Optimal dose of midazolam for sedation during spinal anesthesia was investigated. One hundred and fifteen patients for spinal anesthesia (analgesic area below Th4), 30 to 70 years old, were divided into five groups according to midazolam dose: 0.025mg/ kg (27 cases), 0.05mg/kg (25 cases), 0.075mg/kg (23 cases), 0.1mg/kg (25 cases), and 0.125mg/kg (15 cases). Responses to verbal command and ciliary reflex were significantly more depressed in the 0.05, 0.075, 0.1, and 0.125mg/kg groups than in the 0.025mg/ kg group. The sedative effect of 0.025mg/kg of midazolam was therefore considered to be weak. In more than 25% of cases in the 0.075, 0.1, and 0.125mg/kg groups, respiration was depressed by dropped tongue. Respiratory rate increased significantly in the 0.1 and 0.125mg/kg groups. The numbers of cases who required vasopressor, who had body motion or nausea and vomiting did not differ much among the five groups.Blood pressure was more stable in the 0.025 and 0.05mg/kg groups than in the other three groups.The stabilities of circulation and respiration were better in the 0.025 and 0.05mg/kg groups than in the others.It was concluded that the optimal dose of midazolam for sedation during spinal anesthesia in patients aged 30-70 years is 0.05mg/ kg.

Earlier studies have suggested that halothane may relax smooth muscle in part by opening adenosine triphosphate-sensitive potassium (KATP) channels. We tested this hypothesis in vitro by examining the interaction of halothane with glibenclamide, a KATP channel blocker, and YM934, a KATP channel opener, in strips of canine tracheal smooth muscles mounted in an organ bath system. To examine the specificity of any effects of halothane on the KATP channel, we assessed the interaction of halothane with tetraethylammonium (TEA), an antagonist of the large-conductance, calcium-activated potassium channel. Experiments were conducted with drugs added before exposure to increasing concentrations of acetylcholine (ACh), and with drugs added after stable increases in force produced by ACh were achieved (ACh precontraction). Exposure to halothane 0.62 mmol litre-1 (equivalent to approximately 2 MAC) increased significantly the ED50 for ACh-induced contractions (by 0.24 (SEM 0.07) mumol litre-1). TEA 1 mmol litre-1 but not glibenclamide 10 mumol litre-1 significantly augmented this increase in ED50 (by an additional 0.17 (0.06) mumol litre-1). In strips precontracted with ACh, TEA, but not glibenclamide, potentiated concentration-dependent relaxation induced by halothane. Incubation with YM934 0.32 mumol litre-1 increased significantly the ED50 for ACh-induced contractions (from 0.12 (0.02) to 0.55 (0.11) mumol litre-1), an increase not affected by exposure to halothane 0.72 mmol litre-1. When added to strips precontracted with approximately ACh 0.3 mumol litre-1, YM934 produced concentration-dependent relaxation; halothane had little effect on this relaxation. These results do not support the hypothesis that halothane relaxes canine tracheal smooth muscle in part by opening KATP channels.

Agonist-induced increases in CA2+ sensitivity are mediated in part by mechanisms that increase phosphorylation of the regulatory myosin light chain (rMLC) at constant cytosolic Ca2+ concentration ([Ca2+]i). The current study tested the hypothesis that halothane inhibits acetylcholine (ACh)-induced potentiation of rMLC phosphorylation in beta-escin-permeabilized canine tracheal smooth muscle. ACh plus GTP significantly potentiated the increase in isometric force and rMLC phosphorylation induced by 0.8 microM free Ca2+. However, whereas the potentiation of isometric force was sustained, the potentiation of rMLC phosphorylation was biphasic, peaking at 0.5 min and then declining by approximately 10 min to a steady-state level significantly above that induced by 0.8 microM free Ca2+ alone. This finding suggests that mechanisms in addition to changes in rMLC phosphorylation may mediate ACh-induced Ca2+ sensitization, as has been reported for vascular smooth muscle. Halothane (0.91 +/- 0.10 mM) significantly inhibited ACh plus GTP-induced potentiation of rMLC phosphorylation and isometric force after 2 (peak rMLC phosphorylation) and 15 (steady-state rMLC phosphorylation) min of stimulation. However, the effect of halothane on the potentiation of isometric force was significantly less than that expected from its effect on rMLC phosphorylation (i.e., halothane changed the relationship between rMLC phosphorylation and isometric force). These results demonstrate that halothane inhibits the ACh-induced increase in Ca2+ sensitivity by inhibiting the membrane receptor-coupled mechanisms that increase rMLC phosphorylation at constant submaximal [Ca2+]i. Possible additional effects of halothane on rMLC phosphorylation-independent mechanisms cannot be ruled out.

This study used a beta-escin-permeabilized canine tracheal smooth muscle preparation to test the hypothesis that the volatile anesthetic halothane decreases myofilament Ca2+ sensitivity by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity and not by inhibiting Ca(2+)-calmodulin activation of the contractile proteins. Acetylcholine (ACh) caused a GTP-dependent increase in force at constant submaximal cytosolic Ca2+ concentration. ACh, guanosine-5'-O-(3-thiotriphosphate), and the protein kinase C agonist 12,13-phorbol dibutyrate each significantly decreased the concentration of free Ca2+ producing a half-maximal response from 0.77 +/- 0.09 microM (Ca2+ alone) to 0.16 +/- 0.01, 0.19 +/- 0.02, and 0.37 +/- 0.03 microM, respectively, demonstrating an increase in myofilament Ca2+ sensitivity. Halothane (0.92 +/- 0.12 mM) had no effect on the free Ca2+ concentration-response curves generated by Ca2+ alone. However, in the presence of 3 microM ACh plus 10 microM GTP to maximally activate muscarinic receptors, halothane significantly increased the EC50 for free Ca2+ from 0.17 +/- 0.01 microM to 0.38 +/- 0.03 microM. These findings suggest that halothane decreases myofilament Ca2+ sensitivity in beta-escin-permeabilized canine tracheal smooth muscle by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity.

The optimal administration time for intramuscular injection of midazolam as premedication was studied. Sixty patients ranging in age from 40 to 65 were included. A combination of atropine 0.3-0.5 mg and midazolam 0.08 mg·kg(-1) was given to four groups of 15 subjects each in intramuscular injections 45, 30, 15 min, and immediately before entering the operating room. Blood pressure, heart rate, respiratory rate, depression of the root of the tongue, eyelash reflex, degree of sedation, and amnestic effect at the time of arriving the operating room were compared among the groups. There was no difference among the groups in blood pressure, heart rate, and respiratory rate. The depression of the root of the tongue, disappearance of verbal response, and eyelash reflex were found in the 30- and 45-min groups. The degree of sedation and amnestic effect were good except for the group who received midazolam immediately before entering the operating room. From the above results, intramuscular injection of midazolam 0.08 mg·kg(-1) with atropine 0.3-0.5 mg is considered best when administered 15 min before entering the operating room.