Aim
The overarching aim of this study was to assess the efficacy of the ARM with a low FiO2 (0.4) in preventing atelectasis and associated PPCs.
Study design
This single-center randomized clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200059216). Ethical approval was obtained from the Ethics Committee of the General Hospital of Western Theater Command (approval number 2022EC1-010). All individuals enrolled in the trial participated willingly and provided written informed consent. A flow diagram of the study design is shown in Fig. 1.
The data of 209 patients who underwent thoracoscopic lung surgery between September 2021 and May 2022 at the General Hospital of Western Theater Command were evaluated, and 120 patients were eventually enrolled. The inclusion criteria were as follows: (1) age ≥ 18 years; (2) American Society of Anesthesiologists (ASA) class I–III; (3) requirement of one-lung ventilation during thoracoscopic lung surgery; and (4) expected duration of surgery ≥ 2 h. The exclusion criteria were as follows: (1) patients who had acute respiratory distress syndrome (partial pressure of arterial oxygen [PaO2]/FiO2 < 200 mmHg) or chronic obstructive pulmonary disease (forced expiratory volume in 1 s/forced vital capacity < 60%); (2) those with a body mass index (BMI) of > 35 kg/m2; (3) those who had previously undergone thoracic surgery; (4) those with pneumothorax or bullae diagnosed by chest radiography or computed tomography (CT); (5) pregnancy or lactation; and (6) those with other severe diseases, including neuromuscular disease, intracranial injury or tumor, severe pulmonary hypertension (defined as a pulmonary systolic blood pressure of > 40 mmHg), severe cardiac disease (New York Heart Association class III or IV, acute coronary syndrome, or sustained ventricular tachyarrhythmia).
The 120 patients were randomly divided into groups C (n = 60, ARM with an FiO2 of 1.0 before extubation) and L (n = 60, ARM with an FiO2 of 0.4 before extubation) according to a random number table. The number table was randomly generated using a computer, grouped in a 1:1 ratio, and delivered to the anesthesiologist in an opaque envelope. During the investigation, eight patients were excluded because of surgical changes, high blood loss, or bilateral lung surgery. The drop-out criteria were as follows: (1) operation converted to thoracotomy or bilateral lung surgery; (2) surgery time ≤ 45 min; (3) bleeding (> 500 mL) or severe hypotension (mean blood pressure < 55 mmHg with vasopressor/inotrope use) during surgery. Finally, 55 patients in group C and 57 in group L were included in the final analysis.
The researchers, patients, and ward staff were blinded to this grouping. After surgery, all data were collected by investigators blinded to the groupings.
Anesthesia and mechanical ventilation protocol
All patients underwent similar anesthesia management. Anesthesia was induced intravenously by midazolam 0.03 mg/kg, sufentanil 0.3–1.0 µg/kg, etomidate 0.1–0.4 mg/kg or propofol 1.5–2.5 mg/kg, rocuronium 0.6 mg/kg, or cisatracurium 0.2 mg/kg. Following tracheal intubation with a selected visual double-lumen tracheal tube, anesthesia was maintained using sevoflurane (0.6–1 minimum alveolar concentration), dexmedetomidine, and reverentanil. Rocuronium or cisatracurium was administered intermittently. After the main procedure, the use of dexmedetomidine was stopped; the administration of propofol was continued at 2–8 mg/kg/h, that of sevoflurane was stopped 30 min before the end of the operation, and that of all anesthetic drugs was stopped immediately after the surgery.
The conditions applied during the entire period of mechanical ventilation following tracheal intubation were as follows: pressure-controlled ventilator-volume guaranteed mode, FiO2 1.0, inspiratory to expiratory ratio 1:2, respiratory rates adjusted to maintain the end-tidal carbon dioxide (PETCO2) at 35–45 mmHg. The tidal volume was 6–8 mL/kg (predicted bodyweight, [PBW]) during two-lung ventilation and 5–6 mL/kg PBW during one-lung ventilation. After one-lung ventilation, the ARM was performed with a continuous positive airway pressure of 20 cmH2O for 15–20 s, and the positive end-expiratory pressure was set to 5 cmH2O until extubation. The intraoperative oxygen saturation (SpO2) was maintained at ≥ 92%. The airway pressure was limited to 30 cmH2O. After surgery, the ARM was performed with a continuous positive airway pressure of 30 cmH2O for 15–20 s before extubation. The FiO2 was 1.0 in group C and 0.4 in group L (the ARM was performed when the fractions of inspired and exhaled oxygen monitored by the anesthesia machine were 1.0 and 0.4, respectively). After extubation, the patients were transferred to the post-anesthesia care unit (PACU) with oxygen facemasks at a flow rate of 3000 mL/min, observed for at least 30 min, and returned to the ward. Postoperative chest radiography or CT was performed.
Outcome measures
The primary outcomes were the incidence of pulmonary complications, including atelectasis, respiratory failure, airway infection, aspiration pneumonia, and bronchospasm, within 7 days after surgery. The diagnosis of PPCs was based on the European Joint Task Force published guidelines for perioperative clinical outcome definitions 23. Atelectasis was assessed using postoperative chest radiography or CT findings and lung ultrasound scores (LUSs). If the patient was discharged early, follow-up was performed until discharge. All patients were followed up 7 days after surgery.
Lung ultrasonography was performed using a UMT-500 Plus ultrasound machine (Mindray, Shenzhen, China) and convex array probe. The chest wall was divided into three regions on one side: the parasternal, anterior axillary, and posterior axillary lines. Each region was further separated into upper and lower parts. The bilateral chest walls were divided into 12 areas (Fig. 2) 24. Two qualified pulmonary sonographers scanned the intercostal space in 12 quadrants and systematically recorded assessment scores based on a simple regional assignment of 0–3 points according to a simple grading system (0, normal image, lung slip sign, line A, no lung consolidation; 1, thickened and irregular pleura, ≥ 3 B-lines or minimal subpleural consolidation; 2, thickened and irregular pleura, combined B-line or small subpleural consolidation; and 3, large subpleural lung consolidation) (Fig. 3). Lung ultrasonography was performed before the induction of anesthesia (T1), after extubation (T3), and 1 h after extubation (T5) in both groups.
Secondary outcomes were postoperative inflammatory factors (interleukin [IL]-6, IL-10, tumor necrosis factor-α [TNF-α]), intraoperative vital signs, and arterial blood gas analysis at pre-anesthesia (T1), after the ARM with different fractions of inspired oxygen (T2), and 30 min after extubation (T4). The incidence of postoperative nausea and vomiting, the incidence of reintubation or reoperation, length of stay in the ICU, length of hospital stay, postoperative length of stay, and postoperative drainage tube retention time were recorded. The incidence of postoperative atrial fibrillation, death within 30 days of surgery, and patient costs during hospital stay were noted.
Sample size and statistical analyses
The sample size was estimated using PASS 15 software (NCSS, Kaysville, UT). Reportedly, the incidence of pulmonary complications after thoracic surgery is 15–37.5% 25. It is estimated that the incidence of PPCs was 38% in group C and 15% in group L (α = 0.05, β = 0.2), and the ratio between groups was 1:1. Considering a dropout rate of 10%, 120 patients were included in the study, with 60 patients in each group.
All data were analyzed using the SPSS software (version 26.0; IBM, Armonk, NY). Statistical significance was set at P < 0.05. Counts were expressed as either the number of cases or percentage and analyzed using a chi-squared or Fisher’s exact test. Normally distributed quantitative data were expressed as means ± standard deviations and compared using a T-test. Data satisfying the homogeneity of variance were analyzed using one-way analysis of variance. Data with non-normal or unknown distributions were expressed as medians and ranges (interquartile ranges) and compared using the Mann–Whitney U test.