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.

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.

Laboratory analysis of acute acetaminophen overdose patients in Emergency Medical Centers: including analysis of one toxicological laboratory data: In Chan Kim, Sinae Won, Arum Lee, Haeun Jung, Jeongsun Lee, Bum Jin Oh; J Korean Soc Clin Toxicol. 2021;19(1):31-37. Published online June 30, 2021; DOI: https://doi.org/10.22537/jksct.2021.19.1.31

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Abstract PDF: 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.

Factors of Determining N-acetylcysteine Administration in Patients with Acute Acetaminophen Poisoning: Jeong Hwa Lee, Sangchun Choi, Sang Kyu Yoon, Kyu Cheol Shin; J Korean Soc Clin Toxicol. 2020;18(2):78-84. Published online December 31, 2020; DOI: https://doi.org/10.22537/jksct.2020.18.2.78

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Abstract PDF: Purpose: In acute acetaminophen poisoning, the administration of N-acetylcysteine (NAC) can effectively treat the main complications, such as kidney injury and liver failure. In the current situation, measurements of the acetaminophen concentration are not checked in the usual medical facilities. Therefore, this study examined the factors of determining the administration of NAC in addition to the stated amount of intake. Methods: The medical records of patients who visited Ajou University Hospital emergency center with acetaminophen poisoning from January 2015 to December 2019 were reviewed retrospectively. One hundred and seventy-nine patients were initially included. Among these patients, 82 patients were finally selected according to the inclusion criteria in the study. The inclusion criteria were as follows: patients who were 15 years of age or older; those whose ingested dose, ingested time, and body weight were clearly identified; and patients whose acetaminophen sampling time was within 24 hours. Patients were divided into two groups: NAC administered vs. non-NAC administered. The following variables were compared in these two groups: ingested dose, ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, psychiatric disease history, classification of toxic/non-toxic groups, duration of hospitalization, and laboratory results. Results: Univariate analysis revealed the ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, and psychiatric disease history to be the determining factors in administering NAC. Logistic regression analysis confirmed that the ingested dose per body weight was the only significant factor leading to an NAC treatment decision. (Odds ratio=1.039, 95% Confidential interval=1.009-1.070, p=0.009) Conclusion: The ingested dose per body weight was the only determining factor for administering NAC in patients with acute acetaminophen poisoning. On the other hand, additional criteria or indicators for the NAC administration decision will be necessary considering the inaccuracy of the ingested dose per body weight and the efficiency of NAC administration.

Continuous Control of Acetaminophen Poisoning after Implementation of Regulation for Ease Access of Acetaminophen: Cohort Study from Emergency Department Based in-depth Injury Surveillance: Seung Jik Jo, Hyun Young Gang, Si Jin Lee, Gyu Hyun Bae, Eui Jung Lee, Kap Su Han, Su Jin Kim, Sung Woo Lee; J Korean Soc Clin Toxicol. 2020;18(2):57-65. Published online December 31, 2020; DOI: https://doi.org/10.22537/jksct.2020.18.2.57

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Abstract PDF

Purpose: Since 2012, acetaminophen can be accessed easily not only at pharmacies but also at convenience stores. The relationship between the easy access of acetaminophen and the risk of poisoning has been controversial. Several studies also reported different results regarding the risk of acetaminophen poisoning after access to acetaminophen was relaxed. This study examined the long-term effects on the risk of acetaminophen poisoning after easy access to acetaminophen was implemented. Methods: This was a retrospective analysis of an emergency department (ED)-based in-depth Injury Surveillance Cohort by the Korea Center for Disease Control and prevention from 2011 to 2018. Poisoning cases were selected from the Cohort, and the incidence of acetaminophen poisoning and the characteristics of the cases of acetaminophen poisoning were analyzed. The purchase path and the amount of ingestion in acetaminophen poisoning were sub-analyzed from data of six EDs. Results: Of 57,326 poisoning cases, 4.0% (2,272 cases) were acetaminophen poisoning. Of 2,272 cases of acetaminophen poisoning, 42.8% (974 cases) required in-patient care after ED management. Two hundred and sixty-four of these 964 cases required intensive care. The rates of cases that required in-patient treatment and the rates of cases that required intensive care increased from 29.4% in 2011 to 48.1% in 2018, and from 3.1% in 2011 to 15.2% in 2018, respectively (p<0.001, p<0.001). In the poisoning group with in-depth toxic surveillance (n=15,908), the incidence and proportion of acetaminophen (AAP) poisoning increased from 55 cases per year to 187 cases per year and 4.9% to 6.1%, respectively (p=0.009, p<0.001, respectively). The most common age group of acetaminophen poisoning was teenagers, which is different from the most common age group of other pharmaceutical agents: the middle age group of 40-49 years (p<0.001). Of 15,908 in-depth toxic surveillance patients, 693 patients had AAP poisoning, of whom 377 cases (54.2%) purchased acetaminophen from a non-pharmacy. The proportions of the purchase path from non-pharmacy were 41.4% at 2011-12 and 56.4% (2013-18) (p=0.004). The amount of acetaminophen ingestion was 13.5±14.3 g at 2011-12 and 13.9±15.1 g at 2013-18 (p=0.794). Conclusion: Although the incidence of acetaminophen poisoning did not increase remarkably in the short term after the implementation of the new regulation, the incidence of acetaminophen poisoning has increased slightly during the study period of 2017-18. In addition, the proportion of the purchase path from non-pharmacies has increased since the emergence of new regulations for the easy access of acetaminophen in 2012. The incidence of acetaminophen poisoning might have been affected after the increasing accessibility of acetaminophen in convenience stores. Continuous control of acetaminophen poisoning is required. Furthermore, the prevention of acetaminophen poisoning should be focused on teenagers with specialized school education programs.

Citations

Citations to this article as recorded by

Analysis of 2011-2020 intentional drug poisoning in children and adolescents
Jin Seok Park, Jin Seong Cho, Jae-Hyug Woo, Jae Ho Jang, Woo Sung Choi, Yong Su Lim, Jea Yeon Choi
Pediatric Emergency Medicine Journal.2023; 10(4): 132. CrossRef

Elevation of Procalcitonin in an Adolescent Acetaminophen Intoxication: So Eun Kim, Jae Baek Lee, Young Ho Jin, Jae Chol Yoon, Si On Jo, Tae Oh Jeong; J Korean Soc Clin Toxicol. 2019;17(1):38-41. Published online June 30, 2019; DOI: https://doi.org/10.22537/jksct.2019.17.1.38

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Abstract PDF: Procalcitonin (PCT) is commonly employed in medical practice as a diagnostic biomarker of bacterial infection and also as a monitoring biomarker for antimicrobial therapy. There have been a few published reports concerning elevated PCT levels in people with acute liver injury caused by an overdose of acetaminophen. We report here on a case of PCT elevation in an adolescent with acute acetaminophen poisoning without any bacterial infection or liver injury. A 15-year-old girl had deliberately ingested 20 tablets of 650 mg acetaminophen (13 g) and she presented to our emergency department. The PCT level on admission was elevated to 65.64 ng/mL (reference range: 0-0.5 ng/mL). Her PCT level on the second day peaked up to 100 ng/mL and then it gradually decreased. There was no evidence of liver injury or infection on the computed tomography examination and other lab tests. The patient regained her good health and was discharged on the sixth day of hospitalization.

Evaluation of Cut-off Values in Acute Acetaminophen Intoxication Following the Revised Guideline of the United Kingdom: Sung Jin Park, Kyungman Cha, Byung Hak So, Hyung Min Kim, Won Jung Jeoung; J Korean Soc Clin Toxicol. 2018;16(2):68-74. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.68

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Abstract PDF: Purpose: In 2012, a revised guideline for acute acetaminophen overdose was proposed in the UK, recommending that the treatment threshold should be lowered to 100 mcg/ml at 4 hours after ingestion without risk stratification of hepatotoxicity. However, the poison centers in some developing countries do not have laboratory resources to provide serum drug levels in time. The primary aim of the study is to evaluate the cut-off value of reported dose per kilogram to determine when N-acetylcysteine treatment is warranted under the revised guideline. Methods: Data were collected retrospectively from the toxicology registry of an urban emergency medical center between 1st January 2010 and 30th June 2017. Inclusion criteria were single acute overdose of more than 75 mg/kg in 15 hours from ingestion and over 14 years of age. Subgroups were created by 25 mg/kg increments of reported dose, then sensitivity, specificity, positive predictive value and negative predictive value were calculated for the cut-off values of 100 mg/kg, 125 mg/kg, 150 mg/kg and 175 mg/kg for toxic serum level over '100-treatment line'. Results: A total of 99 patients were enrolled in the study; 24 patients showed toxic serum levels (24.2%). Zero of 17 patients with an ingestion dose under 100 mg/kg showed toxic level (0%), and 0 of 15 under 125 mg/kg (0%), 2 of 14 under 150 mg/kg (14.3%), and 4 of 12 under 175 mg/kg (33.3%) had toxic levels. The higher the ingested dose per kilogram of weight, the higher the frequency of the toxic serum concentration on the first test (${chi}^2$ test for trend, ${chi}^2=22.66$, p-value<0.001) and the sensitivity of each value was 100%, 100%, 92% and 76%. Conclusion: In acute single acetaminophen intoxication, the ingestion dose of 100 mg/kg of weight will be useful in determining the need for the N-acetylcysteine antidote in the indigent laboratory environment.

Usefulness of Predictors for Hepatotoxicity in Acetaminophen Poisoning Patient: Eun Young Kim, Sung Phil Chung, Dong Ryul Ko, Tae Young Kong, Je Sung You, Min Hong Choa, Min Joung Kim; J Korean Soc Clin Toxicol. 2018;16(2):149-156. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.149

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Abstract PDF: Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.

Pharmaceutical Drug Poisoning after Deregulation of Over the Counter Drug Sales: Emergency Department Based In-depth Injury Surveillance: Sung Ho Kim, Hyunjong Kim, Ji Sook Lee, Junseok Park, Kyung Hwan Kim, Dong Wun Shin, Hoon Kim, Joon Min Park, Woochan Jeon; J Korean Soc Clin Toxicol. 2018;16(2):141-148. Published online December 31, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.2.141

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Abstract PDF: Purpose: The Korean government approved selected nonprescription drugs (Over-The-Counter drug; OTC drug) to be distributed in convenience stores from 15. Nov. 2012. This study examined the changes in the incidence and the clinical outcome of acute pharmaceutical drug poisoning after the deregulation of OTC drug sales. Methods: This study analyzed the data of Emergency Department based Injury In-depth Injury Surveillance (EDIIS), Korea Centers for Disease Control and Prevention, from 2011 to 2014. The following items were examined: age, gender, intention, alcohol association, pharmaceutical drugs resulting acute poisoning, the clinical outcomes in emergency department, and the admission rate of intensive care unit (ICU). This is a retrospective cross section observational study. Results: A total of 10,162 patients were subject to pharmaceutical drug poisoning. Acute poisoning by acetaminophen and other drugs were 1,015 (10.0%) and 9,147 (90.0%) patients, respectively. After the deregulation of OTC drug sales, acute poisoning by other drugs increased from 4,385 to 4,762 patients but acute poisoning by acetaminophen decreased from 538 to 477 patients (p<0.05). The rate of admission of acetaminophen poisoning increased from 36.1% (194/538) to 46.8% (223/477). The admission rate to the ICU by acetaminophen poisoning increased from 4.6% (25/538) to 11.3% (54/477) after the deregulation of OTC drug sales (p<0.05). Conclusion: Since the deregulation of OTC drugs sales, pharmaceutical drug poisoning has increased but acetaminophen poisoning has decreased. The rate of hospitalization and ICU admission by pharmaceutical drug poisoning with or without acetaminophen has also increased.

Changes in Toxicological Characteristics after Sales of Nonprescription Drugs in Convenience Stores: Chang Yeong Kim, Eui Jung Lee, Sung Woo Lee, Su Jin Kim, Kap Su Han; J Korean Soc Clin Toxicol. 2018;16(1):42-48. Published online June 30, 2018; DOI: https://doi.org/10.22537/jksct.2018.16.1.42

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Abstract PDF: Purpose: On November 15, 2012, sales of OTC (Over-The-Counter) drugs began at convenience stores, which changed the accessibility of some drugs. As a result, the exposure and access patterns of these drugs could have changed. In this study, we reviewed the changes in the characteristics of drug poisoning patients because of the reposition of nonprescription drugs according to the revised Pharmaceutical Affairs Act. Methods: A retrospective study was conducted to evaluate changes in characteristics of drug poisoning patients between 2008 and 2016. A registry was developed by an emergency medical center in a local tertiary teaching hospital, and patients who visited the center were enrolled in this registry. We compared two periods, from 2008 to 2012 (Pre OTC) and from 2013 to 2016 (Post OTC), for type of intoxicant, time from poisoning to visiting the emergency center, intention, psychiatric history, previous suicidal attempt, alcohol status, and emergency room outcomes. The primary outcome was the number of patients who took acetaminophen and NSAIDs (nonsteroidal anti-inflammatory drugs). Secondary outcomes were ICU admission rate, mortality rate, and number of patients who visited the ER when the pharmacy was closed after taking acetaminophen and NSAIDs (nonsteroidal anti-inflammatory drugs). Results: Among 1,564 patients, 945 and 619 patients visited the emergency room during pre and post OTC periods. The number of patients with acetaminophen and NSAIDs poisoning decreased from 9.2% to 6.1% (p=0.016). The ICU admission rate and mortality rate in the emergency room did not show significant results in the relevant patient groups, and so was the number of patients visiting ER when the pharmacy was closed taking acetaminophen and NSAIDs. Conclusion: Despite the sales of nonprescription drugs at convenience stores, the number of acetaminophen and NSAIDs poisoning patients decreased.

Is it Adequate to Determine Acetaminophen Toxicity Solely on Patients' History? An Analysis on Clinical Manifestation of Intoxication Patients with Positive Serum Acetaminophen Concentrations: Jee Hyun Kim, Won-joon Jeong, Seung Ryu, Yong Chul Cho, Jang Hyuck Moon, Hyun Soo Choi, Song Hee Yang, Hee Sun Chung; J Korean Soc Clin Toxicol. 2017;15(2):94-100. Published online December 31, 2017; DOI: https://doi.org/10.22537/jksct.2017.15.2.94

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Abstract PDF: Purpose: Acute acetaminophen intoxication is a common occurrence that can cause lethal complications. In most domestic emergency departments, clinicians tend to treat acetaminophen intoxication based on patients' history alone, simply due to the lack of a rapid acetaminophen laboratory test. We performed a 20-month study of intoxication patients to determine the correlation between the history of patients and serum laboratory tests for acetaminophen. Methods: We took blood samples from 280 intoxication patients to evaluate whether laboratory findings detected traces of acetaminophen in the sample. Patients were then treated according to their history. Laboratory results came out after patients' discharge. Agreement between patients' history and laboratory results were analyzed. Results: Among the 280 intoxicated patients enrolled, 38 patients had positive serum acetaminophen concentrations; 18 out of 38 patients did not represent a history suggesting acetaminophen intoxication. One patient without the history showed toxic serum acetaminophen concentration. Among the patients with the history, two patients with toxic serum acetaminophen concentration did not receive N-acetylcysteine (NAC) treatment due to their low reported doses, while other 2 patients without significant serum acetaminophen concentration did receive NAC treatment due to their high reported doses. Conclusion: This study showed a good overall agreement between history and laboratory test results. However, some cases showed inconsistencies between their history and laboratory test results. Therefore, in treating intoxication patients, a laboratory test of acetaminophen with rapid results should be available in most domestic emergency departments.

A Case of Acute Hepatic Failure due to Acetaminophen Overdose Treated with Molecular Adsorbents Recirculating System$^{(R)}$: Byung Keun Yang, Je Sung You, Young Seon Joo, Sung Phil Chung, Hahn Schick Lee; J Korean Soc Clin Toxicol. 2014;12(1):31-34. Published online June 30, 2014

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Abstract PDF: We report on a patient who developed acute hepatic failure despite intravenous N-acetyl cysteine therapy who was treated with the Molecular Adsorbents Recirculating System (MARS). She presented 20 hours after the ingestion of 13 g of acetaminophen. The MARS is based on albumin dialysis principle which can be applied for patients with acute poisoning from drugs that have high protein-binding capacity because of its ability to selectively remove from circulation protein-bound toxins. The clinical toxicologist should be consider this technology when treating patients with hepatic failure following acetaminophen poisoning.

Oral vs. Intravenous Administration of N-acetylcysteine in the Acetaminophen Poisoning: Hyo Ju Chae, Nu Ga Rhee, Hyun Jong Kim, Je Sung You, Sung Phil Chung, Hahn Shick Lee; J Korean Soc Clin Toxicol. 2012;10(2):97-102. Published online December 31, 2012

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Abstract PDF: Purpose: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. Methods: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. Results: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. Conclusion: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.

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.

Acetaminophen Poisoning: Sung-Pil Chung, Seung-Ho Kim, Hahn-Shick Lee; J Korean Soc Clin Toxicol. 2008;6(1):1-8. Published online June 30, 2008

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Abstract PDF: Acetaminophen (AAP) overdose can result in potentially serious hepatotoxicity. The ingested dose and time from ingestion to presentation are important prognostic factors. Toxic dose in adult is thought to be at least 10 g or 200 mg/kg. However, early management of acute overdose should be guided by the plasma AAP concentration. The antidote for AAP poisoning is N-acetylcysteine (NAC). It provides complete protection against hepatotoxicity if given within 8 h of acute overdose. If the concentration is above the possible toxicity line as predicted by the Rumack-Matthew nomogram, either the 72-hr oral or the 20-hr intravenous NAC regimen should be administered. NAC is also effective if started late in patients with established hepatic failure. This article summarizes the current consensus of clinical assessment and management for acute AAP overdose.

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