Y. Kamijo et al., Cardiovascular response and stress reaction to flumazenil injection in patients under infusion with midazolam, CRIT CARE M, 28(2), 2000, pp. 318-323
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.