Martikainen Tero J, Tenhunen Jyrki J, Giovannini Ivo, Uusaro Ari, Ruokonen Esko
Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland.
Am J Physiol Gastrointest Liver Physiol. 2005 Mar;288(3):G586-92. doi: 10.1152/ajpgi.00378.2004. Epub 2004 Oct 28.
Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO(2) content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO(2) content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.
肾上腺素在休克治疗中广泛用作血管收缩剂或强心剂，尽管它通常会诱发或加重乳酸性酸中毒。关于高乳酸血症本身是否是组织灌注不足或有氧糖酵解的标志这一问题，目前仍在争论中。我们想要验证肾上腺素对内脏灌注和代谢具有选择性有害作用这一假设。我们进行了严格的局部静脉血气分析以及腹腔内微透析。我们使用数学模型计算局部动静脉二氧化碳含量梯度，并在内毒素输注诱导的长时间低血压休克猪模型（平均动脉血压<60 mmHg）中估计哈代效应的大小。随后，给予血管升压药（肾上腺素或去甲肾上腺素）并进行调整，以维持全身平均动脉血压>70 mmHg达4小时。肾上腺素导致全身高乳酸血症和酸中毒。重要的是，全身和局部静脉乳酸与丙酮酸的比率均升高。尽管内脏总血流量明显维持不变，但肾上腺素与门静脉血流量减少有关。肾上腺素增加了胃静脉与动脉之间的二氧化碳分压梯度和二氧化碳含量梯度，同时哈代效应的大小减小，与去甲肾上腺素输注相比，肾上腺素输注后局部胃呼吸商仍然较高。此外，肾上腺素诱导腹腔内乳酸和甘油释放。在设定相同动脉压目标的情况下，我们未观察到与去甲肾上腺素相关的这些不良血流动力学或代谢变化。我们得出结论，在实验性内毒素休克中，与去甲肾上腺素相比，使用肾上腺素时，哈代效应大小减小的高二氧化碳含量梯度表明胃壁存在最明显的灌注不足。
