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

<div><p>Objectives</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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%, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 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).</p><p>Conclusion</p><p>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.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01101477" target="_blank">NCT01101477</a></p></div

Bronchoscopy and sedative outcomes of the patients receiving complete intervention.

<p>Data are presented by mean (standard deviation) unless otherwise indicated. Abbreviations: A, alfentanil; P, propofol; Ce: effect-site concentration; Cet: target setting of Ce.</p><p>#From starting propofol infusion to Observer Assessment of Alertness and Sedation scale 3∼2.</p>*<p>From insertion of bronchoscope to its removal.</p>†<p>From bronchoscope removal to patients could open eyes spontaneously, correctly recall date of birth, and perform finger-nose test.</p><p>Turkey post hot test. & p = 0.007; ⊕ p = 0.034.</p>¶<p>Data is presented by median (range).</p

Patient disposition.

<p>Patient disposition.</p

Subgroup analysis of patients requiring no adjustment or at least one adjustment of Cet during whole procedures.

<p>Data are presented as mean ± standard deviation or number and percentage in parentheses.</p><p>Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; Ce: effect-site concentration; Cet: target setting of Ce.</p

Proportions of hypoxemia and hypotension during bronchoscopic sedation of the intent-to-treat group^#.

<p>Data are presented as number and percentage.</p><p>Abbreviations: SpO₂: oxyhemoglobin saturation; MAP: mean arterial pressure; SBP: systolic blood pressure.</p>#<p>The proportions of patients with at least one event of hypoxemia (SpO₂<90%) or hypotension (MAP<65mmHg or SBP<90mmHg) during the entire procedure.</p>*<p>From alfentanil administration to Observer Assessment of Alertness and Sedation scale less than 3.</p>†<p>From insertion of bronchoscope to its removal.</p

Energy spectrum of the 20 subjects categorized by energy typing showing their exact distributions of snoring sound energy.

<p>Some cases with low amplitude of snoring sound energy needed adjustment of the Y-axis scales for an easier typing.</p

The spectrum of snoring sound (red line) and background noise (black line).

<p>Note that the duration of snoring sound was between 0.6 and 4.0 seconds (blue box) and noise intensity in sound pressure level was general less than 10 dB when frequencies were higher than 450 Hz (green box).</p

Snoring power spectral data among four snore map types.

<p>SI: snoring index. Imax: maximal sound intensity. Imean: mean sound intensity. Fpeak: peak frequency. Fmean: mean frequency. B1: the band between 40 Hz and 300 Hz. B2: the band between 301 Hz and 850 Hz. B3: the band between 851 Hz and 2000 Hz.</p>†<p>Significance was assessed by a Kruskal Wallis test.</p>‡<p>Significance was tested using a 2-sided Mann-Whitney <i>U</i> test.</p>*<p>A value of <i>P</i><0.05 was considered significant.</p

Demographic characteristics, snoring questionnaires, polysomnographic parameters, and snore map type.

<p>BMI: body mass index. FTP: Friedman tongue position. NC: neck circumference. VAS: visual analogue scale. SOS: snoring outcome survey. SBPS: spouse/bed partners survey. AHI: apnea-hypopnea index. AI: apnea index. HI: hypopnea index. SI: snoring index. OSAS: obstructive sleep apnea syndrome.</p

Scatter plots of clinical parameters versus snore map type.

<p>(A) A scatter plot of body mass index (BMI) versus snore map type. (B) A scatter plot of neck circumference versus snore map type. (C) A scatter plot of apnea-hypopnea index versus snore map type. (D) A scatter plot of severity of obstructive sleep apnea syndrome (OSAS) versus groups of snore map type. After adjustment for BMI and neck circumference, snore map type 3–4 was significantly associated with severity of OSAS (<i>R</i>² = 0.28, <i>P</i> = 0.026). Blue dashed line indicates linear fit line.</p