Effect of sympathetic blockade in non-lethal sepsis

我们在一个完善的人类脓毒症犬模型中研究了细菌性腹膜炎期间两种不同的交感神经阻滞技术对疼痛缓解、血流动力学和生存率的影响。研究了22只专用饲养的比格犬（12-28个月，10-12公斤）。14只动物接受布比卡因和吗啡的硬膜外输注，另外8只动物接受腹腔神经丛阻滞（n=4）或假阻滞（n=4）。22只动物中的18只接受了大肠杆菌(1 ？10 × 10^9 CFU？公斤bw)。在相同剂量的腹腔内植入大肠杆菌(2.5 ？5 × 10^9 CFU？Kg-1 bw)，增加交感神经阻断可协同降低生存时间（p=0.002）和平均左室射血分数（p=0.008），并增加肌酐水平（p=0.02）。在脓毒症期间，与交感神经阻滞相关的TNF水平显著升高（p=0.004），血液内毒素清除率显著降低（p=0.006）。腹腔神经丛阻滞动物的疼痛评分没有改善，主观上比没有腹腔神经丛阻滞的脓毒症动物更差。相比之下，硬膜外阻滞在阻断与低致死剂量腹腔内细菌相关的疼痛和不适方面是有效的，这反映在与未接受细菌攻击的动物相比，疼痛评分没有增加。本研究表明，在严重细菌性腹膜炎期间，维持交感神经张力对于清除细菌毒素、控制促炎介质释放、血流动力学稳定性和生存是必要的。这项研究提出了两个有待进一步研究的领域。首先，了解交感神经张力与控制细菌清除和促炎介质释放之间的关系。第二，是否可以在不影响生存的情况下调节疼痛缓解。

We investigated in a well-established canine model of human sepsis the effects of two different techniques of sympathetic blockade during bacterial peritonitis on pain relief, hemodynamics and survival rate. Twenty-Two purpose-bred beagles (12-28 months, 10-12 kg) were studied. Fourteen animals received an epidural infusion of bupivicaine and morphine, and the other 8 either a celiac plexus block (n=4) or a sham block (n=4). Eighteen of the 22 animals received an intraperitoneal challenge of E. coli (1 ? 10 x 10^9 CFU?kg-1 bw). At comparable doses of intraperitoneal implanted E. coli (2.5 ? 5 x 10^9 CFU?kg-1 bw), the addition of sympathetic blockade produced a synergistic decrease in survival times (p=0.002) and mean left ventricular ejection fraction (p=0.008), and increase in creatinine levels (p=0.02). There was also a significant increase in TNF levels (p=0.004) and decrease in blood endotoxin clearance (p=0.006) associated with sympathetic blockade during sepsis. The celiac plexus blocked animals had no improvement in pain scores and subjectively looked clinically worse than septic animals without a celiac plexus block. In contrast, the epidural block was effective in blocking the pain and discomfort associated with low lethality doses of intraperitoneal bacteria reflected by no increase in pain scores compared to animals not receiving bacterial challenge. This study shows that, during severe bacterial peritonitis, maintenance of sympathetic tone irrespective of pain relief provided is necessary for clearance of bacterial toxins, control of proinflammatory mediator release, hemodynamic stability and survival. This study has presented two areas of further research. First, to understand the relationship between sympathetic tone and control of bacterial clearance and proinflammatory mediator release. Second, whether pain relief can be modulated to be effective without negatively effecting survival.