This prospective randomized double-blind controlled trial was reviewed and approved by the IIT Ethics Review Panel of the Clinical Research Ethics Committee of the First Hospital of Zhejiang University School of Medicine on May 6, 2020 (Session No. 48). The study was registered in the China Clinical Trials Registry (Registration No. ChiCTR2000033380).
2.1. Patients
Written informed consent was obtained from all subjects. The inclusion criteria were ASA classification I-II and no history of serious systemic disease. Exclusion criteria were age > 80 years, history of severe cardiopulmonary, hepatic, and renal disease, history of neuromuscular disease, excessive obesity or malnutrition (body mass index, BMI ≥ 30 or ≤ 20), history of drug allergy, etc. Using SPSS 23 (IBM, Armonk, NY, USA), patients were randomly allocated to three groups (40 patients per group): control group (group A: PEEP = 0), low-level PEEP group (group B: 5 cmH2O), and high-level PEEP group (group C: 10 cmH2O). Randomization was performed by a researcher not involved in the anesthesia or statistical analysis. The attending anesthetist was given an envelope containing the allocation results. The patient, the surgeon, and the resident anesthetist responsible for the records were blinded to the PEEP level. A flowchart of the study is shown in Fig. 1.
2.2. Anesthesia method
After the patient was admitted to the operating room, an invasive arterial puncture was performed in addition to routine monitoring and preoperative blood gas analysis. Induction of anesthesia took place through intravenous administration of etomidate, fentanyl, rocuronium bromide 0.6 mg/kg, followed by tracheal intubation and mechanical ventilation. Ventilation was set to volume-controlled breathing (60% oxygen concentration, mixed air) with an initial tidal volume of 7 mL/kg and a frequency of 12 breaths/min. The PEEP was set to 0, 5, and 10 cmH2O according to the grouping. The parameters were adjusted before pneumoperitoneum to maintain an end-expiratory carbon dioxide partial pressure of 30–35 mmHg. When end-expiratory carbon dioxide reached ≥ 60 mmHg (expected blood carbon dioxide partial pressure of 70 mmHg), hypercapnia was permissive during pneumoperitoneum to increase respiratory rate at first. If end-expiratory carbon dioxide could not be reduced or continued to rise, hypercapnia can continue to increase tidal volume when. No pulmonary resuscitation strategy was used for any ventilation mode. Intraoperative rocuronium bromide 0.6 mg/kg/h was pumped intravenously to maintain deep muscular relaxation at 0 train of four (TOF) stimulation response and 1–2 post tonic counts (PTC). Rocuronium was discontinued at the end of pneumoperitoneum.
2.3. Monitoring
Pulse oximetry, electrocardiogram (ECG), temperature measurement, bispectral index (BIS) monitoring, invasive arterial pressure monitoring, end-expiratory carbon dioxide measurement, pressure-volume loop measurement, accelerometer monitoring of muscle relaxation, and blood gas analysis were performed. Data were recorded for patients in all groups at six time points: after induction (T1), pneumoperitoneum establishment (T2), 0.5 h after pneumoperitoneum (T3), 1 h after pneumoperitoneum (T4), 1.5 h after pneumoperitoneum (T5), and at the end of pneumoperitoneum (T6). Data obtained include tidal volume, respiratory rate, end-expiratory carbon dioxide partial pressure, peak airway pressure, plateau pressure, lung compliance, airway resistance, pulse oximeter, blood pressure, heart rate, duration of surgery, among others. Blood gas analysis was performed after anesthesia induction, 1 h after pneumoperitoneum, and after tracheal extubation. Follow-up visits were performed on postoperative days 1, 3, and one month after surgery. Indicators for postoperative pain and postoperative complications were monitored and recorded.
Table 1
Basic patient characteristics
PEEP (cmH2O) | 0 cmH2O | 5 cmH2O | 10 cmH2O | P-value |
N | 27 | 33 | 29 | |
Age (years) | 65 (60–72) | 70 (65–73) | 69 (63–72) | 0.063 |
Body weight (kg) | 69 (65–71) | 66 (61–71) | 66 (61–70) | 0.592 |
Height (cm) | 170(165–172) | 170 (165–171) | 170 (165–173) | 0.839 |
BMI (kg/m2) | 24 (23–26) | 24 (22–25) | 23 (22–25) | 0.446 |
Surgery time(min) | 157(144–174) | 159 (128–176) | 150 (130–172) | 0.514 |
Data are expressed as median (interquartile range) |
2.4. Statistical Analysis
The Kolmogorov-Smirnov test was used to test the normality of the distributions of all variables. The values of peak inspiratory pressure (Ppeak), mean pressure (Pmean), pulmonary compliance (Crs), airway resistance (Raw),partial pressure of carbon dioxide in artery (PaCO2) and ratio of partial pressure of O2 in arterial blood to fraction of inspired oxygen (PaO2/FiO2) at different timepoints are expressed as median and interquartile ranges, where the data were not normally distributed. Patient characteristics, time to pneumoperitoneum, time to surgery, and time to extubation were expressed as median and interquartile ranges. Differences between multiple time points were analyzed using Kruskal-Wallis and one-way analysis of variance (ANOVA) post hoc tests. The Mann–Whitney U test was used to analyze the differences between two time points and groups. χ2 tests were used to compare the number of patients with agitation upon awakening and that of those with postoperative pulmonary complications in all groups.
To determine the sample size, a pretest was performed. The mean Crs during pneumoperitoneum (Pnp) of 0, 5, 10 cmH2O of PEEP were 27 mL/cmH2O, 32 mL/cmH2O, and 34 mL/cmH2O with standard deviations of 7, 9, and 10, respectively. Considering P value = 0.05 and a degree of certainty of 0.90, to distinguish the Crs of each group, at least 28 patients were required per group.
Crs: respiratory compliance (mL/cmH2O); ΔP: driving pressure (cmH2O); PEEP: positive end-expiratory pressure (cmH2O); data are expressed as medians. T1 post-induction; t2: immediate post-pneumoperitoneum; t3: 0.5 h post-pneumoperitoneum; t4: 1 h post-pneumoperitoneum; t5: 1.5 h post-pneumoperitoneum; t6: end of pneumoperitoneum. * P < 0.05, for the 10 cmH2O group compared with the 0 and 5 cmH2O groups at this time point.
Table 2
Arterial blood gas variables at different time points
| PaCO2(mmHg) | PaO2/FiO2(mmHg) |
| 0cmH2OPEEP | 5cmH2OPEEP | 10cmH2OPEEP | 0cmH2OPEEP | 5cmH2OPEEP | 10cmH2OPEEP |
T1 | 40.9(37.9–44) | 41.1(39.3–42.5) | 41.9(39.7–44.5) | 463(367–532) | 480(407–530) | 440(355–503) |
T4 | 51.1(48.2–74.5) | 56.1(51.9–59.9) | 54.7(46.4–57.9) | 435(335–504) | 422(330–475) | 403(340–483) |
T7 | 44.9(42.8–47.1) | 46.7(45–49) | 44.7(41.5–47.1) | 292(245–423) | 363(227–305) | 262(231–355) |
t7: after tracheal extubation. |