Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock

Abstract

. Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock. Am J Physiol Heart Circ Physiol 287: H2545-H2554, 2004. First published August 19, 2004 doi:10.1152/ ajpheart.00450.2004.-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, 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 Ͻ 0.06), mean arterial pressure (MAP) (P Ͻ 0.05), cardiac index (CI) (P Ͻ 0.02), and ejection fraction (EF) (P ϭ 0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P ϭ 0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P ϭ 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.vasopressors and systemic perfusion; low cardiac output septic shock; vasopressors and acidosis; vasopressors and cardiac function DESPITE CONTINUED IMPROVEMENTS in medical therapy, mortality from septic shock has remained between 30% and 60% for the past three decades (1, 2). Septic shock is a clinically descriptive term that refers to a pathophysiological state of cardiovascular collapse associated with overwhelming infection. After adequate volume resuscitation, severe septic shock is often characterized by a hyperdynamic state with increased cardiac output (CO), hypotension, and decreased systemic vascular resistance (SVR). However, despite adequate volume resuscitation, 20 -25% of adult septic patients and 50 -60% of pediatric septic patients will present with low CO (3, 33, 34). The majority of septic patients will develop myocardial dysfunction and many will die as a consequence of multiple organ failure (17,35,44). During septic shock, tissue perfusion is compromised by hypotension, by the loss of vascul...

Effects of intra-aortic balloon counterpulsation in a model of septic shock*

“…Another approach for low cardiac output septic shock is to switch from norepinephrine to epinephrine. However, in canine sepsis, epinephrine compared to other vasopressors has been associated with delayed cardiac recovery [28] and worsened survival [40]. The risks associated with the use of these vasoactive agents during septic shock may, in part, be why the mortality for low cardiac output septic shock remains so high [3].…”

“…High dose vasopressors have been shown to maldistribute blood flow [41] and in similar sepsis models worsen outcome [40]. IABC reduces cardiac workload by decreasing afterload improving left ventricular ejection and outflow.…”

Glucose metabolism and catecholamines

“…It seems to be unequivocal that epinephrine, according to its highest potency as a ␤ 2 -agonist, produces the most pronounced hyperlactatemic and hyperglycemic response, both in experimental animals (138,139), as well as in patients (134, 139 -141). It is by no means uncontested, however, whether this metabolic response has to be referred to as being a mere calorigenic effect or interpreted as epinephrine-induced metabolic stress.…”

“…Despite the well-established pathophysiologic background (3, 6) and the growing experience with this approach (4), putative drawbacks must be considered, i.e., regional ischemia resulting from vascular overconstriction, in particular, in the hepatosplanchnic area (6, 7, 151-153). In experimental animals, low-dose infusions of vasopressin or its analog, terlipressin, did not produce such effects, provided fluid resuscitation was adequate (154,155), and an even improved tissue energy balance when compared with catecholamines was reported (138,(155)(156)(157). Scarce data, however, are only available about the effect of partial or complete replacement of catecholamines on glucose metabolism.…”

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

“…59 This effect was also observed in two short-term animal models of endotoxemia (Figure 3) but not in a third model using viable E coli intraperitoneal implantation. 60 In addition to increasing glomerular filtration pressure, two other mechanisms have also been proposed to explain the increase in urine output observed in AVP-treated patients with septic shock: 1) activation of oxytocin receptors; and 2) release of atrial natriuretic peptide, causing natriuresis. Interestingly, AVP-induced diuresis is paralleled by an increase in renal permeability in two animal models of endotoxemia ( Figure 3).…”