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。

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。

参考文献

1. River E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med, 2001, 345: 1368-1377.

2. Fiddian-Green RG. Associations between intramucosal acidosis in the gut and organ failure. Crit Care Med, 1993, 21(Suppl): 103-7.

3. Fink MP, Heard SO. Laboratory models of sepsis and septic shock.  J Surg Res, 1990, 49: 186-96.

4. Marx G, Pedder S, Smith L, et al. Resuscitation from septic shock with capillary leakage: hydroxyethyl starch, but not RS’s solution maintains plasma volume and systemic oxygenation.  Shock, 2004, 21: 336-341.

5. Haglund U, Fiddian-Green RG. Assesment of adequate tissue oxygenation in shock and critical illness: Oxygen transport in sepsis. Intensive Care Med, 1989, 15: 475-7.

6. 杨毅, 邱海波, 谭焰, 等. 多巴酚丁胺联用去甲肾上腺素和多巴胺对感染性休克绵羊内脏灌注的影响. 中国危重病急救医学, 2003, 15: 658－661.

7. Lagoa CA, Figueiredo LFP, Jr RJZ, et al.  Effect of volume resuscitation on splanchnic perfusion in canine model of severe sepsis induced by live Escherichia coli infusion. Critical Care, 2004, 8: R221-R228.

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.

10. Fiddian-Green RG, Haglund U, Guillermo G, et al. Goals for the resuscitation of shock. Crit Care Med, 1993, 21 (Suppl): 25-31.

11. Silva E, Backer DD, Creteur J, et al.Effect of fluid challenge on gastric mucosal PCO₂ in septic shock.Intensive Care Med, 2004, 30: 423-429.