The prospective randomized controlled study was conducted from May 2020 to October 2020 and approved by the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College (Ethical No. 2020ER079-1). All subjects signed an informed consent form and completed registration with the China Clinical Trials Center (Approval No. ChiCTR2000033529).
Inclusion criteria were patients with healthy lungs aged 18 to 65 years, with a body mass index (BMI) <35 kg/m2, American Society of Anesthesiologists (ASA) physical status I-II and undergoing gynecologic laparoscopic surgery. The pulmonary evaluation was performed by a specialized radiologist using X-rays and CT on the included subjects. Exclusion criteria were that patients with pulmonary disease, cardiac disease, neuromuscular disease and corresponding surgical history, as well as respiratory tract infections were also excluded. Withdrawal criteria were as follows: (1) patients with preoperative ultrasound suggestive of pulmonary atelectasis; (2) surgical conversion from laparoscopic to open; (3) serious postoperative complications such as severe subcutaneous emphysema and pneumothorax.
Randomisation and blinding
According to the computerized randomization software (www.randomization.com), patients were randomly divided into C group and RM group in the ratio of 1:1. Group assignments were concealed in sealed envelopes that were opened after the anesthesiologist administered general anesthesia to the patient. Except for the anesthesiologist performing the induction of anesthesia and pulmonary ultrasound, who knows the grouping details, neither the patient nor the pulmonary ultrasound evaluator is aware of the details.
Anesthesia and ventilation protocol
All patients received standard general anesthetic protocol. Including 5L·min−1, 100% oxygen mask oxygen to nitrogen about 3 min, induction of 0.04 mg·kg−1 midazolam, 0.5µg·kg−1 sufentanil, 2 mg·kg−1 propofol, 0.6 mg·kg−1 rocuronium and the use of appropriate size of tracheal tube for intubation. The volume-controlled mechanical ventilation mode was performed after intubation with a tidal volume of 8 ml·kg−1, PEEP of 6 cmH2O and 0.4 inspired oxygen fraction (FIO2).The initial respiratory rate was set at 12 breaths·min−1 with an inspiratory: expiratory ratio of 1:2. The ventilator was adjusted to maintain an end-tidal carbon dioxide pressure (PETCO2) at 35-45 mmHg. Anesthesiologists can adjust FIO2 according to their experience when peripheral oxygen saturation <90%. Anesthesia was maintained by intravenous infusion of 0.1-0.3µg·kg−1·min−1 remifentanil and 4-12 mg·kg−1·h−1 propofol, inhalation of 1 %- 3 % sevoflurane. Bispectral index (BIS) was used to monitor the depth of anesthesia and maintain it at 40-60, timely supplement rocuronium to maintain adequate muscle relaxation. After spontaneous breathing recovery, neuromuscular blockade was reversed by neostigmine and glycopyrrolate. After extubation, the patient was sent to PACU, and oxygen was inhaled through the nose in PACU at a flow rate of 3 L·min−1. No analgesics were used postoperatively. Pulse oxygen saturation (SpO2), mechanical ventilation time, PACU stay time and hospital stay time were recorded.
Lung ultrasound was performed by two trained and experienced anesthesiologists using an ultrasound machine (MINDRAY M9) with a probe of 2-5 MHz. Obtain sonograms at 5 scheduled time point: arrival in the operating suite (time point 1, T1), 1 minute after mechanical ventilation (time point 2, T2), at end of surgery (time point 3, T3), 15 min after arrival in the PACU (time point 4, T4), 24 hours after operation (time point 5, T5). Scanning was performed according to the lung ultrasound method described by Monastesse et al .
The thorax was divided into left and right lungs, a total of 12 quadrants. Left and right lungs were divided into upper and lower zones. Each side was divided into anterior, lateral and posterior zones by anterior and posterior axillary line. In the anterior and lateral regions, the probe is placed upright to the costal space, and in the posterior regions the probe is placed parallel to the costal space. In order to quantitatively evaluate the severity of atelectasis, we used the modified lung ultrasound score from Monastesse et al .
Furthermore, the degree of the lung ultrasound score (LUS) was divided into four grades and scored between 0 and 3: (0) 0-2 B lines; (1) ≥3 B lines or 1 or multiple small subpleural consolidations separated by a normal pleural line; (2) multiple coalescent B lines or multiple small subpleural consolidations separated by a thickened or irregular pleural line; and (3) consolidation or small subpleural consolidation of >1×2cm in diameter. We defined atelectasis to be significant if any region had the lung ultrasound score ≥2. The LUS was calculated by adding up the 12 individual quadrant scores, ranging from 0 to 36 points, with higher scores indicating chronic atelectasis.
When atelectasis appeared under ultrasound observation 1 minute after mechanical ventilation and at the end of surgery, patients of the RM group performed recruitment manoeuvres, placing the probe in the area of atelectasis, with airway pressure starting at 10 cmH2O and increasing by 5 cmH2O each time, up to 40 cmH2O, with a 0.4 FIO2 was applied manually until no collapsed lung areas were visible on ultrasound. Then, the pressure was maintained for 40 s. The mean arterial pressure and heart rate changed <15%.
The baseline characteristics were age, BMI, ASA classification. The observation indexes were LUS score and SpO2 at the above 5 time points, fluid volume, mechanical ventilation time, PACU residence time, hospitalization time and PPCs.
Primary and secondary endpoints
The primary endpoint was the incidence of intraoperative and postoperative pulmonary atelectasis and LUS score. The secondary endpoints were oxygen saturation, the incidence of intraoperative cardiovascular adverse reactions, PACU residence time, hospitalization time and PPCs.
Sample size estimation
We calculated the sample size using the data from previous studies. Yang et al.'s study shows that the frequency of atelectasis following a lung recruitment manoeuvre was 50%, compared with 95% in adults after laparoscopic colorectal surgery who did not receive a recruitment manoeuvre . The sensitivity of lung ultrasound detection of atelectasis was 88% . According to our preliminary experiment, the incidence of atelectasis was 81% in lung-healthy patients after gynecologic laparoscopic surgery, which was reduced to 40% by LRMs. Therefore, if we assume an alpha error of 0.05, power of 80% and allowing for a dropout rate of 10%, the required sample size would be 20 patients per group.
Anthropometric data and demographics were collected from the individual patient. Following the normality of data testing, the Mann-Whitney U test or t test was used for intergroup comparisons as applicable. Friedman test or paired t test was used for intra-group comparison. Chi-square test or Fisher’s exact test was used for categorical variables. A two-sided P value less than 0.05 was considered significant unless Bonferroni adjustments were made. SPSS 25 and Graph Pad Prism 8 software were used for statistical analyses.