Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs

Abstract

Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 ± 9% versus awake (P < 0.05). This was due to a reduction of 52 ± 9% in NE spillover (P < 0.05) accompanied by a reduction of 27 ± 5% in NE clearance (P < 0.005). The clearance changes were dose-dependent: reductions were 34 ± 4% at 1.5 MAC (P < 0.05 vs. 1.0 MAC) and 45 ± 5% at 2.0 MAC (P < 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia. Propofol (6 mg/kg followed by 0.8 mg·kg-1·min-1, n = 8) was equivalent to 2.0 MAC halothane in terms of spillover reduction (73 ± 5% vs. 72 ± 4%, P < 0.05), yet propofol had significantly less effect than did 2.0 MAC halothane on clearance (22 ± 4% reduction vs. 45 ± 5%, P < 0.01) and on systolic blood pressure (23 ± 5% reduction vs. 43 ± 3%, P < 0.01). Our data demonstrate that both halothane and propofol in anesthetic doses produce significant sympathetic inhibition. They also show that halothane and propofol differ in their relative potencies for spillover reduction and clearance reduction. Plasma NE concentrations alone are therefore inadequate for comparison of the sympathetic inhibitory effects of these two agents.