Study design and population
This retrospective observational study was conducted at a tertiary university-affiliated hospital from May 2015 to September 2017. It was approved by the local Institutional Review Board (IRB no. CUH 2019-06-028). The patients were stratified into the remifentanil group and midazolam/propofol group according to the drugs used during flexible bronchoscopy.
Flexible fiberoptic bronchoscopy was performed with standard fiberscopes by two professional pulmonologists. A flexible bronchoscope (BF-F260, BF-6C260, 1T260, BF-Q290, 1TQ290, Olympus, Tokyo, Japan) was inserted via the nasal approach with subjects in the supine position.
All consecutive patients who were spontaneously breathing were eligible. All patients had fasted for at least eight hours prior to the start of the procedure and had an intravenous catheter. Topical anesthesia was performed using 4% lidocaine spray in the oral cavity. While the vocal cords and carina were visualized, 4 ml of 2% lidocaine was delivered through the bronchoscope channel to suppress cough. Additional topical anesthesia was applied to the major bronchi as needed (at the bronchoscopists’ discretion) for a maximum total lidocaine dose of 7 mg/kg.
Pretreatment with 1-2 mg midazolam (Midazolam®, Bukwang, Seoul, Republic of Korea) was used to relieve significant preprocedural anxiety. Patients were treated with an additional 1mg of midazolam if necessary. Next, propofol (Anepol®, Hana Pharmaceutical Co., Seoul, Republic of Korea) was administered according to our hospital’s protocol (Table 1).
Patients received no premedication in the remifentanil group. Remifentanil (Ultiva®, GlaxoSmithKline, Seoul, Republic of Korea) was initially administered with a bolus dose of the study drug (0.5-1 mcg/kg), followed by a 0.02–0.04mcg/kg/min continuous infusion at the discretion of the bronchoscopist. A bolus dose of the study drug in proportional volumes was administered slowly (over a period of 60 s) to minimize known adverse effects, such as respiratory depression, hypotension, and bradycardia. The fiberscope was inserted into the patient 3-5 minutes after the remifentanil initial onset time. The remifentanil infusion was immediately stopped if bradypnea/apnea or hemodynamic collapse occurred.
The primary outcomes included the incidences of oxygen desaturation and oxygen saturation trend between the two groups. Oxygen desaturation was defined as an oxygen saturation < 90% for more than 10s. In the event of oxygen desaturation, oxygen delivery was increased from 4 to 10 liter/min. Additional assistance (including reservoir bag-mask, high flow nasal cannula, and intubation followed by bag valve mask ventilation) was performed in a stepwise manner as needed. Secondary outcomes included hemodynamic variables, the incidence of hemodynamic adverse events, and recovery time.
Vital signs were continuously monitored before, during, and after the procedure by the bronchoscopist and nurses. Bradycardia (defined by a heart rate < 60 beats/min or a decrease of >15 beats/min from baseline) was treated with intravenous atropine 0.5 mg. Hypotension (defined by a systolic blood pressure <90 mm Hg or a decrease of >20 mmHg from baseline) was treated with intravenous epinephrine 5 mg. Bradypnea (defined by a respiratory rate <12/min or apnea >10s), and other adverse reactions were noted throughout the procedure.
Immediately after the procedure, the patients and bronchoscopists were asked about their level of satisfaction with the procedure (with regard to recall, pain, and discomfort for patients, and ease of the procedure). Patients were also asked if they would be willing to undergo repeat bronchoscopy if needed. This response was recorded as ‘yes’ or ‘no.’.
After the bronchoscopy, the patient was moved to the recovery room. In the recovery room, the recovery of the patient was assessed using the modified Aldrete score  every 3-5 minutes by the attending nurses. Recovery time was defined as the time taken after the end of bronchoscopy until the recovery, which was defined ≥ 9 for the modified Aldrete score . Recovery time was classified as fast and delayed according to the median value of recovery time.
Continuous variables are presented as means (SD) or medians (interquartile range, [IQR]). Categorical variables are presented as counts (%). Continuous variables were compared using the Mann-Whitney U test or T-test for continuous variables. Categorical variables were compared using the chi-square test or Fischer’s exact test, as appropriate. In order to evaluate the factors associated with fast recovery time, we performed univariable and multivariable logistic regression analyses. The following factors were included in the multivariable model: age, sex, body mass index, chronic obstructive pulmonary disease or asthma, chronic heart disease, bronchoscopy indication, procedure purpose, and type of sedative drugs. Two-sided p values < 0.05 were considered significant. All statistical analyses were performed using R (ver. 3.2.3; R Foundation for Statistical Computing, Vienna, Austria) and STATA version 15 (StataCorp LP, College Station, TX, USA).