Cardiovascular response and stress reaction to flumazenil injection in patients under infusion with midazolam

Objectives: To evaluate the cardiovascular response and acute stress reacti on after arousal induced by a benzodiazepine antagonist, flumazenil, in pat ients sedated with midazolam. Design: Prospective study. Setting: Emergency center in a university hospital. Patients: A total of 12 patients were ventilated mechanically under sedatio n with midazolam. interventions: We monitored the consciousness level, heart rate, systemic b lood pressure, pulmonary artery pressure, and pulmonary artery occlusion pr essure before and after a bolus injection of 0.5 mg of flumazenil. The scor e for the consciousness level represents the sum of the scores for eye open ing and best motor response, as determined by the Glasgow Coma Scale. We me asured the cardiac output, concentrations of norepinephrine, epinephrine, a nd 3-methoxy-4-hydroxyphenylethyleneglycol in plasma, and concentration of cortisol in serum. We calculated the left ventricular ejection fraction, ca rdiac index, systemic vascular resistance index, pressure-rate product, sys temic oxygen delivery, and systemic oxygen consumption at 0, 10, 30, and 60 mins after injection of flumazenil. Measurements and Main Results: The serum benzodiazepine's receptor binding activity in serum was in the range from 50 to 1000 ng/mL before injection o f flumazenil. Flumazenil improved the consciousness level from 6.7 +/- 2.0 to 8.9 +/- 1.6 and induced transient elevations in heart rate, blood pressu re, systolic pulmonary artery pressure, and pulmonary artery occlusion pres sure. Left ventricular ejection fraction, oxygen delivery index, and pressu re-rate product increased significantly, from 61% +/- 8%, 640 +/- 170 mL/mi n/m(2), and 13,300 +/- 2600 mm Hg/min at 0 mins to 67% +/- 5%, 710 +/- 220 mL/min/m(2), and 16,500 +/- 4400 mm Hg/min at 10 mins, respectively. Concen trations of norepinephrine and epinephrine in plasma increased significantl y, from 890 +/- 840 pg/mL and 220 +/- 360 pg/mL, respectively, at 0 mins to 990 +/- 850 pg/mL and 270 +/- 300 pg/mL, respectively, at 10 mins. There w ere no significant changes in the plasma concentration of 3-methoxy-4-hydro xyphenylethyleneglycol, the serum concentration of cortisol after the admin istration of flumazenil. Conclusions: Flumazenil did not result in a significant acute stress reacti on in midazolam-sedated patients, but it increased myocardial oxygen consum ption by enhancing sympathetic nervous activity or antagonizing cardiovascu lar depression induced by midazolam.