Serum trough concentration threshold and risk factors of cefoperazone-induced coagulopathy in critically ill patients: A retrospective case-control study

Eur J Clin Pharmacol. 2024 May;80(5):737-746. doi: 10.1007/s00228-024-03634-4. Epub 2024 Feb 14.

Abstract

Purpose: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration.

Methods: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis.

Results: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy.

Conclusion: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction.

Keywords: Cefoperazone; Coagulopathy; Risk factors; Serum trough concentration.

MeSH terms

  • Blood Coagulation Disorders* / chemically induced
  • Case-Control Studies
  • Cefoperazone / adverse effects
  • Critical Illness
  • Humans
  • Intensive Care Units
  • Liver Diseases*
  • Retrospective Studies
  • Risk Factors
  • Vitamin K

Substances

  • Cefoperazone
  • Vitamin K