Journal of The Korean Society of Clinical Toxicology (대한임상독성학회지)

Korean society of Clincal Toxicology (대한임상독성학회)
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Predicting serum acetaminophen concentrations in acute poisoning for safe termination of N-acetylcysteine in a resource-limited environment

약물농도를 알 수 없는 환경에서 acetaminophen 급성 중독환자의 안전한 N-acetylcysteine 치료 종료를 위한 혈중약물 검출 예측

  • Dahae Kim (Department of Emergency Medicine, St. Vincent's Hospital) ;
  • Kyungman Cha (Department of Emergency Medicine, St. Vincent's Hospital) ;
  • Byung Hak So (Department of Emergency Medicine, St. Vincent's Hospital)
  • 김다해 (가톨릭대학교 성빈센트병원 응급의학과) ;
  • 차경만 (가톨릭대학교 성빈센트병원 응급의학과) ;
  • 소병학 (가톨릭대학교 성빈센트병원 응급의학과)
  • Received : 2023.09.26
  • Accepted : 2023.10.18
  • Published : 2023.12.31
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Abstract

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.

Keywords

Acknowledgement

본 연구를 위한 독성 데이터 수집에 헌신적인 노력을 해 준 성빈센트병원 응급의료센터 조은수 선생님께 본 지면을 빌어 깊은 감사를 전한다.

References

  1. Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871-6. https://doi.org/10.1542/peds.55.6.871
  2. Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002;40:3-20. https://doi.org/10.1081/clt-120002882
  3. Medicine and Healthcare Products Regulatory Agency, The Commission on Human Medicines. Paracetamol overdose: simplification of the use of intravenous acetylcysteine [Internet]. London: Medicine and Healthcare Products Regulatory Agency; 2012 [cited 2023 Sep 20]. Available from: https://webarchive.nationalarchives.gov.uk/20150110162216/http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON178225
  4. Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012;50:91-8. https://doi.org/10.3109/15563650.2012.659252
  5. Koppen A, van Riel A, de Vries I, Meulenbelt J. Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine. Neth J Med 2014;72:251-7.
  6. Bateman DN, Dear JW. Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use. Toxicol Res (Camb) 2019;8:489-98. https://doi.org/10.1039/c9tx00002j
  7. Senarathna SM, Sri Ranganathan S, Buckley N, Fernandopulle R. A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka. BMC Clin Pharmacol 2012;12:6. https://doi.org/10.1186/1472-6904-12-6
  8. Duffull SB, Isbister GK. Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. Clin Toxicol (Phila) 2013;51:772-6. https://doi.org/10.3109/15563650.2013.830733
  9. Jeong HH, Cha K, Choi KH, So BH. Evaluation of cut-off values in acute paracetamol overdose following the United Kingdom guidelines. BMC Pharmacol Toxicol 2022;23:5. https://doi.org/10.1186/s40360-021-00547-1
  10. University Hospital of Leicester NHS Trust. Paracetamol poisoning: performa to guide ED management of oral ingestion in adults [Internet]. Leicester: University Hospital of Leicester NHS Trust; 2023 [cited 2023 Oct 7]. Available from: https://secure.library.leicestershospitals.nhs.uk/PAGL/Shared%20Documents/Paracetamol%20Overdose%20UHL%20Emergency%20Department%20Guideline.pdf
  11. University Hospital of Leicester NHS Trust. Paracetamol poisoning in adults and children [Internet]. Leicester: University Hospital of Leicester NHS Trust; 2023 [cited 2023 Oct 7]. Available from: https://secure.library.leicestershospitals.nhs. uk/PAGL/Shared%20Documents/Paracetamol%20Overdose%20UHL%20Guideline.pdf
  12. Department of Health and Human Services, Food and Drug Administration. The new drug application for the use of Acetadote (acetylcysteine) injection [Internet]. Silver Spring (MD): Food and Drug Administration; 2004 [cited 2023 Sep 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/21539ltr.pdf
  13. Department of Health and Human Service, Food and Drug Administration. Intravenous N-acetylcysteine [Internet]. Silver Spring (MD): Food and Drug Administration; 2004 [cited 2023 Sep 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21539_N-acetylcysteine_lbl.pdf
  14. Critchley JA, Nimmo GR, Gregson CA, Woolhouse NM, Prescott LF. Inter-subject and ethnic differences in paracetamol metabolism. Br J Clin Pharmacol 1986;22:649-57. https://doi.org/10.1111/j.1365-2125.1986.tb02953.x
  15. Lee HS, Ti TY, Koh YK, Prescott LF. Paracetamol elimination in Chinese and Indians in Singapore. Eur J Clin Pharmacol 1992;43:81-4. https://doi.org/10.1007/BF02280759
  16. Critchley JA, Critchley LA, Anderson PJ, Tomlinson B. Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects. J Clin Pharm Ther 2005;30:179-84. https://doi.org/10.1111/j.1365-2710.2004.00626.x