The Potential Regimen of Target-Controlled Infusion of Propofol in Flexible Bronchoscopy Sedation: A Randomized Controlled Trial

Objectives
Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation.
Methods
After alfentanil bolus, initial induction Ce of propofol was targeted at 2 μg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 μg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded.
Results
The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 μg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 μg/ml, p = 0.005) and the Ce of procedures was higher at 0.5 μg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 μg/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 μg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively).
Conclusion
Titration at 0.5 μg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation.
Trial Registration
ClinicalTrials.gov NCT01101477

研究目标
靶控输注（Target-controlled infusion, TCI）可对效应室（即脑部）的丙泊酚浓度实现精准药代动力学调控。本预实验旨在评估柔性支气管镜检查（flexible bronchoscopy, FB）镇静中应用靶控输注的可行性与最优给药方案。

方法
在给予阿芬太尼推注后，将丙泊酚的初始诱导效应室浓度靶控设置为2 μg/ml。将患者随机分为3个滴定组，分别以0.5、0.2及0.1 μg/ml的梯度调整浓度，以维持稳定的镇静水平与生命体征。记录不良事件、给药调整频次、药物总剂量、诱导及苏醒时间。

结果
由于0.5 μg/ml滴定组出现了显著严重的低氧血症事件（血氧饱和度<70%），本研究提前终止。研究终止前，3组分别纳入49、49及46例患者。各组低氧血症事件发生率存在显著差异（67.3% vs. 46.9% vs. 41.3%，p=0.027）。低血压事件发生率、诱导与苏醒时间及丙泊酚总剂量组间无显著差异。各组诱导效应室浓度存在显著差异（2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 μg/ml，p=0.005），且0.5 μg/ml滴定组的术中效应室浓度更高（2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 μg/ml，p=0.006）。0.1 μg/ml滴定组的调整频次有升高趋势，但未达到统计学显著性差异（2(0~6) vs. 3(0~6) vs. 3(0~11)）。亚组分析显示，14%的患者在整个镇静过程中无需进一步调整给药方案。对比至少接受过1次给药调整的患者与无需调整的患者，前者诱导时间更短（87.6±34.9 vs. 226.9±147.9秒，p<0.001），诱导剂量与效应室浓度更低（32.5±4.1 vs. 56.8±22.7 mg，p<0.001；1.76±0.17 vs. 2.28±0.41，p<0.001），且低氧血症与低血压发生率更低（15.8% vs. 56.9%，p=0.001；0% vs. 24.1%，p=0.008）。

结论
以0.5 μg/ml梯度滴定用于柔性支气管镜检查镇静存在风险。存在一类患者无需额外靶控输注调整，且并发症更少。未来仍需开展进一步研究以确定柔性支气管镜检查镇静的最优靶控输注方案。

试验注册
ClinicalTrials.gov NCT01101477