of the ingested OP. Data regarding mortality and the development of complications were collected and compared among groups. Results: There were no differences in the baseline characteristics and severity scores at presentation between the three groups. No fatalities were observed in the terbufos group. The fatality rates in the EPN and phosphamidon groups were 11.8% and 28.6%, respectively. Patients poisoned with EPN developed respiratory failure later than those poisoned with phosphamidon and also tended to require longer mechanical ventilatory support than phosphamidon patients. The main cause of death was pneumonia in the EPN group and hypotensive shock in the phosphamidon group. Death occurred later in the EPN group than in the phosphamidon group. Conclusion: Even though all three drugs are classified as WHO class Ia OPs (extremely hazardous pesticides), their clinical courses and the related causes of death in humans varied. Their treatment protocols and predicted outcomes should therefore also be different based on the chemical formulation of the OP.

A Case Report of Acute Nicotine Poisoning from Subcutaneous Injection of Nicotine Solution for Electronic Cigarette: Jiun Choi, Dong Ryul Ko, Je Sung You, Sung Phil Chung; J Korean Soc Clin Toxicol. 2017;15(1):60-64. Published online June 30, 2017; DOI: https://doi.org/10.22537/jksct.2017.15.1.60

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Abstract PDF: Nicotine-poisoning related to the electronic cigarettes (e-cigarette) is increasing worldwide. Moreover, the American Association of Poison Control Centers has advised the public to use caution with e-cigarette devices and highly concentrated liquid nicotine after a surge in related poisonings. We report here the first case of nicotine poisoning from self-injected e-cigarette fluid in Korea. A 17-year-old male patient subcutaneously injected himself with 0.5 ml of nicotine solution for an electronic cigarette via the dorsum of his hand, after which he complained of nausea, vomiting, dizziness and dyspnea. His vital signs were within the normal range, but his mental status was drowsy. He was admitted for observation and the symptoms disappeared the following day. Sinus bradycardia with a rate of 45/min was observed on the third hospital day, but improved after 6 hours. He was discharged without complications.

Effect of Intravenous Lipid Emulsion in the Patient with Acute Poisoning : A Systematic Review: Jinwoo Myung, Dong Ryul Ko, Taeyoung Kong, Young Seon Joo, Je Sung You, Sung Phil Chung; J Korean Soc Clin Toxicol. 2015;13(1):1-10. Published online June 30, 2015

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Abstract PDF: Purpose: The purpose of this study was to evaluate the usefulness of intravenous lipid emulsion as well as adverse events in acute poisoning patients. Methods: Literature was accessed through PubMed, EMBASE, Cochrane library, Web of science, and KoreaMed. All forms of literatures relevant to human use of intravenous lipid emulsion for acute poisoning were included. Cases reports or letters without description of clinical outcomes for each case were excluded. The literature search was conducted by two investigators in March, 2015, with publication language restricted to English and Korean. The effect, onset time, and adverse event of lipid emulsion and final outcome of each case were analyzed. Results: Eighty-one published articles were included, excluding articles whose title and abstract were not relevant to this study. No articles were classified as high level of evidence. Sixty-eight case reports were identified, consisting of 25 local anesthetics and 43 other drugs, such as tricyclic antidepressants and calcium channel blockers. Although most cases described significant clinical improvements, some of them showed no beneficial effect or worsening of clinical course. Several adverse events including hyperamylasemia and laboratory interference were reported. Conclusion: Although there were many case reports illustrating successful use of lipid for various drug poisonings, the effect cannot be estimated due to significant possibility of publication bias. Therefore, lipids might be considered in severe hemodynamic instability resulting from lipophilic drug poisoning, however further studies should follow to establish the use of lipid as the standard of care.

Recent Epidemiologic Features of Carbon Monoxide Poisoning in Korea: A Single Center Retrospective Cohort Study: Byung Ho Choi, Jin Jeon, Seung Mok Ryoo, Dong Woo Seo, Won Young Kim, Bum Jin Oh, Kyoung Soo Lim, Chang Hwa Sohn; J Korean Soc Clin Toxicol. 2012;10(2):80-85. Published online December 31, 2012

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Abstract PDF: Purpose: The aim of this study was to describe the epidemiologic characteristics of adult patients with carbon monoxide poisoning who presented to the emergency department in recent years. Methods: This was a retrospective cohort study on adult consecutive patients with carbon monoxide (CO) poisoning who presented to the emergency department of a tertiary care university-affiliated hospital from January 1, 2008 to December 31, 2011. Results: A total of 91 patients were included in this study; there were 56(61.5%) unintentional and 35(38.5%) intentional poisonings. For the unintentional CO poisonings, the principal sources of exposure to CO were fire (39.3%), charcoal (17.9%), briquette charcoal (7.1%), wood burning boiler (7.1%), gas boiler (5.4%), automobile heater (3.6%), briquette boiler (3.6%), firewood (3.6%), and other items (12.5%). For the intentional CO poisonings, the sources were ignition charcoal (60.0%), briquette (31.4%), charcoal (5.7%) and butane gas (2.9%). For the unintentional CO poisonings, the places of poisoning were the home (58.9%), workplace (10.7%), public accommodation (8.9%), tent (8.9%), automobile (3.6%) and parking place (1.8%). For the intentional CO poisonings, the places of poisoning were the home (77.1%), public accommodation (11.4%) and automobile (11.4%). The proportion of intentional CO poisonings among total poisonings has increased significantly in recent years; 0.0% in 2008, 3.3% in 2009, 5.5% in 2010, and 29.7% in 2011. Conclusion: This study showed that in recent years in Korea, the source of CO has diversified broadly and intentional CO poisonings from burning ignition charcoal or briquettes has increased. Prevention efforts should consider these factors.

Clinical Review of Toxic Alcohol Poisoning Cases in Korea: Nu-Ga Rhee, Sung-Phil Chung, In-Cheol Park, Kyeong-Ryong Lee, Hyun-Jin Kim, Gun-Bea Kim, Young-Soon Cho, In-Ho Kwon, Seung-Whan Kim; J Korean Soc Clin Toxicol. 2012;10(1):15-21. Published online June 30, 2012

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Abstract PDF: Purpose: Toxic alcohols are responsible for accidental and suicide motivated poisonings, resulting in death or permanent sequelae for the afflicted patients. Major therapeutic modalities in these cases include treatment with alcohol dehydrogenase inhibitors and extracorporeal elimination. There have been a number of case reports of toxic alcohol intoxication in Korea. The purpose of this study was to review the clinical characteristics of patients suffering toxic alcohol intoxication. Methods: We retrospectively reviewed the medical records of patients who presented with toxic alcohol intoxication at 8 emergency departments (ED) from Jun 2005 to Nov 2011. Patients who ingested methanol, isopropyl alcohol, ethylene glycol, and other alcohols except ethanol, were included in this study. The clinical characteristics of these patients were analyzed to include anion and osmolar gap, and estimated concentration of alcohol in the body. Results: During the study period, 21 patients were identified who had ingested toxic alcohol (methanol; 12 patients, ethylene glycol; 9 patients). At ED arrival, the mean anion gap was $18.7{pm}6.9$ and the osmolar gap was elevated in 13 patients. Oral and IV ethanol were administrated to 11 patients in order to inhibit alcohol dehydrogenase. Extracorporeal elimination procedures such as hemodialysis were performed in 9 patients. There were no fatalities, but the one patient suffered permanent blindness. Conclusion: This study found that ethylene glycol and methanol were the substances ingested which produced toxic alcohol intoxication. The patients presented with high anion gap metabolic acidosis and were typically treated with oral ethanol and hemodialysis.

Clinical Features of Acute Acetanilide Herbicide Poisoning: Cheol-Sang Park, Mi-Jin Lee, Seong-Soo Park, Won-Joon Jeong, Hyun-Jin Kim; J Korean Soc Clin Toxicol. 2011;9(2):49-55. Published online December 31, 2011

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Abstract PDF: Purpose: Acetanilide has been in widespread use as an amide herbicide compound. However, available data regarding acute human poisoning is scarce. The aim of this study was to analyze the clinical characteristics of acetanilide poisoning in order to identify the risk factors associated with severity. Methods: We conducted a retrospective observational study encompassing the period January 2005 to December 2010, including adult ED patients suffering from acetanilide intoxication. Toxicological history, symptoms observed, clinical signs of toxicity, and laboratory test results were collected for each patient. The patients were classified into two groups for analysis, according their poisoning severity score (PSS). Resulting clinical data and prognostic variables were compared between mild-to-moderate poisoning (PSS 1/2 grades), and severe poisonings and fatalities (PSS 3/4 grades). Results: There were a total of 37 patients, including 26 alachlor, 6 s-metolachlor, 4 mefenacet, and 1 butachlor cases. The majority of patients (81.1%) were assigned PSS 1/2 grades. Changes in mental status and observation of adverse neurologic symptoms were more common in the PSS 3/4 group. The median ingested volume of amide herbicide compound was 250 ml (IQR 200-300 ml) in the PSS 3/4 group, and 80 ml (IQR 50-138 ml) in the PSS 1/2 group. Also, the median GCS observed in the PSS 3/4 group was 13 (IQR 10-14), which was markedly low as compared to a median GCS of 15 in the PSS 1/2 group. Overall mortality rate was 5.4%, and profound cardiogenic shock was observed prior to death in all fatalities. Conclusion: When compared to previous reports, acute acetanilide poisoning resulted in relatively moderate severity. The presence of neurologic manifestations, hypotension, lower GCS score, and larger ingested volumes was associated with more serious effects and mortalities.

Veiled Paraquat Poisoning - A Focus on Clinical Characteristics: Ye-Wan Song, Sang-Cheon Choi, Young-Yeol You, Yeoun-Ho Shin, Eun-Jung Park, Jung-Hwan Ahn, Young-Gi Min, Yoon-Seok Jung; J Korean Soc Clin Toxicol. 2011;9(1):14-19. Published online June 30, 2011

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Abstract PDF: Purpose: Most paraquat poisonings are easily diagnosed by history taking on physical examination, however, some are failed to be diagnosed initially if the poisoning was veiled. The purpose of this study was to explore the clinical characteristics of veiled paraquat poisoning. Methods: We retrospectively reviewed the medical records of patients whose discharge diagnosis was paraquat poisoning in one university teaching hospital between 1 Jan, 2001 and 31 Dec, 2010. Veiled paraquat poisoning was determined when there was a positive urine paraquat kit in patients who did not mention paraquat poisoning in an initial physical examination or had unknown cause of pulmonary fibrosis, acute renal failure, or multi-organ failure. Results: Of the 117 patients with paraquat poisoning during the study period, 6 patients (5.1%) had veiled paraquat poisoning. The clinical characteristics were 1) proteinuria - 6 (100%), 2) increased creatinine - 4 (66.7%), 3) green skin stains - 2 (33.3%), 4) mucosal ulcer - 3 (50%). Blood chemistry results were variable. Conclusion: We should suspect veiled paraquat poisoning for patients who have proteinuria, increased creatinine, green skin stain, mucosal ulcer and vomiting, or if they have rapidly progressing acute renal failure or multi-organ failure with unknown cause, even if patients didn't mention about paraquat poisoning upon the initial physical examination. In cases with the above clinical conditions, a thorough repeated physical examination including history taking and use of urine paraquat kits should be performed.

Clinical Experience with Continuous Renal Replacement Therapy as a Method of Extracorporeal Elimination and as performed by Emergency Room Physicians for Patients with Poisoning: Jung-Hwan Ahn, Sang-Cheon Choi, Yoon-Seok Jung, Young-Gi Min; J Korean Soc Clin Toxicol. 2009;7(2):150-155. Published online December 31, 2009

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Abstract PDF: Purpose: Extracorporeal elimination of drugs is a critical part of managing poisonings, although the indications and optimal method remain a matter of debate. The aim of this study is to report our clinical experiences with continuous renal replacement therapy (CRRT), as performed by emergency room physicians, as method of extracorporeal drug elimination in patients with poisoning. Methods: This study was a retrospective study of the consecutive patients who underwent CRRT, as performed by an emergency room physician, for acute poisoning. The patient characteristics, the kinds of drugs and the method of extracorporeal elimination were analyzed by reviewing the patients' charts. Results: During eleven months, 26 patients with acute poisoning underwent extracorporeal elimination (2 patients; intermittent hemodialysis, 24 patients; CRRT). The mean time from the decision to performing extracorporeal elimination was $206.0{pm}36.8$ minutes for intermittent hemodialysis, $62.9{pm}8.5$ minutes for continuous venoveno-hemodiafiltration (CVVHDF) and $56.6{pm}6.8$ minutes for charcoal hemoperfusion. For the patients with CRRT, CVVHDF was conducted in 10 patients (3 patients; valproic acid, 2 patients; Lithium, 1 patient; salicylates, 1 patient; methanol) and charcoal hemoperfusion by using CRRT was done in 14 patients (13 patients; paraquat, 1 patient; dapsone). For the 12 patients who required hemodialysis due to severe poisoning, 7 patients underwent CRRT because of their unstable vital signs. Conclusion: CRRT was an effective method of extracorporeal drug elimination in patients with acute poisoning, and especially for the cases with unstable vital sign and for those patients who required an early start of extracorporeal elimination according to the characteristics of the drug. (ED note: the writing of the abstract was not clear. Check it carefully.)

Clinical Characteristics of Acute Dichlorvos Poisoning in Korea: Mi-Jin Lee, Joon-Seok Park, Woon-Yong Kwon, Eun-Kyung Eo, Bum-Jin Oh, Sung-Woo Lee, Joo-Hyun Suh, Hyung-Keun Roh; J Korean Soc Clin Toxicol. 2008;6(1):9-15. Published online June 30, 2008

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Abstract PDF: Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.

Characteristics and Prognostic Factors of Carbamate Poisoning in Korea: Woon-Yong Kwon, Joon-Seok Park, Eun-Kyung Eo, Bum-Jin Oh, Mi-Jin Lee, Sung-Woo Lee, Joo-Hyun Suh, Hyung-Keun Roh, Gil-Joon Suh; J Korean Soc Clin Toxicol. 2007;5(1):1-7. Published online June 30, 2007

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Abstract PDF: Purpose: The aim of this study was to evaluate the characteristics and the prognostic factors of carbamate poisoned patients who visited emergency departments. Methods: From August 2005 to July 2006, we investigated the demographic feature, dose of exposure, time of exposure, alcohol intake, route of exposure, reason of exposure, site of exposure, pre-existing medical condition, time from exposure to emergency department (ED), transfer from other hospitals, vital sign at ED arrival, symptom or sign at ED arrival, and result of care of the patients who visited the ED of thirty-eight hospitals in Korea. According to the result of care, we divided the patients into two groups, the survival and the dead. To evaluated the prognostic factors, we calculated the odds ratio of each factor for the survival. Results: Among the sixty-eight patients, fifty-five patients (80.9%) were survival and thirteen patients (19.1%) were dead. The patients in the dead were older than the patients in the survival. The Glasgow coma scale (GCS) of the patients in the dead was lower than the GCS in the survival. The odds ratio of the GCS at ED arrival for the survival was 1.58 (95% CI; 1.23-2.05). Other factors showed no statistical significances. Conclusion: The GCS at emergency department arrival was the prognosis factor of the carbamate poisoned patients who visited emergency departments. If the carbamate poisoned patients showed altered mentalities, they should be provided intensive care, immediately.

A Case Report of Saliva-type Hyperamylasemia in Mad Honey Poisoning: Kun-Woo Lee, Kyu-Nam Park, Mi-Jin Lee; J Korean Soc Clin Toxicol. 2006;4(2):166-169. Published online December 31, 2006

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Abstract PDF: Poisonings caused by 'mad honey' are known to occur in response to grayanotoxins, which bind to sodium channels in the cell membrane, increasing membrane sodium permeability and preventing inactivation. Mild symptoms of mad honey intoxication are dizziness, weakness, hypersalivation, nausea, vomiting, and paresthesia. Severe intoxication, however, leads to serious cardiac manifestations such as atrioventricular block, dose-dependent hypotension, bradycardia, and respiratory depression. Atropine and vasoactive drugs improve symptoms of both bradycardia and respiratory rate depression. We report an unusual case of saliva-type hyperamylasemia in a mad honey poisoning patient who developed clinically significant bradycardia. She recovered fully within 3 days following atropine administration and medical treatment.

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