Minneci Peter C, Deans Katherine J, Banks Steven M, Costello Renee, Csako Gyorgy, Eichacker Peter Q, Danner Robert L, Natanson Charles, Solomon Steven B
Critical Care Medicine Department, National Institutes of Health, 10 Center Dr., Bldg 10, Rm 7D43, Bethesda, MD 20892, USA.
Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2545-54. doi: 10.1152/ajpheart.00450.2004. Epub 2004 Aug 19.
During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 microg.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 microg.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P <0.06), mean arterial pressure (MAP) (P <0.05), cardiac index (CI) (P <0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.
在脓毒症期间，关于血管升压药对生存率影响的可用数据有限，难以指导治疗。因此，我们在犬类脓毒性休克模型中比较了三种血管升压药对生存率的影响。将78只清醒的犬通过腹腔注射不同剂量的大肠杆菌以产生递增的死亡率，随机分为接受肾上腺素（0.2、0.8或2.0微克·千克⁻¹·分钟⁻¹）、去甲肾上腺素（0.2、1.0或2.0微克·千克⁻¹·分钟⁻¹）、血管加压素（0.01或0.04单位/分钟）或安慰剂治疗，同时给予抗生素和液体。测量系列血流动力学和生化变量。细菌剂量增加导致生存率（P<0.06）、平均动脉压（MAP）（P<0.05）、心脏指数（CI）（P<0.02）和射血分数（EF）（P=0.02）逐渐下降。肾上腺素对生存率的影响与去甲肾上腺素和血管加压素显著不同（P=0.03）。肾上腺素对生存率有有害影响，且与药物剂量显著相关（P=0.02），但与细菌剂量无关。去甲肾上腺素和血管加压素对生存率有有益影响，在所有药物和细菌剂量下均相似。与同期感染对照组相比，肾上腺素导致CI、EF和pH下降幅度更大，全身血管阻力和血清肌酐升高幅度比去甲肾上腺素和血管加压素更大。这些肾上腺素诱导的变化与所给予的肾上腺素剂量显著相关。在本研究中，血管升压药的作用与感染严重程度无关，但取决于所用血管升压药的类型和剂量。与去甲肾上腺素和血管加压素相比，肾上腺素对器官功能、全身灌注和生存率有不利影响。在所研究的范围内，在脓毒症期间，去甲肾上腺素和血管加压素比肾上腺素具有更有利的风险效益比。
