6%羟乙基淀粉和林格氏液对感染性休克犬内脏器官灌注的影响

来源： 2010-08-24 11:34:52

Comparison effect of 6% hydroxyethyl starch to Ringer’s solution on splanchnic perfusion in canine with septic shock<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

YANG Yi, QIU Haibo, LIU Songqiao, CHEN Yongming, SHEN Jufang, LI Na.

Department of Critical Care Medicine, Zhong-Da Hospital and School of Clinical Medcine，Southeast University, Nanjing 210009, China

AIM：To compare the effect of 6% hydroxyethyl starch (HES) to Ringer’s solution (RS) on splanchnic perfusion in canine with septic shock. <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

Methods：Twenty-four mongrel dogs with septic shock induced by lipopolysaccharides were randomized to be divided into two groups (HES group and RS group). Each group were to receive an intravenous infusion of HES or RS (1ml/kg/min) for 60 min, then followed by normal saline for 180 min with same speed. Hemodynamic and oxygendynamic and splanchnic perfusion parameters were repeated at 0, 30, 60, 120, 180, 240min after basic measurement (pre-LPS).

Results：(1) After LPS infusion, mean arterial pressure (MAP) and cardiac output index (CI) decreased significantly (P<0.05). Compared to 0 min, MAP, CI and increased by fluid therapy in both groups, but there were no difference between HES and RS group. (2) Compare with pre-LPS, oxygen delivery (DO₂) reduced, arterial pH decreased and arterial lactate level increased markedly at 0 min (P<0.05). DO₂ increased by fluid therapy in both groups, but DO₂ was higher in HES group at the same time (P<0.05). Compared to 0 min, arterial lactate level decreased at 180 min in both groups. (3) Mesenteric blood flow decreased after LPS infusion in all animals (P<0.05). Mesenteric blood flow increased from 70 ± 35 to 100 ± 40 mL/min after 60min in HES group, also intramucosal pH (pHi) increased and Pg-aCO₂ decreased significantly (P<0.05 ), but there were no difference in RS group. At the same time, mesenteric blood flow and pHi was higher in HES group than that in RS group.

Conclusion：Both HES and RS could improve MAP and DO₂ in dogs with septic shock, but HES was better than RS on splanchnic perfusion.

Key Words：septic shock; intramucosal pH; splanchnic perfusion; hemodynamics; fluid therapy

目前，感染性休克仍然是危重病患者主要的病死原因。由于血管内皮受损、血管张力下降以及血管通透性的升高，休克必然导致绝对或相对血管内容量不足。因此，积极补充血管内容量是感染性休克复苏首要而重要的治疗手段。研究表明，早期积极的液体复苏可以明显降低严重感染的病死率，改善预后^[1]。液体复苏后即使血流动力学恢复正常，胃肠道和肝脏等内脏器官仍可能存在灌注不良。而内脏器官的缺血缺氧与多器官功能障碍综合征的发生密切相关^[2]。因此，改善器官组织灌注，特别是内脏器官灌注，逆转组织缺血，是休克液体复苏的关键。但目前对于选择胶体还是晶体进行液体复苏仍有争议。6%羟乙基淀粉(HES)是一种新型的人工胶体，已逐渐在临床上推广使用，但有关HES对内脏灌注影响的报道不多。本研究利用内毒素(LPS)静脉注射复制的犬感染性休克模型，观察HES和林格氏液(RS)复苏对感染性休克犬内脏灌注的影响，为临床上对感染性休克患者提供合适液体复苏提供依据。

1.材料和方法<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

1.1 材料

成年健康杂种犬共24只，体重12.1±0.9kg，雌雄各半，由东南大学医学院实验动物中心提供。LPS (血清型O127:B4 ) 购自美国Sigma公司。

1.2 动物准备和复制犬感染性休克模型动物称重后，给予2%戊巴比妥钠 (30mg/kg) 静脉注射麻醉，仰卧位固定。经口气管插管(7^#)，接Evita 4 呼吸机 (德国Drger公司)。容量控制通气，潮气量10 ml/kg，呼气末正压(PEEP) 4cmH₂O (1cmH₂O = 0.098kPa)，吸气时间0.6s，呼吸频率30 次/min，吸入氧浓度(FiO₂) 40％。经股静脉置管给予LPS 300mg/kg/h(20分钟内匀速泵入)，而后以每10分钟增加200 mg/kg/h持续泵入。当犬动脉收缩压下降到基础值的60% (1kPa=7.5mmHg) 时，感染性休克模型成功^[3]。

1.3 监测

1.3.1血流动力学监测：监护仪 (1500型，美国Spacelab公司) 持续监测犬心电图，记录心率 (HR)。经犬右颈内静脉置肺动脉漂浮导管 (Swan-Ganz导管，美国Arrow公司), 监测心输出量(CO)、中心静脉压(CVP)、肺动脉嵌顿压(PAWP)，计算心脏指数(CI)。左股动脉置 PiCCO动脉导管，后接 PiCCO仪(Pulsion Medical System，德国)，监测胸腔内血管容量(ITBVI)，并持续监测平均动脉压 (MAP)。

1.3.2 全身氧代谢监测：经PiCCO导管抽取动脉血，肺动脉漂浮导管肺动脉端抽取混合静脉血，进行血气分析，记录动脉pH及乳酸水平，计算氧输送指数(DO₂)、氧耗指数(VO₂)。

1.3.3 内脏灌注的监测：腹部正中切口，逐层进入，暴露并分离肠系膜上动脉，置入电磁流量计(NIHON KOHDEN, Japan)，记录肠系膜血流量。暴露空肠，胃肠张力计(TRIP, Tonocap, Finland)置入空肠内，予以荷包缝合固定，逐层关腹。监测肠粘膜二氧化碳分压(PgCO₂)，计算肠粘膜动脉二氧化碳分压差(Pg-a CO₂)、肠粘膜pH值(pHi)。

1.4 实验方案：

动物根据随机数字表法分为两组(HES组和RS组)。模型成功后稳定1小时记为0min，两组分别静脉滴注HES (200/0.5) 和RS 60min(1ml/kg/min)，而后生理盐水以相同速度维持180min。记录模型前、复苏开始0, 30, 60, 120, 180, 240min血流动力学、氧代谢及内脏器官灌注等指标。

1.5 观察条件

实验期间，2%戊巴比妥钠10 mg/kg/h持续静脉泵入维持麻醉状态，使犬处于全麻状态。呼吸机控制通气，调整呼吸机参数，维持动脉氧分压(P_aO₂) > 12 kPa，二氧化碳分压 4.7-6.0kPa。生理盐水2ml/kg/h持续静脉输入补充不显性失水，加盖毛毯维持犬血温在36-37℃。

1.6 统计学方法

数据以均值±标准差 (x±s) 表示，统计学处理采用SPSS11.5软件进行。组间比较采用单因素方差分析，样本均数间的两两比较采用q检验。p<0.05有统计学意义。

肠道在休克早期时极易发生损伤，因此被认为是多器官功能衰竭的始动器官^[7]。在全身血流动力学及氧代谢改善后，尤其关注肠道灌注。Pg-aCO₂和pHi是反应肠道缺血缺氧的敏感指标，Pg-aCO₂的升高和pHi降低表明肠道组织存在缺氧、低灌注。而粘膜的酸中毒、粘膜的损伤必然增加粘膜的通透性，增加肠道细菌和毒素的移位，最终可能导致多器官功能衰竭^[8,9]。因此，休克时pHi值的监测显得尤为重要，休克复苏需以恢复pHi为治疗目标^[10]。本研究结果显示，HES组在液体复苏后60、120min 肠道血流明显升高，同时伴有Pg-aCO₂的降低和pHi明显上升，而RS组复苏后Pg-aCO₂仍然明显升高，pHi呈下降趋势，显著低于同时期HES组。强烈提示HES较RS可以更好的改善内脏灌注，而这种效应与CI和DO₂的提高无明显关系，可能与肠道血流重新分布有关^[6]。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

值得注意的是，全身血流动力学的恢复不代表组织缺氧状态的纠正。本研究显示，两组动物在液体复苏后即使血压、CI及DO₂都明显恢复，但反映内脏灌注的Pg-aCO₂和pHi并没有恢复到模型前水平，表明虽然积极液体复苏，组织缺氧未能纠正。这与Silva的研究一致^[11]。其可能的原因是本研究中液体复苏的量不够，还需要继续补充血容量，其次是休克发生后肠道血流重分布已经发生，液体复苏短期内不能逆转，还可能与肠道血流恢复后再灌注损伤有关。

总之，积极的液体复苏有利于纠正感染性休克血流动力学紊乱。在纠正全身血流动力学紊乱的同时，应关注内脏的灌注，以利于休克的根本纠正。与RS液比较，HES可能更有利于内脏灌注的改善。

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8. Levy B, Gawalkiewicz P, Vallet B, et al. Gastric capnometry with air-automated tonomety predicts outcome in critically ill patients.Crit Care Med, 2003, 31: 474-480.

9. 王忠堂,姚咏明,肖光夏,等.双歧杆菌对烫伤大鼠肠道粘膜机械及生物屏障的改善作用.中国危重病急救医学, 2003, 15: 154－158.

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