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Desflurane has been reported to produce more tachycardia and hypertension on induction than isoflurane. The present study employed microneurography to determine whether these cardiovascular effects were related to sympathetic outflow.In 14 healthy, young (age 20–31 yr) volunteers, arterial pressure was measured from the radial artery, forearm blood flow was derived by strain gauge plethysmography, and sympathetic nerve activity (SNA) directed to skeletal muscle blood vessels was recorded from a tungsten needle placed percutaneously into the peroneal nerve. Heart rate, blood pressure, muscle SNA, respiration, tidal volume, end-tidal carbon dioxide, and desflurane or isoflurane concentrations (infrared spectroscopy) were continuously monitored before and during anesthesia. Two minutes after administering thiopental (5 mg/kg) and vecuronium (0.2 mg/kg), desflurane (n = 7) or isoflurane (n = 7) was titrated gradually to the inspired gas over several minutes to 1.5 MAC.The initiation of desflurane anesthesia resulted in significant changes that included a 2.5-fold increase in SNA, hypertension (peak mean arterial pressure 114 ± 3 mmHg), tachycardia (peak heart rate 102 ± 6 beats/min), facial flushing, and tearing. Moderate upper airway obstruction developed in three subjects approximately 4 min after initiating desflurane, despite neuromuscular blockade. These responses were not observed in subjects receiving isoflurane. After tracheal intubation, the anesthetic concentration was maintained at 0.5 MAC for 30 min. Steady-state measurements of hemodynamics and SNA were obtained. Similar steady-state measurements were obtained 15 min after establishing 1.0 and 1.5 MAC. Both anesthetics produced a progressive reduction in blood pressure and forearm vascular resistance, and muscle SNA gradually increased. In subjects receiving desflurane, heart rate remained unchanged until the 1.5-MAC level was reached, at which time tachycardia (a 10-beat/min increase) was noted. The transition from 1.0 to 1.5 MAC desflurane resulted in significant heart rate increases (>30 beats/min), hypertension (>30 mmHg), and a doubling of SNA that persisted for several minutes. These responses did not occur in the isoflurane group.Titration of desflurane following thiopental induction and increasing the concentration of desflurane from 1.0 to 1.5 MAC result in sympatho-excitation, hypertension and tachycardia in healthy, young volunteers. Until methods are determined to attenuate these responses, desflurane should be administered with great caution to patients who may be placed at risk by these responses.