FENTANYL, ESMOLOL, AND CLONIDINE BLUNT THE TRANSIENT CARDIOVASCULAR STIMULATION-INDUCED BY DESFLURANE IN HUMANS

Background: A rapid increase in the end-tidal concentration of desflurane to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating epinephrine and vasopressin concentrations. We hypothesized that drugs that block sympathetic activity or decrease sympathetic outflow (an opioid, a beta-adrenergic antagonist, and an alpha(2)-adrenergic agonist) would blunt these responses. Methods: After induction of anesthesia with intravenous propofol 2 mg/kg in ten healthy male volunteers age 25 +/- 1 yr (mean +/- standard error), anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. Controlled ventilation provided normocapnia. We then increased the end-tidal desflurane concentration within 1 min to 8% (1.1 MAC) and maintained this concentration for 10 min. On separate days, five of these volunteers were similarly anesthetized except that 5 min before the increase to 8% desflurane, we administered intravenous fentanyl 1.5 mu g/kg and on another day 4.5 mu g/kg (dose randomly assigned). On 2 separate days, intravenous esmolol 0.75 mg/kg was given to five volunteers 1.5 min before, or clonidine 4.3 mu g/kg by mouth to four volunteers 90 min before, the increase from 4% to 8% desflurane. Results: Without pretreatment, the increase to 8% desflurane increased heart rate (from 57 +/- 2 to 118 +/- 6 beats/min at peak, mean +/- standard error) and mean arterial blood pressure (from 66 +/- 2 to 118 +/- 5 mmHg). At the time of peak hemodynamic changes (within 1-2 min of the increase in desflurane concentration), plasma epinephrine and norepinephrine concentrations increased (from 22 +/- 6 to 339 +/- 83 pg/ml and from 205 +/- 19 to 283 +/- 30 pg/ml, respectively). Fentanyl 1.5 and 4.5 mu g/kg attenuated the heart rate increase by 61 +/- 14% and 70 +/- 7% and the mean arterial blood pressure increase by 31 +/- 16% and 46 +/- 11% but did not alter the epinephrine or norepinephrine response at the time of peak cardiovascular changes. Esmolol attenuated the heart rate response but no other response. Clonidine attenuated all responses except that of norepinephrine and also caused postanesthesia sedation. Conclusions: Fentanyl, esmolol, and clonidine blunt the transient cardiovascular response to a rapid increase in desflurane concentration. Fentanyl may be the most clinically useful of these drugs because it blunts the Increase in heart rate and blood pressure, has minimal cardiovascular depressant effects, and imposes little postanesthetic sedation.