连续性静脉-静脉血液滤过对内毒素休克羊血液动力学和炎性介质的影响

Effects of continuous veno-venous hemofiltration on hemodynamics and proinflammatory cytokines during endotoxic shock in sheep

目的观察连续性静脉.静脉血液滤过(CVVH)对内毒素休克血液动力学和炎性介质的影响。方法 雄性绵羊12只,随机分为两组。对照组(A组,n=6),内毒素以1 mg·kg-1静脉泵注,30min内完成,同时静脉输注林格液15 ml·kg-1·h-1,持续6 h;血滤组(B组,n=6),于开始泵注内毒素后1 h给予CVVH治疗5 h,其余处理同A组。所有动物均给予气管插管、镇静、肌松、控制呼吸,行有创血液动力学监测;两组分别于内毒素泵注前(T0)、开始泵注后30、60、90、120、210、360 min(T1～T6)采静脉血及超滤液4ml,测定血浆及超滤液中内毒素、TNF-α、IL-6、IL-10的浓度。结果 血滤组CVVH治疗后(T1-T6)平均动脉压及体循环阻力指数明显上升、心率显著性下降。TNF-α于泵注内毒素后(T1-T6)两组均显著性增高,血滤组于CVVH治疗60 min(T4)时较治疗前(T2)虽无明显改变,但明显低于同时点对照组(P<0.01),CVVH治疗150～300 min(T5-T6)时TNF-α浓度较对照组及治疗前(T2)均显著性降低(P<0.05);IL-10虽呈增高趋势,但较治疗前和对照组无显著性变化;而两组IL-6水平则无明显差异。超滤液中可检测到TNF-α、IL-6、IL-10。结论 血滤治疗有利于纠正促炎细胞因子过度释放和抗炎细胞因子失衡,改善内毒素休克血液动力学。

Objective The effectiveness of continuous veno-venous hemofiltration (CVVH) in clearing cytokines and reducing mortality in endotoxic shock is still controversial. The purpose of this study was to investigate the effects of CVVH on hemodynamies and plasma proinflammatory cytokines (TNF-α, IL-6, IL-10) during endotoxic shock in sheep. Methods Twelve male sheep weighing 14.5-20.5 kg were randomly divided into two groups of six animals :(A) control group and (B) CVVH group. Endotoxin (L-2880 sigma) 1 mg·kg-1 was infused intravenously(i.v. ) over 30 min and lactated Ringer's solution at 15 mlf44kg-1 f44h-1 for 6h in both groups. In CVVH group (B) CVVH was used for 5 h starting from 1h after the beginning of endotoxin infusion. The animals were anesthetized with midazolam and vecuronium. After tracheal intubation the animals were mechanically ventilated. Femoral artery was cannulated for continuous direct BP monitoring. 5F Swan-Ganz catheter was inserted into pulmonary artery via right internal jugular vein. Cardiac output ( CO), stroke volume ( SV), cardiac index (CI), MPAP, PAWP, SVRI, PVRI and LVSWI were measured, calculated and recorded before endotoxin infusion (T0 , baseline) and at 30, 60, 90, 120, 210 and 360 min (T6) after endotoxin infusion was started. Blood and ultrafiltrate samples were taken at T6 for determination of TNF-a,IL-6 and IL-10 concentrations. Results MAP and SVRI were significantly decreased while HR and SVRI were significantly increased after T, in both groups. MAP and SVRI were significantly higher at T6 in CVVH group than in control group ( P < 0.01) . HR was significantly decreased after CVVH at T6 than at T2 (before CVVH) in CVVH group and was significantly lower than that in control group (P < 0.05) . Plasma TNF-a concentration was significantly increased at T6 as compared with baseline value (T0 ) in both groups ( P < 0.01) , but was significantly lower in CVVH group than in control group (P<0.01) . There was no significant difference in plasma level of IL-6 and IL-10 between the two groups. TNF-α, IL-6 and IL-10 were detected in the ultrafiltrate. Conclusion CVVH can effectively improve hemodynamics and change the balance between pro- and anti-inflammatory cytokines to some extent in endotoxic shock.