Effect of sympathetic blockade in non-lethal sepsis

交感神经阻滞对非致死性脓毒症的影响

• 批准号: 6825124
• 负责人: Steven Solomon
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6825124
• 关键词: Escherichia coli; bacterial disease; bacterial toxins; disease /disorder model; dogs; epidural anesthesia; hemodynamics; morphine; pain; peritonitis; sympathetic block

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.

我们在一个完善的犬人败血症模型中研究了两种不同的交感神经阻滞技术在细菌性腹膜炎期间对疼痛缓解、血流动力学和存活率的影响。研究了22只专门饲养的比格犬（12-28个月，10-12 kg）。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只动物中有18只接受了E. coli（1？10 x 10^9 CFU？kg-1体重）。腹腔内植入E. coli（2.5？5 x 10^9 CFU？kg-1 bw）时，交感神经阻滞的加入产生了存活时间（p=0.002）和平均左心室射血分数（p=0.008）的协同降低，以及肌酸酐水平的增加（p=0.02）。在脓毒症期间，与交感神经阻滞相关的TNF水平也显著增加（p=0.004），血液内毒素清除率降低（p=0.006）。腹腔神经丛阻滞动物的疼痛评分没有改善，主观上看起来比没有腹腔神经丛阻滞的脓毒症动物更差。相比之下，硬膜外阻滞可有效阻断与低致死剂量腹腔内细菌相关的疼痛和不适，与未接受细菌激发的动物相比，疼痛评分未增加。这项研究表明，在严重的细菌性腹膜炎，维持交感神经紧张，无论提供的疼痛缓解是必要的细菌毒素的清除，控制促炎介质的释放，血流动力学稳定和生存。这项研究提出了两个进一步研究的领域。首先，了解交感神经紧张与细菌清除和促炎介质释放的控制之间的关系。第二，疼痛缓解是否可以被调节为有效而不会对生存产生负面影响。