不同目标血压复苏对创伤失血性休克患者外周血炎性因子和血流动力学的影响

摘要

Objective To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. Methods Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. Results Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt):0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). Conclusions When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.%目的 探讨创伤失血性休克患者限制性液体复苏的目标血压水平.方法 选择2016年1月至2018年12月蚌埠医学院第一附属医院收治的60例创伤失血性休克患者.按入院顺序编号,根据随机数字表法选择符合标准的研究对象依次入组,所有患者入院后均接受醋酸钠林格液复苏,根据复苏不同目标平均动脉压(MAP)分为低MAP(60 mmHg≤MAP ＜65 mmHg,1 mmHg＝0.133 kPa)、中MAP(65 mmHg≤MAP ＜70 mmHg)和高MAP(70 mmHg≤MAP ＜75 mmHg)3组,每组20例.复苏30 min未达目标MAP者予以排除,并顺延补充病例.检测各组患者限制性液体复苏前及复苏30 min和60 min血清炎性因子表达并实时监测血流动力学变化,推测最合适的复苏血压水平.变量的相关性采用Pearson相关分析.结果 液体复苏前,3组患者血流动力学和血清炎性因子表达量差异均无统计学意义;复苏30 min分别达到目标血压水平并维持30 min.随液体复苏时间延长,3组患者中心静脉压(CVP)、心排血量(CO)和心排血指数(CI)均缓慢升高,在复苏30 min前后基本达到平稳状态,以高MAP组和中MAP组升高更为显著.3组患者血清炎性因子表达量均随液体复苏时间延长呈持续升高趋势.复苏30 min时,中MAP组在抑制促炎因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6 (IL-6)表达和促进抑炎因子IL-10表达方面均优于低MAP组和高MAP组〔TNF-α mRNA(2-ΔΔCt):0.21±0.13比 0.69±0.34、0.57±0.35,IL-6 mRNA(2-ΔΔCt):0.35±0.31 比 0.72±0.39、0.59±0.42,IL-10 mRNA(2-ΔΔCt):1.25±0.81比0.61±0.46、0.82±0.53,均P＜0.05〕,但在促进IL-4表达方面3组间比较差异无统计学意义.复苏60 min时,中MAP组在抑制TNF-α、IL-6表达和促进IL-10表达方面亦均优于低MAP组和高MAP组〔TNF-α mRNA(2-ΔΔCt):0.72±0.35比1.05±0.54、1.03±0.49,IL-6 mRNA(2-ΔΔCt):0.57±0.50比1.27±0.72、1.01±0.64, IL-10 mRNA(2-ΔΔCt):1.41±0.90比0.81±0.48、0.94±0.61,均P＜0.05〕;中MAP组在促进IL-4表达方面优于高MAP组(2-ΔΔCt :1.32±0.62比0.91±0.60,P＜0.05).低MAP组与高MAP组液体复苏后各时间点血清炎性因子表达量差异均无统计学意义(均P＞0.05).相关性分析显示,中MAP组MAP与TNF-α、IL-6、IL-10的mRNA表达存在较强的线性相关关系(r值分别为0.766、0.719、0.692,均P＜0.01),但与IL-4无相关性(r＝0.361, P＝0.059);拟合线性回归分析结果显示,MAP每增加1 mmHg,TNF-α的mRNA表达量增加0.027〔95%可信区间(95%CI)＝0.023～0.031,P＜0.001〕,IL-6 mRNA表达量增加0.021(95%CI＝0.017～0.024,P＜0.001), IL-10 mRNA表达量增加0.049(95%CI＝0.041～0.058,P＜0.001).结论 创伤失血性休克患者接受限制性液体复苏目标MAP维持在65～70 mmHg时,其减缓全身炎症反应和改善血流动力学的效果优于目标MAP在60～65 mmHg或70～75 mmHg,提示65～70 mmHg可能是限制性液体复苏比较理想的目标MAP 水平.