The protocol for this study was approved by the Nagoya City University Graduate School of Medical Sciences and Nagoya City University Hospital Institutional Review Boards (Nagoya, Japan, approval number: 60-18-0073). According to our institutional review board’s code of ethics, we used an opt-out method and posted a description of the research protocol on the website of the Nagoya City University Graduate School of Medical Sciences on July 30, 2018, and the patients could withdraw from the study.
Data source and study population
The present retrospective observational study included patients who underwent lung resection between April of 2015 and March of 2018. We included patients who underwent DLT intubation with a Macintosh laryngoscope and a neuromuscular blocking drug, who were ≥15 years of age, and who had an American Society of Anesthesiologists physical status classification (ASA-PS) of 1 or 2. Patients with preoperative hoarseness, those who were intubated with a video laryngoscope, those who required emergency surgery, and those with missing data were excluded from this study.
Study variables
The exposure of interest was DLT intubation performed by a trainee or senior anesthesiologist. We divided patients into 2 groups: one group comprising patients who were intubated by a trainee anesthesiologist and the other comprising those who were intubated by a senior anesthesiologist. Anesthesiologists in Japan can only be certified as Qualified Anesthesiologists according to the Japanese Society of Anesthesiologists after completing a 2-year training program. Therefore, we defined trainee anesthesiologists as “anesthesiologists with less than two years of anesthesia experience” and senior anesthesiologists as “those with more than two years of anesthesia experience”. These definitions were the same as those used in a previous study [7]. We collected the following clinical variables: age, gender, height, weight, body mass index (BMI), ASA-PS, duration of anesthesia, intraoperative fluid balance, DLT size, intubation depth, number of intubation attempts, intracuff pressure of the DLT, Mallampati score, and Cormack–Lehane grade.
Outcome measures
The primary outcome was incidence of postoperative hoarseness 24 h after surgery. Anesthesiologists in charge of postanesthetic rounds at our hospital must use a checklist of postanesthetic adverse events and determine the presence of hoarseness 24 hours after surgery. The investigator (YK), who did not perform DLT intubation or manage anesthesia, collected data on postoperative hoarseness from electronic medical records using a checklist of postanesthetic adverse events. We defined postoperative hoarseness as “a patient-assessed change in voice quality”. We did not qualitatively or objectively evaluate postoperative hoarseness. We investigated whether the anesthesiologist who assessed postoperative hoarseness was the same one who provided anesthesia for the patient and whether he or she was a trainee or senior anesthesiologist.
Perioperative patient treatment
There are no standardized methods for induction or maintenance of anesthesia. Electrocardiography, pulse oximetry, and invasive blood pressure monitoring were performed after patients arrived at the operating room. Patients received a combination of general and epidural anesthesia. General anesthesia was induced with propofol (a bolus dose of 1–2 mg/kg or a target-controlled infusion at 3–3.5 μg/ml), fentanyl (1–4 μg/kg) and remifentanil (0–0.3 μg/kg/min) following placement of a thoracic epidural catheter. An attending trainee or senior anesthesiologist performed DLT intubation with a Macintosh laryngoscope after bolus administration of rocuronium (0.6–1 mg/kg). Neuromuscular monitoring was not performed during tracheal intubation. Blade size (3 or 4) was chosen based on anesthesiologist preference and the patient’s physique. Portex® Blue Line® Endobronchial Tubes-left (Smiths Medical, Minneapolis, MN, USA) with a stylet were used in all procedures and a water-soluble lubricant without lidocaine was applied to the tube. We used a 37-Fr DLT for men and a 35-Fr DLT for women, but tube size was determined by the attending anesthesiologist based on the patient’s height [8]. The attending anesthesiologist guided the DLT into position via a flexible bronchoscope and assessed tube placement after changing patient to the lateral decubitus position. Anesthesia was maintained with 1%–2.5% sevoflurane or propofol (target-controlled infusion at 2–3.5 μg/mL) and the Bispectral Index® value was kept between 40 and 60 throughout the entire procedure. Residual neuromuscular blockade was reversed with sugammadex (2–4 mg/kg), postoperatively, and the DLT was removed in the operating room.
Statistical analysis
For sample size calculation, we assumed that the incidence of postoperative hoarseness 24 h after surgery in patients who underwent intubation by a trainee or senior anesthesiologist would be 20% and 5%, respectively, based on previous reports [4,5,6]. Thus, 89 patients in each group were required to provide 80% power to detect a statistical difference between groups using Fisher’s exact test with a two-sided significance level of 5%.
We conducted propensity score analyses to account for differences in baseline characteristics between the 2 groups. The c-statistic for evaluating goodness of fit was calculated and we performed one-to-one propensity score matching by nearest neighbor matching without replacement. Caliper width was set to 25% of the standard deviation of the propensity scores. Furthermore, the confounding factors used in the propensity score model were age, gender, height, weight, BMI, ASA-PS, duration of anesthesia, intraoperative fluid balance, tube size, tube depth, number of intubation attempts, intracuff pressure, Mallampati score, and Cormack–Lehane grade. We assessed the differences between the 2 groups before and after propensity score matching with standardized differences. Standardized differences of <10% were considered negligible imbalances in the baseline characteristics between the 2 groups. We compared the incidence of hoarseness 24 h after surgery between the 2 groups using Fisher’s exact test for before matching and the McNemar test for after matching. A P value <0.05 was considered statistically significant. All statistical analyses were performed using the R software package (version 3.5.0, R Foundation for Statistical Computing, Vienna, Austria).