Ethics, consent, and permission
The study was registered on 13/09/2020(ChiCTR2000038212) on chictr.org.cn, and was approved by the Medical Ethics Committee of Shanghai General Hospital with approval number [No. 202036]. All research procedures adhered to the CONSORT guidelines, and written informed consent was obtained from all patients. All methods were carried out in accordance with Declaration of Helsinki
Study design and patient population
The study included consecutive patients with American Society of Anesthesiologists physical status I-II who underwent elective laparoscopic abdominal surgery, including rectal or colon resection. The exclusion criteria were as follows: age <20 years or >65 years; obesity (>28 kg/m2); previous known respiratory or cardiovascular disease; or throat, oesophageal, or any other disorders that may affect transoesophageal echocardiography (TEE).
Randomisation and masking
This was a randomised controlled study. Randomisation was carried by a computer-generated allocation sequence. Participants were divided into two groups (n=20/group). People who had access to the randomisation information were not involved in any experimental trial procedure.
The patients were blinded to the treatment allocation. Intraoperative data were collected by an unblinded investigator. TEE measurements were performed and recorded using a multiplane 5-MHz and an echocardiographic device (Vivid 7 Dimension; GE Vingmed Ultrasound AS, Horten, Norway). All measurements were performed by the same examiner who was blinded to the allocation and were recorded on video. The saved results were reviewed postoperatively by two experienced echocardiographers who were not involved in the study.
The duration of preoperative fasting was 8-10 h. Upon arrival in the operating room, patients received 5 mL/kg Ringer’s lactate solution. The fluid treatment was continued at 5 mL/kg/h during surgery. Electrocardiogram (ECG), heart rate (HR), non-invasive blood pressure, end-tidal CO2 pressure, peripheral oxygen saturation, and bispectral index (EEG VISTA monitor, Covidien, Boulder, CO) were measured. Arterial blood samples were collected to assess partial pressures of CO2 and O2 (PaCO2 and PaO2, respectively).
Anaesthesia was induced with midazolam (1-2 mg), sufentanyl (0.2-0.4 μg/kg), propofol (1.5-2.5 mg/kg), and rocuronium (0.6-1 mg/kg), and maintained with sevoflurane (0.8-1.0 minimum alveolar concentration) and remifentanil (0.5 μg/kg/h). Sufficient levels of muscle relaxation and analgesia during surgery were achieved using increments of rocuronium (0.2 mg/kg) according to the twitch monitor (Innervator, Fisher & Paykel, Laguna Hills, CA).
Ventilation settings and study protocol
Pre-oxygenation was performed for 5 min at a fraction of inspired oxygen (FiO2) of 1.0 with a tightly sealed face mask. The lungs were ventilated after a recruitment manoeuvre of 40 cmH2O continuous positive airway pressure applied for 30 s by hand bagging with FiO2 of 60% in a volume-controlled mode. The tidal volume (VT) was 6-8 mL/kg of ideal body weight calculated as 50+0.91 × (height [cm] – 152.4) for men and 45.5+0.91 × (height [cm] – 152.4) for women  and VT and respiratory rate were adjusted to maintain peak inspiratory pressure (PIP) below 35 cmH2O and end-expiratory PaCO2 (PetCO2) between 35 and 45 mmHg throughout the procedure. After intubation, a TEE probe was inserted into the oesophagus.
Patients were changed to a steep Trendelenburg position after PNP was induced. The intra-abdominal pressure (IAP) was maintained up to 12 mmHg (UHI-4, Olympus Medical Systems, Tokyo, Japan). After the second recruitment manoeuvre, the PEEP increment trial was initiated in the study group (Group T) with steps of 2 cmH2O from 5 cmH2O until the maximal Cdyn was obtained. Volume-controlled ventilation and individualised PEEP levels were then established after the third recruitment manoeuvre and maintained throughout the study period. In the control group, the same procedures were followed, except for PEEP titration; PEEP was set at a fixed level of 5 cmH2O (Fig. 1).
An S/5 monitor (GE Healthcare, Chicago, IL) was used to monitor the mean arterial pressure, HR, PetCO2, VT, RR, PIP, and plateau inspiratory pressure continuously. The gas sampling tube using the side-stream technique to record Cdyn was connected to the respiratory circuit. Arterial blood samples were collected for blood gas analysis to record arterial PaCO2 and arterial PaO2. Each measurement was obtained and recorded at three time points including: immediately after anaesthesia induction (T0), 5 min after PNP and Trendelenburg positioning (T1), and 30 min after mechanical ventilation with PEEP (T2).
Tricuspid annular plane systolic excursion (TAPSE) was measured using the M-mode from a standard apical four-chamber view centred on the right ventricle (RV). The cursor was aligned parallel to the longitudinal displacement of the tricuspid valve plane with the RV free wall carefully. Electronic callipers were used to calculate the displacement between the most basilar position of the tricuspid annulus at end-diastole and at end-systole with the leading-edge method (Fig. 2A).
A four-chamber view was used to measure the RV end-diastolic area (RVEDA) and the left ventricular (LV) end-diastolic area (LVEDA) by tracing the endocardium in the end-diastole period. The RVEDA/LVEDA ratio was calculated from these values (Fig. 2B).
Pulsed-wave Doppler ultrasonography was used to measure the ratio of the tricuspid peak velocity of early filling (E) to the peak velocity of late filling (A) (E/A ratio) by scanning from the apical four-chamber view with the sample volume positioned at the valvular leaflet tips (Fig. 2C).
All measurements were performed on five consecutive beats during sinus rhythm.
Other derived variables were calculated according to the following equations:
ΔP = Pplat–PEEP; 
VD/VT = 1.14 × (PaCO2 – PetCO2)/PaCO2 – 0.005,  where VD is dead space; and
No studies to date have specifically studied parameters of RV function in relation to changes in PEEP during laparoscopic abdominal surgery. We calculated from a pilot study that 18 participants in each group would be sufficient to identify a difference of 0.4 in TAPSE between individualised and intentional PEEP groups with α and β errors of 0.05 and 0.2, respectively, with a power of 0.8 using PASS software (version 11.0.7, NCSS, Kaysville, UT). Considering the potential loss to follow-up and missing data, the sample size of each group was increased to 20.
Numbers with percentages in parentheses are used to present categorical data. Continuous data are presented as mean ± standard deviation; otherwise, medians with interquartile ranges are used.
Statistical analyses were performed using Prism 8.0 (GraphPad Software, San Diego, CA). We used the Kolmogorov-Smirnov test to verify the normality of data. Comparisons between groups or different timepoints were performed using two-way repeated-measures analysis of variance, and comparisons of categorical variables between groups were performed using the chi-squared test. A P value less than 0.05 was accepted as statistically significant.