Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO₂ content gradients and lactate-to-pyruvate ratios

Abstract

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.

Levosimendan: A New Therapeutic Option in the Treatment of Primary Graft Dysfunction After Heart Transplantation

“…13,14 The treatment of PGD is limited to ameliorating its symptoms. The first-choice drug of inotropic support used in patients with PGD leads to an impaired perfusion of gut and kidneys, 15,16 resulting additionally in elevated serum levels of lactate, which makes the diagnosis of intestinal ischemia more difficult. [17][18][19] These side effects, especially the limited intestinal perfusion, are more often of clinical relevance the longer the duration of application lasts.…”

Evaluation of the Efficacy of Epinephrine as a Vasopressor in the Management of Severe Sepsis: A Randomized Controlled Study

“…Similar to the study of Bollaert et al, [13] where epinephrine was effective in attaining MAP even in patients in whom dopamine had failed, our study also lends accreditation to the fact that epinephrine is a very effective vasopressor but there are three concerns regarding the use of epinephrine, 1) epinephrine increases myocardial oxygen demand; (2) epinephrine increases serum glucose and lactate, [14] which is largely a calorigenic effect (increased release and anaerobic breakdown of glucose); and (3) epinephrine appears to have adverse effects on splanchnic blood flow. [15][16][17] Concern about the effect of increased serum lactate and hyperglycemia has limited the use of epinephrine. However, it is unclear whether lactate is harmful in sepsis, [18] and concern regarding hyperglycemia appears to be fading.…”

Treatment of severe lactic acidosis during the pre-anhepatic stage of liver transplant surgery with intraoperative hemodialysis

“…Epinephrine, a potent vasoconstrictor, may decrease tissue perfusion, thereby increasing lactate synthesis [20,21]. In addition, vasoconstriction of the portal [20] and renal [22] vessels may decrease blood flow to the liver and kidneys, in turn reducing lactate clearance by these organs. In the case presented, epinephrine infusion was started 8 hours into the surgery (5 hrs after lactic acidosis was detected).…”