柠檬酸盐抗凝技术在危重烧伤脓毒症患者床旁连续性血液净化中的应用效果

Effects of application of citrate anticoagulation burn patients with sepsis

目的观察柠檬酸盐抗凝技术在危重烧伤脓毒症患者床旁连续性血液净化（CBP）中的应用效果，为该类患者CBP治疗中抗凝剂的选择提供参考。方法2014年1月—2017年7月，笔者单位烧伤重症监护病房收治符合入选标准的危重烧伤脓毒症患者30例。按照计算机随机法将患者分为肝素组和柠檬酸盐组，每组15例。2组患者均接受床旁CBP治疗，肝素组患者采用局部肝素抗凝，柠檬酸盐组患者采用局部柠檬酸盐抗凝。统计患者预计单次CBP治疗时间、单次CBP治疗时间、累计CBP治疗时间、CBP治疗时间达标率。监测患者治疗前后凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、国际标准化比值（INR）、纤维蛋白原（FIB）及血清降钙素原（PCT）、C反应蛋白（CRP）的变化。观察患者CBP治疗期间和治疗后创面、气管切开、动静脉置管处出血情况及其他并发症。对数据行独立样本t检验、χ2检验。结果（1）2组患者的预计单次CBP治疗时间一致。柠檬酸盐组患者单次CBP治疗时间、累计CBP治疗时间长于肝素组。柠檬酸盐组患者CBP治疗时间达标率明显高于肝素组（χ2＝16.655，P〈0.01）。（2）2组患者CBP治疗前的PT、APTT、INR、FIB、血清PCT、CRP比较，差异无统计学意义（t＝0.203、－1.006、0.203、0.039、－1.591、－0.824，P〉0.05）。柠檬酸盐组患者CBP治疗后的PT、APTT、INR、FIB分别为（14.2±1.6）s、（45±7）s、1.13±0.12、（3.5±0.6）g/L，PT、APTT明显短于肝素组的（15.5±1.4）、（53±6）s，INR明显小于肝素组的1.24±0.12，FIB明显高于肝素组的（3.0±0.6）g/L（t＝2.395、3.321、2.395、－2.427，P〈0.05或P〈0.01）。柠檬酸盐组患者CBP治疗后的血清PCT、CRP明显低于肝素组（t＝2.520、2.710，P〈0.05）。柠檬酸盐组患者CBP治疗后的血清PCT、CRP降低程度分别为（1.8±0.6）ng/mL、（143±69）mg/L，显著高于肝素组的（0.9±0.6）ng/mL、（95±50）mg/L（t＝－4.033、－2.170，P〈0.05或P〈0.01）。（3）CBP治疗期间肝素组患者共21例次出现创面出血加重；10例次新发出血，其中气管切开处2例次，动静脉置管处8例次。柠檬酸盐组患者未出现出血加重及新发出血。CBP治疗后肝素组患者未出现电解质紊乱，柠檬酸盐组1例患者出现低钙血症。结论柠檬酸盐抗凝技术应用于危重烧伤脓毒症患者床旁CBP，对全身系统凝血状态影响较小，能有效降低烧伤脓毒症炎症反应，且出血发生率低。

Objective To investigate the effects of application of citrate anticoagulation in bedside continuous blood purification （CBP） of severe burn patients with sepsis, so as to provide reference for choosing anticoagulants in CBP of these patients. Methods Thirty severe burn patients with sepsis, conforming to the study criteria, were admitted to our burn intensive care unit from January 2014 to July 2017. Patients were divided into heparin group and citrate group according to computer randomization method, with 15 cases in each group. Patients in two groups all received bedside CBP treatment. Patients in heparin group used local heparin anticoagulation, while patients in citrate group used local citrate anticoagulation. Time of predicted single-time CBP treatment, time of single-time CBP treatment, time of accumulative CBP treatment, and rate of reaching the standard of CBP treatment time were counted. Changes of prothrombin time （PT）, activated partial thromboplastin time （APTT）, international normalized ratio （INR）, fibrinogen, serum procalcitonin, and C-reactive protein （CRP） of patients before and after treatment were monitored. Hemorrhage in wounds, incision on trachea, and arteriovenous intubation point, and other complications during and after CBP treatment were observed. Data were processed with independent sample t test and chi-square test. Results （1） Time of predicted single-time CBP treatment of patients in the two groups was equal. Time of single-time CBP treatment and time of accumulative CBP treatment of patients in citrate group were longer than those in heparin group. Rate of reaching the standard of CBP treatment time of patients in citrate group was significantly higher than that in heparin group （χ2=16.655, P〈0.01）. （2） There was no statistically significant difference in PT, APTT, INR, fibrinogen, serum procalcitonin, and CRP of patients in the two groups before CBP treatment （t=0.203, -1.006, 0.203, 0.039, -1.591, -0.824, P〉0.05）. PT and APTT of patients in citrate group after CBP treatment were （14.2±1.6） and （45±7） s, respectively, significantly shorter than （15.5±1.4） and （53±6） s in heparin group （t=2.395, 3.321, P〈0.05 or P〈0.01）. INR of patients in citrate group after CBP treatment was 1.13±0.12, significantly lower than 1.24±0.12 in heparin group （t=2.395, P〈0.05）. Fibrinogen of patients in citrate group after CBP treatment was （3.5±0.6） g/L, significantly higher than （3.0±0.6） g/L in heparin group （t=-2.427, P〈0.05）. Serum procalcitonin and CRP of patients in citrate group after CBP treatment were significantly lower than those in heparin group （t=2.520, 2.710, P〈0.05）. Decreased degree of serum procalcitonin and CRP of patients in citrate group after CBP treatment were （1.8±0.6） ng/mL and （143±69） mg/L, respectively, significantly higher than （0.9±0.6） ng/mL and （95±50） mg/L in heparin group （t=-4.033, -2.170, P〈0.05 or P〈0.01）. （3） During CBP treatment, patients in heparin group experienced 21 times of exacerbation of wound hemorrhage and 10 times of new hemorrhage, including 2 times of hemorrhage at incision on trachea and 8 times of hemorrhage at arteriovenous intubation point. No exacerbation of hemorrhage or new hemorrhage happened in patients of citrate group. After CBP treatment, no electrolyte disturbance happened in patients of heparin group, but 1 patient in citrate group experienced hypocalcemia. Conclusions Application of citrate anticoagulation in bedside CBP of severe burn patients with sepsis shows light impact on systematic coagulation status, and can effectively decrease inflammation reaction of burn sepsis with low rate of hemorrhage.