Keywords: anesthesia, anesthetic gases, cholecystectomy, compliance, laparoscopy, low-flow anesthesia, lung function tests, peak inspiratory pressure, postoperative, surgery
Abstract
Low-flow anesthesia aims to minimize anesthetic gas consumption while maintaining adequate anesthesia. To examine the effects of minimal-flow anesthesia on perioperative lung dynamics and postoperative pulmonary function tests, a prospective, randomized controlled study was conducted between October 2023 and March 2024 at Atatürk University. A total of 66 patients (15 males, 45 females) with confirmed American Society of Anesthesiologists (ASA) grade I–II, aged 18–65 years, and scheduled for elective laparoscopic cholecystectomy were included in the study. Patients were randomized into two groups: MeFA (medium flow anesthesia, 2 L/min fresh gas flow) and MiFA (minimal flow anesthesia, 0.5 L/min fresh gas flow). In both groups, dynamic compliance values, peak inspiratory pressure (PIP) values, total inhalation anesthetic drug consumption, total remifentanil drug consumption, duration of anesthesia, duration of surgery, and spirometry test results were recorded. Respiratory measurements were recorded at the 5th minute after intubation (T1), 5th (T2), 10th (T3), 30th (T4), and 60th (T5) minutes after surgical incision and immediately after the surgical suturing (T6) pulse. There was no significant difference in compliance or PIP values between the groups from T1 to T5 (P > 0.05). However, at T6, the MeFA group exhibited a significant decrease in compliance and an increase in PIP compared with the MiFA group (P < 0.05). Additionally, significant differences in compliance and PIP values were found across all time intervals compared with those at T1, except for the T5–6 compliance values in the MiFA group (P < 0.001). No significant difference in respiratory function test values was noted between the groups (P > 0.05). The MiFA group exhibited a relatively milder reduction in compliance values and a lesser elevation in PIP values. Compared with medium-flow anesthesia, minimal-flow anesthesia may help mitigate perioperative lung function deterioration. These findings suggest potential benefits in preserving lung mechanics, warranting further research. This trial was registered at clinicaltrials.gov (identifier No. NCT06055335, registered March 25, 2023).
Introduction
The primary purposes of the low-flow anesthesia technique are to minimize anesthetic and medical gas consumption, maintain relatively humid and warm air in the respiratory tract and respiratory circuit, and reduce waste gas production simultaneously.1 Low-flow anesthesia maintains moisture in the airways and minimizes the impact on mucociliary activity after anesthesia. Reducing secretion decreases the risk of bronchial plugs, shunts, and inactive lung units, which contribute to atelectasis.2 The low consumption of anesthetic and medical gases significantly reduces the cost-effectiveness for healthcare providers. Moreover, low-flow anesthesia reduces environmental pollution by limiting waste gas emissions.3,4
Laparoscopic cholecystectomy (LC) surgeries are used frequently in many centers due to their less invasive technique, reduced incision size, postoperative pain, hospital stay, loss of labor, and cost.5,6 Pneumoperitoneum can reduce lung expansion by exerting pressure under the diaphragm with the extra effect of positions that may affect respiratory dynamics, such as breathing. Atelectasis caused by decreased functional residual capacity under anesthesia and airway closures secondary to organ compression may cause respiratory problems during and after the operation.7
This prospective, randomized, controlled study investigated the potential benefits of low-flow anesthesia (< 0.5 L/min) in reducing lung complications associated with laparoscopic surgeries. The primary objective was to assess the impact of minimal-flow anesthesia on intraoperative lung dynamics in patients undergoing LC. The secondary objective was to evaluate its effects on postoperative pulmonary function tests.
Methods
The study was approved by the Atatürk University Faculty of Medicine Ethics Committee (approval No. 106; dated: March 25, 2021) and was registered at clinicaltrials.gov (identifier No. NCT06055335; registered March 25, 2023). The study was conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from all participants prior to enrollment. Between October 2023 and March 2024, a total of 66 American Society of Anesthesiologists Physical Status Classification System (ASA) I–II patients aged 18–65 years (15 males, 45 females) scheduled for elective laparoscopic cholecystectomy were recruited at Atatürk University Health Research and Application Center in the general surgery operating theaters. Patients who were smokers, had a body mass index > 40 kg/m2, had cardiovascular system disease, had chronic respiratory diseases, were unable to perform pulmonary function tests due to technical issues or unsatisfactory test results during evaluation by a pulmonology consultant were excluded. Patients were randomized via the closed-envelope method and assigned to one of two groups. The patients in the MiFA group received minimal flow anesthesia with 0.5 L/min fresh gas flow, the patients in the MeFA group received medium flow anesthesia with 2 L/min fresh gas flow, and the patients were blinded to group allocation (Figure 1).
Figure 1.
A flowchart of this study.
Anesthesia and surgical procedures
Patients were routinely monitored using electrocardiography, non-invasive arterial blood pressure, and pulse oximetry. In addition to standard monitoring, the bispectral index (BIS; BISTM, Medtronic, Minneapolis, MN, USA) was used to assess the depth of anesthesia, while the train of four (TOF) (NMT Troubleshooting Type N3, GE HealthCare, Chicago, IL, USA) was chosen to ensure minimal muscle activity during compliance measurements. Patients were continuously monitored throughout the procedure. After preoxygenation with 100% oxygen and basal BIS measurement, anesthesia induction was started. Intravenous propofol (2%, Polifarma, İstanbul, Turkey) 2.5 mg/kg and 1 mg/kg fentanyl (Talinat, VEM İlaç, İstanbul, Turkey) were administered. TOF measurements were performed, and 0.7 mg/kg rocuronium (Muscobloc, Polifarma) was administered after the basal value was obtained. Endotracheal intubation was performed on patients with T1 twitch below 10% after loss in T1 stimulation in TOF measurements. TOF activity was assessed every 5 minutes. If muscle activity above 10% was observed in the evaluation of TOF activity, 10 mg of rocuronium was administered. The inhaler anesthesia concentration was adjusted to keep the BIS result between 40% and 60%. Initially, remifentanil (Rentanil, VEM İlaç) infusion was started at a dose of 0.125 μg/kg/min. In the case of a 20% or greater increase or decrease in the patient’s initial pulse and arterial blood pressure values, the dose of remifentanil was adjusted by applying 10% increases or decreases, as in our routine clinical practice. At the end of the surgery, neuromuscular reversal was performed with 2 mg/kg sugammadex (Brimadeks, Polifarma). Patients suitable for extubation (respiratory rate > 8 breaths, spontaneous respiration, and minimum tidal volume > 6 mL/kg) were extubated and referred to the post-anesthesia care unit. Patients with modified Aldrete scores above 8 were transferred to the ward.8
In both groups, surgeries were performed via a laparoscopic technique. Pneumoperitoneum was terminated with an upper limit of 12 mmHg. There was no indication for a nasogastric tube during surgery. LC was performed with the same technique for all patients by the same surgeon.
Minimal and medium flow anesthesia management
Following endotracheal intubation, patients were monitored using the Datex Ohmeda Aisys Anesthesia Machine (GE HealthCare). A GE Aladin 2 casette vaporizer was used for desflurane. Each morning, before the first patient was enrolled, the CO₂ absorbent canister was replaced with fresh absorbent. Safety and leak tests were performed with the anesthesia machine before inclusion in the study for all patients. In both the MiFA and MeFA groups, anesthesia induction was initiated using a 4 L/min fresh gas flow with a 50% O₂–50% air mixture and 8% desflurane in combination with remifentanil infusion until a minimum alveolar concentration (MAC) of 1 was achieved. Minimal flow anesthesia (0.5 L/min) was subsequently initiated in the MiFA group, while medium flow anesthesia (2 L/min) was initiated in the MeFA group. In both groups, the oxygen concentration was maintained at a minimum of 50% using end-tidal control monitoring, and the MAC values were adjusted on the basis of the BIS score. At the completion of the final surgical suture, the vaporizer was turned off, and the fresh gas flow was increased to 6 L/min with 80% oxygen for both groups.
All patients were allowed to start surgery after intubation in the supine position, after tidal volume, respiratory rate, positive end-expiratory pressure, and peak inspiratory pressure (PIP) values were adjusted by selecting the pressure-controlled ventilation volume guaranteed ventilation mode to reach the maximum dynamic compliance value before starting surgery. The respiratory rate of the patients was adjusted so that the partial pressure of arterial carbon dioxide was between 30 and 40 mmHg. In both groups, the 5th minute after intubation (T1), 5th (T2), 10th (T3), 30th (T4), 60th (T5) minutes after surgical incision, and immediately after surgical suturing (T6), pulse, systolic and diastolic blood pressure, oxygen saturation, end-tidal carbon dioxide pressure, dynamic compliance values, PIP values and total inhalation anesthetic drug consumption after extubation, total remifentanil drug consumption, duration of anesthesia, and duration of surgery were recorded. All data related to dynamic compliance values, peak inspiratory pressure, total inhalation anesthetic consumption, anesthesia duration, and surgery duration were directly retrieved from the anesthesia machine.
Pulmonary function test
The forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC values of the patients in both groups were evaluated and recorded by a pulmonologist 24 hours before the operation (SFT-1) and at the 2nd (SFT-2), 8th (SFT-3), and 24th (SFT-4) hours postoperatively using a spirometry device (Spirometre Device: SP10, Medwelt, Berlin, Germany). In accordance with the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2019 guidelines, patients were informed of the rules they should follow before spirometry.9 The test maneuver was explained by a trained technician, and each patient performed three acceptable spirograms. Tests complying with the pulmonary function test reproducibility and acceptability criteria published by the ATS/ERS in 2019 were included in the study.9 The lower limits of the normal parameters determined for the healthy population are calculated via a spirometry device in accordance with the criteria in this declaration. Patients who reported a visual analog scale (VAS) score > 4 in the sitting position despite analgesic administration were excluded from the study.10
All patients were administered 8 mg of dexamethasone (Deksamet, Osel İlaç, İstanbul, Turkey) and 10 mg of metoclopramide (Primperan, Biofarma, İstanbul, Turkey) to prevent postoperative nausea and vomiting. In the event of nausea and vomiting, the administration of 3 mg of granisetron was planned. For postoperative pain management, patients received 50 mg of dexketoprofen (Arveles, Menarini, İstanbul, Turkey) intravenously within the first 30 minutes of surgery. At the end of the procedure, a local infiltration block with 10 mL of 5% bupivacaine was applied to the trocar incision sites. During the postoperative period, patients received 1000 mg of paracetamol (Paracerol, Polifarma) twice daily. Additionally, tramadol (Contramal, Abdi İbrahim, İstanbuli, Turkey) was administered using a patient-controlled analgesia device for pain control.
Sample size calculation
The primary aim of the study was to compare the change in compliance value as a percentage between T1 and T6. To determine the required sample size, a preliminary study was performed with six patients per group. The difference was 95.84 ± 10.45% in the MiFA group (n = 6) and 85.82 ± 10.53% in the MeFA group (n = 6). For differences, a sample size of 25 was calculated using GPower (version 3.1.9.2, Heinrich-Heine-University, Dusseldorf, Germany), with an alpha probability of 0.05, a power of 0.95, and an effect size of 0.95. Considering possible dropouts, we included 32 patients in each group.
Statistical analysis
For statistical analyses, SPSS 20 software package (IBM Corp., Armonk, NY, USA) was used. Numeric data were evaluated with the Kolmogorov‒Smirnov test, the Mann‒Whitney U test was used to evaluate different groups to analyze nonparametric data, the Friedman test was used to evaluate intergroup data to analyze nonparametric data, and the Wilcoxon signed rank test was used for the evaluation of sequential data. For the evaluation of categorical data, the chi-square test and Fisher’s exact test were applied, and the results are expressed as numbers. Descriptive data are expressed as the mean ± standard deviation (SD). P values > 0.05 were considered statistically significant.
Results
Patient characteristics and anesthetic drug consumption
A total of 66 patients were included in the study. Six patients were excluded from the study: one patient in the MiFA group due to the need for laparotomy, three patients in the MeFA group for the same reason, and two patients in the MeFA group due to circuit leakage in the anesthesia device. At the T4 and T5 time points, the number of patients included in the analysis decreased due to the early completion of some surgeries before these assessments could be performed. Specifically, at T4, data were available for of 24 patients in the MiFA group and 28 in the MeFA group, while at T5, data were available for 11 and 9 patients, respectively. No statistically significant differences were found between the groups in terms of age, weight, height, sex, ASA classification, comorbidities, remifentanil consumption, anesthesia duration, and surgery duration (P > 0.05). Desflurane consumption was significantly lower in the MiFA group than in the MeFA group (P < 0.05; Table 1).
Table 1.
Demographic data between the MiFA and MeFA groups
| MiFA (n = 32) | MeFA (n = 28) | P value | |
|---|---|---|---|
| Age (yr) | 43.5(33.5–52) | 47(37–51) | 0.727a |
| Weight (kg) | 78.5(66–92.5) | 78(70.5–90) | 0.824a |
| Height (cm) | 162.5(158.5–169) | 163.5(160–173.5) | 0.586a |
| Sex (male/female) | 7/25 | 8/20 | 0.567b |
| ASA (I/II) | 4/28 | 10/18 | 0.064c |
| Complication | 0.150b | ||
| DM | 1 | 3 | |
| Hypertension | 1 | 4 | |
| Hypothyroidism | 1 | 3 | |
| DM+hypertension | 1 | – | |
| Consumption of desflurane (mL) | 24(18–31) | 51.5(38–71) | < 0.001a |
| Consumption of remifentanyl (μg) | 250(100–550) | 300(200–425) | 0.823a |
| Duration of anesthesia (min) | 75(52.5–102.5) | 75(51–97.5) | 0.911a |
| Duration of surgery (min) | 50.5(30–72.5) | 52.5(38–72.5) | 0.772a |
Data are expressed as the median (25–75% quartile) or number. aData were analyzed by the Mann–Whitney U test. bData were analyzed by the chi-square test. cData were analyzed by Fisher's exact test. ASA: American Society of Anesthesiology score; DM: diabetes mellitus; MeFA: medium flow anesthesia; MiFA: minimal flow anesthesia.
Intraoperative respiratory parameters
Compared with those at T1, the PIP values at all time intervals were significantly greater in both groups (P < 0.05). Compared with those in T1, the compliance values in the MeFA group showed a significant reduction at all time intervals (P < 0.05). In the MiFA group, compliance values were significantly lower at T2–4 than at T1 (P < 0.05), whereas no significant difference was observed at T5 and T6 compared with T1 (P > 0.05). No significant differences were observed between the two groups in terms of end-tidal CO₂ and SpO₂ levels (P > 0.05; Figure 2).
Figure 2.
Comparisons of compliance, peak inspiratory pressure (PIP), SpO2, end-tidal CO2 and respiratory function test values between medium- and minimal-flow anesthesia.
The data are expressed as the mean ± SD. *P < 0.05, vs. T1; #P < 0.05, vs. preoperative (Wilcoxon signed-rank test). CO2: Carbon dioxide; FVC: forced vital capacity; FEV: forced expiratory volume; MeFA: medium flow anesthesia; MiFA: minimal flow anesthesia; SFT-1–4: 24 hours before the operation (SFT-1) and at the 2nd (SFT-2), 8th (SFT-3), and 24th (SFT-4) hours postoperatively; SpO2: oxygen saturation; T1–T5: the 5th minute after intubation (T1), 5th (T2), 10th (T3), 30th (T4), and 60th (T5) minutes after surgical incision; T6: immediately after the surgical suturing.
Postoperative pulmonary function test
The postoperative pulmonary function test results showed no statistically significant differences between the groups (P > 0.05; Figure 2).
Discussion
Compared with the values after endotracheal intubation and at the end of surgery, the MeFA group presented significantly lower compliance values and higher PIP values. No significant differences were observed between the preoperative and postoperative pulmonary function test results.
LC is commonly employed in cholecystectomy surgeries.11 Pneumoperitoneum, patient positioning (e.g., Trendelenburg), decreased muscle tone following anesthesia, and imbalances in the forces acting on the chest wall, along with changes in the lung’s elastic tissue, all negatively impact respiratory dynamics during LC12 (Figure 3). The pressure created by pneumoperitoneum on intra-abdominal organs, along with the diaphragm being pushed toward the thorax, leads to a decrease in lung expansion capacity and functional residual capacity.11 As a result, atelectasis, airway closure, and a disrupted ventilation/perfusion balance are observed.13 At the same time, continuous ventilation of patients with dry air due to mechanical ventilation applied under anesthesia can cause the formation of mucus plugs; respiratory passage is partially blocked in proportion to the size of these mucus plugs, atelectasis occurs and results in increases in peak pressures.14 Beyond mucus accumulation, diminished alveolar expansion can precipitate alveolar collapse owing to reduced surface tension stemming from decreased humidity within the alveolar microenvironment. In our study, compliance values decreased by 20–25% after intubation at T2–5 compared with baseline values measured at T1 due to pneumoperitoneum. When the PIP values were evaluated, an increase of 31–37.5% was observed at T2–5, based on the PIP values at T1.
Figure 3.
Positional changes in the diaphragm and lungs of patients during the awake state, under general anesthesia, and throughout laparoscopic surgery.
Created with Microsoft PowerPoint (Version 2019).
Anesthesia techniques, including medium flow (1–2 L/min), low flow (0.5–1 L/min), minimal flow (0.25–0.5 L/min), and metabolic flow (< 0.25 L/min), help reduce costs by minimizing anesthetic and medical gas consumption while also reducing environmental pollution.15,16 As the flow rate decreases, the removal of medical gases and moisture is minimized. Consequently, reducing the flow not only lowers costs but also helps maintain a humidified respiratory tract, thereby supporting the preservation of lung dynamics. The vast majority of sophisticated anesthesia devices today allow a flow of less than 2 L/min. Additionally, anesthesia machines allow metabolic flow at 0.20 L/min. Patient oxygen consumption and carbon dioxide production during low-flow application should also be closely monitored.17 Some of the most common complications of low-flow anesthesia are hypoxia, hypercapnia, and the use of unstable anesthetic agents.18 To avoid these complications, the anesthesiologist should be well acquainted with the anesthesia machine used, and patient follow-up should be carried out sensitively. In this study, the inspired oxygen concentration was maintained at 50% throughout the surgery to avoid a reduction in oxygen levels. During the follow-up of the patients, carbon dioxide absorbers were changed daily without allowing carbon dioxide gas to be seen on the gas monitor.19
During lung compliance measurements, thoracic structures must allow for maximal lung expansion. Therefore, it is essential to minimize muscle activity and surgical response as much as possible. In our study, TOF activity was maintained at a minimum, with the BIS and anesthesia depth maintained between 40% and 60%. Appropriate medications were administered to ensure that vital signs remained within physiological limits. Similar protocols have been employed in other clinical studies assessing lung mechanics.20,21
Although there was no difference between the groups in terms of the PIP values and compliance values measured at T1–5, there was a significant difference at T6 between the groups. Despite the termination of surgery and pneumoperitoneum, PIP values increased and compliance values decreased in the medium-flow group; that is, similar volumes were created at higher pressure levels. The patients’ lung compliance and PIP values did not significantly differ before and after surgery with the minimal flow anesthesia applied in this study. A study on post-intubation and intraoperative compliance in gynecological surgeries reported a significant decline in compliance in both the laparotomy and laparoscopy patient groups compared with pre-intubation values.22 Importantly, this decrease in compliance was more pronounced in the laparoscopic cohort. These findings underscore the importance of minimizing the impact on lung dynamics, particularly in laparoscopy patients, during the administration of anesthesia. In addition to the increase in intrathoracic pressure, the preservation of intrapulmonary dynamics is of paramount importance. Our study revealed that closure or narrowing of the airways in patients who underwent minimal flow anesthesia during the perioperative period was either prevented or tolerated.
In a study evaluating the pulmonary function tests of patients who had undergone laparoscopic and laparotomic cholecystectomy, the FVC, FEV1, and FEV1/FVC values of patients with LC were higher than those of patients who had undergone laparotomic surgery. This study revealed that the less invasive the surgery is, the less respiratory functions are affected.23 For this reason, as in many centers, we prefer laparoscopic techniques for cholecystectomy surgery at our center. However, although it is considered less invasive, general anesthesia applied during LC has the potential to cause respiratory problems during and after the surgical position and pneumoperitoneum. Similarly, in our study, pulmonary function tests evaluated during the postoperative period revealed that the FEV1, FVC, and FEV1/FVC ratios of the patients decreased. Another study found no significant differences in FEV1, FVC, or FEV1/FVC between the high-flow and low-flow anesthesia groups at any of the measured time points (preoperatively and 2, 8, and 24 hours postoperatively).24 In a different study in which medium- and low-flow anesthesia were applied, there was no significant difference between the groups in terms of FVC, FEV1, and FEV1/FVC ratio during the preoperative and postoperative periods.25 In our study, although the pain scores were reduced to 4 or less in the sitting position in all our patients who underwent cholecystectomy, the pulmonary function test scores (FEV1, FVC and FEV1/FVC) were lower in the first 24 hours than the preoperative lung function test scores.
This study has several limitations. Airway compliance measurements during mechanical ventilation are evaluated when there is no resistance, that is, no flow (static compliance). Measurements made while waiting for the equalization of alveolar and airway pressure within the respiratory cycle are somewhat affected by pressure changes. For this reason, measurements made at the end of expiration or inspiration are required. For this reason, in routine practice, static compliance cannot be measured continuously, and follow-ups are followed by dynamic compliance calculations applied during the normal respiratory cycle. For these reasons, we used dynamic compliance data in this study. The second limitation of the study is that temperature and humidity differences between medium flow and minimal flow cannot be evaluated with numerical data since temperature and humidity monitoring cannot be performed during low-flow anesthesia. The third limitation of the study is that the number of patients at T5 was less than that at other time points.
In conclusion, the increase in PIP values and the decrease in compliance values were less pronounced in patients under minimal flow anesthesia than in those under medium flow anesthesia. Despite these changes in compliance and PIP values, there was no difference between the pulmonary function tests performed in the preoperative and postoperative periods. In light of these data, minimal flow anesthesia can be used to reduce the cost and waste gas rate and protect respiratory dynamics. However, these changes were not substantial enough to affect respiratory test results in the postoperative period.
Funding Statement
Funding: This study was supported by the Atatürk University Scientific Research Project (No. TAB-2021--9116).
Footnotes
Conflicts of interest: There are no conflicts of interest.
Declaration of AI and AI-assisted technologies in the writing process: The authors declare that no Generative AI was used in the preparation of this manuscript.
Data availability statement:
Not applicable.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Not applicable.