不同剂量低分子肝素钙对慢性阻塞性肺疾病伴呼吸衰竭患者微循环的影响

Effects of Different Doses of Low Molecular Weight Heparin on Microcirculation in Patients with Chronic Obstructive Pulmonary Disease and Respiratory Failure

目的:观察不同剂量低分子肝素钙对急性加重期慢性阻塞性肺疾病(慢阻肺)伴呼吸衰竭(呼衰)患者临床疗效、微循环和肺功能指标的影响。方法:选取90例急性加重期慢阻肺伴呼衰患者进行前瞻性研究。采用随机数字表法将入选患者分为小剂量低分子肝素治疗组、中剂量治疗组与大剂量治疗组,各30例。均予常规综合治疗基础上皮下注射低分子肝素钙,大剂量组5 000IU/次,3次/天;中剂量组5 000IU/次,2次/天;小剂量组5000IU/次,1次/天,连续7天。平行观察三组临床疗效及治疗前、后微循环指标(包括管襻畸形率、白微栓数量、微血管血流速度)、血液黏度(包括全血高切、低切黏度及血浆黏度)和肺功能指标[包括第一秒用力呼气容积(FEVl)、第一秒用力呼气容积占用力肺活量百分比(FEVl/FVC)]变化以及各组出血发生率。结果:中剂量组和大剂量组的临床疗效高于小剂量组(P<0.05),中、大剂量组组间比较差异无统计学意义(P>0.05)。三组间治疗前、治疗后的甲襞微循环管襻畸形率、白微栓数量、微血管血流速度差异均无统计学意义(P>0.05);各组治疗后白微栓数量较同组治疗前显著减少,微血管血流速度较同组治疗前显著加快(均P<0.01),但管襻畸形率各组治疗前后差异无统计学意义(P>0.05);治疗前三组血黏度各指标及肺功能各指标差异均无统计学意义(P>0.05);治疗后三组全血高切黏度、低切黏度、血浆黏度较同组治疗前显著降低(P<0.05或P<0.01),FEV1、FEVl/FVC均较同组治疗前显著升高(P<0.05或P<0.01);治疗后各组全血高切黏度、低切黏度、血浆黏度随低分子肝素钙使用剂量由小到大逐渐降低,呈显著负相关(r值分别为—0.341、—0.693、—0.446,P<0.05或P<0.01);FEV1、FEVl/FVC值随剂量由小到大逐渐增加,呈显著正相关(r值分别为0.551、0.633,均P<0.01)。三组均未见明显颅内出血;大剂量组出血发生率36.67%(11/30),中剂量组13.33%(4/30),小剂量组10.00%(3/30),大剂量组显著高于中剂量组和小剂量组(均P<0.05),中小剂量与小剂量组间差异无统计学意义(P>0.05)。结论:常规治疗联合中剂量低分子肝素钙皮下注射可提高急性加重期慢阻肺合并呼衰患者临床疗效,有效改善微循环、降低血黏度、提高肺功能,且出血风险较小。

Objective： To observe the effects of different doses of low molecular weight heparin on clinical efficacy, microcirculation and lung function parameters in patients with chronic obstructive pulmonary disease （COPD） and respiratory failure. Method： A total of 90 acute exacerbation COPD patients with respiratory failure were selected for prospective study. The patients were divided into three groups： low dose group, middle dose group and high dose group by random number table, with 30 cases in each group. Three groups were given conventional comprehensive treatment, on the basis of the application the low-molecular-weight heparin was used. The high-dose group： 5 000IU/time, 3 times/d; middle dose group： 5 000IU/time, 2 times/d; low dose group：5 000IU/time, 1 time/d, three consecutive application of 7d. The clinical efficacy and indexes of microcirculation （including tube deformity rate, blood flow velocity, white micro-embolism and capillary flow rate）, indexes of blood viscosity （including whole blood high-shear viscosity, whole blood low-shear viscosity and plasma viscosity）, pulmonary function indicators [including forced expiratory volume in the first second （FEVl）, forced expiratory volume in the first second （FEVl/FVC）, total adverse reaction rate were compared among three groups. Result： Significant differences were found among the three groups for significant, effective, and ineffective （ P 〈0.01）. Comparison between the two groups, the clinical efficacy of the medium-dose group and large-dose group were higher than that of low-dose group （ P 〈0.05）, and there was no significant difference between the medium-dose group and the large-dose group （ P 〉0.05）. There were no significant difference in the rate of malformation, the number of white microemboli, and the microvessel blood flow rate between the three groups before and after treatment （ P 〉0.05）. After treatment, the number of microemboli in each group were significantly reduced compared than before treatment, and the microvessel blood flow velocity was significantly faster than before treatment in the same group （ P 〈0.01）, but the difference in tuberculosis malformation rate before and after treatment were not statistically significant （ P 〉0.05）. After treatment, there were no significant correlation between the rate of malformation of microarrythral fistula, the number of white microthrombi, and the velocity of microvessel flow and the dose in all groups. There were no significant difference in the viscosity index and lung function index between the three groups before treatment （ P 〉0.05）. After treatment, the whole blood hyperviscosity, whole blood low-cut viscosity and plasma viscosity were significantly lower than those before treatment in the same group （ P 〈0.05 or P 〈0.01）, the FEV1, FEV1/FVC were significantly higher than those before treatment in the same group （ P 〈0.05 or P 〈0.01）. After treatment, the whole blood hyperviscosity, whole blood hypoviscosity, and plasma viscosity gradually decreased with increasing doses, showed a significant negative correlation, r values were -0.341,-0.693,-0.446, P 〈0.05 or P 〈0.01. The FEV1, FEV1/FVC values increased gradually from small to large, showed a significant positive correlation, r values were 0.551, 0.633, all P 〈0.01. No significant intracranial hemorrhage was seen in all three groups. The incidence of hemorrhage was 36.67% （11/30） in the high dose group, 13.33% （4/30） in the middle dose group, and 10.00% （3/30） in the low dose group. The incidence of hemorrhage in high-dose group was significantly higher than that in middle-dose group and low-dose group （all P 〈0.05）. There was no significant difference between low-dose group and middle-dose group （ P 〉0.05）. Conclusion： Low molecular weight heparin is effective in the treatment of acute exacerbation chronic obstructive pulmonary disease with respiratory failure, and it can effectively improve the microcirculation, blood viscosity and lung function, and the risk of bleeding is small.