DESFLURANE-MEDIATED NEUROCIRCULATORY ACTIVATION IN HUMANS - EFFECTS OF CONCENTRATION AND RATE OF CHANGE ON RESPONSES

Background: Rapid increases in the inspired concentration of desfluran e have been associated with sympathetic activation, tachycardia, hyper tension, and in select cases, myocardial ischemia, The current study e xamined the effects of the rate of change of the desflurane concentrat ion on the sympathetic and hemodynamic responses to desflurane and sou ght to determine whether a finite concentration (end-tidal) of desflur ane consistently initiated these responses. Methods: After Institution al Review Board approval, 23 healthy male volunteers were instrumented for electrocardiogram (heart rate (HR)), intraarterial blood pressure , and peroneal nerve microneurography (sympathetic nerve activity (SNA )). Subjects were given propofol (2.5 mg/kg) and vecuronium (0.15 mg/k g), and their lungs were mechanically ventilated for 30 min at a minim um alveolar concentration of 0.5 MAC with either desflurane or isoflur ane (random assignment). The end-tidal concentration was increased at either 1% per min (n = 7) or 0.5% per min (n = 7) for desflurane or 0. 16% per min (n = 9) for isoflurane (MAC-multiple comparable to 1% per min desflurane group) until 1.5 MAC was reached. HR, blood pressure, a nd SNA were averaged over 1-min segments from 0.5 to 1.5 MAC levels. R esults: Awake neurocirculatory variables did not differ among the thre e groups. At 0.5 MAC, blood pressure had decreased (12-15%) and HR inc reased (12-20%) similarly in both groups. SNA decreased 77% in the iso flurane group but was not significantly changed in the desflurane grou ps. In the desflurane groups, the threshold (end-tidal concentration a ssociated with a 10% increase in the measured variable) ranged between 4% and 10% for HR and between 4% and 7.7% for SNA. In the isoflurane group, the threshold occurred between 1.0% and 1.6% for HR and between 0.7% and 1.3% for SNA. The rate of change did not affect the threshol d concentration or the peak HR increase in the desflurane groups, In c ontrast, SNA responses to desflurane were directly proportional to the rate of change. Conclusions: There was no consistent threshold for th e neurocirculatory activation associated with desflurane, and the HR a nd SNA thresholds generally were less than 1 MAC. The HR increase asso ciated with desflurane was not rate- or concentration-dependent. In co ntrast, SNA responses were proportional to the rate of change and the concentration of desflurane.