Purpose: Valproic acid is a drug used for the treatment of convulsive disorders and for mood stabilization. Acute intoxication can result in gastrointestinal disturbances, neurologic symptoms, and hematologic toxicity. This study aims to identify factors that may predict patient prognosis.
Methods In this single-center retrospective observational study, medical records from January 1, 2013, to December 31, 2022, were reviewed. The initial clinical features, laboratory results, and serum valproic acid levels of patients with acute valproic acid intoxication who presented to the emergency department were analyzed. Patients were divided into two groups: those who developed hematologic toxicity (hematotoxicity group) and those who did not (non-hematotoxicity group).
Results A total of 115 patients were included in the analysis, of whom 23 (20%) developed hematotoxicity. The median age of patients with hematotoxicity was 39 years (interquartile range [IQR], 32.0–50.5), which was significantly higher than in the non-hematotoxicity group (p=0.001). The Glasgow Coma Scale score was lower in the hematotoxicity group, with a median of 12 points (IQR, 9.0–14.5) (p=0.013). Intensive care unit admission was more frequent in the hematotoxicity group (p=0.003). Compared with the non-hematotoxicity group, patients with hematotoxicity had a higher incidence of pneumonia, acute kidney injury, rhabdomyolysis, metabolic acidosis, and hyperlactatemia (all p<0.001, except p=0.009 for hyperlactatemia). The initial serum valproic acid concentration was also higher in the hematotoxicity group, with a median of 121.6 μg/mL (IQR, 59.8–154.3) (p<0.001). Multivariate analysis showed that the odds ratio for hematotoxicity was 6.20 (p=0.018) in the presence of metabolic acidosis and 8.32 (p<0.001) when the initial valproic acid concentration exceeded 115.0 μg/mL.
Conclusion In patients with suspected acute valproic acid poisoning, early evaluation of arterial pH and serum valproic acid concentration is essential for predicting the prognosis.
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.
Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced cellular toxicity in SH-SY5Y neuroblastoma cells.
Methods Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively.
Results MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SH-SY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment.
Conclusion MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.
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.
Traditionally, most cases of nicotine poisoning have been due to ingestion of nicotine pesticides. However, the increasing use of electronic cigarettes (e-cigarettes) has resulted in both intentional and unintentional exposure to concentrated liquid nicotine or “eliquid” leading to an increase in nicotine poisoning cases. However, fatalities following the ingestion of the e-liquid are extremely rare. We report a rare case of cardiac arrest and severe encephalopathy following the intentional ingestion of e-liquid. We present the case of a 20-year-old woman who intentionally ingested liquid nicotine intended for e-cigarette use. She was found in asystole and experienced a return of spontaneous circulation (ROSC) after undergoing approximately 46 mins of cardiopulmonary resuscitation. Her plasma nicotine levels were >500 ng/ml. Despite aggressive supportive care, she was found to have encephalopathy consistent with severe anoxic brain injury on magnetic resonance imaging. In recent times, there have been some reports of deaths following liquid nicotine ingestion. Our case illustrates the potential for fatal nicotine toxicity from ingestion of e-cigarettes.
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A Systematic Review on Health Impact of Electronic Cigarettes in South Korea Eunsil Cheon, Hana Kim, Naeun Kang, Susan Park, Sung-il Cho, Jieun Hwang Journal of the Korean Society for Research on Nicotine and Tobacco.2024; 15(2): 29. CrossRef
Purpose: Despite previous studies reporting the development of rhabdomyolysis (RM), this affliction tends to be neglected as an envenomation sign in South Korea. The current retrospective study investigates the prevalence and prognosis of RM after a snakebite. We further searched for predictors of snakebite-induced RM, which can be observed at presentation. Methods: This study included 231 patients who presented to the ED within 24 hours after a snakebite. The patients were classified according to the severity of RM, and the data, comprising baseline characteristics and clinical course including the level of creatine kinase (CK), were collected and compared according to the severity of RM. Results: The prevalence of RM and severe RM were determined to be 39% and 18.5%, respectively. Compared to the group without RM or with mild RM, the group with severe RM had a higher grade of local swelling, a higher frequency of acute kidney injury and neurotoxicity, and a greater need for renal replacement therapy and vasopressor administration. However, the incidence of acute renal injury in the RM group was 7.7%, with two patients needing renal replacement therapy. No mortalities were reported at discharge. Results of the multinomial logistic regression model revealed that the WBC levels are significantly associated with the risk of severe RM. Conclusion: RM should be considered the primary clinical sign of snake envenomation in South Korea, although it does not seem to worsen the clinical course. In particular, physicians should pay attention to patients who present with leukocytosis after a snakebite, which indicates the risk of developing RM, regardless of the CK level at presentation.
N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.
Elapid snakes have neurotoxic venom which causes diverse neuroparalytic manifestations, including fatal respiratory failure. In South Korea, since elapid snakebites are very rare, the cobra antivenom, which is effective against neurotoxicity, was only introduced recently. Most physicians in South Korea have little experience in the treatment of patients who have been bitten by elapid snakes. A 19-year-old man was brought to the emergency department with sudden diplopia, 1 hour after a snakebite on the left 2nd finger. The patient presented with drowsiness and complained of mild dizziness and binocular diplopia. After 1 hour, he had sudden onset of dyspnea and dysphagia and appeared to be agitated. He was immediately intubated and received mechanical ventilation as he was unable to breathe on his own. A total of 2.5 mg of neostigmine diluted with normal saline was slowly infused, and 1 vial of cobra antivenom was infused for an hour, 5 times every 2 hours, for a total of 5 vials. He slowly recovered self-breathing; on the 3rd day of hospitalization, he showed tolerable breathing and was extubated. He was discharged without any neurological deficits or other complications.
Purpose: Glyphosate herbicide (GH) is a widely used herbicide and has been associated with significant mortality as poisoned cases increases. One of the reasons for high toxicity is thought to be toxic effect of its ingredient with glyphosate. This study was designed to determine differences in the clinical course with the salt-type contained in GH. Methods: This was a retrospective study conducted at a single hospital between January 2013 and December 2017. We enrolled GH-poisoned patients visited the emergency department. According to salt-type, patients were divided into 4 groups: isopropylamine (IPA), ammonium (Am), potassium (Po), and mixed salts (Mi) groups. The demographics, laboratory variables, complications, and their mortality were analyzed to determine clinical differences associated with each salt-type. Addtionally, we subdivided patients into survivor and non-survivor groups for investigating predictive factors for the mortality. Results: Total of 348 GH-poisoned patients were divided as follows: IPA 248, Am 41, Po 10, and Mi 49 patients. There was no difference in demographic or underlying disease history, but systolic blood pressure (SBP) was low in Po group. The ratio of intentional ingestion was higher in Po and Mi groups. Metabolic acidosis and relatively high lactate level were presented in Po group. As the primary outcome, the mortality rates were as follows: IPA, 26 (10.5%); Am, 2 (4.9%); Po, 1 (10%); and Mi, 1 (2%). There was no statistically significant difference in the mortality and the incidence of complications. Additionally, age, low SBP, low pH, corrected QT (QTc) prolongation, and respiratory failure requiring mechanical ventilation were analyzed as independent predictors for mortality in a regression analysis. Conclusion: There was no statistical difference in their complications and the mortality across the GH-salt groups in this study.
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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
Glufosinate-containing herbicides is a non-selective herbicide commonly used worldwide. As the use of them increased gradually since paraquat was banned in 2012, the number of suicides by their ingestion is also increasing continuously. Complications of glufosinate-containing herbicide poisoning include various central nervous system (CNS) toxicities such as convulsions, loss of consciousness, memory impairment, and respiratory depression, which may be accompanied by hemodynamic changes such as bradycardia and hypotension. However, it is very rare that arrhythmias other than bradycardia occurred and Takotsubo cardiomyopathy was combined due to cardiotoxicity. A 71-year-old female patient was transferred to our hospital after ingesting 500 mL of glufosinate-containing herbicide and receiving 5 L of gastric lavage at a local hospital. A few hours later, she presented stuporous mentality, respiratory depression, and convulsions, and was accompanied by hypotension and bradycardia. On the second day of admission, electrocardiogram (ECG) showed bradycardia and QTc prolongation with hemodynamic Instability. Accordingly, we conducted the early treatment with continuous renal replacement therapy (CRRT) and the application of temporary cardiac pacemaker. An echocardiogram demonstrated decreased ejection fraction (EF) and Takotsubo cardiomyopathy on the third day of admission. Then, she was discharged safely with conservative treatment. At the follow-up after 1 year, Takotsubo cardiomyopathy, EF and QTc prolongation were recovered on echocardiogram and ECG. Because cardiac toxicity after glufosinate-containing herbicide poisoning may cause life-threatening consequences, caution is required while treating the patient. Therefore, if electrocardiogram changes are seen in the elderly with a large amount of glufosinate herbicide ingestion, additional cardiac function test through echocardiography should be concerned, and early treatment through CRRT or artificial cardiac pacing should be considered.
Chlorfenapyr is a widely used insecticide, that is very lethal if ingested. It exhibits delayed toxicity in which there are few symptoms at first which suddenly worsen after a few days. A 66-year-old female patient ingested about 90 mL of chlorfenapyr liquid hydrating agent (Chlofenapyr 10%) and showed stable vital signs with no specific symptoms and findings other than a mild fever, vomiting, and nausea. From the 3rd day of ingestion, creatine kinase was high, and rhabdomyolysis was suspected. From the 4th day of ingestion, pancreatic enzymes began to gradually increase. A diffusion-weighted image showed a multifocal high signal intensity in the white matter and corpus callosum area. On the 8th day after ingestion, she suffered a high fever and a heart attack and died. Thus, if a patient is suspected of taking chlorfenapyr, he/she needs active treatment and monitoring even if he/she does not exhibit any symptoms.
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Understanding Chlorfenapyr Toxicity: An Overview of Acute Human Exposure and Clinical Outcomes Dalia Alsaied Moustafa Ahmed, Nermin Mahmoud Emam, Mohamed Moharram Badawy Journal of Applied Toxicology.2026;[Epub] CrossRef
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Purpose: Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient's blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs. Methods: We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory. Results: We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years). Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p<0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p<0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p<0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours). The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p<0.01, regional 5.7±0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours). Conclusion: Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.
Tetramine toxicity due to sea snail ingestion is generally mild and has a good prognosis. Tetramine toxicity acts on the acetylcholine receptor, affecting the neuromuscular junction and autonomic nervous system. A 78-year-old female patient visited the emergency room with vomiting and dyspnea after eating sea snails. At the time of admission, the vital signs recorded were 140/80 mmHg-105/min-24/min-36.5℃, and 90% oxygen saturation. Arterial blood test revealed hypercapnia (pCO2 58.2 mmHg) and respiratory acidosis (pH 7.213, HCO3- 22.5 mmol/L), whereas other blood tests showed no specific findings. Due to decreased consciousness and hypoxia, endotracheal intubation and mechanical ventilation were administered to the patient. Successful weaning was accomplished after 12 hrs, and the patient was discharged without any further complications. Although tetramine toxicity rarely results in acute respiratory failure due to paralysis of the respiratory muscle, caution is required whilst treating the patient.
Purpose: This study evaluated aggressive hyperbaric oxygen therapy (HBOT) by understanding various exposure routes of acute carbon monoxide (CO) poisoning, the risk factors causing acute cardiovascular, and neurological toxicity caused by poisoning. Methods: A retrospective study was conducted based on the medical records of 417 acute CO poisoning patients who visited the emergency care unit from March 2017 to August 2019. The exposure routes, HBOT performance, age, sex, medical history (hypertension, diabetes mellitus, ischemic heart disease, heart failure), intentionality, loss of consciousness (LOC), intake with alcohol or sedatives, and initial test results (carboxyhemoglobin (COHb), troponin-I, electrocardiography, echocardiography, brain MRI) were examined. Comparative analysis of the clinical information was conducted between the groups that showed acute cardiovascular toxicity and neurological toxicity, and groups that did not. Results: Among 417 patients diagnosed with acute CO poisoning, 201 cases (48.2%) were intentional, and charcoal briquette was the most common route (169 patients (40.5%)). Two hundred sixteen cases (51.8%) were accidental, and fire was the most common route (135 patients (32.4%)). The exposure route was more diverse with accidental poisoning. Three hundred ninety-nine patients were studied for acute cardiovascular toxicity, and 62 patients (15.5%) were confirmed to be positive. The result was statistically significant in intentionality, LOC, combined sedatives, initial COHb, HTN, and IHD. One hundred two patients were studied for acute neurological toxicity, which was observed in 26 patients (25.5%). The result was statistically significant in age and LOC. Conclusion: Active HBOT should be performed to minimize damage to the major organs by identifying the various exposure routes of CO poisoning, risk factors for acute cardiovascular toxicity (intentionality, LOC, combined sedatives, initial COHb, HTN, IHD), and the risk factors for acute neurological toxicity (age, LOC).
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