ABSTRACT
Objective:
Anesthetic and surgical stress may complicate the delicate immune state of obese patients. The immunomodulatory potential of anesthetics may play a role in minimizing complications. This study evaluates desflurane versus total intravenous anesthesia (TIVA) with propofol on surgical stress response in patients undergoing laparoscopic bariatric surgery, comparing interleukin-6 (IL-6) levels as a marker of neuroendocrine stress response between groups.
Methods:
Thirty adult patients aged 18–75 years, who underwent laparoscopic bariatric surgery, were studied in this prospective, randomized, single-blinded pilot study. Participants were randomly assigned to receive either desflurane (Group D) or propofol (Group P) anesthesia. Blood samples were collected after induction and extubation for the IL-6 assay. The investigator analyzing IL-6 levels was blinded to group allocations.
Results:
IL-6 increase was not significantly different between patients receiving desflurane or propofol. The choice of surgical procedure and its duration significantly impacted the inflammatory response. Other recovery parameters and adverse events did not differ significantly between the groups, except for nausea which was higher in the desflurane group.
Conclusion:
Both desflurane and TIVA with propofol are viable options for managing anesthesia in obese patients, with each having distinct advantages.
KEYWORDS: Bariatric surgery, biomarker, chronic inflammation, desflurane, interleukin-6, obesity, propofol
INTRODUCTION
Obesity is characterized by a low-grade chronic inflammatory state. Hypertrophic and hyperplastic adipocytes in obesity secrete pro-inflammatory substances known as adipokines which cause lung inflammation and contribute to vascular and cardiac remodeling, impairing microvascular regulation.[1] In addition, they act as chemoattractants, causing macrophage and T-cell recruitment to the adipose tissue, worsening the existing inflammatory state. This ongoing inflammation is central to metabolic syndrome and insulin resistance.
This chronic inflammatory milieu adversely affects the immune response to surgical and anesthetic stress, impacting postoperative recovery. While a moderate inflammatory response aids wound healing, excessive inflammation may increase infection risk and delay recovery. Anesthetic agents, by modulating immune and neuroendocrine responses, play a critical role in influencing these outcomes. Inhalational anesthetics have demonstrated immunosuppressive effects on immune cells,[2] whereas propofol has been shown to reduce superoxide generation, elastase release, and chemotaxis.[3]
Despite the clinical relevance, there is a paucity of data on immunomodulation in obese surgical patients. Previous studies have shown conflicting results: Abramo et al. compared total intravenous anesthesia (TIVA), sevoflurane, and xenon in obese patients, finding significantly reduced postoperative tumor necrosis factor alpha (TNF-α) levels with xenon, although differences in other cytokines were minimal.[4] Animal studies further suggest that obesity impairs anesthetic preconditioning; sevoflurane-induced cardioprotection observed in lean animals was absent in obese models, and neuroprotection by isoflurane was similarly attenuated.[5]
Given these uncertainties, this pilot study evaluated the effects of two anesthetic techniques – desflurane and TIVA with propofol – on the surgical stress response in obese patients undergoing laparoscopic bariatric surgery. The primary objective was to compare the rise in serum interleukin-6 (IL-6) levels, a marker of neuroendocrine surgical stress, between groups.
Amongst secondary objectives, pre-operative IL-6 levels (T1) were correlated with body mass index (BMI), gender, presence of obstructive sleep apnea, and other comorbidities. Post-operative IL-6 (T4) levels were correlated with the type of surgery, duration of surgery and anesthesia, and length of hospital stay.
In addition, hemodynamic and respiratory parameters, frequency of adverse effects intraoperatively (hypotension, bradycardia, and desaturation) and postoperatively (nausea, vomiting, decreased respiratory rate, respiratory pauses, desaturation), time to awakening, length of hospital stay, rate of postoperative pulmonary complications (POPC) were also compared between the two groups.
METHODS
This pilot study is a prospective, randomized, single-blinded trial conducted at the All India Institute of Medical Sciences, New Delhi, India. We included adult patients aged 18–75 years, of both sexes with BMI >30 (BMI in kg m−2), who underwent laparoscopic bariatric surgery between March 2020 and September 2021. Patients who refused to participate, having known allergy to propofol, had impaired cardiopulmonary, hepatic, or renal function, a history of chronic inflammatory conditions, or those receiving treatment with immunosuppressants were excluded.
The trial protocol was registered in the national Clinical Trial Registry of India (CTRI/2020/03/024154) before patient recruitment, and ethical approval was obtained from the Institute Ethics Committee (IECPG-769/30.01.2020). All participants provided informed written consent. Every recruited patient received their allocated treatment, and outcome data were collected for all participants.
Patients meeting the eligibility criteria were randomly assigned in a 1:1 ratio to the desflurane (Group D) or the propofol group (Group P) using a computer-generated permuted block randomization method, and the allocation was concealed. All procedures and measurements were as per institutional protocols. Standard American Society of Anesthesiologists monitoring along with neuromuscular and bispectral index (BIS) monitoring, was used.
Anesthesia was induced with intravenous (IV) midazolam 1 mg, fentanyl 2 μg kg−1 lean body weight (LBW), propofol 2 mg kg−1 LBW, and suxamethonium 1.5 mg kg−1 TBW (total body weight; maximum 200 mg) followed by intubation in Group D. Propofol for induction was administered by target controlled infusion (TCI) pump in Group P (Marsh model; Effect site concentration; Ce = 6 μg mL−1).
Maintenance of anesthesia in Group D was using desflurane in an air-oxygen mixture, whereas in Group P, TCI propofol with Ce = 2–4 μg mL−1 with air-oxygen was administered.
A BIS value of 40–60 and hemodynamic parameters were maintained within 20% of baseline.
Pressure-controlled ventilation mode was utilized to deliver a tidal volume of 5–10 mL kg−1 IBW, respiratory rate adjusted to obtain end-tidal carbon dioxide concentration 36–44 mmHg, a positive end-expiratory pressure (PEEP) of 8 cm H2O applied initially, and, inspired oxygen concentration was adjusted to maintain saturation >95%. PEEP adjustment and recruitment maneuvers were utilized upon desaturation at the discretion of the anesthesiologist.
For analgesia, IV fentanyl infusion was initiated at 1 μg kg−1 LBW/hour, IV paracetamol 1 g before incision, and fentanyl boluses (0.5–1 μg/kg LBW) as needed. Ketorolac 30 mg IV was administered at the end of surgery.
Hemodynamic (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP]), and respiratory parameters (peak pressures, compliance, were measured at five time points namely T1, 10 min after induction; T2, 20 min after pneumoperitoneum creation; T3, at the end of surgery; T4, after extubation and T5, 3 h postoperatively. Arterial blood gas analysis was done at T1 and T4.
At the end of surgery, the inhalation anesthetic was stopped, and neuromuscular blockade was reversed using neostigmine (50 μg kg−1 adjusted body weight [ABW]; maximum 5 mg and glycopyrrolate 10 μg kg−1 ABW). Trachea was extubated once the clinical endpoints of adequate reversal were achieved and a train-of-four ratio of 0.9 was confirmed.
Time to awaken (in minutes) was noted from stopping the anesthetic to the patient following commands. Patients were transferred to the postanesthesia care unit (PACU). Adverse events such as decreased RR (<10 bpm), respiratory pauses, desaturation (<90%), nausea, and vomiting were noted. Patients were discharged to the ward upon achieving a score ≥9 on the Modified Aldrete scoring system. The postoperative incidence of adverse events and time spent in PACU were recorded.
Postoperatively, POPC occurrence and hospital stay length were also noted after follow-up till the day of discharge. POPC, defined by the European Perioperative Clinical Outcome guidelines (2015), included respiratory infection, failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis, with pneumonia, ARDS, and pulmonary embolus as individual adverse outcomes.
The investigator analyzing plasma IL-6 levels was blinded to group allocations. Sampling and serological analysis were performed in the following manner. After induction of anesthesia, radial artery was cannulated for invasive blood pressure monitoring. Blood samples were collected from the radial arterial line at induction (T1) and just before extubation (T4). A 2 ml blood sample in a serum separating tube was kept at room temperature for 1 h for serum separation, and centrifuged at 3000 rpm for 5 min. The separated serum (200 μl) was transferred to a microcentrifuge tube and stored at − 80°C until analysis.
An enzyme-linked immunosorbent assay (ELISA) kit (Quantikine ELISA R&D Systems, category number: D6050) was used to assess IL-6 levels. A 96-well ELISA microplate pre-coated with IL-6 was used. Collected serum and control samples and reference standards were added to the wells. After 2 h of incubation, the wells were washed with wash buffer to remove unbound cytokines. Human IL-6 conjugate was then added to each well, followed by another 2 h incubation and washing. A substrate solution was added to measure IL-6 levels, and the plate was incubated for 2 min. The reaction was stopped with a stop solution, and optical density (OD) was measured using a microplate reader at 450 nm, with corrections at 570 nm.
Duplicate readings for each standard, control, and sample were averaged, and the average zero standard OD was subtracted from these values. A standard curve was generated from the OD values of the reference standards, which was then used to calculate IL-6 levels in patient samples and controls.
Statistical analysis
No similar study was reported in the morbidly obese population. Hence, in the absence of available evidence, a pilot study was undertaken with 15 patients in each arm (n = 30).
Data were recorded in Microsoft Excel and analyzed using the Statistical Package for the Social Sciences (SPSS v.23 IBM, Chicago, Illinois, USA). Descriptive statistics included means and standard deviations and medians/interquartile ranges for continuous variables, and frequencies/percentages for categorical variables. Group comparisons employed independent sample t-tests for normally distributed data and Wilcoxon tests for nonnormally distributed data. Chi-squared tests were used for categorical comparisons, with Fisher’s Exact test applied when needed (in case the expected frequency in the contingency tables was found to be <5 for >25% of the cells). Linear correlations used Pearson’s or Spearman’s tests, depending on data distribution. Statistical significance was set at P < 0.05.
RESULTS
Thirty patients undergoing laparoscopic bariatric surgery were recruited and received either desflurane (Group D) or propofol (Group P) for maintenance of anesthesia [Figure 1]. Blood samples were taken after induction (T1) and after extubation (T4) to measure IL-6 levels. Hemodynamic, ventilatory, and recovery parameters were recorded at T1-T5 time points for all 30 patients. Two samples, one from each group, did not reveal results on serological analysis and were excluded.
Figure 1.
Consolidated standards of reporting trials diagram showing study design. TIVA = Total intravenous anesthesia
Baseline characteristics were comparable in both groups, and the mean age was 38 years (±10 years) [Table 1].
Table 1.
Baseline data and characteristics for patients undergoing bariatric surgery who received desflurane or total intravenous anesthesia as anesthetic approach
| Parameters | Group | P* | |
|---|---|---|---|
|
| |||
| D (n=15), n (%) | P (n=15), n (%) | ||
| Age (years) | 38.67±10.99 | 38.07±13.12 | 0.893a |
| Gender | |||
| Male | 5 (33.3) | 5 (33.3) | 1.000c |
| Female | 10 (66.7) | 10 (66.7) | |
| BMI (kg/m²) | 46.77±5.90 | 44.58±6.75 | 0.353a |
| 35.0–39.9 | 1 (6.7) | 3 (20.0) | 0.833b |
| 40.0–44.9 | 6 (40.0) | 5 (33.3) | |
| 45.0–49.9 | 4 (26.7) | 5 (33.3) | |
| 50.0–54.9 | 1 (6.7) | 0 | |
| ≥55.0 | 3 (20.0) | 2 (13.3) | |
| Total body weight (kg) | 123.33±31.83 | 119.73±23.98 | 0.950d |
| Ideal body weight (kg) | 56.73±12.12 | 55.40±9.36 | 0.983d |
| Adjusted body weight (kg) | 82.60±19.36 | 84.80±12.81 | 0.340d |
| Lean body weight (kg) | 61.44±16.50 | 59.61±11.46 | 0.775d |
| Co-morbidities: Any (yes) | 12 (80.0) | 11 (73.3) | 1.000b |
| OSA (yes) | 11 (73.3) | 8 (53.3) | 0.256c |
| Procedure | |||
| LSG | 6 (40.0) | 6 (40.0) | 1.000b |
| MGB | 5 (33.3) | 4 (26.7) | |
| RYGB | 4 (26.7) | 4 (26.7) | |
| OAGB | 0 | 1 (6.7) | |
| Duration of anesthesia (min) | 190.33±75.56 | 175.67±56.60 | 0.553a |
| Duration of surgery (min) | 166.33±70.09 | 155.33±53.60 | 0.633a |
*Significant at P<0.05, at-test, bFisher’s exact test, cChi-squared test, dWilcoxon–Mann–Whitney U-test. BMI=Body mass index, LSG=Laparoscopic sleeve gastrectomy, MGB=Mini gastric bypass, RYGB=Roux-en-Y gastric bypass, OSA=Obstructive sleep apnea, OAGB=One anastomosis gastric bypass
In Group D, IL-6 levels increased significantly from T1 to T4. (Wilcoxon Test: V = 0.0, P < 0.001) Similar statistically significant change was noted in Group P also (Wilcoxon Test: V = 0.0, P < 0.001) [Table 2]. However, this change in IL-6 (Δ IL-6) revealed no significant difference between the two groups (P = 0.618).
Table 2.
Comparison of the two groups in terms of change in interleukin-6 over time points T1–T4 (n=28)
| IL-6 | Group | P value for comparison of the two groups at each of the timepoints (Wilcoxon–Mann–Whitney test) | |||
|---|---|---|---|---|---|
|
| |||||
| D | P | ||||
|
|
|
||||
| Mean±SD | Median (IQR) | Mean±SD | Median (IQR) | ||
| T1 | 19.63±20.29 | 16.44 (3.41–29.83) | 15.45±13.18 | 11.23 (3.03–28.82) | 1.000 |
| T4 | 44.17±28.38 | 39.29 (30.46–44.12) | 36.74±21.44 | 39.76 (16.01–54.55) | 0.910 |
| P value for change in IL-6 over time within each group (Wilcoxon test) | <0.001 | <0.001 | |||
| Overall P value for comparison of change in IL-6 over time between the two groups (Generalized Estimating Equations) | 0.618 | ||||
IQR=Interquartile range, SD=Standard deviation, IL=Interleukin
The study also explored correlations between pre-operative (T1) IL-6 levels and patient characteristics such as BMI, gender, and comorbidities. A significant preoperative difference in IL-6 levels between males and females (P = 0.019) was noted, but no other correlations were derived [Table 3].
Table 3.
Correlation between interleukin-6 at T1 (preoperatively) with body mass index, total body weight, gender, and comorbidities
| Parameters | IL-6 (T1) | P* |
|---|---|---|
| BMI (kg/m²) | Correlation coefficient (rho)=0.02 | 0.912a |
| 35.0–39.9 | 11.75±12.77 | 0.490b |
| 40.0–44.9 | 19.92±20.91 | |
| 45.0–49.9 | 13.39±13.03 | |
| 50.0–54.9 | - | |
| ≥55.0 | 26.09±17.06 | |
| Total body weight (kg) | Correlation coefficient (rho)=0.16 | 0.421a |
| Gender | ||
| Male | 30.34±22.63 | 0.019c |
| Female | 12.42±11.04 | |
| Comorbidities: Any | ||
| Yes | 18.67±17.78 | 0.426c |
| No | 14.15±14.74 | |
| OSA | ||
| Yes | 19.34±19.54 | 0.778c |
| No | 14.76±12.20 |
*Significant at P<0.05, aSpearman correlation, bKruskal–Wallis test, cWilcoxon–Mann–Whitney U-test. IL=Interleukin, BMI=Body mass index, OSA=Obstructive sleep apnea
We identified a significant correlation between the type of surgical procedure, duration of surgery, anesthesia, and postoperative IL-6 levels (T4). Patients undergoing laparoscopic sleeve gastrectomy (LSG) had lower IL-6 levels compared to those undergoing Roux-en-Y gastric bypass (RYGB) or mini gastric bypass (MGB) (P = 0.015) [Table 4]. Increase in IL-6 levels post-operatively correlated significantly with the type of surgical procedure performed (LSG/RYGB/MGB) (P = 0.015). Surgical technique used and procedure duration were critical factors affecting post-operative IL-6 levels.
Table 4.
Correlation between interleukin-6 at T4 (postoperatively) with procedure type, duration of anesthesia and surgery, postoperative pulmonary complications, and length of stay
| Parameters | IL-6 (T4) | P |
|---|---|---|
| Procedure*** | ||
| LSG | 25.82±13.29 | 0.015b |
| MGB | 56.33±24.43 | |
| RYGB | 42.72±28.34 | |
| OAGB | - | |
| Duration of anesthesia (min)*** | Correlation coefficient (rho)=0.46 | 0.013a |
| Duration of surgery (min)*** | Correlation coefficient (rho)=0.5 | 0.007a |
| POPC | ||
| Yes | 42.73±26.23 | 0.672c |
| No | 39.55±25.09 | |
| Duration of hospital stay (days)*** | Correlation coefficient (rho)=0.38 | 0.047a |
***Significant at P<0.05, aSpearman correlation, bKruskal–Wallis test, cWilcoxon–Mann–Whitney U-test. POPC=Postoperative pulmonary complications, IL=Interleukin, LSG=Laparoscopic sleeve gastrectomy, MGB=Mini gastric bypass, RYGB=Roux-en-Y gastric bypass, OAGB=One anastomosis gastric bypass
Higher IL-6 levels were associated with longer hospital stays (P = 0.047), indicating a correlation between inflammatory response and recovery duration. However, the occurrence of POPC did not correlate with elevated IL-6 levels (P = 0.672) [Table 4].
Hemodynamic variables such as HR, SBP, and DBP were compared at four different time points. The only significant finding was a greater decrease in HR after pneumoperitoneum creation (T2) in Group P. Blood gas analysis at two different time points showed no significant differences in ventilatory or oxygenation parameters. Postoperative outcomes, including time to awakening, duration of PACU stay, and early complications, were similar for both groups. Time to awakening and meeting discharge criteria showed no significant differences. In the PACU, the incidence of nausea was significantly higher in the desflurane group. The incidence of POPC and the duration of hospital stay were similar.
DISCUSSION
We observed that the increase in IL-6 levels post-operatively did not differ statistically whether the anesthesia was maintained with desflurane or propofol. The surgical technique emerged as a crucial factor affecting post-operative inflammation, underscoring the impact of surgical complexity and duration on recovery outcomes in bariatric surgery.
Desflurane is often preferred in obese patients for its rapid recovery profile over other inhalational agents. However, studies comparing TIVA and desflurane suggest that propofol may offer a superior quality of recovery, likely due to reduced postoperative nausea and vomiting.[6,7] In terms of immunologic effects, inconsistent results were obtained across surgeries.[8,9,10,11,12,13,14,15]
In open thoracic surgery with one-lung ventilation, Schilling et al. reported higher serum cytokine levels with desflurane compared to propofol and sevoflurane, although desflurane reduced alveolar cytokines, an effect not seen with propofol.[11] Koksal et al. found that desflurane triggered greater systemic and intrapulmonary pro-inflammatory responses than sevoflurane, with notable increases in TNF-α and IL-6.[14] Conversely, Although Sofra et al. observed no difference in postoperative IL 6 levels with TCI propofol or isoflurane in bladder cancer surgery, but both were deemed suitable since propofol increased Th1 expression and inhalational agents reduced regulatory T cells post-operatively (implicated in metastasis).[10]
While the clinical significance of these inflammatory variations remains unclear, some evidence favors propofol. Roh et al. demonstrated that propofol attenuates inflammatory responses during pneumoperitoneum and improves intraoperative urine output compared to desflurane during RALRP.[8] Baki et al. reported lower S100β levels – a marker of better neuroprotection – with propofol in on pump coronary artery bypass grafting (CABG) patients, although IL 6 and IL 8 levels were actually lower with desflurane.[9] Another study comparing isoflurane, high-dose, and low-dose propofol during on-pump CABG found that high-dose propofol was associated with lower troponin levels, better hemodynamics, and shorter intensive care unit stays, challenging the traditional belief of superior anesthetic preconditioning by inhalational agents.
Our study proposes a significant link between the type and duration of bariatric surgery and post-operative IL-6 levels. Patients undergoing LSG exhibited lower IL-6 levels compared to those undergoing RYGB, MGB, or OAGB (P = 0.015). Longer duration of surgery and anesthesia consistently led to higher IL-6 levels. Shorter procedure duration of LSG may have resulted in reduced tissue damage and lower inflammation.[3]
Elevated IL-6 levels were associated with longer hospital stays (P = 0.047), indicating a possible link between inflammation and recovery time; however, larger studies are required to prove this. Complex procedures with longer duration would lead to higher IL-6 levels as well as longer hospital stay. However, POPC did not correlate with IL-6 levels (P = 0.672). Surprisingly, a compelling link between obesity and POPCs remains missing. In the obese population subset, those afflicted with obesity hypoventilation syndrome alone had an increased incidence of POPCs. In a meta-analysis, TIVA was found equivalent to inhalational anesthesia in reducing mortality and postoperative complications in noncardiac surgeries, while demonstrating superior outcomes in cardiac surgeries.[16,17,18,19,20]
A recent meta-analysis by O’Bryan et al. confirmed that the inflammatory response also indicated that post-operative inflammation was more influenced by the patient and surgical factors than by the type of anesthesia.[20] We observed similar results in our study with desflurane and propofol, emphasizing that surgical stress, rather than the mode of anesthesia, primarily drives an increase in IL-6 level.
IL-6 was selected as it reliably correlates with surgical trauma, is released by leukocytes within minutes, and peaks within 12–24 h. We chose the end of surgery for sampling to capture the maximal impact of short-acting agents such as desflurane and propofol. However, single-point biomarker measurement may oversimplify inflammatory dynamics and may not align with outcomes such as length of stay or POPC, which are better associated with peak IL-6 levels. Other limitations include its pilot nature due to limited research on perioperative obesity and anesthetic immunomodulation, and a small sample size restricting generalizability.
CONCLUSION
This study suggests that anesthetic agents, whether desflurane or TIVA with propofol, have a limited role in modulating the postsurgical inflammatory response in this small cohort of obese patients. Instead, surgical factors such as procedure type and duration play a more significant role in this regard.
AUTHOR’S CONTRIBUTIONS
Sukriti Jha: Contributed to acquisition, analysis, and interpretation of data along with drafting the manuscript. Puneet Khanna: Contributed to concept and design of study and revised manuscript critically. Lokesh Kashyap: Formulated the study design and methodology and revised manuscript critically. Ashwin M: Added valuable content after extensive literature review and revised manuscript critically. Sandeep Aggarwal: Contributed to acquisition of data and reviewed manuscript, providing valuable insights to shape the drafts. Lata Singh: Contributed to study design, data analysis and interpretation, reviewed manuscript content, and edited manuscript. Virender Kumar Mohan: Contributed to concept of study and data interpretation along with drafting of manuscript. Dilip Shende: Contributed to acquisition of data and valuable insights into the concept of study along with drafting of manuscript.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
Dr. Seema Kashyap, Professor, Department of Ocular Pathology, Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Dr. Ajisha Aravindan, Associate Professor, Department of Anesthesiology, Pain medicine and Critical care, All India Institute of Medical Sciences, New Delhi, India.
Funding Statement
Nil.
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