Gudivada Kiran Kumar, Krishna Bhuvana, Sampath Sriram
Department of Critical Care Medicine, St John's Medical College and Hospital, Bengaluru, Karnataka, India.
Indian J Crit Care Med. 2023 Mar;27(3):183-189. doi: 10.5005/jp-journals-10071-24417.
N-methylthiotetrazole side chain (NMTT) of cefoperazone was attributed to inhibit the vitamin K epoxide enzyme. This mechanism is similar to warfarin; thus, vitamin K was suggested to antagonize the hematological effects of cefoperazone. The literature on critically ill patients receiving cefoperazone and its clinical significance on bleeding diathesis is sparse.
To assess the incidence of cefoperazone-induced coagulopathy (CIC), its clinical impact on bleeding episodes, and transfusion requirements. Predisposing factors and the role of prophylactic and therapeutic vitamin K were evaluated.
Prospective observational study of adult intensive care unit (ICU) patients (>18 years) receiving cefoperazone between December 2017 and December 2018. We excluded those on warfarin, those with preexisting elevated /international normalized ratio (PT/INR), and with bleeding manifestations. Relevant laboratory investigations and specific outcomes were noted for 6 days following therapy. Panel data regression was used to determine predictors of coagulopathy.
Among 65 patients, 17 (26%) had probable CIC. Hypoalbuminemia and vancomycin co-administration were risk factors for CIC. Hemoglobin drops and blood transfusions were not different between INR non-elevated and elevated groups (11 vs 8 gm/dL; = 0.06 and 11 vs 8 units; = 0.23, respectively). Prophylactic vitamin K did not offer any benefit toward preventing INR elevation. Therapeutic vitamin K significantly reduced INR when elevated [absolute risk reduction (ARR):57.5% and number needed to treat (NNT):1.7].
Results of this study revealed that CIC is not uncommon in ICUs. Based on the findings of the study, we suggest INR monitoring in patients receiving nephrotoxic agents and patients with hypoalbuminemia. We also recommend vitamin K administration in patients with elevated INR.
Gudivada KK, Krishna B, Sampath S. Cefoperazone-induced Coagulopathy in Critically Ill Patients Admitted to Intensive Care Unit. Indian J Crit Care Med 2023;27(3):183-189.
头孢哌酮的N-甲基硫代四唑侧链（NMTT）被认为可抑制维生素K环氧还原酶。该机制与华法林相似；因此，有人提出维生素K可拮抗头孢哌酮的血液学效应。关于重症患者接受头孢哌酮治疗及其对出血素质的临床意义的文献较少。
评估头孢哌酮诱导的凝血病（CIC）的发生率、其对出血事件的临床影响以及输血需求。评估了易感因素以及预防性和治疗性维生素K的作用。
对2017年12月至2018年12月期间接受头孢哌酮治疗的成人重症监护病房（ICU）患者（>18岁）进行前瞻性观察研究。我们排除了服用华法林的患者、既往凝血酶原时间/国际标准化比值（PT/INR）升高的患者以及有出血表现的患者。治疗后6天记录相关实验室检查和特定结局。采用面板数据回归确定凝血病的预测因素。
65例患者中，17例（26%）可能发生CIC。低白蛋白血症和联合使用万古霉素是CIC的危险因素。INR未升高组和升高组之间的血红蛋白下降和输血情况无差异（分别为11 vs 8 g/dL；P = 0.06和11 vs 8单位；P = 0.23）。预防性维生素K对预防INR升高无任何益处。治疗性维生素K在INR升高时可显著降低INR[绝对风险降低率（ARR）：57.5%，治疗所需人数（NNT）：1.7]。
本研究结果显示，CIC在ICU中并不少见。基于本研究结果，我们建议对接受肾毒性药物治疗的患者和低白蛋白血症患者进行INR监测。我们还建议对INR升高的患者给予维生素K治疗。
Gudivada KK, Krishna B, Sampath S. 重症监护病房收治的重症患者中头孢哌酮诱导的凝血病。《印度重症监护医学杂志》2023；27(3):183 - 189。
