Journal of The Korean Society of Clinical Toxicology

Up-to-date treatment of acetaminophen poisoning: Phil Chung Sung, Moon Jeongmi, Chun Byeongjo; J Korean Soc Clin Toxicol. 2022;20(2):39-44. Published online December 31, 2022; DOI: https://doi.org/10.22537/jksct.2022.20.2.39

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Abstract PDF: 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.

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.

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.

Extended Blood Drug Concentrations in Extended Release Formulated Acetaminophen Overdose Patients: Jin-Ho Bum, Nu-Ga Rhee, Min-Joung Kim, Jung-Suk Park, Hyun-Jong Kim, Sung-Pil Chung, Hahn-Shick Lee; J Korean Soc Clin Toxicol. 2011;9(2):71-76. Published online December 31, 2011

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Abstract PDF: Purpose: The Rumack-Matthew nomogram cannot be applied in managing overdose by extended release (ER) preparation acetaminophen (AAP). This study analyzed the clinical characteristics of ER preparation AAP overdose in order to develop a treatment recommendation. Methods: We retrospectively reviewed the medical records of patients presented to the emergency department as a result of AAP overdose from Jan 2008 to Dec 2010. Only those patients who ingested an ER preparation of AAP were included in the study. Their blood AAP concentrations were measured at 4 and 8 hours after ingestion. Clinical variables related to AAP intoxication were analyzed. Results: Of the total 108 AAP overdose patients identified during the 3-year period, 20 suffered specifically with ER preparation AAP overdose. The mean estimated ingestion amount was 167.5 mg/kg. Treatments including gastric lavage, activated charcoal, and N-acetyl cysteine (NAC) were performed on 10, 14, and 11 patients, respectively. Hepatotoxicity was diagnosed in only one patient who was then successfully treated with NAC. In another case, blood AAP concentration continued to increase until at least 11-hours after ingestion. Conclusion: This study suggested that blood AAP concentrations associated with ingestion of ER formulations of AAP, may increase in an extended manner. Therefore, multiple sampling and longer periods between samples assessing AAP blood concentration may be required for incidences of extended release overdose.

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