Study Recruitment
This randomized controlled study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University, and registered in the China Clinical Trial Register (ChiCTR1800014690). Written informed consent was obtained from all enrolled patients.
Patients
ASA I-III patients, aged 18-65 years and undergoing selective FB for diagnosis between February and April 2018, were included. Patients unable to cooperate, with a known allergy to local anesthetic, asthma, pregnancy, major cardiac disorders, renal or liver dysfunction, pre-existing neurological deficits, and psychiatric illness were excluded. Patients undergoing endobronchial ultrasoundguided transbronchial needle aspiration endobronchial ultrasonography (EBUS-TBNA) and transbronchial needle aspiration (TBNA) were also excluded because the procedure times exceeded the effective duration of single dose of lidocaine anesthesia.
Randomization
One hundred patients undergoing diagnostic FB were randomly allocated into two groups according to a computerized random number generator (Figure1). group C patients received topical lidocaine through the working channel of the bronchoscope, whereas group E patients received topical lidocaine via a triple-orifice epidural catheter.
Study Protocol
All patients were fasted from solids for eight hours before the procedure, and from liquids for two hours before the operation. Intravenous (IV) access was established before the procedure. Proper inspection of the anesthesia machine was performed preoperatively. Standard monitoring was instituted before the induction of anesthesia, including ECG, noninvasive blood pressure (BP), and oxygen saturation (SpO2). Prior to the procedure all the patients received oral and nasal lidocaine at a volume of 2 mL 2% lidocaine (100mg/5mL, 31710302, Tianyao Pharma. Co. Ltd, China). Thereafter the patient received midazolam 1 mg and sufentanil 10 ug IV for sedation. Anesthesia induction was achieved with 0.1 mg/kg etomidate (10 mg/10mL, 20171116, NhwaPharma.Corporation, China.) followed by 1 mg/kg propofol (200 mg/20mL, 16LF8047, Fresenius Kabi Deutschland GmbH D-61346 Bad Homburg v.d.H. Germany) IV. All patients were intubated nasotracheally, and maintained spontaneous breathing.
While advancing the flexible bronchoscope in the airway, 2% lidocaine was delivered using the “spray-as-you-go” technique through the bronchoscope by the conventional method (direct application via syringe), or by a triple-orifice epidural catheter. The epidural catheter (20-gauge, Haisheng Medical Equipment co. LTD. China) used in this study was designed with three orifices oriented in a helicoidal distribution along the long axis of the catheter in the distal 10 mm segment (Figure 2,3). Lidocaine 2% 3 ml was administered supraglottically, and three aliquots of 5 ml of lidocaine 2% were applied to the trachea as well as the right and left main stem bronchi, consecutively. The bronchoscopist waited for one minute after applying the topical anesthesia to the glottis before passing the bronchoscope through the vocal cords. Extra lidocaine aliquots were instilled at the discretion of the respiratory physician for cough suppression. Additional propofol 0.4 mg/kg was added at the discretion of the anesthetist to blunt any patient reflexive responses. Whenever the oxygen saturation dropped below than 90%, the patients received supplemental manual ventilation via the nasotracheal tube to maintain an oxygen saturation above 90%. Additionally, the heart rate and blood pressure were kept within ±20% of the baseline values. After the procedure, the patients were transferred to the post-anesthesia care unit (PACU) and evaluated using the post-anesthesia outpatient discharge criteria (PADC), which were modified by the Department of Anesthesiology, the First Affiliated Hospital Medical University and to be stricter than the previous post-anesthesia discharge scoring system (Table 1).[12] The criterion used for patient discharge was a PADC score of >8 and the nurse recorded the recovery time of each patient in the PACU.[12]
All the airway anesthesia was conducted by one bronchoscopist. The respiratory physcians and nurses who participated in the bronchoscopy were the same clinical team members. They were blinded to the groups and came into the operating room after airway anesthesia. At the end of the procedure, they independently assessed the cough using the visual analog scale (VAS) during FB. We included 6 nurses and 3 respiratory physcians and have explained the VAS for cough before the study. The anesthesiologist was responsible for the general anesthesia and airway management throughout the procedure and assessed cough severity via “4-point” scale. Another study assistant was responsible for recording data.
Outcome Measures
The primary outcome of this study was cough severity. Cough severity was assessed by the anesthesiologist using a 4-point scale (1=no cough; 2=slightly cough; 3=moderate cough; 4=severe cough).[11 13] Coughing during the procedure was considered slight if < 2 coughs occurred in sequence, moderate if 3 to 5 coughs occurred in sequence, and severe if more than 5 coughs occurred in sequence.[11, 13]
The secondary outcomes were as follows. The bronchoscopists and the assisting nurses independently evaluated the cough intensity during FB using a visual analogue scale (VAS), where 0 represented no cough and 10 represented incessant cough. The numbers of patient coughs during the bronchoscope placement in the glottis, trachea, left and right bronchi were recorded for each group. The highest respiratory rate (H-RR), heart rate (H-HR), and blood pressure (H-SBP, H-DBP), as well as the lowest oxygen saturation (L-SpO2) during the procedure were documented. The duration and type of diagnostic procedures were recorded for each patient at the end of FB. The patients were followed up by telephone concerning the extent of coughing and level of satisfaction (recall, pain, and discomfort) two hours after the procedure. Any adverse events, such as nausea and vomiting, arrhythmia, hypoxemia, bronchospasm, and local anesthetic toxicity, were recorded.
Sample Size
The sample size was calculated using the Power Sample Size Program (PASS11.0). In the preliminary study, the cough severity scores of group C and group E were 2.50±0.26 and 2.30±0.21, respectively. The minimum sample size required was 44 patients per group for a power of 0.9 with a two-tailed significance level of 0.05 (β = 0.1 and α = 0.05). Assuming a dropout rate of 10%, the final sample size was set at 50 patients in each group.
Statistical analysis
Analysis was performed using SPSS software version 19.0 (SPSS Inc, Chicago, IL, USA). The Shapiro-Wilk test was used to a test for normal distribution. The normally distributed data were presented as the mean with standard deviation, and the non-normally distributed data were presented as a median with an interquartile range. Categorical variables were expressed as a number with the percentage. The height, weight, BMI, HR, SBP, and SDP at the baseline, H-HR, H-SBP, and H-SDP during the procedure; the duration of the procedure; and the PACU stay time were compared using Student’s unpaired t-tests. The ASA physical classification, VAS scores, cough severity, RR and SpO2 at baseline, H-RR andL-SpO2 during the procedure, as well as the total consumption of lidocaine and propofol were compared using Mann-Whitney U-tests for intergroup differences. The correlation between the judgements of the bronchoscopist and the assistant nurse was compared using Spearman correlation analysis. The sex, adverse effects, and frequency requirements for propofol and lidocaine were compared by χ2 test. A P<0.05 was considered statistically significant.