Anesthesia plays an important role in supporting surgical procedures by controlling physiological and pharmacological processes, especially during surgical procedures.1 Anesthesia, in general, uses the lungs as a conduit to carry drugs, which may affect lung physiology during and after surgery. This effect usually manifests itself as a limitation in the function of the lungs. The development of restrictive lung dysfunction following general anesthesia is thought to be a consistent and repeatable observation.2 The choice of anesthetic agent may influence the degree of postoperative lung dysfunction.3

The choice of anesthesia is an important factor affecting the level of lung function after surgery.4 Although standard methods for assessing pre- and post-lung function for major surgical operations are available, their routine application is limited and has previously been hampered by the lack of tools to adequately measure in bed. However, the advent of reliable and accurate pulmonary function testing (PFT) equipment has reduced this problem and can assess anesthesia-induced respiratory depression.5 Spirometry is an important bedside PFT that provides important information about lung airflow and helps differentiate between restrictive and obstructive lung disease, although it requires significant patient involvement in pain.6

Inhalational anesthetic agents are effective, reliable, safe, easy to deliver, stable, and without major end, organ sequelae thus making balanced anesthesia with halogenated anesthetics perhaps the most popular general anesthesia technique being used now. The resistance of the entire respiratory system including the airways and parenchyma increases post-induction. This factor provides the upper hand of volatile anesthetic agents compared to IV agents as they have an intrinsic bronchodilation property.7

The best anesthesia for outpatients should be effective, and efficient, provide rapid recovery, and have minimal side effects. These drugs, especially sevoflurane and desflurane, are halogenated ethers with rapid induction properties due to their low blood: fat partition coefficient, making them suitable for surgeries requiring rapid recovery.8 Although studies show that healing is faster with desflurane compared to sevoflurane, its effect on the subsequent healing phase is problematic and superiority has not been demonstrated. A difference in early recovery was observed between sevoflurane and isoflurane in elective surgery.

This study is novel in that it directly compares head-to-head the effects of three Inhalational anesthetic agents on respiratory function through assessment by spirometry. This study aims to examine changes in lung function tests after surgery with isoflurane, sevoflurane, or desflurane as the inhalational agent.

Study Design and Setting: This was an observational study conducted among the patients posted for Laparoscopic Cholecystectomy in the Department of General Surgery at AIIMS Patna, India, and spanned one year from December 2020 to October 2021.

Study Participants: The study included otherwise healthy patients scheduled for laparoscopic cholecystectomy.

Sample size calculation: Based on information for mean FEV1 values pre-operative and post-operative, the sample sizes for three groups taking α=0.05/3=0.0166 and power to detect a difference of 0.32 units of FEV1, 50 for each group.

Study Procedure: The study involved 150 healthy patients who tested negative for COVID-19 and underwent laparoscopic cholecystectomy under general anesthesia. Preoperative spirometry was conducted using the MIR SPIROLAB spirometer, measuring six parameters in a 30° head-up position. Patients were divided into three groups to receive Isoflurane (I group), Desflurane (D group), or Sevoflurane (S group) as anesthetics. Standard anesthesia induction protocol was followed, including preoxygenation, propofol, and vecuronium for neuromuscular blockade. An IGEL supraglottic airway device was inserted, and inhalational agents were adjusted to maintain anesthesia depth, monitored by an infrared analyzer. Post-surgery, pain management included diclofenac and paracetamol, with additional analgesics administered based on the VAS pain score. Spirometry was repeated one hour and five hours post-operation to assess the immediate and residual effects of surgery and anesthetic agents. Recovery times were monitored, and patients were discharged from the PACU with a Modified Aldrete score above 9. The assessment of recovery times for determining when patients can open their eyes, follow commands, and be oriented to their name and place/time were assessed by an observer at 1-minute intervals on discontinuing the volatile anesthetics in the operating room. The patient was then transferred to the post-anesthesia care unit.

Analysis: Data collected were analyzed using SPSS IBM version 25 statistical software. Spirometry values at different time points were compared using repeated measure ANOVA.

Ethical Approval: Approval was obtained from the Institute Research Committee and Institutional Ethics Committee of All India Institute of Medical Sciences Patna. Informed consent was obtained from patients or their relatives.

In this study, we analyzed 150 patients undergoing lap cholecystectomy and aimed to compare the effects of the commonly used inhalational agents on pulmonary function in the postoperative period.

Table 1. Demographic Distribution of the Participants

The study cohort comprised 67% females and 33% males. Normal distribution of age, weight, height, and BMI was confirmed through Q-Q plots. The mean age was similar across the Desflurane (36.6 ± 11.96), Isoflurane (37.42 ± 11.33), and Sevoflurane (37.7 ± 10.52) groups, with no significant difference (P=0.880). BMI values were 24.01 ± 4.69 kg/m² for Desflurane, 25.99 ± 4.25 kg/m² for Isoflurane, and 26.13 ± 4.37 kg/m² for Sevoflurane, again with no significant difference (P=0.106). ASA classification indicated 87.3% ASA 1 and 12.7% ASA 2 patients, with all Desflurane patients being ASA 1, while Isoflurane and Sevoflurane groups had 84% and 78% ASA 1 patients, respectively. The duration of anesthesia was nearly identical among the groups, averaging 55.52 ± 8.15 minutes for Desflurane, 56.48 ± 8.26 minutes for Isoflurane, and 56.55 ± 7.26 minutes for Sevoflurane, with no significant difference (P=0.264). The mean surgery duration was also similar, with Desflurane at 43.96 ± 5.64 minutes, Isoflurane at 43.7 ± 7.36 minutes, and Sevoflurane at 44.4 ± 6.93 minutes, without significant difference (P=0.116).

Table 2. Measurement of values according to different categories across different time intervals

The data, normally distributed as per Q-Q plots, underwent a one-way repeated measures ANOVA. Due to the violation of sphericity, indicated by Mauchly's test (p < 0.05), Greenhouse-Geisser corrections were applied (ε = 0.935). FEV1 values decreased significantly from the preoperative period to post-anesthesia, with the F test showing (F (1.90, 279.6) = 191, p < 0.001). This trend was consistent across the Desflurane, Sevoflurane, and Isoflurane groups, all showing significant decreases (p < 0.001). FEV6 values also followed a decreasing trend, with the F test indicating (F (2, 274) = 196, p < 0.001). Each anaesthetic group exhibited significant reductions in FEV6 values at 1 hour and 5 hours post-anesthesia (p < 0.001). FVC values mirrored the decreasing pattern, with the F test yielding (F (2, 274) = 196, p < 0.001). All groups showed significant decreases in FVC from the preoperative period to 1 hour and 5 hours post-anesthesia (p < 0.001). PEF values decreased from the preoperative period to 1-hour post-extubation, with a recovery noted by the 5th hour. The F test reported (F (1.7, 250) = 166, p < 0.001), and all anaesthetic groups had significant changes in PEF values (p < 0.001). FEV1/FVC ratio experienced significant changes over time, with the F test revealing (F (1.80, 264) = 5.024, p < 0.05 ). Each group showed significant alterations in the ratio from the preoperative period to 1 hour and 5 hours post-anesthesia (p < 0.001). Lastly, F25-75 values significantly decreased from pre-op to post-extubating, with the F test indicating (F (1.80, 267) = 72.85, p < 0.05 \). All groups demonstrated significant decreases in F25-75 values at 1 hour and 5 hours post-anesthesia (p < 0.001).

Table 3. Comparison of mean fall in PEF at 1 and 5 hours according to different agents in Liters

In Table 3 the effects of general anesthesia on pulmonary function, the mean change in FEV1, FVC, FEV6, PEF, and F25-75 was measured across three groups: Desflurane, Isoflurane, and Sevoflurane. At the 1st hour post-anesthesia, the mean fall in FEV1 was 0.76, 0.83, and 0.94 liters respectively, with no significant difference between the agents (Welch F (2, 92) = 1.040, p = 0.35). The mean fall in FVC was 1.06, 0.97, and 1.12 liters respectively, also showing no significant difference (Welch F (2, 92.61) = 0.91, p = 0.4). Similarly, FEV6 values decreased by 1.01, 0.96, and 1.10 liters respectively, without a significant difference (Welch F (2, 92.15) = 0.76, p = 0.46). However, PEF values showed a significant decrease at the 1st hour, with mean falls of 1.48, 2.13, and 2.16 liters respectively, indicating a significant difference between the groups (ANOVA F (2,147) = 3.15, p = 0.046). The F25-75 values also significantly decreased, with mean falls of 0.43, 0.98, and 0.91 liters respectively, and a significant difference was observed (ANOVA F (2,147) = 5.79, p = 0.004). At the 5th hour post-anesthesia, the mean change in FEV1 was 0.21, 0.29, and 0.45 liters respectively, with a significant difference between the groups (ANOVA F (2,145) = 3.68, p = 0.023). No significant differences were found in the mean change in FEV6, FVC, and FEV1/FVC values. However, a significant difference was observed in the mean fall in F25-75 values at the 5th hour, with changes of 0.39, 0.36, and 4.17 liters respectively (ANOVA F (2,147) = 4.29, p = 0.01).

Out of the 150 patients posted for laparoscopic cholecystectomy under GA in AIIMS PATNA, 67% (101) were females and 33% (49) were males. The male age group was evaluated in many studies as a reason for conversion to open cholecystectomy from laparoscopy, but they could not find a significant difference among the sexes.9 The majority of the patients undergoing laparoscopic cholecystectomy were females in our study. The mean BMI values in kilogram per square meter in the Desflurane group is 24.01 4.69 kg/m2, in the isoflurane group is 24.99  4.25 kg/m2 and sevoflurane group is 26.13  4.37 kg/m2. The three groups were comparable in terms of BMI. We have excluded patients with a BMI of more than 30 kg/m2, as postoperative reduction in spirometric volumes is more significant in obese patients in previous studies.10

Our analysis revealed that all 6 parameters showed statistically significant change from the pre-operative to the post-operative period among all agents. The change was statistically significant for only 3 values in the first hour, FEV1/FVC, F25-75, and PEF implying a significant difference among the three groups in terms of these parameters. The recovery of the FEV1 (p =0.023) and F25-75 (p =0.01) values only showed a statistically significant difference at the 5th hour in our analysis. We found a statistically significant difference in the time to eye-opening, time to follow commands, and time to get oriented to time, place, and person between the three inhalational agents. Due to the lack of statistically significant difference in the pulmonary function parameters assessed, we cannot recommend one agent as being superior to another in terms of both recovery from anesthesia and its effect on pulmonary function based on this observational study.

Sharma et al.11 studied sixty patients of either gender, aged 18-60 years, with ASA status I/II who were scheduled for mastoid surgery and were randomly assigned to one of two groups. In Group B, anesthesia was maintained with desflurane, nitrous oxide, and oxygen, while in Group T, anesthesia was maintained using TIVA. Preoperatively, as well as 1, 3, and 24 hours afterward, pulmonary function tests (PFT) were performed, unlike our study where it was done at 1 hour and 5 hours post-surgery.  The TIVA group had a larger drop in FEV1 and peak expiratory flow rate (PEFR) one hour after surgery (p=0.044 and 0.042, respectively). The decline in MEFR and PEFR was again larger with TIVA three hours after surgery (p=0.005 and 0.008, respectively), while the MEFR recovered to preoperative levels in Sevoflurane. By 24 hours, TIVA forced vital capacity (FVC), MEFR, and PEFR had returned to preoperative levels, however, Group B's FVC had remained lower (p=0.006). Both anesthetic agents compromise lung function after surgery, although TIVA induced a higher fall in PFT in the early postoperative period, as well as a faster recovery. Balanced anesthesia with desflurane, on the other hand, was linked to a higher drop in PFT at 24 hours. In our study, we were not able to comment on the later recovery profiles due to the lack of follow-up after 5 hours post-procedure.

Rothen et al.12 in his study comparing nitrous oxide with 30 % oxygen and 100 % oxygen inhalational technique concluded that the extent of the atelectasis in turn influences the extent to which FVC or FEV1 is reduced. Even at the time of induction of general anesthesia in patients with healthy lungs, gas composition has an important role in atelectasis formation and the changes in ventilation-perfusion relations. We were unable to quantify the extent of atelectasis in our study because of the lack of a post-operative CT scan as conducted by Rothen et al. He postulated that atelectasis also depends on the gas mixture that is administered and the oxygen concentration in the mixture. This was consistent with the study by Nathanson et al. 13 They conducted a study on 42 healthy, unpremeditated women undergoing laparoscopic sterilization. Use of desflurane led to a more rapid emergence (4.8 +/- 2.4 vs 7.8 +/- 3.8 min) and shorter time to extubating (5.1 +/- 2.2 vs 8.2 +/- 4.2 min) compared to sevoflurane. They also assessed the recovery of cognitive function and time to discharge which was not done in our study. Based on the findings of this observational study, Desflurane may be recommended as the best agent for laparoscopic cholecystectomy in terms of Operating room recovery parameters. Desflurane has the advantage of having a faster recovery time in the operating room. The effects of the three 85 inhalational agents on the PFT parameters in the first hour and 5th hour were variable and none of them could produce a consistent change in all the post-operative PFT parameters. Due to the lack of statistically significant difference in the pulmonary function parameters assessed, we cannot recommend one agent as being superior to another in terms of BOTH recoveries from anesthesia and its effect on pulmonary function based on this observational study. They concluded that Sevoflurane is an acceptable alternative to desflurane for the maintenance of outpatient anesthesia.

Jindal et al.14 compared desflurane and sevoflurane in a prospective study on one hundred females scheduled to undergo short daycare gynecological procedures. The emergence characteristics assessed by them included a response to painful stimuli, eye-opening, verbal commands, and spontaneous eye-opening. They concluded that emergence from anesthesia was significantly faster in desflurane compared to the sevoflurane group for a given duration of anesthesia.

Both Sevoflurane and Desflurane are less soluble agents compared to Isoflurane and in our analysis, we found that Desflurane held the upper hand in terms of all three recovery parameters, followed by Sevoflurane and Isoflurane. This is consistent with the study by Apfelbam et al.15 where they compared volatile agents with propofol. In the case of the time taken to follow commands mean time taken in the sevoflurane group was higher than Isoflurane which was an isolated finding in our case.  Desflurane, hence proved itself once again as a suitable agent for laparoscopic surgeries and may be used as the preferred agent of laparoscopic cholecystectomies under day care surgery.

During this trial of 150 patients undergoing laparoscopic cholecystectomy, neither bouts of nausea or vomiting, nor any other adverse effects, were reported. Newer improved laparoscopic techniques and the pharmacotherapies aimed at reducing the incidence of emesis could have been a reason for this. In contrast, in a study by Gupta et al.16 where they examined surgical recovery and complications using four distinct anesthetic techniques: Propofol, Isoflurane, Desflurane, and Sevoflurane, the isoflurane group had a higher Relative risk of postoperative problems such as nausea (NNT, 8), vomiting (NNT, 10) and headache (NNT, 22). When propofol was used instead of isoflurane, the incidence of nausea, vomiting, headache, and post-discharge nausea and vomiting was lower (P 0.05).

The study found that all three inhalational agents (Desflurane, Sevoflurane, and Isoflurane) used for laparoscopic cholecystectomy caused a decline in lung function after surgery. There was a statistically significant difference in spirometry readings from pre-operative to 1st hour and 5 hours post-surgery. For Sevoflurane and Desflurane, all values except FEV1/FVC dropped in the first hour. For isoflurane, all parameters declined in the first hour. The recovery of FEV1, FVC, and FEV6 with isoflurane was greatest in the fifth hour, with little variation from pre-operative values and Desflurane provided the greatest recovery of FEV1/FVC, F25-75, and PEF values. But statistically significant change was obtained only for FEV1/FVC, F25-75, and PEF values in the first hour and F25-75 and FEV1 measurements in the 5th hour.

All three inhalational agents in the study Desflurane, Sevoflurane, and Isoflurane elicit postoperative pulmonary function depression at 1 hour and 5 hours in patients undergoing laparoscopic cholecystectomy. This depression of the spirometry parameters in the first hour could be due to the type of surgery with the inhalational agent used as a significant contributing factor. We were able to demonstrate this difference across all three agents. When the agents were compared with each other, a statistically significant difference was not obtained uniformly for all the parameters at 1 hour and 5 hours, implying that one agent cannot be regarded as better than the others. The significant change obtained in some of the flow values was an isolated finding and could be the result of the residual effect of the other anesthetic agents used which cannot be commended now and needs further research. In the case of the recovery parameters patient receiving Desflurane took the least amount of time to open the eyes, follow commands, and become oriented to time, place, and person, followed by Sevoflurane and Isoflurane.

Future studies with a larger sample size and more elaborate designs are needed to definitively determine if one inhalational agent offers an advantage in terms of postoperative lung function or recovery time, especially regarding discharge readiness. Additionally, these studies should investigate the link between the agents and the development of atelectasis (collapsed lung segments).

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