A prospective, randomized study was conducted in the Sisli Hamidiye Etfal Training and Research Hospital between March and July 2020. Study was started after obtaining approval from the local ethics committee with the approval number: 1496. Registration of study at ClinicalTrials.gov was made at 25/01/2021 with the NCT04723043 number. Informed consent was taken from all patients. All procedures that performed in our study were made in accordance with the ethical standards of the Helsinki declaration (2008).
Sample size calculation and randomization
Considering the difference in large effect size (effect size=0.8) between the groups, the sample size was calculated as 70 cases in total for 95% Power, alpha significance level 0.05. Randomization was done with closed envelopes before the procedure.
Inclusion and exclusion criteria
For the study period patients that underwent elective laparoscopic cholecystectomy were enrolled for the study. Patients aged between 18 and 65, with American Society of Anesthesiology (ASA) score 1 and 2, body mass index (BMI) <30 kg / m2, were included.
Patients who did not give informed consent, patients who underwent previous thoracic/abdominal surgery, patients who underwent emergency laparoscopic cholecystectomy, patients who have ASA score ≥3, hematocrit value ≤ 30 and, BMI> 30 kg / m2 were excluded. Patients with a history of cardiac, neuromuscular, hepato-renal, endocrine, major pulmonary disease (defined as a decrease in capacity or flow rates below 70% in pulmonary function tests) were also excluded. Patients who returned to laparotomy for surgical reasons after starting laparoscopically, who developed perioperative hemodynamic instability and who used respiratory mechanics outside the study protocol were excluded from the study.
Primary-Secondary Outcomes
The primary outcomes of the study were the cerebral oxygenation measured with NIRS, peak pressure and plateau pressure of the patients in both groups, the secondary findings were the patients' SpO2, end-tidal carbon dioxide and partial oxygen pressure in arterial blood gases.
Preoperative care
All patients underwent standard anesthesia evaluation for the procedure. Premedication was done with 0,07 mg/kg intravenous midazolam.
Intraoperative care
Single derivation electrocardiogram, pulse-oximetry, noninvasive arterial pressure and EtCO2 parameters were monitored. NIRS monitoring was performed using a Masimo (Irvine, CA, USA) device. NIRS cerebral probes were placed in the right and left frontal regions. A 20-gauge cannula was inserted into the radial artery. Anesthesia induction is by intravenous administration of 2 mg/kg propofol, 1 mg/kg lidocaine, 1.5 mcg/kg fentanyl and 0.6 mg/kg rocuronium bromide. Anesthesia maintenance was done with sevoflurane %2 and remifentanil 0.15-0.25 mcg/kg/hour. During the maintenance process, the oxygen-air flow was set to 4 lit/min and the FiO2 set to 40%. During anesthesia, mechanical ventilation was applied to the patients with a Drager (Medical, Lübeck, Germany) brand device.
Mechanical ventilation settings applied to all patients were adjusted according to ideal body weight. In the P group, inspiratory pressure (Pinsp) was set to create a tidal volume of 8 ml / kg in pressure-controlled mode, while in the V group, the tidal volume was set as 8 ml / kg in the volume-controlled mode. In both groups, the initial respiratory frequency was 12 breaths/minutes, the inspiration/expiration time ratio was 1/2, FiO2 was 40%, and positive end expiratory pressure (PEEP) was 5cm/H2O. While applying mechanical ventilation in all patients, it was aimed to keep the EtCO2 value between 33-35 mmHg. If the EtCO2 was above 35 mmhg, the respiratory frequency was primarily increased by 2 units every five minutes in both groups. In this increase, the frequency was accepted as the upper limit of 18 breaths/minute. If the EtCO2 values did not decrease under 35 mmHg at the 5th minute after reaching 18 breaths per minute, the Pinsp value of the patients in the P group was increased by 2 cm/H2O every five minutes as needed. In the V group, the volume settings were increased by 1 ml/kg every five minutes as needed. The upper limit was determined as 30 cm/H2O for the P group and 10 ml/kg for the V group. Patients whose CO2 values did not decrease under 35mmhg despite mechanical ventilation with all these upper limit values were excluded from the study by making more complicated changes in mechanical ventilation and insufflation pressures. If EtCO2 values were below 33 mmHg, in both groups, it was first reduced to 10 breaths/min, and if there was no increase after five minutes, Pinsp values were decreased by 2 cm/H2O every five minutes in the P group, while the tidal volume was decreased by 1 ml/kg in the V group. However, tidal volume was not allowed to fall below 6 ml/kg in both groups.
Demographic data (gender, age, height, weight, and ASA score) as well as operative data (anesthesia, operation, and insufflation duration) were recorded in both groups, T0 was defined as T0 before anesthesia, T1 after intubation, T2 5 minutes after insufflation, T3 just before desufflation, and T4 5 minutes after desufflation. Heart rate, systolic/diastolic arterial pressure values, saturation of pulse-oximetry (SpO2) and NIRS values were recorded at all time points. Additionally, EtCO2 in T1, T2, T3 and T4; arterial blood gas results for pH, pO2, pCO2, HCO3, BE and Lactate; Tidal volume, respiratory frequency, peak pressure (Ppeak), plateau pressure (Pplateau) and, PEEP was recorded.
Statistical analysis
SPSS 15.0 for Windows program was used for statistical analysis. Descriptive statistics; numbers and percentages for categorical variables, mean, standard deviation, minimum and maximum for numerical variables were given. Comparisons of numerical variables in two independent groups were made using the Student t-Test (when the normal distribution exists), the Mann Whitney U test (when the normal distribution condition was not exist). The rates in the groups were compared with Chi-Square Analysis. Statistical alpha significance level was accepted as p<0.05.