Study design and patient objectives
This was a single center, randomized controlled trial to assess the effect of two different negative suction pressures on lung injury, pulmonary lavage status and pulmonary function in patients with pneumoconiosis undergoing WLL.
The protocol was approved by the ethics committee of Emergency General Hospital, China. Written consent was obtained from each participant. This study was registered in Chinese Clinical Trial Registry on March 21, 2020 (Registration number: ChiCTR2000031024). It also followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
A total of 24 pneumoconiosis patients who underwent WLL from May 2020 to July 2020 were enrolled in this study. The inclusion criteria were (i) 18 years < age < 80 years; (ii) Sex unlimited; (iii) Pre-operative forced expiratory volume in one second (FEV1%) ≥ 65%; (iv) Pre-operative arterial partial pressure of oxygen (PaO2) > 70 mmHg; (v) According to epidemiological and occupational history, the patients were diagnosed as pneumoconiosis by X-ray, and needed bilateral lung lavage at the same time. The exclusion criteria were (i) Patients who underwent WLL within one year; (ii) Patients with severe tracheobronchial malformations that prevented the double lumen trachea catheter from being in place; (iii) Patients with acute respiratory tract infection and had not been cured; (iv) Patients with bullae whose diameter of subpleural were more than 2 cm; (v) Patients with severe emphysema; (vi) Patients with coagulation dysfunction; (vii) Patients with uncontrolled hypertension; (viii) Patients with leukopenia.
The patients were randomly divided into two groups: high negative suction pressure group (group H, n = 13, negative suction pressure of 300-400 mmHg) and low negative suction pressure group (group L, n = 11, negative suction pressure of 40-50 mmHg). Group allocation number was placed in an envelope. The negative suction pressure regulation, sample collection, clinical follow-ups and laboratory research were carried out by different researchers who were all blind to the grouping situation. The patients and surgeons were all blind to the grouping situation. The details were as shown Fig. 1.
Anesthetic settings and maintenance
Standardized approach of anesthesia induction was performed and left DLT was inserted in place. Intraoperative maintenance: propofol 4 ~ 8 mg kg−1·h−1, remifentanil 0.15 ~ 0.3 μg·kg−1·min−1, intermittent administration of rocuronium 0.2 ~ 0.4 mg·kg−1 to maintain anesthesia depth and muscle relaxation.
After the DLT was placed, bilateral lung isolation was judged by clinical signs, and then determined by auscultation and fiberoptic bronchoscopy [10]. The parameters of the ventilator were set at 12 ~ 14 breaths/min, with volume of 8 ~ 10 ml/kg, I:E = 1:2, and oxygen concentration of 100%. The parameters of one-lung ventilation were set at 14 ~ 18 breaths/min, with a volume of 6 ~ 8 ml·kg−1 at inspired oxygen concentration of 100%. Airway pressure was maintained < 50 cm H2O.
The procedures of whole lung lavage
The infusion tube and the drainage tube were connected to one side of the DLT through a Y-tube. The lavage fluid was infused by gravity, and suspended at the level of 40 cm above the axillary midline. The lavage fluid was drained out by suction apparatus. Negative suction pressure is set to 300-400 mmHg or 40-50 mmHg. The lavage fluid was saline at 37℃. The order of lavage was right lung followed by left lung during the procedure. At the end of lavage, the negative pressure attraction should be thorough to reduce the residual liquid in the lavage side lung as much as possible. When the patient woke up and recovered spontaneous breathing, the DLT tube was removed, and then the patient was sent back to ward.
Observe indicators and assessment
Demographic and clinical characteristics of study population in both groups were recorded. Arterial blood gas (ABG) analysis at T1-before anesthesia induction, T2-before left lung lavage, T3-at the end of operation when bilateral lung ventilation recovery and T4-six hours after operation were recorded. Lung lavage time and volume of lavage fluid in both groups were recorded during operation.
Serum was collected at T1, T3 and T5- the third day after operation, and lavage fluid was collected at T3. The concentration of inflammation and the oxidation factors in them were measured by enzyme-linked immunosorbent assay (ELISA). Inflammation and the oxidation factors include tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD).
The pulmonary function parameters in both groups before operation (T1), one month after operation (T1-mon) and two months after operation (T2-mon) were also recorded, including maximal volumtary ventilation (MVV); forced vital capacity (FVC); FEV1%; residual volume (RV); total lung capacity (TLC); carbon monoxide dispersion factor (DLCO%); forced expiratory volume in one second/ forced vital capacity (FEV1/FVC%).
Statistical analysis
The sample size was estimated by the formula of n = (μα + μβ)2σ2/δ2 with a standard deviation of 0.8, and bilaterally equal to 0.05, or even 0.2 (power = 0.8). The concentration of inflammation and oxidation factors in serum and WLL fluid were the main primary and secondary outcome. The results were expressed as mean ± S.D, or the number and percentage. SPSS 20.0 software was used for data collation and statistical analysis. Parameters changes over time from baseline within each group were determined by repeated measures univariate analysis of variance (ANOVA). Differences between the groups at each time point were evaluated by 1-way ANOVA. Enumeration data was tested by χ2 or Fisher precision test. A value of P < 0.05 was considered statistically significant.