Predicting the Need for Continuation of N-acetylcysteine Treatment among Acute Paracetamol Overdose Patients with Psi Parameter

Pattaraporn  Mekavuthikul; Sunsern  Cheamanunkul; Pinsumon  Chomchai; Jariya  Phuditshinnapatra

doi:10.33192/Smj.2022.77

Authors

Pattaraporn Mekavuthikul Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
Sunsern Cheamanunkul Division of Science, Mahidol University International College, Mahidol University, Nakhon Pathom
Pinsumon Chomchai Shrewsbury International School Bangkok Riverside, Bangkok
Jariya Phuditshinnapatra Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok

DOI:

https://doi.org/10.33192/Smj.2022.77

Keywords:

Paracetamol, acute liver injury, N-acetylcysteine, prognosis, psi Introduction

Abstract

Objective: AcetaCalc was used to evaluate Psi’s accuracy in predicting cases that required prolonged NAC therapy, as well as Psi’s optimal cut-off.
Materials and Methods: This is a retrospective study of patients with acute paracetamol overdose who were treated with NAC at Siriraj Hospital between 2007 and 2016. The Psi parameter was calculated using the Acetacalc after entering paracetamol concentrations, blood sampling times, and NAC onset times. Indications for NAC continuation is in accordance with the guidelines, which recommended that NAC treatment be continued if the follow-up aminotransferase reached 50 U/L or higher.
Results: We enrolled 403 patients, the proportion of NAC prolongation was 50.4 %. Psi was shown to be a significant predictor of NAC prolongation (p < 0.001) with area under the receiver operational characteristics curve 0.766 (95% confidence interval (CI) 0.719-0.813). The Psi cutoff with highest Youden index was 1.757 mM-hour. The sensitivities and specificities of the cutoff were 0.517 (95% CI 0.449-0.585) and 0.940 (95% CI 0.898-0.965), respectively.
Conclusion: Psi parameter calculated through AcetaCalc is a useful tool for the prediction of cases where extension of NAC therapy beyond the standard regimen is indicated.

References

Chiew AL, Buckley NA. Acetaminophen Poisoning. Crit Care Clin. 2021;37(3):543-61.

Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol. 2002;40(1):3-20.

Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990;335(8705):1572-3.

Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. Bmj. 1991;303(6809):1026-9.

Chiew AL, Reith D, Pomerleau A, Wong A, Isoardi KZ, Soderstrom J, et al. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust. 2020;212(4):175-83.

Curtis RM, Sivilotti ML. A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose. Clin Toxicol (Phila). 2015;53(9):849-55.

Wong A, Graudins A. Risk prediction of hepatotoxicity in paracetamol poisoning. Clin Toxicol (Phila). 2017;55(8):879-92.

Chomchai S, Chomchai C, Anusornsuwan T. Acetaminophen psi parameter: a useful tool to quantify hepatotoxicity risk in acute acetaminophen overdose. Clin Toxicol (Phila). 2011;49(7):664-7.

Sivilotti ML, Good AM, Yarema MC, Juurlink DN, Johnson DW. A new predictor of toxicity following acetaminophen overdose based on pretreatment exposure. Clin Toxicol (Phila). 2005;43(4):229-34.

Chomchai S, Lawattanatrakul N, Chomchai C. Acetaminophen Psi Nomogram: a sensitive and specific clinical tool to predict hepatotoxicity secondary to acute acetaminophen overdose. J Med Assoc Thai. 2014;97(2):165-72.

Sivilotti ML, Yarema MC, Juurlink DN, Good AM, Johnson DW. A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. Ann Emerg Med. 2005;46(3):263-71.

Chomchai S, Chomchai C. Predicting acute acetaminophen hepatotoxicity with acetaminophen-aminotransferase multiplication product and the Psi parameter. Clin Toxicol (Phila). 2014;52(5):506-11.

Akobeng AK. Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatr. 2007;96(5):644-7.

Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.

Cairney DG, Beckwith HK, Al-Hourani K, Eddleston M, Bateman DN, Dear JW. Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol (Phila). 2016;54(5):405-10.

Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018;2(2):Cd003328.

Chomchai S, Mekavuthikul P, Phuditshinnapatra J, Chomchai C. Sensitivity of dose-estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack-Matthew Nomogram. Pharmacol Res Perspect. 2022;10(1):e00920.

Hoegberg LCG, Shepherd G, Wood DM, Johnson J, Hoffman RS, Caravati EM, et al. Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose. Clin Toxicol (Phila). 2021;59(12):1196-227.