Seddighi Reza, Egger Christine M, Rohrbach Barton W, Cox Sherry K, Doherty Thomas J
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Vet Anaesth Analg. 2011 May;38(3):195-202. doi: 10.1111/j.1467-2995.2011.00615.x.
To determine the possible additive effect of midazolam, a GABA(A) agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC(NM) ) in response to noxious stimulation.
Randomized cross-over experimental study.
Six healthy, adult intact male, mixed-breed dogs.
After baseline isoflurane MAC(NM) (MAC(NM-B) ) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg(-1) and constant rate infusion (CRI) (2.5 μg kg(-1) minute(-1)) (LDL), followed by an Ld (0.4 mg kg(-1)) and CRI (5 μg kg(-1) minute(-1)) (LDH). The MDS was an Ld (0.8 mg kg(-1)) and CRI (10 μg kg(-1) minute(-1)) (MDL) followed by an Ld (1.6 mg kg(-1)) and CRI (20 μg kg(-1) minute(-1)) (MDH). The HDS was an Ld (3.2 mg kg(-1)) and CRI (40 μg kg(-1) minute(-1)) (HDL) followed by an Ld (6.4 mg kg(-1)) and CRI (80 μg kg(-1) minute(-1)) (HDH). MAC(NM) was re-determined after each dose in each series (MAC(NM-T)).
The median MAC(NM-B) was 1.42. MAC(NM-B) did not differ among groups (p > 0.05). Percentage reduction in MAC(NM) was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC(NM) reduction (r = 0.36).
Midazolam doses in the range of 10-80 μg kg(-1) minute(-1) significantly reduced the isoflurane MAC(NM) . However, doses greater than 10 μg kg(-1) minute(-1) did not further decrease MAC(NM) indicating a ceiling effect.
确定γ-氨基丁酸A（GABA(A)）激动剂咪达唑仑对异氟烷呼气末浓度的可能相加作用，该浓度可防止对有害刺激产生的运动反应（无运动反应最低肺泡有效浓度[MAC(NM)]）。
随机交叉实验研究。
6只健康成年雄性杂种犬。
在测定基础异氟烷MAC(NM)（MAC(NM-B)）后，给予咪达唑仑低剂量系列（LDS）、中剂量系列（MDS）或高剂量系列（HDS）。每个系列由低剂量和高剂量两个剂量水平组成。LDS为负荷剂量（Ld）0.2mg/kg(-1)和持续输注速率（CRI）（2.5μg/kg(-1)分钟(-1)）（LDL），随后是Ld（0.4mg/kg(-1)）和CRI（5μg/kg(-1)分钟(-1)）（LDH）。MDS为Ld（0.8mg/kg(-1)）和CRI（10μg/kg(-1)分钟(-1)）（MDL），随后是Ld（1.6mg/kg(-1)）和CRI（20μg/kg(-1)分钟(-1)）（MDH）。HDS为Ld（3.2mg/kg(-1)）和CRI（40μg/kg(-1)分钟(-1)）（HDL），随后是Ld（6.4mg/kg(-1)）和CRI（80μg/kg(-1)分钟(-1)）（HDH）。在每个系列的每次给药后重新测定MAC(NM)（MAC(NM-T)）。
MAC(NM-B)中位数为1.42。各组间MAC(NM-B)无差异（p>0.05）。与MDS（30±5%）和HDS（32±5%）相比，LDS组MAC(NM)降低百分比显著更低（11±5%）。血浆咪达唑仑浓度与MAC(NM)降低百分比之间存在弱相关性（r=0.36）。
10 - 80μg/kg(-1)分钟(-1)范围内的咪达唑仑剂量显著降低异氟烷MAC(NM)。然而，大于10μg/kg(-1)分钟(-1)的剂量并未进一步降低MAC(NM)，表明存在天花板效应。
