Effect of sympathetic blockade in non-lethal sepsis

在已建立的人类脓毒症犬模型中，我们研究了细菌性腹膜炎期间两种不同的交感神经阻断技术对疼痛缓解、血流动力学和存活率的影响。对22只12~28月龄、体重10~12公斤的特殊用途比格犬进行了研究。14只动物接受硬膜外注射布比卡因和吗啡，另8只动物接受腹腔神经丛阻滞(n=4)或假麻醉(n=4)。22只动物中有18只接受了大肠杆菌(1？10×10~(-9)cfu·kg~(-1)bw)的攻击。在同等剂量(2.5×109cfu·kg-1bw)下，交感神经阻滞剂可协同减少小鼠的存活时间(p=0.002)和平均左心室射血分数(p=0.008)，并增加肌酐水平(p=0.02)。脓毒症期间交感神经阻断导致肿瘤坏死因子水平显著升高(p=0.004)，血内毒素清除量显著降低(p=0.006)。腹腔神经丛阻断的动物在疼痛评分方面没有改善，主观上看起来比没有腹腔神经丛阻滞的败血症动物更糟糕。相比之下，与未接受细菌攻击的动物相比，硬膜外阻滞有效地阻断了与低致死量腹膜内细菌相关的疼痛和不适，反映在疼痛评分没有增加。这项研究表明，在严重细菌性腹膜炎期间，维持交感神经张力是清除细菌毒素、控制促炎介质释放、血流动力学稳定和生存所必需的，而不考虑疼痛的缓解。这项研究提出了两个进一步研究的领域。首先，了解交感神经张力与控制细菌清除和促炎介质释放的关系。第二，疼痛缓解是否可以在不对生存产生负面影响的情况下有效。

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.