Tizanidine, an alpha2-adrenoceptor agonist, has an antinociceptive effect in animals. In humans premedicated with oral tizanidine, the increase in blood pressure associated with laryngoscopy and intubation was attenuated, and the amount of midazolam required for loss of consciousness was significantly reduced. We speculated that the oral administration of tizanidine might reduce the minimum alveolar anesthetic concentration (MAC) of sevoflurane. Fifty-two ASA physical status I-II patients, aged 24-56 yr, were randomly allocated into two groups: a Control group (n = 26) and a Tizanidine group (n = 26). As premedication, the Control group received a placebo, and the Tizanidine group received 4 mg of oral tizanidine 90 min before surgical skin incision. Anesthesia was induced in all patients by using vital capacity rapid inhaled induction with sevoflurane (5%). Loss of consciousness was defined as both the loss of the eyelid reflex and the lack of a response to a verbal command. MAC was determined by a technique adapted from the conventional up-down method for quantal responses. The MAC of sevoflurane was 2.2% +/- 0.2% in the Control group and 1.8% +/- 0.2% in the Tizanidine group (P = 0.0004). The time to loss of consciousness in the Tizanidine group (60.2 +/- 22.5 s) was significantly shorter than that in the Control group (73.7 +/- 26.3 s) (P = 0.03). The oral administration of tizanidine 4 mg successfully reduced the MAC of sevoflurane by 18% in human adults.
Implications: Oral tizanidine (4 mg), an alpha2-adrenoceptor agonist, reduces the minimum alveolar concentration of sevoflurane by 18%.