From the Department of Anesthesia, Intensive Care and Pain Management, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Department of Anesthesia and Intensive Care, Faculty of Medicine, Assiut University, Assiut, Egypt.
Anesth Analg. 2021 Feb 1;132(2):456-464. doi: 10.1213/ANE.0000000000005108.
Buccal dexmedetomidine (DEX) produces adequate preoperative sedation and anxiolysis when used as a premedication. Formulating the drug as a gel decreases oral losses and improves the absorption of buccal DEX. We compared pharmacokinetic and pharmacodynamic properties of 3 doses of buccal DEX gel formulated in our pharmaceutical laboratory for sedative premedication in women undergoing modified radical mastectomy for breast cancer.
Thirty-six patients enrolled in 3 groups (n = 12) to receive buccal DEX gel 30 minutes before surgery at 0.5 µg/kg (DEX 0.5 group), 0.75 µg/kg (DEX 0.75 group), or 1 µg/kg (DEX 1 group). Assessments included plasma concentrations of DEX, and pharmacokinetic variables calculated with noncompartmental methods, sedative, hemodynamic and analgesic effects, and adverse effects.
The median time to reach peak serum concentration of DEX (Tmax) was significantly shorter in patients who received 1 µg/kg (60 minutes) compared with those who received 0.5 µg/kg (120 minutes; P = .003) and 0.75 µg/kg (120 minutes; P = .004). The median (first quartile-third quartile) peak concentration of DEX (maximum plasma concentration [Cmax]) in plasma was 0.35 ng/mL (0.31-0.49), 0.37 ng/mL (0.34-0.40), and 0.54 ng/mL (0.45-0.61) in DEX 0.5, DEX 0.75, and DEX 1 groups (P = .082). The 3 doses did not produce preoperative sedation. The 1 µg/kg buccal DEX gel produced early postoperative sedation and lower intraoperative and postoperative heart rate values. Postoperative analgesia was evident in the 3 doses in a dose-dependent manner with no adverse effects.
Provided that it is administered 60-120 minutes before surgery, sublingual administration of DEX formulated as an oral-mucosal gel may provide a safe and practical means of sedative premedication in adults.
颊用右美托咪定（DEX）作为术前用药可产生足够的镇静和抗焦虑作用。将药物制成凝胶可减少口腔损失并改善颊用 DEX 的吸收。我们比较了在我们的制药实验室中制备的 3 种剂量的颊用 DEX 凝胶在接受改良根治性乳房切除术的乳腺癌女性中作为镇静术前用药的药代动力学和药效学特性。
36 名患者分为 3 组（每组 12 名），在手术前 30 分钟接受颊用 DEX 凝胶：0.5µg/kg（DEX 0.5 组）、0.75µg/kg（DEX 0.75 组）或 1µg/kg（DEX 1 组）。评估包括 DEX 的血浆浓度、非房室法计算的药代动力学变量、镇静、血液动力学和镇痛作用以及不良反应。
接受 1µg/kg（60 分钟）的患者达到 DEX 血清峰浓度（Tmax）的中位时间明显短于接受 0.5µg/kg（120 分钟；P=0.003）和 0.75µg/kg（120 分钟；P=0.004）的患者。血浆中 DEX 的中位数（第一四分位数-第三四分位数）峰浓度（最大血浆浓度[Cmax]）分别为 0.35ng/mL（0.31-0.49）、0.37ng/mL（0.34-0.40）和 0.54ng/mL（0.45-0.61），在 DEX 0.5、DEX 0.75 和 DEX 1 组中（P=0.082）。3 种剂量均未产生术前镇静作用。1µg/kg 颊用 DEX 凝胶在术后早期产生镇静作用，并降低术中及术后心率值。3 种剂量均以剂量依赖性方式产生术后镇痛作用，且无不良反应。
如果在手术前 60-120 分钟内给药，颊用 DEX 制成口腔黏膜凝胶可能为成人提供一种安全实用的镇静术前用药方法。
