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The impact of anesthetic agents on the body varies widely and is influenced by the drug type, route of administration, and individual patient- and procedure-related factors [,]. The middle ear is particularly sensitive to changes induced by anesthetic drugs, particularly inhalational agents. Such agents may alter middle ear physiology, potentially altering middle ear pressure (MEP) and contributing to complications such as hematoma, serous otitis, and temporary or permanent hearing loss, particularly during middle ear operations. Therefore, an ideal anesthetic agent should minimally affect MEP to prevent these adverse effects [,,,]. The term “negative myringotomy” describes a scenario in which no middle ear effusion is found despite clinical or tympanometric findings suggesting its presence, which can also be a result of anesthetic agents []. Marshall and Cable suggested that fluctuations in MEP produced by anesthetic gases may displace middle ear effusion via the eustachian tube, explaining unexpectedly dry ears during the surgery []. Given the existing literature on how different anesthetic agents affect MEP, our objective was to conduct a systematic review and meta-analysis comparing these agents and examining their effects on MEP and potential complications.

The included 12 studies () covered a range of anesthetic agents and patient demographics. Acar et al. [] conducted a prospective case-control study involving 38 children aged 2 to 13 years to investigate the effects of isoflurane and desflurane during inguinal hernia surgery. Tympanometry was performed pre-anesthesia and at 5, 10, and 15 minute post-anesthesia, focusing on MEP changes. Ozturk et al. [] conducted a randomized controlled trial (RCT) with 25 male children aged 2–11 years undergoing circumcision, comparing total intravenous anesthesia (TIVA) with propofol and sevoflurane, and assessing MEP pre and post anesthesia. Teixeira et al. [] performed a prospective cohort study on 50 patients aged 18 to 76 years undergoing general surgery with nitrous oxide, measuring tympanometric changes before and after anesthesia. Kanai et al. [] evaluated 97 adult patients under nitrous oxide during general surgery, with MEP measured pre- and post-anesthesia. Duger et al. [] compared desflurane and sevoflurane in a RCT with 56 patients aged 18–60 years, measuring MEP at baseline, 5, 15- and 30 minutes post-anesthesia induction.

Dogan et al. [] conducted an RCT involving 57 patients aged 18 to 65 years comparing sevoflurane and propofol-remifentanil, with MEP measured at multiple time points post-induction. Firat et al. [] studied 60 patients aged 18 to 60 years in a prospective clinical trial investigating the effect of dexmedetomidine on tympanometric peak pressure (TPP) and tympanometric width (TW) at pre, intra, and postoperative stages. Chinn et al. [] compared 2 groups receiving halothane with or without nitrous oxide, assessing MEP changes pre and post anesthesia in 138 patients undergoing tympanometry and myringotomy. Gates et al. [] conducted observational and randomized controlled studies, with a sample size of 69, focusing on tympanometry and its correlation with effusion presence and middle ear pressure changes in pediatric patients undergoing grommet or pressure equalization (PE) tube insertion under standard general anesthesia with halothane, with or without nitrous oxide. Lastly, Johnson et al. [], Kennedy et al. [], and Tom et al. [] examined the effects of nitrous oxide and halothane anesthesia on tympanometry and myringotomy outcomes. Johnson et al. [] assessed negative myringotomy rates and MEP changes in 102 ears, while Kennedy et al. [] followed 75 ears over 2 weeks to assess tympanogram changes and predictive accuracy. Tom et al. [] studied 213 ears in pediatric patients, focusing on MEP changes and the accuracy of tympanometry in predicting effusion during myringotomy and PE tube insertion. ()

These studies revealed the distinct effects of various anesthetic agents on MEP. Acar et al. [] found that desflurane increased MEP more significantly than isoflurane at 5 and 10 minutes post-anesthesia ( p < 0.05). Ozturk et al. [] reported a significant increase in MEP with sevoflurane compared to TIVA with propofol ( p < 0.001), with no complications noted. Teixeira et al. [] observed that 48% of patients developed Type C tympanograms post-operatively after using nitrous oxide. Kanai et al. [] also noted a significant reduction in MEP at 1-2 days post-surgery, which stabilized by 5-9 days with nitrous oxide. Duger et al. [] demonstrated that desflurane significantly increased MEP compared to sevoflurane, particularly at 15 min post-anesthesia ( p < 0.05). Dogan et al. [] showed a stable MEP in patients anesthetized with propofol, whereas sevoflurane increased MEP significantly ( p < 0.05). Firat et al. [] found that dexmedetomidine increased MEP significantly compared to controls at 30 minutes post-anesthesia. Using Halothane with or without nitrous oxide, Chinn et al. [], and Kennedy et al. [] found no significant MEP changes, Gates et al. [] observed pressure increases in 33 patients and stability in 1, with 85% of cases showing no change in tympanogram type, Johnson et al. [] reported a mean MEP shift of +257 mm H 2 O, and Tom et al. [] noted a non-significant MEP increase post-anesthesia of +20 decapascal (daPa). ()

These studies have demonstrated key differences in the effects of anesthetic agents on MEP. Acar et al. [] concluded that desflurane increases MEP more than isoflurane, suggesting that isoflurane may be safer for middle ear surgeries. Ozturk et al. [] found that sevoflurane significantly increased MEP compared with TIVA with propofol, recommending TIVA with propofol as a better option for middle ear surgeries. Teixeira et al. [] reported that nitrous oxide significantly affects MEP postoperatively, advising caution when used in middle ear surgery. Similarly, Kanai et al. [] cautioned about nitrous oxide due to its significant reduction in MEP post-surgery. Duger et al. [] favored sevoflurane over desflurane for middle ear surgery because of its lower impact on MEP. Dogan et al. [] concluded that propofol is a more stable anesthetic option for middle ear operations. Firat et al. [] recommended careful consideration of dexmedetomidine due to its significant impact on MEP. ()

This meta-analysis summarized the effects of different anesthetic agents on MEP. Isoflurane was found to be safer for middle ear surgeries, with only minor changes in MEP from baseline to 5 and 10 minutes post-anesthesia. However, desflurane significantly increased MEP in all studies, particularly at 5 and 10 minute post-anesthesia, warranting caution during its use in middle ear surgeries. TIVA with propofol showed stable MEP readings with minimal increases post-anesthesia, suggesting it may be preferable for middle ear surgeries. Sevoflurane significantly increased MEP in 2 studies, yet remained a viable option compared to other anesthetic agents. Nitrous oxide caused significant reductions in MEP, necessitating caution during its use in middle ear surgery, especially in patients with pre-existing conditions. Dexmedetomidine also significantly increased MEP in the 1 study in which it was tested, highlighting the need for careful management during middle-ear surgeries. (,)

This systematic review and meta-analysis aimed to elucidate the impact of various anesthetic agents on MEP by conducting a comprehensive analysis of the existing literature. Based on the studies included in this review, strong evidence was observed for differential effects of anesthetic agents. In the present meta-analysis, these anesthetic agents had a significant effect on MEP (p < 0.001). These findings are supported by other studies’ outcomes. For instance, in a retrospective study, 90 patients were divided into 3 anesthetic groups: i) group 1 received high-flow desflurane, ii) group 2 received low-flow desflurane, iii) and group 3 received high-flow propofol and remifentanil (Ultiva). A significant difference was observed post-induction, with the first group showing greater MEP increases than the second and third groups []. In the present study, desflurane demonstrated a pronounced increase in MEP shortly after administration, compared with isoflurane. Similarly, a study comparing the effects of isoflurane and sevoflurane on MEP in children undergoing tonsillectomy found that MEP was measured at baseline, during the operation, postoperatively, and after anesthesia withdrawal. MEP was significantly increased across all observation periods compared with baseline, suggesting that isoflurane is safer than sevoflurane []. Our findings also align with another study that compared 2 anesthetic agents, sevoflurane and desflurane, in 50 adult patients and observed that MEPs at the 10th and 15th minutes intraoperatively and at the 30th minute postoperatively were significantly higher in the desflurane group than in the sevoflurane group []. This suggests that although desflurane may be effective in certain surgical contexts, its use may be problematic in procedures involving the middle ear, where a stable MEP is crucial. Conversely, isoflurane showed minimal changes in MEP, indicating its relative safety in patients undergoing middle-ear surgery []. Our meta-analysis suggests that MEP is stable with halothane alone and decreases with nitrous oxide, as reported in previous studies []. However, a question arises as to why MEP increases with administration of these anesthetic agents; a possible explanation is that inhaled anesthetics such as desflurane relax the respiratory muscles. These agents reduce the Eustachian tube's efficiency, which is responsible for equalizing pressure between the middle ear and the external environment. Reduced eustachian tube ventilation can cause air to become trapped in the middle ear and expand during inhalation.

Additionally, inhalational anesthetic agents often increase mucosal blood flow in the middle ear, altering local gas partial pressures and further disrupting pressure equilibrium []. Agents such as desflurane, known for their rapid tissue uptake and low solubility, can cause more pronounced pressure changes due to their rapid diffusion into air-filled spaces []. Such physiological changes tend to be most pronounced during the early anesthetic phase, when pressure gradients shift rapidly. In addition, patient position, inhalation, intravenous anesthesia, and airway pressure affect MEP during middle ear surgery. Care should be taken in cases of middle ear effusion (MEE) while using agents proven to change MEP, and not depend on intraoperative findings, as false-negative myringotomy can lead to delayed management. Furthermore, the meta-analytical results of the present study provide a clearer picture of these dynamics, highlighting that while desflurane consistently raised MEP levels, isoflurane maintained them at safer levels. The minimal changes observed with TIVA suggest its potential as the anesthetic of choice for otologic surgeries, balancing efficacy and safety.

Subgroup analysis in the present study revealed that patient demographics, such as age and underlying conditions, can influence outcomes, suggesting the need for tailored anesthetic strategies based on individual patient profiles. Changes in MEP during anesthesia can affect middle ear procedures. Maintaining a stable middle ear morphology is critical for precision and surgical outcomes. The results of the present study suggest that desflurane increases MEP compared with other anesthetic agents; however, isoflurane is comparatively safe, making it a preferable choice for patients undergoing otologic surgery. These results highlight the importance of improving anesthesia techniques to reduce MEP changes, particularly in high-risk patients. This study also emphasizes the need for preoperative tympanic membrane testing to identify patients at risk for MEP changes and to guide anesthetic medication selection. Future research should investigate the consequences of MEP changes induced by different anesthetics and provide clear anesthesia instructions for middle ear surgery to improve patient safety and surgical success rates.

This review offers meaningful insights into the effects of different anesthetics on MEP and related complications. It synthesizes data from multiple studies to increase the reliability of the findings. In addition, a meta-analytic technique was used to quantify the differences between these agents. However, the limitations include potential differences in the study methods. Variability in MEP measurement techniques and differences in patient characteristics underscore the complexity of generalizing findings across diverse clinical settings and patient populations. A few studies with small sample sizes were retrieved from the literature search. Moreover, the heterogeneity observed in the study methodologies and populations necessitates cautious interpretation of the results. In conclusion, this systematic review and meta-analysis demonstrated the impact of anesthetic drugs on MEP. Desflurane and sevoflurane pose difficulties in preserving steady-state MEP. Isoflurane and TIVA with propofol are preferable for middle ear surgery. The risk associated with nitrous oxide emphasizes the necessity of using it with caution. Future studies should explore alternative anesthetic techniques that improve patient outcomes during otologic surgery and establish a standardized protocol for MEP monitoring.