重症肺部感染患者多西环素血药浓度与凝血功能指标的相关性研究OA
Study on the Correlation between Doxycycline Blood Concentration and Coagulation Function Indicators in Patients with Severe Pulmonary Infection
目的 探讨重症肺部感染患者多西环素稳态血药浓度与凝血功能指标的相关性,为临床个体化给药提供依据.方法 前瞻性纳入2023 年 1 月至2025 年 1 月我院 ICU收治的重症肺部感染患者 110 例,根据是否使用多西环素分为观察组(n=60)和对照组(n=50).观察组于给药第3天测定稳态峰浓度(C0)及谷浓度(C0),动态监测两组治疗前及治疗第 3、7 天的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、国际标准化比值(INR)及血小板计数(PLT).采用Pearson 相关、多元线性回归分析血药浓度与凝血指标的关系.结果 观察组治疗第 3 天PT、APTT、INR较基线显著升高(P<0.05),FIB、PLT显著降低(P<0.05),第7天恢复至基线水平;对照组各指标治疗前后差异无统计学意义(P>0.05).观察组多西环素 C2 为(3.28±1.15)μg/mL,C0 为(1.46±0.62)μg/mL.C0 与ΔPT、ΔAPTT、ΔINR呈显著正相关(r=0.582、0.517、0.603,P<0.001),与 ΔFIB、ΔPLT 呈显著负相关(r=-0.493、-0.446,P<0.01);C0 与各指标无显著相关.多元回归显示,多西环素 C2(β=0.412)、联用头孢哌酮舒巴坦(β=0.306)、基线APTT延长(β=0.251)是 PT升高的独立危险因素(P<0.05).结论 多西环素可导致重症肺部感染患者一过性凝血功能异常,其影响程度与稳态峰浓度呈显著正相关,当 C0>3.95 μg/mL 时凝血功能障碍风险显著增加.建议临床开展血药浓度监测,避免与头孢哌酮舒巴坦联用.
Objective To explore the correlation between doxycycline steady-state blood drug concentration and coagulation function indicators in patients with severe pulmonary infections,providing a basis for clinical individualized medication.Method A total of 110 patients with severe pulmonary infections admitted to our ICU from January 2023 to January 2025 were prospectively included and divided into an observation group(n=60)and a control group(n=50)based on whether doxycycline was used or not.On the third day of administration,the observation group measured the steady-state peak concentration(C0)and trough concentration(C0),and dynamically monitored the prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),fibrinogen(FIB),international normalized ratio(INR),and platelet count(PLT)of both groups before treatment and on the third and seventh days of treatment.Pearson correlation and multiple linear regression were used to analyze the relationship between blood drug concentration and coagulation indicators.Result On the third day of treatment,PT,APTT,and INR in the observation group significantly increased compared to baseline(P<0.05),while FIB and PLT significantly decreased(P<0.05).On the seventh day,they returned to baseline levels;There was no significant difference in the indicators of the control group before and after treatment(P>0.05).The observation group's doxycycline C2 was(3.28±1.15)μg/mL,and C0 was(1.46±0.62)μg/mL.C2is significantly positively correlated withΔPT,ΔAPTT,and ΔINR(r=0.582,0.517,0.603,P<0.001),and significantly negatively correlated with ΔFIB and ΔPLT(r=-0.493,-0.446,P<0.01);There is no significant correlation between C0 and various indicators.Multiple regression analysis showed that doxycycline C0(β=0.412),combined use of cefoperazone sulbactam(β=0.306),and baseline APTT prolongation(β=0.251)were independent risk factors for PT elevation(P<0.05).Conclusion Doxycycline can cause transient coagulation dysfunction in patients with severe pulmonary infections,with the degree of impact significantly correlated with the steady-state peak concentration.When C0>3.95 μg/mL,the risk of coagulation dysfunction increases significantly.It is recommended to monitor blood drug concentrations clinically and avoid concomitant use with cefoperazone-sulbactam.
张沛;李楠;韩佳琳
郑州市第一人民医院药学部,河南 郑州 450000郑州市第一人民医院药学部,河南 郑州 450000郑州市第一人民医院药学部,河南 郑州 450000
医药卫生
多西环素重症肺部感染血药浓度凝血功能治疗药物监测
doxycyclinesevere pulmonary infectionblood drug concentrationcoagulation functiontherapeutic drug monitoring
《哈尔滨医药》 2026 (2)
7-10,4
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