Midazolam and Propofol Synergism for Induction of Anesthesia / 대한마취과학회지

The mechanism by which propofol exerts its action is poorly understood, but may involve a non-specific effect on lipid membrane and has been shown to potentiate GABA-mediated synaptic inhibition. And, midazolam also acts through GABA receptor mediated increased chloride conductance. The aim of this study was to evaluate the dose response of midazolam, propofol and combination of these drugs, and determine possible interaction between two drugs in patients. The effect of propofol on the dose response curve for midazolam was studied in 260 nonpremedicated ASA physical status I or II female patients who were scheduled for elective operation. The response to the verbal command was used as an end-point of hypnosis. Dose response curves for midazolam, propofol, and their type of interaction was determined using Instat software package, nonlinear regression analysis, and algebraic(fractional) analysis of interaction. ED of midazolam and propofol was 0.11 mg/kg, 1.13 mg/kg and ED95 was 0.18 mg/kg, 1.67 mg/kg respectively. ED50 of combined drug(midazolam+propofol) in comhined dose response curve was 29% of each drug and the type of interaction between two drugs was found to be synergistic.

A Comparison of Midazolam and Propofol on Hemodynamic Changes and Postanesthetic Recovery as Hypnotics for Total Intravenous Anesthesia(TIVA) / 대한마취과학회지

Total intravenous anesthesia(TIVA) is a anesthetic technique where hypnosis, analgesia and muscle relaxation are provided solely by intravenously administered drug without the use of anesthetic vapors or gases including nitrous oxide. For TIVA, midazolam and propofol have been used as hypnotics because of their relatively short elimination half life. Hemodynamic function during induction of anesthesia, the fentanyl and naloxone requirements, and speed of recovery from TIVA with midazolam/fentanyl(group M, n=20) or prapofol/fentanyl (group P, n=20) were compaired in patients undergoing surgery. Forty patients were randomly assigned to receive either 0.2 mg/kg midazolam in 5 min followed by 0.4 mg/kg/hr for 20 min, 0.3 mg/kg/hr for next 20 min, 0.05~0.2 mg/kg/hr until 10~15 min before skin closure, or 2 mg/kg propofol in 5 min followed by 9 mg/kg/hr for 30 min and 4.5 mg/kg/hr until 10~15 min before skin closure. Simultaneously, a variable rate infusion of fentanyl was given. Patients were intubated with an aid of vecuronium and ventilated with 40% oxygen in air. In both groups, mean arterial pressure decreased significantly(P0.05). The total dose, duration and rate of infusion of fentanyl was similar in both groups. 16 patients in group M and 9 patients in gmup P needed naloxone for recovery of respiration and 10 patients in group M needed flumazenil for recovery of consciousness. Recovery as judged by scoring system(sedation score, comprehension score, orientation score) was shorter in group P than group M. Among side effects, resedation was more frequent in group M(9 pts) than P group(0 pt). In conclusion, both midazolam and propofol were useful hypnotics for TIVA. But, group M showed more stable hemodynamics than group P during induction period and P group showed earlier recovery than group M. We concluded that the selection of hypnotics between midazolam and propofol for TIVA depends on situation such as better hemodynamics during induction period or earlier recovery.

The Effect of Tetraethylammonium Chloride on the Impulse Conduction Block by bupivacaine / 대한마취과학회지

Potassium channel blockers slow depolarization, broaden the action potential, and thus pro- mote the open and inactivated Na+ channel states. The ability of local anesthetics to reduce the amplitude of compound action potential(CAP) of rat sciatic nerve was examined in the presence and absence of teteraethylammonium chloride(TEA) that selectively block K+ channels, In the presence of 1.3X10-5 M bupivacaine that inhibit the CAP by 22.5% at tonic stimulation, the addition of TEA(10-1M) increased this inhibition by another 27.5% and increased another 50% by phasic stimulation(20Hz). Also, dose response curve of bupivacaine in the presence of TEA(10-1M) showed marked shift to left of curve. The re- covery kinetics of bupivacaine in the presence of various coneentration of TEA(10-2-10-1M) showed marked delay of recovery(2X10-2 M), reocurrence of inhibition(90min,5X10-2 M), even no recovery(10-1M). TEA alone slightly depolarized the resting membrane which was represented as increment of CAP height from 0.9%(3min) to 12.3%(80min), and broadened mid-peak amplitude width by 2 times in 5X10-1M, 5.3 times in 1M. These experiments directly demonstrated that TEA potentiated the inhibition of CAP by bupivacaine and showed the poesibility of mixture of TEA and local anesthetics to potenti- ate impulse conduction blockade.

Effect of verapamil and bupivacaine alone or in combination of both on the nerve conduction in isolated rat sciatic verve preparation / 대한마취과학회지

Racemic verapamil has been shown to have local anesthetic activity, and fast sodium channel blockade is responsible for its inhibitory effect on nerve conduction. This study de- scribes the dose response inhibition of nerve conduction hy verapamil and bupivacaine alone as well as in combination of both on an isolated rat sciatic nerve preparation. In addition, it describes the effect of caleium ion concentration on this in vitro nerve preparation. Sciat- ic nerve preparation from rats were placed in mammarian ringer solution(MRS) adjusted to pH 7.4 at 22degrees C. Each nerve was mounted in a nerve conduction chamber containing MRS in the presence of verapamil(10-5M-2X10-3 M), bupivacaine(10-6M-10-3M) or a combination of both. Each nerve was stimulated with a square wave pulse at twice threshold potential(4 -7V), 0.02msec of duration, 10Hz of frequency. Compound action potentials(CAP) were photographed and measured on a Tektronix oscilloscope. The nerve was first equilibrated in the nerve conduction chamber in MRS, (pH 7.4, 22degrees C for 30min) and CAP was recorded for control(100% recovery). Then, the nerve was exposed to increasing concentrations of verapamil and bupivacaine for 12 minutes and a CAP was measured after each exposure. All CAP were compared to the control CAP and the results were expressed as a % of control CAP. We got dose response curve of verapamil, bupivacaine and combination of both. Also, we determined EC 25%, 50%, 75% from these data(EC % : Effective concentra- tions of drug for % CAP inhibition). Each of the experiments was performed on at least 4 nerves and differences between groups were analyzed using ANOVA test. Verapamil is shown to inhibit nerve conduction with an EC 25% = 2.2X10-4M, EC 50%=3.8X10-4M, EC 75% =6.3X10-4M and EC 50% for bupivacaine was 5.0X10-5 M. When verapamil dose response curves were performed in the presence of a wide range of CaCl2 containing MRS solutions, there was no significant differences in the response curve(P>0.05). In conclusion, racemic verapamil was shown to have dose dependent local anesthetic activity with a relative potency of 1/8 of bupivacaine. When combined with bupivaeaine, local anesthetic activity inereased in an additive manner. This suggests that these two drugs act on the nerve membrane in a similar fashion. Various CaCl2 concentrations have no effect on nerve conduction inhibition of verapamil. This implicates sodium channel blockade as the mechanism of local anesthetic activity of verapamil.