Patients
The study was approved by the review committee of the Second Affiliated Hospital of Zhejiang University (IR2018001133, 2018/12/05) and registered at ClinicalTrials.gov (NCT03802175) before patient enrolment. Informed consent was obtained from all patients. Adult patients who received general anaesthesia and suffered hypoxaemia in the PACU were included in this study. Postoperative hypoxaemia was defined as decreased oxygen saturation measured by pulse oximetry (SPO2) less than 92% for greater than 30 seconds while under ambient air conditions 20 minutes after extubation.15 The exclusion criteria included the following: covered surgical dressings from open thoracic or breast surgery preventing ultrasound examination; body mass index (BMI) greater than 40 kg/m2; lack of cooperation due to cognitive dysfunction; residual muscle relaxants resulting in incomplete recovery of muscle strength (train-of-four stimulation, TOF < 0.9); respiratory forgetfulness from residual opioid; haemodynamic instability; anaemia; and significant bleeding, fever or hypothermia. In addition, patients were withdrawn if their SPO2 declined to 85% or less or if admission to the intensive care unit (ICU) occurred.
Anaesthesia Protocol
Before the induction of anaesthesia, all patients were preoxygenated with an inspiration oxygen fraction (FiO2) of 1.0 for 3 minutes. Anaesthesia was induced with midazolam 0.05-0.1 mg/kg, sufentanil 25-35 µg, etomidate 0.2-0.4 mg/kg and rocuronium 0.5-0.7 mg/kg. A proper double-lumen endotracheal tube was intubated to perform one-lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS), whereas a common tracheal tube was inserted for two-lung ventilation (TLV) during non-VATS. Continuous intravenous propofol, remifentanil and inhalational sevoflurane were utilized for anaesthesia maintenance after intubation. Supplemental cisatracurium was provided for adequate muscle relaxation when needed. Volume-controlled ventilation with tidal volume of 5-8 mL/kg (5-6 mL/kg for OLV and 6-8 mL/kg for TLV), respiratory rate (RR) of 12-15 breaths/min, FiO2 of 0.5-0.6 and positive end-expiratory pressure (PEEP) of 5 cm H2O was utilized to maintain an end-tidal carbon dioxide pressure (PETCO2) between 35 and 45 mmHg and a peak airway pressure of less than 30 cmH2O (specific parameter was adjusted according to the type of surgery and patient's condition). Depth of anaesthesia monitoring was completed by bispectral index (BIS) with an appropriate value of 40-60. Before closing the chest, each patient undergoing VATS received a recruitment manoeuvre (RM) by forcing sustained inspiration at the level of 30-40 cm H2O airway pressure for 10-20 seconds, and then OLV was converted to TLV until extubation. In addition, a chest tube was connected to a water-sealed bottle to provide drainage of any leaked air or fluid. Those undergoing non-VATS did not receive RM. All patients were transported to the PACU after the operation. Before extubation, the mechanical ventilations in the PACU was the same as that in the operating room. Extubation was performed when the following criteria were met: VT > 5 mL/kg, minimal RR of 11 breaths/min, haemodynamic stability (a maximum variation in mean arterial pressure and heart rate was 20% around the baseline value), normothermia, and TOF ≥0.9. Neostigmine (0.02 mg/kg) was used for the reversal of neuromuscular blocking before extubation. After extubation, the patient inhaled oxygen through a face mask at 3-6 L/min for approximately 15 minutes, and then the face masks were removed. Patients were supplemented with oxygen again through masks as temporary treatment if the SPO2 declined to less than 92%.
Lung Ultrasound Examination
With a 2 to 5 MHz convex probe in an ultrasound device (Mindray, Guangdong, China), LUS imaging was performed immediately in the PACU by two trained anaesthesiologists (Chen X and Kai S, both with more than 1 year of ultrasound training) once hypoxaemia occurred. The anterior and posterior axillary lines divided each hemithorax into three regions (anterior, lateral and posterior), and each region was further divided into two quadrants (superior and inferior) (Figure 1). The anaesthesiologists performed LUS examination from the left lung to the right in the above order. Atelectasis was diagnosed as a tissue-like pattern or hypoechoic juxta-pleural consolidations with hyperechoic static air bronchograms.10 A juxta-pleural consolidation or tissue-like structure may also indicate pneumonia. However, the visualization of dynamic air bronchograms helps exclude atelectasis.16 With a negative predictive value of 100%, the presence of lung sliding excluded the diagnosis of pneumothorax.17 Moreover, the diagnosis of pneumothorax should be combined with the lung point, barcode sign on M mode and absence of lung sliding.13,18-20 On this basis, the absence of pleural sliding in the anterior, lateral or posterior chest on LUS was defined as small, medium or large pneumothorax.21 The presence of anechoic area fluctuating with respiration indicated pleural effusion. 22 Examination of pleural effusion was performed with the patient in the semi-recumbent position. A large pleural effusion was diagnosed when the maximal interpleural distance was more than 25 mm on ultrasonography, and the effusion must be visible in at least three intercostal spaces. Less than 15 mm of maximal interpleural distance was defined as a small effusion.23 Combined with symptoms such as dyspnoea, a minimum of 3 B-lines in at least two anterior or lateral quadrants in each thorax may benefit from the consideration of pulmonary oedema.24
LUS scores (0-36, calculated by summing all 12 individual quadrant scores) are used to assess aeration changes, and a higher grade represents more serious aeration loss but is inapplicable for pneumothorax (Figure 2).25-27 The scoring system is as follows: score 0, healthy lung, equidistant A-lines parallel to the sliding pleura; score 1, moderate aeration loss, no fewer than 3 dispersive B lines originated from the pleural cavity; score 2, serious aeration loss, presence of coalescent B lines with pleural irregularities; and score 3, absolute aeration loss, subpleural consolidation. The stored video of the worst irregularity was analysed off-line by Chen X and Kai S. In case of disagreement, a third anaesthesiologist (Lina Y, with 5 years of ultrasound training) reviewed the uncertain images and made the final diagnosis.
Computed Tomography Scan
After LUS examination, every patient with stable haemodynamic and spontaneous respiration was transported to the radiology department by a nurse anaesthetist for thoracic CT scan within 1 hour after LUS examination. During transport, all patients received oxygen through face masks. Scanning from the apex to the diaphragm with the patient in the supine position, the examination was performed with a 128-slice spiral CT device (Siemens, Amberg, Germany). With a window width of 1500 Hounsfield units and a section thickness of 0.5 mm, all CT sections were stored for reconstruction and computerized analysis. A trained radiologist blinded to the study reported the CT findings by assessing the absence or presence of consolidation, effusion or pneumothorax as negative (-) or positive (+) in the same anatomic quadrant.
Data Collection
Demographic data, including sex, age, height, weight, American Society of Anesthetist (ASA) score, BMI, vital signs and smoking habit, were recorded. Medical history, pulmonary function test and physical examinations were extracted from the Electronic Medical Record. At the bedside, we collected surgical information, duration of mechanical ventilation and PACU stay, time needed for LUS examination and time needed for CT scan (transportation plus CT scan plus oral report). Cumulative opioid dose (calculated by duration and weight), volume of fluid administration (sum of crystalloid and colloid), blood products and arterial blood gas at the end of the operation, including haemoglobin, arterial partial pressure of oxygen (PaO2), and arterial partial pressure of carbon dioxide (PaCO2), were also recorded.
Statistical Analysis
PASS software (version 16.0) was used to calculate the sample size. Assuming the allowable error was 10% and α was 0.05 (bilateral), on the basis of a previous study, the estimated sensitivity and specificity of LUS were 87.7% and 92.1%, respectively.28 The calculated sample sizes for sensitivity and specificity were 50 cases and 38 cases, respectively. Considering that the same sample size was adopted for both LUS examination and CT scan, 100 cases were taken from each group of 50 patients. The total sample size was 110 patients when considering a dropout rate of 10%. After testing the normality distribution, the mean ± standard deviation or median (interquartile range) was used to describe continuous variables, and comparisons were performed with a paired t test or Mann–Whitney U-test as appropriate. Categorical variables are expressed as frequencies and percentages and were compared with the chi-squared test or Fisher’s exact test. Spearman’s correlation coefficient was used to assess possible factors that may be associated with LUS scores. Correlation coefficient (r) values < 0.3 indicated nearly no correlation, r values between 0.3 and 0.5 indicated weak correlation, r values between 0.5 and 0.8 indicated moderate correlation and r values > 0.8 indicated a high level of correlation. Cohen’s kappa was used to test for agreement between the observers. Kappa equal to 0-0.20 indicated slight agreement, 0.21-0.40 indicated fair agreement, 0.41-0.60 indicated moderate agreement, 0.61-0.80 indicated substantial agreement, and 0.81-1 showed almost perfect agreement. SPSS statistical software version 23.0 (IBM Corp, Armonk, NY, USA) was used for data statistics and analysis.