From the Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn.
Institute for Breathing and Sleep, Austin Hospital, Melbourne.
J Clin Psychopharmacol. 2019 Sep/Oct;39(5):446-454. doi: 10.1097/JCP.0000000000001101.
PURPOSE/BACKGROUND: As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear.
METHODS/PROCEDURES: Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 μg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 μg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV).
FINDINGS/RESULTS: Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits.
IMPLICATIONS/CONCLUSIONS: Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.
目的/背景:作为一种单一制剂,氯胺酮会使驾驶能力急剧受损;然而,与辅助镇静药物右美托咪定或芬太尼联合使用后的表现尚不清楚。
方法/程序:采用随机、自身对照设计,39 名参与者(平均年龄±标准差,28.4±5.8 岁)接受 0.3mg/kg 静脉推注,随后静脉输注 0.15mgkg h 氯胺酮(持续 3 小时),同时接受(i)0.7μgkg h 右美托咪定输注 1.5 小时(n=19;KET/DEX)或(ii)3 次 25μg 芬太尼注射 1.5 小时(n=20;KET/FENT)。仅在氯胺酮(KET/DEX 或 KET/FENT)和治疗后 2 小时测定全血药物浓度。使用标准化视觉模拟量表评估主观效应。使用经过验证的计算机驾驶模拟器在基线和治疗后评估驾驶表现。主要结局指标包括横向位置标准差(SDLP)和转向变异性(SV)。
结果/发现:与芬太尼相比,氯胺酮与右美托咪定联合使用后,2 小时时 SDLP(F1,18=22.60,P<0.001)显著增加,SV(F1,18=164.42,P<0.001)显著降低。与 KET/FENT 组相比,KET/DEX 组的这些缺陷更大(t37=-5.21[P<0.001]和 t37=5.22[P<0.001])。对于 KET/DEX 组,载体对照(SV)和自我评估的表现(视觉模拟量表)与氯胺酮和去甲氯胺酮的血液浓度(纳克/毫升)呈反比关系,但 SDLP 无此关系。更大的主观效应与驾驶缺陷呈中度相关。
结论/意义:在阿片类药物剂量的氯胺酮与右美托咪定联合使用后,驾驶模拟器的性能显著受损,但与芬太尼联合使用则不会。建议在治疗后进行一段时间的监督司机禁欲,并完成额外的评估,以评估家庭准备情况。