Patients
The study was approved by the review committee of Second Affiliated Hospital of Zhejiang University (IR2018001133, 2018/12/05) and registered at ClinicalTrials.gov (NCT03802175) before patient enrollment. Informed consents were obtained from all patients. Adult patients who received general anesthesia and suffered hypoxemia in the PACU were included in this study. Postoperative hypoxemia was defined as a decreased oxygen saturation measured by pulse oximetry (SPO2) less than 92% for greater than 30 seconds while on room air 20 minutes after extubation.15 Exclusion criteria included: covered surgical dressings from opening 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 resulted in incomplete recovery of muscle strength (Train of four stimulation, TOF < 0.9); respiratory forgetfulness from residual opioid; hemodynamic instability; anemia; significant bleeding, fever or hypothermia. Besides, patients were withdrawn if SPO2 decline to 85% or less or admission of intensive care unit (ICU) happened.
Anesthesia Protocol
Before induction of anesthesia, all patients were preoxygenated with an inspiration oxygen fraction (FiO2) of 1.0. Anesthesia was induced with midazolam 0.05-0.1mg/kg, sufentanil 0.5-0.6 ug/kg, etomidate 0.2-0.4 mg/kg and rocuronium 0.8-1.0 mg/kg. Proper double-lumen endotracheal tube was intubated to perform one-lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS), whereas common tracheal tube was inserted for two-lung ventilation (TLV) during non-VATS. Continuous intra-venous propofol, remifentanil with inhalational sevoflurane was utilized for anesthesia 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 anesthesia monitoring was completed by bispectral index (BIS) with an appropriate value of 40-60. Before closing chest, each patient undergoing VATS received a recruitment maneuver (RM) by forcing sustaining inspiration at the level of 30-40 cm H2O airway pressure for 10-20 seconds, then OLV was converted to TLV until extubation. Besides, 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 operation. Before extubation, the set of mechanical ventilation in the PACU was same with that in the operating room. Extubation was performed when the following criteria were met: VT > 5 mL/kg; and minimal RR of 11 breaths/min; hemodynamic stability (a maximum variation of mean arterial pressure and heart rate was 20% around the baseline value); normothermia. Neostigmine (0.02mg/kg) was used for reversal of neuromuscular blocking before extubation. After extubation, the patient inhaled oxygen through a face mask at 3-6L/min for about 15 minutes then the face masks were removed. During the next time, 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 by two trained anesthesiologists (Chen X, Kai S, both with more than 1 year of ultrasound learning) once hypoxemia occurred. The anterior and posterior axillary lines divided each hemithorax into three regions (anterior, lateral and posterior), each region was further divided into two quadrants (superior and inferior) (Figure 1). The anesthesiologist 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 consolidations or tissue-like structure may also indicate pneumonia. However, the visualization of dynamic air-bronchogram helps exclude atelectasis.16 With a negative predictive value of 100%, presence of lung sliding excluded the diagnosis of pneumothorax.17 Meanwhile the diagnosis of pneumothorax should combine 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 size of pneumothorax.21 Presence of anechoic area fluctuating with respiration identified 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 effusion must be visible on at least three intercostal spaces. Less than 15 mm of maximal interpleural distance was defined as small effusion.23 Combined with symptoms such as dyspnea, a minimum of 3 B-lines in at least two anterior or lateral quadrants in each thorax may benefit for the consideration of pulmonary edema.24
LUS scores (0-36, calculated by adding up all the 12 individual quadrant scores) assess aeration changes and a higher grade represents more serious aeration loss but inapplicable for pneumothorax (Figure 2).25-27 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; score 2, serious aeration loss, presence of coalescent B lines with irregular pleural; scoring 3, absolute aeration loss, subpleural consolidation. The stored video of the worst irregularity was analyzed off-line by Chen X and Kai S. In case of disagreement, a third anesthesiologist (Lina Y, with 5 years of ultrasound learning) reviewed the uncertain images and made the final diagnosis.
Computed Tomography Scan
After LUS examination, every patient with stable hemodynamic and spontaneous respiration was transported to radiology department by a nurse anesthetist for thoracic CT scan within 1 hour after LUS examination. During transport, all patients received oxygen through face masks. Scanning from apex to diaphragm with the patient in 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. Blinded to our study, a trained radiologist reported the CT findings by judging negative (-) or positive (+) for absence or presence of consolidation, effusion or pneumothorax in the same anatomic quadrant.
Data Collection
Demographic data including gender, 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 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) as well as blood products, arterial blood gas at the end of operation including hemoglobin, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) were also recorded.
Statistical Analysis
PASS software (version16.0) was used to calculate the sample size. Estimated the sensitivity and specificity of LUS are based on the previous study (sensitivity 87.7%, specificity 92.1%)28, assumed the allowable error is 10% and α error of 0.05 (bilateral). The calculated sample size for sensitivity and specificity was 50 cases and 38 cases, respectively. Considering the same sample size was adopted for both LUS examination and CT scan, 100 cases were taken from each group of 50 cases. The total sample size was 110 cases when combined with a dropout rate of 10% at last. A total of 110 patients were needed with previous study and following assumptions: an α error of 0.05, a β value equal to 0.15 and a dropout rate of 10%. With after testing normality distribution, mean ± standard deviation or median (interquartile range) were used to describe continuous variables and comparison of them were performed with a paired-t test or Mann–Whitney U-test as appropriate. Categorical variables were expressed as frequency and percentage, and compared with Chi-squared test or Fisher’s exact test. Spearman’s correlation coefficient was used to assessed 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 medium 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 meaning slight agreement, 0.21-0.40 indicated fair, 0.41-0.60 indicated moderate,0.61-0.80 indicated substantial while 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.