Cardiovascular response and stress reaction to flumazenil injection in patients under infusion with midazolam.
OBJECTIVE
To evaluate the cardiovascular response and acute stress reaction after arousal induced by a benzodiazepine antagonist, flumazenil, in patients sedated with midazolam.


METHODS
Prospective study.


METHODS
Emergency center in a university hospital.


METHODS
A total of 12 patients were ventilated mechanically under sedation with midazolam.


METHODS
We monitored the consciousness level, heart rate, systemic blood pressure, pulmonary artery pressure, and pulmonary artery occlusion pressure before and after a bolus injection of 0.5 mg of flumazenil. The score for the consciousness level represents the sum of the scores for eye opening and best motor response, as determined by the Glasgow Coma Scale. We measured the cardiac output, concentrations of norepinephrine, epinephrine, and 3-methoxy-4-hydroxyphenylethyleneglycol in plasma, and concentration of cortisol in serum. We calculated the left ventricular ejection fraction, cardiac index, systemic vascular resistance index, pressure-rate product, systemic oxygen delivery, and systemic oxygen consumption at 0, 10, 30, and 60 mins after injection of flumazenil.


RESULTS
The serum benzodiazepine's receptor binding activity in serum was in the range from 50 to 1000 ng/mL before injection of flumazenil. Flumazenil improved the consciousness level from 6.7+/-2.0 to 8.9+/-1.6 and induced transient elevations in heart rate, blood pressure, systolic pulmonary artery pressure, and pulmonary artery occlusion pressure. Left ventricular ejection fraction, oxygen delivery index, and pressure-rate product increased significantly, from 61%+/-8%, 640+/-170 mL/min/m2, and 13,300+/-2600 mm Hg/min at 0 mins to 67% +/-5%, 710+/-220 mL/min/m2, and 16,500+/-4400 mm Hg/min at 10 mins, respectively. Concentrations of norepinephrine and epinephrine in plasma increased significantly, 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 were no significant changes in the plasma concentration of 3-methoxy-4-hydroxyphenylethyleneglycol, the serum concentration of cortisol after the administration of flumazenil.


CONCLUSIONS
Flumazenil did not result in a significant acute stress reaction in midazolam-sedated patients, but it increased myocardial oxygen consumption by enhancing sympathetic nervous activity or antagonizing cardiovascular depression induced by midazolam.
Kamijo
Y
Y
Department of Emergency and Critical Care Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Masuda
T
T
Nishikawa
T
T
Tsuruta
H
H
Ohwada
T
T
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000931:Antidotes / Q000009:adverse effects*; D016292:Procedural Sedation / Q000379:methods; D003243:Consciousness / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods; D004837:Epinephrine / Q000097:blood; D005260:Female; D005442:Flumazenil / Q000009:adverse effects*; D018757:GABA Modulators / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced*; D015238:Sulfotransferases / Q000097:blood
D000931:Antidotes; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D005442:Flumazenil; C021563:3-methoxy-4-hydroxyphenylethyleneglycol sulfotransferase; D015238:Sulfotransferases; D008874:Midazolam; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine