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 mu g/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 mu g/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 mg/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 mu g/ml, p = 0.005) and the Ce of procedures was higher at 0.5 mu g/ml titration (2.4 +/- 0.5 vs. 2.1 +/- 0.4 vs. 2.2 +/- 0.3 mu g/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 mg/ml but was not statistically significant (2 (0 similar to 6) vs. 3 (0 similar to 6) vs. 3 (0 similar to 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 mu g, 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 mu g/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.