Comparing Perioperative Outcomes of Total Intravenous Anesthesia (TIVA) With Volatile Anesthesia in Patients With Obesity: A Systematic Review

In this systematic review, the perioperative outcomes of total intravenous anesthesia (TIVA) and volatile anesthesia were compared in obese adults (BMI ≥ 30 kg/m²) undergoing elective surgery. The review analyzed data from 12 randomized-controlled trials involving 935 patients, sourced from PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane, Scopus, and Web of Science databases. The focus was on intraoperative vital signs, emergence time, postoperative nausea and vomiting (PONV), duration of post-anesthesia care unit (PACU) stay, and ICU admission rates. Findings showed that TIVA (using propofol) might reduce PONV, but there were no significant differences in other outcomes compared to volatile anesthesia (with desflurane as the most common agent). The review highlights the need for more research, especially comparing sevoflurane with TIVA, to establish clear clinical guidelines for anesthesia in obese patients.


Introduction And Background
Obesity poses a significant risk for the development of heart disease, stroke, diabetes, and cancer, which are among the top 10 leading causes of death in the United Kingdom, the United States, and Canada [1][2][3][4][5].It is defined as a body mass index (BMI) ≥ 30 kgm 2 .Global projections anticipate a rise in obesity from around 13% in 2016 [6] to 23-27% by 2035 [7].The escalating incidence of obesity has led to a proportional increase in bariatric surgeries [8], posing greater challenges to anesthesiologists in the perioperative period [9].Obesity is associated with increased incidence and severity of postoperative complications [10].It results in an increase in both fat and lean mass; however, the increase in lean mass is considerably lower than fat, affecting the apparent volume of distribution of lipid-soluble anesthetic drugs [1].Thus, the perioperative anesthetic strategy must be meticulously planned to address the altered physiology and pharmacokinetics in patients with obesity [11].
General anesthesia (GA) is commonly administered in one of two ways: balanced anesthesia utilizing a combination of intravenous and inhaled agents, or total intravenous anesthesia (TIVA), typically propofolbased, which only uses intravenous anesthetic agents for both induction and maintenance [12].Existing comparisons between these techniques in patients with obesity are limited and lack consensus [13,14].
Propofol is an ideal drug for TIVA, given its rapid onset and short duration of action on the gammaaminobutyric acid (GABA) receptors, altering cellular communication [15].Although it is highly lipophilic, propofol has not consistently demonstrated prolonged effects of anesthesia in patients with obesity.This is potentially because the lipophilic properties of propofol are offset by the decreased perfusion of adipose tissue [16].Similarly, during routine operations, the newer volatile anesthetic agents (desflurane, sevoflurane) have not demonstrated an increase in anesthetic time in patients with obesity compared to those with a normal BMI [16].
The aim of this systematic review was to compare the perioperative outcomes of volatile anesthetics and those with TIVA, specifically in patients with obesity undergoing elective surgery.The outcomes of interest in this review were evaluating intraoperative vital signs, time to emerge from anesthesia, the incidence of postoperative nausea and vomiting (PONV), length of stay in the post-anesthesia care unit (PACU), rates of admission to the ICU and reasons for admission to the ICU.Increased incidence of PONV can lead to delayed recovery and extended hospital stays [17], thereby increasing the risk of patients contracting hospitalacquired illnesses.Additionally, a lower incidence of PONV is likely to reduce PACU and hospital stay times, thereby having a positive impact on healthcare costs and effective resource utilization [17,18].Recognizing the scarcity of literature in this area, an updated review was indicated to address the rising challenges presented in the perioperative care of patients with obesity.

Review Methods
As the first comprehensive review in this area, our primary objective was to map and analyze the existing literature.This approach helped identify research gaps and assess the feasibility of future meta-analyses.We conducted this systematic review using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions [19] and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [20,21].This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42023491794).

Search Strategy
We searched PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) (Table 1), Scopus (Table 2), Cochrane (Table 3), and Web of Science (Table 4) databases using Medical Subject Headings (MeSH) and free-text terms related to our study on 05/11/2023.

Types of Study
Strict inclusion and exclusion criteria were used to identify robust studies for analysis.The aim of this study was to conduct a systematic review of relevant studies available in English, with no constraints on the date of publication.We methodically screened and studied randomized controlled trials (RCTs).The studies that were chosen to be included in this review met the following inclusion criteria: RCTs comparing the effects of different types of GA; either a combination of volatile and intravenous agents, or TIVA.We excluded case reports, case series, case-control, cohort studies, comment publications, book chapters, protocol articles, reviews, dissertations, letters to the editor, editorials, news articles, and pro-con debates.Additionally, we excluded research articles that were not available in full text or could not be accessed through interlibrary loans, as well as ones that did not provide a clear description of their operationalization.

Types of Participants
This review had clear participant selection criteria.Adults (patients over the age of 18 years) of all genders and ethnicities, who had a BMI ≥ 30 kgm 2 , and had undergone elective surgery under GA, were included in the study.Studies reporting on the outcomes of using GA in the pediatric population, in animals, or in patients with a BMI of < 30 kgm 2 were excluded.Additionally, patients undergoing emergency surgery were excluded as the morbidity and mortality in these patients can be unpredictable.

Types of Intervention and Comparator
Articles included in this study must have reported on the intra-and postoperative effects of GA used in adult patients with obesity.The intervention group would be patients who received TIVA.The comparator would be patients who received a combination of intravenous and volatile anesthetic agents.Studies reporting on patients who only received sedation or local/regional anesthesia were excluded.

Outcomes
The outcomes of interest in this review were intraoperative vital signs (heart rate, respiratory rate, blood pressure, mean arterial pressure, and oxygen saturation), time to emerge from anesthesia (measured as the time to tracheal extubation, time to eye opening, Aldrete score, or other specified measures), the incidence of PONV, length of stay in the PACU, rates of admission to the ICU, and reasons for admission to the ICU.Any studies that did not report on at least one of these outcomes were excluded.

Selection of Studies and Extraction of Data
In an initial screening based on the title and abstract, two reviewers (ECM and NDS) independently selected trials for inclusion in this review using predetermined inclusion and exclusion criteria.This search was performed using Rayyan [22] to extract relevant data, and duplicates were filtered.Keywords were employed to highlight inclusion and exclusion criteria-related words on Rayyan [22].Any disagreements about the inclusion of studies were resolved by consulting a third review author (FAK).
Subsequently, a full-text analysis was conducted, with two reviewers (GBS and LYF) independently selecting trials for inclusion in this review using predetermined inclusion and exclusion criteria.Disagreements about the inclusion of studies were resolved by consulting a third review author (FAK).

Data Evaluation: Assessment of Risk of Bias in Included Studies
To assess the quality of studies included in the systematic review, we applied the Cochrane Risk of Bias 2.0 Tool [23] for RCTs.Two independent reviewers evaluated the risk of bias in each study (LYF and NMI), considering the specific criteria and guidelines provided by the respective tools.Any discrepancies between the reviewers were resolved by consulting with a third, blinded reviewer (ECM).The methodological components of the trials were assessed as having some concerns, a low or high risk of bias in accordance with the Cochrane Handbook [19].

Study Identification and Selection
Across the databases, we were able to narrow the pool of possible articles down to 1120 articles.After a thorough examination, 227 duplicate articles were eliminated.Following the screening of the titles and abstracts of 893 articles, 31 publications were selected for full-text screening.Their eligibility and quality was assessed and 12 studies were selected for inclusion in this review.Figure 1 shows the PRISMA [20] flowchart depicting the studies' selection procedure, and Figure 2 shows the assessment of the risk of bias of articles using the appropriate Cochrane Risk-of-Bias tool 2.0 [23].

Author
There was no significant difference in eye opening in response to verbal stimulus or in time taken for the patient to orientate to time, place, and person.# At least 17 patients were excluded from the results for various reasons which included PONV, oversedation and postoperative pain, however, as this was not their primary measured outcome, it was not reported which group these patients belonged to.
Propofol doses varied, administered based on either the corrected body weight (CBW) as described by Servin and colleagues [37] or on the ideal body weight (IBW).One study used a patented closed-loop anesthesia delivery system (CLADS) for TIVA dosing [36].Induction with propofol in this study was based on lean body weight, whereas maintenance with propofol was based on adjusted body weight.The automated administration of propofol by the CLADS system was programmed to maintain a target bispectral index (BIS) value of 50.The inhalational anesthesia maintenance dosing varied considerably between studies.
Risk of bias: As shown in Figure 2, five studies had a low risk of bias, with no concerns in any of the domains regarding their process of randomization, deviations from the intended intervention, bias due to missing outcome data or its measurement, or bias in selection of the reported results [29,31,32,35,36].Another five studies had some concerns of bias overall in their methodology [26][27][28]33,34].Lastly, two studies were deemed to have an overall high risk of bias in their methodology.In one study, this was due to concerns in measurement of the outcome [25] and in the second study, it was because of missing outcome data from several patients [30].

Intraoperative Vital Signs
Eight studies reported on intraoperative vital signs.Four studies reported no statistically significant differences in the heart rates in a total of 336 patients [28,29,34,35].One study reported that in all 100 patients studied, despite having comparable heart rates at baseline, the TIVA group recorded significantly lower heart rates from induction to discharge from PACU [31].Another study reporting on 40 patients found no significant difference in the heart rates and non-invasive mean arterial pressure (MAP) between the two 2024 Kamal et al.Cureus 16(2): e54094.DOI 10.7759/cureus.54094groups intraoperatively; however, when measured following extubation, reported heart rates were higher in the desflurane group [36].A third study (60 patients) reported that the heart rates in the TIVA group were higher than in the volatile anesthesia (sevoflurane) group, with statistically significant values at baseline (preoperative measurement), at 10 minutes following induction and between 40 minutes and 75 minutes of operating time [33].However, these statistically significant differences in heart rate did not occur consecutively.The other studies did not report intraoperative heart rates.
The intraoperative MAP was also variable between the different studies.Five studies (336 patients) reported no difference between the two groups [29,[33][34][35][36], while one study (100 patients) reported higher MAP in patients who received TIVA [28] and two studies (140 patients) reported a lower MAP [27,31] in the TIVA group as compared with volatile anesthesia.Three articles reported on the SpO2 values, with two (101 patients) finding no difference between the groups [27,29], and one (60 patients) reporting a statistically significant drop in the SpO2 between 50 minutes and 60 minutes of operative time in the TIVA group [33].
The rest of the vital signs were not reported in the included studies.

Time to Emerge from Anesthesia
Eight studies (620 patients) reported on the time to emerge from anesthesia.The outcomes were variable.
The time to extubation and/or time to eye opening was found to be significantly longer in the TIVA group in three studies (157 patients) [26,29,33], significantly shorter in the TIVA group in one (100 patients) [28], and no statistically significant differences were found in time to emerge from anesthesia between the TIVA and volatile group in four studies (363 patients) [27,30,32,36].

PONV
Of the five studies (396 patients) that reported PONV, three found no difference in the incidence of PONV (176 patients) [26,30,36], and two studies (220 patients) reported that patients who received TIVA had a lower incidence of these effects [31,35].

Length of Recovery and PACU Stay
Aldrete's scoring system [38] as well as the scoring systems developed by Chung [39] and White [40] were used to assess when postsurgical patients were ready to be discharged from PACU.Of the six studies (totaling 461 patients) that measured the Aldrete score, none found a statistically significant difference in the recorded scores [25,28,29,31,35,36].Only one study (100 patients) measured Chung and White scores in addition to the Aldrete score and found these two scores to be significantly lower in the volatile (sevoflurane) anesthesia group [28].Length of stay in the PACU was reported in three studies (256 patients); none of these demonstrated any significant difference between the use of TIVA or volatile anesthesia [26,30,35].

ICU Admissions
Only two studies reported a patient each who was admitted to the ICU, but these patients' data were excluded from their analysis.Both reported patients who developed bronchospasm around the time of extubation, requiring sedation, mechanical ventilation, and subsequent admission to ICU [26,29].Both patients were in the volatile anesthesia groups: desflurane [29] and isoflurane [26].

Discussion
This systematic review evaluated the intraoperative and postoperative outcomes of TIVA and volatile anesthesia, focusing on intraoperative vital signs, time to emerge from anesthesia, PONV, length of PACU stay, and rates of ICU admissions.
Overall, the studies that reported on the length of PACU stay and recovery scores (measured using the Aldrete score) consistently showed no significant difference between the two anesthetic regimens.While a trend emerged favoring TIVA in reducing the incidence of PONV from the studies evaluated in this review, other outcomes did not exhibit conclusive differences.

Intraoperative Vitals
There was limited literature reporting on intraoperative vital signs and the results of this review showed great variability, making it challenging to establish a superior anesthetic regimen.Significant heterogenicity in the effects of TIVA and volatile anesthetics on intraoperative heart rates and oxygen saturations suggest both anesthetic techniques are suitable in patients with obesity without increasing the risk of rate-or hypoxia-related complications.
Similarly, no consistent evidence emerged regarding the effects on intraoperative MAP, with considerable variability in reported results.A recent systematic review and meta-analysis reported that TIVA resulted in significantly decreased MAP [13]; however, this conclusion was based on only one study and, therefore, cannot establish a reliable association.A lack of definitive results may be attributable to the fact that blood pressure and heart rates are complex physiological parameters that are controlled by various centers in the body and display considerable variability between individuals.Moreover, while the hypotensive effects of both propofol and volatile anesthetic agents are well-documented in literature [41][42][43][44], substantial research directly comparing differences in physiological parameters between the two techniques is lacking.

Emergence from Anesthesia
There was no clear superiority demonstrated between TIVA and volatile anesthesia regarding the time to emerge from anesthesia.It is worth noting that the eight studies that reported on this chose different variables to measure this outcome.Delayed emergence from anesthesia is multifactorial; residual action of several different agents can cause this, especially benzodiazepines, opioids, and propofol [45].Inappropriate dosing with propofol is not uncommon when using open target-controlled infusion (TCI) systems to provide TIVA.Most TCI pumps predict plasma and effect site concentration of infusing drugs [46], extrapolating from algorithms based on populations from the 1990s which did not include patients of either extreme of weight [47,48].Obesity can alter the pharmacokinetics of certain drugs due to the increase in adipose tissue, changes in lean body mass, alterations in cardiac output associated with obesity, and an increase in extracellular fluid volume [16,49].The mismatch between the TCI pump algorithm and the physiological behaviors of patients with obesity can make it challenging for anesthesiologists to accurately dose weightbased drugs, leading to unpredictable anesthetic effects [50].
Alternative models for TCI pump algorithms are now being explored, including the Eleveld model, which accounts for extremes of weight [51].Furthermore, due to its high lipid solubility, propofol may display unusual pharmacokinetics in patients with obesity, particularly during longer surgeries [52].Volatile anesthetic agents also display variable degrees of lipid solubility but to a lesser degree than propofol [52].A previous systematic review and meta-analysis comparing various volatile agents and propofol found that patients who had been under desflurane maintenance had a shorter time to eye opening, extubation, and stating their names compared to patients in isoflurane and propofol groups.The same study found no difference in time to emerge from anesthesia between propofol, isoflurane, and sevoflurane groups [13].These findings were partially supported by another systematic review and meta-analysis which, although evaluating effects in non-obese patients, showed significantly shorter time to emerge from desflurane compared to propofol.It also reported a significantly shorter time to obey commands in sevoflurane compared to propofol, but no significant differences between isoflurane and propofol [53].Variability in the results could also be due to several other confounding factors, such as differences in the combinations of drugs used, length of surgeries, anesthesiologists' training and experience, and equipment available at different institutions.Consequently, it is difficult for strong recommendations to be made on the preferred anesthetic technique for faster emergence in patients with obesity.However, overall, there is some evidence that desflurane may deliver favorable outcomes in this population.

Length of PACU Stay and Recovery Scores
All studies which reported on either the length of PACU stay or the Aldrete score to assess patients' readiness to be discharged from PACU, found no significant difference comparing TIVA to volatile anesthetics.A previous systematic review of patients with obesity has reported similar results [13].
Interestingly, one study [28] in the present review found no difference when using the modified Aldrete score but reported significantly shorter recovery times in the sevoflurane groups when using the Chung and the White recovery scores.These scores differ from the modified Aldrete score in that they also evaluate PONV and postoperative pain.The study did not provide a clear explanation to address the inconsistencies in the results of the different scoring systems [28].

PONV
Out of the three studies that showed no significant differences in the incidence of PONV between TIVA and volatile anesthesia [26,30,36], two were deemed to have some concerns [26] or high risk for bias [30] (Figure 2).This was largely due to the number of patients that were excluded from their studies, possibly due to outcomes of interest such as severe PONV.On the other hand, the two studies [31,35] that reported a statistically significant decrease in PONV in the TIVA groups were among the studies that were deemed to be of high quality due to their low risk of bias in all domains and no missing participant data.Furthermore, these two studies [31,35] reported data from a much larger sample size than each of the other three studies [26,30,36], and therefore, their results were deemed to be more reliable than the others.This conclusion was corroborated by other recent systematic reviews and meta-analyses which compared outcomes with the use of TIVA and volatile anesthesia.One review found that there was a significantly reduced incidence of PONV in patients receiving TIVA [14].This was further supported by another systematic review conducted in non-obese patients which found a significant reduction in rates of PONV in TIVA compared to isoflurane, desflurane, and sevoflurane [53].Although conducted in pediatric patients, a further systematic review and meta-analysis found significantly lower incidences of PONV in patients who received TIVA [54].Although another systematic review found no difference in PONV between TIVA and inhaled anesthesia, it is worth noting that this conclusion was formed after the evaluation of only one study [13].Considering the breadth of evidence in favor of TIVA regarding reduced PONV, it can be reliably concluded that TIVA may be a better option for patients who are at an increased risk of PONV.While obesity itself is not a risk factor for PONV [55,56], it is associated with longer operating times.A 30-minute increase in operating time may increase the risk of PONV by 60% [57].Although an individual approach is always recommended when considering the anesthetic options for each patient, patients who have a higher inherent risk of PONV, or are undergoing surgeries that are known to increase the risk of PONV (intraabdominal, gynecological, maxillofacial) [58], are likely to benefit from TIVA.

ICU Admissions
Two patients were admitted to the ICU in two different studies, both due to bronchospasm occurring immediately following extubation [26,29].It is worth noting that both patients were part of the inhalational anesthesia groups.However, there is insufficient evidence to suggest an association between volatile anesthesia and the incidence of ICU admission as there is no information about the possibility that this outcome was due to a register of blood transfusion or administration of other drugs [59].

Limitations
While this systematic review provides a comprehensive comparison between total intravenous and volatile anesthesia in patients with obesity, filling a critical gap in recent literature, there are some notable limitations.The majority of included studies compared TIVA with desflurane; only a small percentage drew comparisons between TIVA and sevoflurane.As more centers recognize the harmful environmental effects and significant cost of desflurane [60,61], and discontinue its use in regular clinical practice, the perceived benefits of desflurane over TIVA seem less relevant.Some of these benefits did, however, have an influence on the conclusions drawn in this study.Therefore, this review demonstrates the critical need for comprehensive trials comparing the effects of TIVA with sevoflurane in patients with obesity, in order to highlight potential differences which are more clinically relevant and useful.Additionally, this review exclusively retrieved articles published in English that were publicly available without institutional access.It is therefore possible that some high-quality research was inadvertently excluded.Furthermore, some registered trials meeting the inclusion criteria were excluded due to unreported results.Finally, despite evaluating more studies than previous comparable systematic reviews, the small sample size may limit the generalizability of the findings to a broader population of patients with obesity.Perhaps this could also be a reason why some studies found no significant differences in their investigated outcomes.With the rising incidence of obesity, larger, high-quality randomized-controlled trials are essential to establish more definitive conclusions and to better guide perioperative care to reduce complications.

Conclusions
This systematic review compared perioperative outcomes of TIV with those of balanced anesthesia using volatile agents.While TIVA demonstrated a potential benefit in reducing the incidence of PONV, other outcomes did not show conclusive differences.The small number of available studies for evaluation, their small sample sizes of patients, and the scarcity of trials specifically investigating the effects of sevoflurane compared with TIVA, underscores the necessity for further research.As the prevalence of obesity continues to rise, future research endeavors in this field should prioritize larger, high-quality RCTs to refine anesthetic strategies and improve outcomes in this population.Guidelines can then be developed explaining the safest anesthesia techniques to meet their unique physiological needs, thereby allowing an improvement in the quality of patient care.

FIGURE 1 :
FIGURE 1: PRISMA flowchart Summary of the process of selection of studies included in this systematic review.

TABLE 1 : Search on PubMed Search Results intravenous
AND anesthesia AND volatile AND anesthesia AND obesity 697

and year Country Type of Study Population Characteristics Number of Patients Intervention and Comparator Results *
30lues and mobility at PACU admission were significantly improved in the desflurane group compared to the other two groups (p < 0.05).Sedation was significantly less pronounced in the desflurane group at30and 120 mins postoperatively compared to 2024 Kamal et al.Cureus 16(2): e54094.DOI 10.7759/cureus.54094gastroplasty Group 3: Isoflurane the other two groups (p < 0.05).There were no significant differences in PONV or length of PACU stay.One patient in the isoflurane group experienced bronchospasm after eye opening, requiring admission to ICU.Sevoflurane Intraoperative and early postoperative MAP values were significantly lower in the TIVA group (p < 0.05).
No significant differences in MAP or heart rate were found between the TIVA and sevoflurane groups.
There were no statistically significant differences in intraoperative vital signs between the two groups.Time to eye opening and extubation were significantly shorter with desflurane (p < 0.05).There were no significant differences in recovery scores, measured using the Aldrete score.One patient in the desflurane group experienced bronchospasm during extubation, requiring admission to ICU.No significant difference in intraoperative MAP was found.The difference in heart rates and oxygen saturations between the two groups were not consistently statistically significant.Recovery time was significantly longer in the TIVA group compared to the 2024 Kamal et al.Cureus 16(2): e54094.DOI 10.7759/cureus.54094gastrectomySevoflurane sevoflurane group (p < 0.001).to-shiftscore from operating table to transport bed.There was no significant difference in time to achieve a modified Aldrete score > 9/10.No significant difference in intraoperative heart rate or MAP was found.However, following extubation, the heart rate was significantly higher in the desflurane group (p < 0.05).There was no significant difference in the postoperative sedation score, or in the visual analogue scores for incidence of PONV in the first 24 hours post-surgery.

TABLE 5 : General outcomes of included studies
RCT: Randomized-Controlled Trial, BMI: Body Mass Index, BIS: Bispectral Index, TIVA: Total Intravenous Anesthesia, PSI: Patient State Index, MAP: Mean Arterial Pressure, PONV: Postoperative Nausea and Vomiting, PACU: Post-Anesthesia Care Unit * Relevant to the measured outcomes of this systematic review.