丙帕他莫相关术后肝酶异常: 临床预测列线图模型研究

doi:10.5246/jcps.2025.04.025

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (4): 334-344.DOI: 10.5246/jcps.2025.04.025

丙帕他莫相关术后肝酶异常: 临床预测列线图模型研究

梁淑红¹, 孟海阳¹, 孔凯², 康超颖³, 刘宁⁴, 袁倩倩⁵, 杨杰¹^,^*()

^1. 郑州大学第一附属医院药学部, 河南郑州 450000
^2. 虞城县第二人民医院药剂科, 河南商丘 476299
^3. 浚县中医院药剂科, 河南鹤壁 456250
^4. 安阳殷都区人民医院药剂科, 河南安阳 455004
^5. 兰考县中心医院药剂科, 河南开封 475399

收稿日期:2024-11-13 修回日期:2025-01-23 接受日期:2025-02-18 出版日期:2025-05-02 发布日期:2025-05-02
通讯作者: 杨杰

Propacetamol-related postoperative liver enzyme abnormalities: insights from a clinical prediction nomogram study

Shuhong Liang¹, Haiyang Meng¹, Kai Kong², Chaoying Kang³, Ning Liu⁴, Qianqian Yuan⁵, Jie Yang¹^,^*()

¹ Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China
² Department of Pharmacy, Yucheng County Second People’s Hospital, Shangqiu 476299, Henan, China
³ Department of Pharmacy, Xunxian Traditional Chinese Medicine Hospital, Hebi 456250, Henan, China
⁴ Department of Pharmacy, Anyang Yindu District People’s Hospital, Anyang 455004, Henan, China
⁵ Department of Pharmacy, Lankao County Central Hospital, Kaifeng 475399, Henan, China

Received:2024-11-13 Revised:2025-01-23 Accepted:2025-02-18 Online:2025-05-02 Published:2025-05-02
Contact: Jie Yang
Supported by:
The Medical Education Research Program of Henan Province, China (Grant No. WJLX2023015) and the Chinese International Medical Foundation for Clinical Pharmacy, China (Grant No. Z-2021-46-2101).

摘要/Abstract

摘要：

本文探讨应用丙帕他莫与患者出现术后肝酶异常之间的关系。对2023年1月至6月郑州大学第一附属医院胸外科757例住院患者进行回顾性分析, 通过更新的RUCAM量表评估患者应用丙帕他莫与发生术后肝酶异常之间的因果关系, 通过单因素和多因素分析, 建立术后肝酶异常的临床预测模型并进行验证。研究共纳入247例患者, 丙帕他莫日剂量(OR (95% CI), 4.831 (2.797, 8.344), P < 0.001)与术后用药数量(OR (95% CI), 10.007 (3.878, 25.823), P < 0.001)是两个独立危险因素, 据此建立的临床预测模型具有满意的区分度(AUC (95% CI), 0.811 (0.750, 0.872))和校准度, 以及良好的临床适用度(10% to 90%)。丙帕他莫日剂量与术后用药数量是患者发生术后肝酶异常的独立危险因素, 预测模型为临床提供了一个评估和降低术后肝酶异常风险的工具。

关键词: 丙帕他莫, 列线图, 肝酶异常, 围术期, 药物性肝损伤

Abstract:

To investigate the correlation between propacetamol and postoperative liver enzyme abnormalities among patients, a retrospective analysis was conducted on inpatients in the thoracic surgery department spanning from January 1 to June 30, 2023. Causality assessment regarding propacetamol and postoperative liver enzyme abnormalities was performed using the updated Roussel Uclaf Causality Assessment Method (RUCAM). Furthermore, independent risk factors for liver enzyme abnormalities were identified through both univariate and multivariate analyses, followed by the construction and validation of a clinical nomogram. A total of 247 patients who received propacetamol were ultimately included in the study. Liver enzyme abnormalities post-surgery were more accurately predicted by considering the daily dose of propacetamol and the number of medications (OR (95% CI), 4.831 (2.797, 8.344), P < 0.001; 10.007 (3.878, 25.823), P < 0.001). A clinical predictive nomogram model was developed, incorporating these two independent risk factors, which exhibited favorable discrimination (AUC (95% CI), 0.811 (0.750, 0.872)), calibration, and decision curve analysis (DCA) demonstrating the highest net benefits across a broad spectrum of threshold probabilities (10% to 90%). The daily dose of propacetamol and the number of medications were found to be independently associated with postoperative liver enzyme abnormalities. This user-friendly nomogram, comprising these two factors, might assist clinicians in assessing the risks of propacetamol-related liver dysfunction following surgery.

Key words: Propacetamol, Nomogram, Liver enzyme abnormalities, Postoperative period, Drug-induced liver injury

Supporting:

梁淑红, 孟海阳, 孔凯, 康超颖, 刘宁, 袁倩倩, 杨杰. 丙帕他莫相关术后肝酶异常: 临床预测列线图模型研究[J]. 中国药学(英文版), 2025, 34(4): 334-344.

Shuhong Liang, Haiyang Meng, Kai Kong, Chaoying Kang, Ning Liu, Qianqian Yuan, Jie Yang. Propacetamol-related postoperative liver enzyme abnormalities: insights from a clinical prediction nomogram study[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(4): 334-344.

图/表 7

Figure 1. Enrollment illustration of patients treated with propacetamol in the postoperative period in the study.

Table 1. Characteristics of the 247 patients enrolled in the study.

Table 2. Multivariate logistic regression analysis of the predictors.

Figure 2. A nomogram is developed with the daily dose of propacetamol and the number of medications for predicting abnormal liver enzymes after surgery.

Figure 3. ROC curve (a) and a 500 bootstrap ROC curve (b) of the nomogram for predicting abnormal liver enzymes after surgery. AUC: area under the curve; CI: confidence interval.

Figure 4. Calibration curve of the nomogram. The y-axis represents the actual probabilities, and the x-axis represents nomogram-predicted probabilities. The black dashed line represents a perfect prediction by an ideal model. The red and blue solid lines (nomogram and bias-corrected model) have a closer fit to the black dashed line, indicating a good prediction of our nomogram.

Figure 5. Clinical DCA for the nomogram. The y-axis measures the net benefit, and the x-axis shows the threshold probability. Threshold probability was the minimum probability at which further intervention would be warranted. The red line presents the nomogram. The yellow line presents the model with the daily dose of propacetamol. The green line presents the model with the number of medications.

参考文献 40

[1]	Hyzny, E.J.; Chan, E.G.; Morrell, M.; Harano, T.; Sanchez, P.G. A review of liver dysfunction in the lung transplant patient. Clin. Transplant. 2021, 35, e14344.
[2]	Diab, M.; Sponholz, C.; von Loeffelholz, C.; Scheffel, P.; Bauer, M.; Kortgen, A.; Lehmann, T.; Färber, G.; Pletz, M.W.; Doenst, T. Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients. Infection. 2017, 45, 857–866.
[3]	Chacon, M.; Schulte, T.E. Liver dysfunction in cardiac surgery - what causes it and is there anything we can do? J. Cardiothorac. Vasc. Anesth. 2018, 32, 1719–1721.
[4]	Nazer, R.I.; Alburikan, K.A.; Ullah, A.; Albarrati, A.M.; Hassanain, M. Transient liver dysfunction increases surgical site infections after coronary surgery. Asian Cardiovasc. Thorac. Ann. 2018, 26, 439–445.
[5]	Gupta, R.; Kaman, L.; Dahiya, D.; Gupta, N.; Singh, R. Effects of varying intraperitoneal pressure on liver function tests during laparoscopic cholecystectomy. J. Laparoendosc. Adv. Surg. Tech. A. 2013, 23, 339–342.
[6]	M’Koma, A.E.; Longo, W.E. Postoperative liver enzyme abnormalities are related to staged restorative proctocolectomy. Int. J. Colorectal Dis. 2007, 22, 283–288.
[7]	Goldberg, D.J.; Surrey, L.F.; Glatz, A.C.; Dodds, K.; O’Byrne, M.L.; Lin, H.C.; Fogel, M.; Rome, J.J.; Rand, E.B.; Russo, P.; Rychik, J. Hepatic fibrosis is universal following fontan operation, and severity is associated with time from surgery: a liver biopsy and hemodynamic study. J. Am. Heart Assoc. 2017, 6, e004809.
[8]	Hatipoglu, S.; Yildiz, H.; Bulbuloglu, E.; Coskuner, I.; Kurutas, E.B.; Hatipoglu, F.; Ciralik, H.; Berhuni, M.S. Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice. World J. Gastroenterol. 2014, 20, 3320–3326.
[9]	Cai, X.P.; Cai, H.Q.; Cai, H.; Wang, J.; Yang, Q.; Guan, J.; Deng, J.W.; Chen, Z. Molecular pathogenesis of acetaminophen-Induced liver injury and its treatment options. J. Zhejiang Univ. Sci. B. 2022, 23, 265–285.
[10]	Stravitz, R.T.; Lee, W.M. Acute liver failure. Lancet. 2019, 394, 869–881.
[11]	Tsai, M.S.; Wang, Y.H.; Lai, Y.Y.; Tsou, H.K.; Liou, G.G.; Ko, J.L.; Wang, S.H. Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice. Toxicol. Lett. 2018, 290, 97–109.
[12]	Flouvat, B.; Leneveu, A.; Fitoussi, S.; Delhotal-Landes, B.; Gendron, A. Bioequivalence study comparing a new paracetamol solution for injection and propacetamol after single intravenous infusion in healthy subjects. Int J. Clin. Pharmacol. Ther. 2004, 42, 50–57.
[13]	McNicol, E.D.; Ferguson, M.C.; Haroutounian, S.; Carr, D.B.; Schumann, R. Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain. Cochrane Database Syst. Rev. 2016, 2019, CD007126.
[14]	Kang, S.; Durey, A.; Suh, Y.J.; Kim, A.J. Hemodynamic changes after propacetamol administration in patients with febrile UTI in the ED. Am. J. Emerg. Med. 2018, 36, 935–941.
[15]	Lee, H.J.; Suh, Y.J.; Kim, A.J.; Han, S.B.; Durey, A. Hemodynamic changes in patients with influenza A after propacetamol infusion in the emergency department. Am. J. Emerg. Med. 2018, 36, 1–4.
[16]	Picetti, E.; De Angelis, A.; Villani, F.; Antonini, M.V.; Rossi, I.; Servadei, F.; Caspani, M.L. Intravenous paracetamol for fever control in acute brain injury patients: cerebral and hemodynamic effects. Acta Neurochir. 2014, 156, 1953–1959.
[17]	Tsai, M.S.; Chien, C.C.; Lin, T.H.; Liu, C.C.; Liu, R.H.; Su, H.L.; Chiu, Y.T.; Wang, S.H. Galangin prevents acute hepatorenal toxicity in novel propacetamol-induced acetaminophen-overdosed mice. J. Med. Food. 2015, 18, 1187–1197.
[18]	Danan, G.; Teschke, R. RUCAM in drug and herb induced liver injury: the update. Int. J. Mol. Sci. 2015, 17, 14.
[19]	Common Terminology Criteria for Adverse Events (CTCAE) \| Protocol Development \| CTEP. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm (accessed 2023-11-02).
[20]	Pluchart, H.; Bailly, S.; Chanoine, S.; Moro-Sibilot, D.; Bedouch, P.; Toffart, A.C. Impact of polypharmacy and comorbidity on survival and systemic parenteral treatment administration in a cohort of hospitalized lung-cancer patients. BMC Cancer. 2023, 23, 585.
[21]	Nightingale, G.; Hajjar, E.; Swartz, K.; Andrel-Sendecki, J.; Chapman, A. Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer. J. Clin. Oncol. 2015, 33, 1453–1459.
[22]	Chalasani, N.P.; Maddur, H.; Russo, M.W.; Wong, R.J.; Reddy, K.R.; Practice Parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am. J. Gastroenterol. 2021, 116, 878–898.
[23]	Bozdogan, H. Akaike’s information criterion and recent developments in information complexity. J. Math. Psychol. 2000, 44, 62–91.
[24]	Harrell, F.; Califf, R.; Pryor, D.; Lee, K.; Rosati, R. Evaluating the yield of medical tests. JAMA. 1982, 247, 2543–2546.
[25]	Harrell, F.E.; Lee, K.L.; Mark, D.B. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat. Med. 1996, 15, 361–387.
[26]	Kramer, A.A.; Zimmerman, J.E. Assessing the calibration of mortality benchmarks in critical care: The Hosmer-Lemeshow test revisited. Crit. Care Med. 2007, 35, 2052–2056.
[27]	Balachandran, V.P.; Gonen, M.; Smith, J.J.; DeMatteo, R.P. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015, 16, e173–e180.
[28]	Collins, G.S.; Reitsma, J.B.; Altman, D.G.; Moons, K.G.M. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ. 2015, 350, g7594.
[29]	Reuben, A.; Tillman, H.; Fontana, R.J.; Davern, T.; McGuire, B.; Stravitz, R.T.; Durkalski, V.; Larson, A.M.; Liou, I.; Fix, O.; Schilsky, M.; McCashland, T.; Hay, J.E.; Murray, N.; Shaikh, O.S.; Ganger, D.; Zaman, A.; Han, S.B.; Chung, R.T.; Smith, A.; Brown, R.; Crippin, J.; Harrison, M.E.; Koch, D.; Munoz, S.; Reddy, K.R.; Rossaro, L.; Satyanarayana, R.; Hassanein, T.; Hanje, A.J.; Olson, J.; Subramanian, R.; Karvellas, C.; Hameed, B.; Sherker, A.H.; Robuck, P.; Lee, W.M. Outcomes in adults with acute liver failure between 1998 and 2013. Ann. Intern. Med. 2016, 164, 724.
[30]	Lee, W.M. Acetaminophen (APAP) hepatotoxicity—Isn’t it time for APAP to go away? J. Hepatol. 2017, 67, 1324–1331.
[31]	Hayward, K.L.; Powell, E.E.; Irvine, K.M.; Martin, J.H. Can paracetamol (acetaminophen) be administered to patients with liver impairment? Br. J. Clin. Pharmacol. 2016, 81, 210–222.
[32]	Clarke, R.S.J.; Doggart, J.R.; Lavery, T. Changes in liver function after different types of surgery. Br. J. Anaesth. 1976, 48, 119–128.
[33]	Reuben, A.; Koch, D.G.; Lee, W.M.; Acute liver failure study group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatol. Baltim. Md. 2010, 52, 2065–2076.
[34]	Nguyen, N.T.; Braley, S.; Fleming, N.W.; Lambourne, L.; Rivers, R.; Wolfe, B.M. Comparison of postoperative hepatic function after laparoscopic versus open gastric bypass. Am. J. Surg. 2003, 186, 40–44.
[35]	Smilkstein, M.J.; Knapp, G.L.; Kulig, K.W.; Rumack, B.H. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N. Engl. J. Med. 1988, 319, 1557–1562.
[36]	Rumack, B.H. Acetaminophen hepatotoxicity: the first 35 years. J. Toxicol. Clin. Toxicol. 2002, 40, 3–20.
[37]	McGill, M.R.; Hinson, J.A. The development and hepatotoxicity of acetaminophen: reviewing over a century of progress. Drug Metab. Rev. 2020, 52, 472–500.
[38]	McGill, M.R.; Jaeschke, H. Mechanistic biomarkers in acetaminophen-induced hepatotoxicity and acute liver failure: from preclinical models to patients. Expert Opin. Drug Metab. Toxicol. 2014, 10, 1005–1017.
[39]	Schwarz, C.C.; Plass, I.; Fitschek, F.; Mittlböck, M.; Kampf, S.; Asenbaum, U.; Starlinger, P.; Stremitzer, S.; Bodingbauer, M.; Kaczirek, K. Value of indocyanine green clearance assessment to predict postoperative liver dysfunction in patients undergoing liver resection. J. Am. Coll. Surg. 2018, 227, S183.
[40]	Granieri, S.; Bracchetti, G.; Kersik, A.; Frassini, S.; Germini, A.; Bonomi, A.; Lomaglio, L.; Gjoni, E.; Frontali, A.; Bruno, F.; Paleino, S.; Cotsoglou, C. Preoperative indocyanine green (ICG) clearance test: Can we really trust it to predict post hepatectomy liver failure? A systematic review of the literature and meta-analysis of diagnostic test accuracy. Photodiagn. Photodyn. Ther. 2022, 40, 103170.

丙帕他莫相关术后肝酶异常: 临床预测列线图模型研究

Propacetamol-related postoperative liver enzyme abnormalities: insights from a clinical prediction nomogram study

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 40

相关文章 2

编辑推荐

Metrics

本文评价

[1]	靳永文, 席莉莉, 魏玉辉, 武新安. 基于大鼠血清胆酸盐水平构建药物性肝损伤随机森林分类模型[J]. 中国药学(英文版), 2022, 31(9): 677-688.
[2]	沈洁, 杨凯, 孙彩华, 蒋程, 郑敏霞. 含何首乌的中成药致肝损伤的临床分析[J]. 中国药学(英文版), 2022, 31(4): 289-297.