T he induction of general anesthesia is associated with sympatholysis 1 and a decrease in circulating norepinephrine (NE) and epinephrine (E) concentrations. 2,3 Yet, the associated hypotension is commonly treated with phenylephrine (PE), a synthetic vasoconstrictor. 4,5 Theoretically, NE might better combat this general anesthesia-induced hypotension by restoring decreased circulating concentrations of this catecholamine and maintaining cardiac output (CO). However, NE is rarely used in these circumstances. In this article, I will propose that patients might be better served by using NE rather than PE as the primary vasopressor to combat hypotension during general anesthesia.
PHARMACOLOGYThe pharmacology of PE and NE is well known and is summarized in Table 1. 6-8 PE is now readily accepted as a first-line agent to combat hypotension from both general and spinal anesthesia. 4,9 In contrast, NE has been viewed with some trepidation. This is reflected in the moniker, "leav-em-dead" when referring to its common trade name, Levophed. 10 Thus, NE use has been largely confined to "sicker patients" and restricted to cardiac anesthesia and the management of sepsis. 11,12 PE, because of α 1 selectivity, has purely vasoconstrictor effects on vascular beds. 6,13 Arteriolar vasoconstriction results in an increase in arterial blood pressure, which in turn results in a baroreceptor-triggered, vagally mediated, decrease in heart rate and CO. In venous capacitance vessels, such vasoconstriction may increase vascular return and so potentially improve CO. However, this effect on CO may be impaired with PE because of an increase in venous resistance, limiting venous return to the heart. 13,14 An increase in venous resistance is not found with NE, which has both α 1 and β 1 effects as well as some β 2 effects, 7 resulting in a β-induced venous vascular relaxing effect on venous resistance. Hence, NE better enhances venous return to the heart and so CO. 14,15 The β 1 effects also result in a positive inotropic effect on the myocardium with little to no chronotropic effect when compared with E. 6 Thus, NE increases arterial blood pressure through arteriolar vasoconstriction and an increase (or maintenance) of heart rate, stroke volume, and CO. [16][17][18][19] NE is the neurotransmitter of the sympathetic nervous system. 20 Plasma levels are reported as being 264 ± 162 pg/mL (mean ± SD; n = 27) before induction of anesthesia with thiopental and 127 ± 78 pg/mL afterward, during isoflurane and sufentanil anesthesia. 2 Only 2% of circulating NE is attributed to release from the adrenal medulla. 20,21 Plasma NE concentrations are dependent on the net amount of "spillover" from sympathetic nerve terminals and NE clearance by organ tissue. 20 The net NE spillover into surrounding venous beds is a function of immediate neuronal reuptake. Spillover may be increased by disease (hypothyroidism, depression, renal failure) and drugs (chlorthalidone) or decreased by them (hyperthyroidism, clonidine, desipramine, and PE). 20 Plasma clearance by th...