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Open research questions in Anesthesia and Sedative Agents

46 unresolved questions extracted from the limitations and future-work sections of 687 Anesthesia and Sedative Agents papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Future research should focus on further eluci- the biological signal, characterized by disrupted GABAergic dating the role of other ion channels in insomnia and their transmission and hyperarousal, may have limited our ability influence on anesthetic responses and dose requirements, to detect true differences in the doses required to maintain with larger, more controlled studies to better understand BIS-guided anesthetic depth.

    The impact of insomnia on propofol and remifentanil requirements during total intravenous anesthesia · 2026 · DOI

  • ABSTRACT Background Routine replacement of calculated fasting deficits is common during pediatric anesthesia, but it remains uncertain whether formula‐based deficit replacement is necessary to maintain intraoperative stability or postoperative recovery.

    Routine Replacement of Fasting Deficits in Pediatric Ambulatory Anesthesia: A Propensity‐Matched Retrospective Cohort Study · 2026 · DOI

  • The trial addresses a gap in the literature: both TIVA and OETA are widely used for intraoral sur- gery, but evidence comparing their effects on reco- very quality and functional outcomes in this specific population is limited.

    TIVA versus sevoflurane for quality of recovery after intraoral surgery: a study protocol · 2026 · DOI

  • AMSTAR-R is not a specific tool for evaluating systematic reviews of patient-reported outcome measures, however, no alternative instrument was found to perform the risk of bias analysis. AMSTAR had two items missing from the analysis, but the items refer to statistical analysis and it was expected by the authors of this review that these types of systematic reviews would not perform meta-analysis. The deletion of two items may have altered the validation of the instrument, however we included a brief description of all instruments indicated by the reviews so that the reader can make their own judgment without considering the analysis of the systematic reviews included.

    Quality assessment of the satisfaction degree in anesthesia: overview of systematic reviews · 2026 · DOI

  • Consequently, it remains unclear whether esketamine effectively prevents chronic pain in patients undergoing thoracoscopic lung cancer resection. Secondly, the data collection for this trial was limited to the first 3 days postoperatively and did not track patients’ long-term recovery outcomes, such as chronic pain. Finally, this trial was limited to a single type of surgical procedure and did not include patients undergoing open surgery.

    The esketamine-based multimodal low-opioid anaesthesia improves quality of recovery in elderly patients undergoing radical lung cancer surgery: a randomized controlled trial · 2026 · DOI

  • Although several studies have explored the use of objective moni- toring tools such as BIS and capnography during painless gastroscopy, direct comparisons with traditional clinical indicators remain limited, and the results are heterogeneous. Furthermore, while combining empirical clinical signs with objective monitoring appears promising, no standardized protocol or consensus has been established regarding the optimal combination strategy. Therefore, current clinical practice still largely depends on clinician experience, and further well-designed prospective studies are needed to establish evidence-based criteria for optimal insertion timing.

    Optimizing the timing of painless gastroscope insertion: integrating advanced monitoring tools to enhance safety and efficacy: a narrative review · 2026 · DOI

  • Currently, clinical practice largely relies on the operator’s experience and the patient’s external signs to judge the timing of insertion. However, such subjective judgments exhibit considerable individual variability and lack reproducibility and standardization. In addition, traditional physiological monitoring methods (such as blood pressure and heart rate) are insensitive to the depth of sedation and airway responses, making it difficult to meet the requirements of precise operations. Therefore, it is necessary to introduce more objective assessment tools to assist in determining the timing of insertion. 2.1 Eyelash reflex The eyelash reflex is a classic indicator used to assess light anesthesia. When the patient is in a relatively shallow anesthetic state, gently touching the eyelashes with a cotton swab can trigger a slight In painless gastroscopy procedures, properly timing the insertion is crucial for reducing patient stress responses, minimizing intraoperative coughing, and decreasing gastroscope intolerance events. Using the eyelash reflex as an evaluation criterion, disappearance of this reflex suggests the patient has entered a sufficiently deep anesthetic state, facilitating safe and smooth gastroscope insertion. This method is simple, intuitive, and requires no instrument assistance, making it especially suitable for clinical settings with limited equipment or where rapid assessment is needed. In clinical practice of painless gastroscopy, the disappearance of the eyelash reflex has been widely adopted as a marker for initiating gastroscope insertion in multiple observational studies. These studies generally indicate that using this criterion is associated with a lower incidence of intraoperative movement and higher endoscopist satisfaction (19). However, some studies have suggested that relying solely on the disappearance of the eyelash reflex as the indicator for gastroscope insertion may be insufficient. In certain patients, even after the eyelash reflex has disappeared, stronger pharyngeal stimulation (such as passage of the gastroscope) may still provoke severe coughing or unpredictable body movements (20). As a single reflex indicator, the eyelash reflex is susceptible to individual variability and subjective influence by the operator, resulting in relatively limited specificity and sensitivity. Research by Li et al. (7) indicates that in gastroscopy anesthesia protocols using fentanyl combined with target-controlled infusion of propofol, the target propofol concentration should be set at twice the concentration when the eyelash reflex disappears, implying that the anesthetic depth at eyelash reflex disappearance is insufficient to completely suppress the stress response caused by gastroscope insertion. Other studies have shown that inserting the gastroscope 30 s after the disappearance of the eyelash reflex can reduce the incidence of adverse reactions, decrease the propofol dose, and shorten patient postoperative recovery time (21). The subjectivity and delay in judging the disappearance of the eyelash reflex remain unresolved. 2.2 Hemodynamic parameters In clinical practice, after anesthesia induction, if the patient’s blood pressure and heart rate gradually stabilize—particularly if they show a certain degree of decline compared to baseline values (e.g., a 10–20% decrease in systolic blood pressure and heart rate returning to or slightly below baseline)—it usually indicates that the patient has entered a relatively stable anesthetic state (22). During this period, sympathetic nervous system activity is reduced and the stress response is controlled, making it a potentially appropriate time for gastroscope insertion (23). Conversely, if blood pressure and heart rate remain elevated or fluctuate significantly after induction, this often suggests inadequate anesthetic depth, and insertion may trigger adverse events such as coughing, agitation, or involuntary movements. In addition, heart rate variability (HRV) has also been used to assess the depth of anesthesia. By analyzing HRV, information about autonomic nervous system activity can be obtained, thereby indirectly reflecting anesthetic depth (24).

    Optimizing the timing of painless gastroscope insertion: integrating advanced monitoring tools to enhance safety and efficacy: a narrative review · 2026 · DOI

  • At present, the application of these advanced monitoring tools in painless gastroscopy appears to remain in its early exploratory phase. However, BIS and PI may be increasingly used in clinical practice to guide the sedation and assess the optimal timing of endoscope inser- tion, though the overall evidence base could indicate limited support. Ultrasound-based vocal cord angle assessment, as a novel, non-inva- sive, real-time, and dynamic technique, has also attracted attention for potential utility in evaluating sedation depth. Nevertheless, clinical implementation is hindered by challenges such as lack of standardized thresholds and inconsistent measurement protocols. Therefore, future research should focus on development of standardized, multicenter, and large-sample protocols to clarify sensitivity and specificity of these monitoring modalities. Moreover, with continuous evolution of precision medicine and advancement of intelligent healthcare systems, the assessment of inser- tion timing during painless gastroscopy may be expected to progress toward multidimensional integration and intelligent decision-making. Given that reliance on a single parameter could often lead to insuffi- cient sensitivity or specificity, the significant integration of these mul- tiple physiological indicators—such as BIS, PI, capnography, and ultrasound-based vocal cord angle assessment—into a composite decision-making framework might reasonably be expected to enhance the clinical accuracy and practicality. Furthermore, application of arti- ficial intelligence in image recognition and physiological signal analysis may offer potential for real-time predictive alerts and procedural guid- ance. Thus, this could improve precision and safety of endoscopic operations. Additionally, it appears essential to establish standardized operating procedures and interpretation protocols to ensure reproduc- ibility and inter-institutional consistency. In light of these develop- ments, the targeted training programs for endoscopists and anesthesiologists might be necessary to enhance familiarity with emerging monitoring technologies and promote effective integration into routine clinical workflows.

    Optimizing the timing of painless gastroscope insertion: integrating advanced monitoring tools to enhance safety and efficacy: a narrative review · 2026 · DOI

  • The paper's conclusion that intraoperative physiological variables (MAP, anesthesia duration, blood loss) have minimal influence on POCD outcomes lacks direct measurement of target organ perfusion thresholds during controlled hypotension. Future studies should define critical MAP thresholds specific to FESS populations and correlate individual hypotension tolerance (via cerebral autoregulation monitoring) with POCD risk across different anesthetic techniques.

    Sevoflurane–Dexmedetomidine versus Propofol-based TIVA for Controlled Hypotension in Functional Endoscopic Sinus Surgery: Effects on Postoperative Cognitive Dysfunction · 2026 · DOI

  • The study identified cognitive reserve (educational level) and age as dominant patient-related determinants of POCD but did not prospectively stratify anesthetic technique comparisons (sevoflurane–dexmedetomidine versus propofol TIVA) by cognitive reserve subgroups. Future research should investigate whether anesthetic choice differentially affects POCD outcomes across low, moderate, and high cognitive reserve populations in FESS under controlled hypotension.

    Sevoflurane–Dexmedetomidine versus Propofol-based TIVA for Controlled Hypotension in Functional Endoscopic Sinus Surgery: Effects on Postoperative Cognitive Dysfunction · 2026 · DOI

  • This controlled hypotension FESS study did not measure inflammatory markers (IL-1β, IL-6, TNF-α) or cerebral perfusion/oxygenation status via NIRS monitoring. Subsequent investigations should simultaneously quantify these biomarkers and real-time cerebral hemodynamics to establish mechanistic links between anesthetic technique-induced neuroinflammation and POCD development under controlled hypotension conditions.

    Sevoflurane–Dexmedetomidine versus Propofol-based TIVA for Controlled Hypotension in Functional Endoscopic Sinus Surgery: Effects on Postoperative Cognitive Dysfunction · 2026 · DOI

  • Cognitive assessments in this FESS study were limited to a 72-hour postoperative window using only the MMSE, which lacks sensitivity to subtle executive function and working memory deficits. Future studies should extend follow-up assessment to medium-term (weeks to months) and long-term (6-12 months) outcomes using comprehensive neuropsychological batteries to capture delayed POCD manifestations in sevoflurane–dexmedetomidine versus propofol-based TIVA protocols.

    Sevoflurane–Dexmedetomidine versus Propofol-based TIVA for Controlled Hypotension in Functional Endoscopic Sinus Surgery: Effects on Postoperative Cognitive Dysfunction · 2026 · DOI

  • Currently, our ability to treat ACS is significantly limited by the low availability of well-known antidotes and hemodialysis agents, which encourages the use of alternative intensive therapy options.

    Anticholinergic syndrome in the perioperative period (review). Part 2 · 2025 · DOI

  • Introduction: This study investigates the application of bispectral index (BIS) monitoring in rigid bronchoscopy to enhance anesthetic delivery and patient outcomes, a topic that remains underexplored.

    Bispectral index monitoring: Optimizing anesthesia in rigid bronchoscopy · 2024 · DOI

  • OBJECTIVE: Intratracheal (IT) and intravenous (IV) lignocaine suppress airway reflex and hemodynamic response during extubation, but studies regarding this are sparse.

    A randomized controlled trial to study the effect of intratracheal and intravenous lignocaine on airway and hemodynamic response during emergence and extubation following general anaesthesia · 2021 · DOI

  • Since her postop respiration was insufficient, she was intubated and followed for 45 minutes till her second blood gas analysis was normal, and soon was extubated.

    Caesarean Anesthesia In Myastenic Crisis · 2015 · DOI

  • Further studies into the effects of alphaxalone-alpha- dolone on the CO2 response curve in fit volunteers and in patients with respiratory disease will be reported separately.

    Controlled Sedation with Alphaxalone-Alphadolone · 1974 · DOI

  • Schedules of reinforcement and other operant arma- ments should be applied with greater frequency toward the analysis and prevention of disturbing ward practices under controlled labora- tory settings, and the retardate's natural ecology should be examined for possible development of many stimulus and response properties. Durable behavioral control by stimuli associated with positive reinforcement contingencies is less easy to answer because of limited research on this score.

    Operant Procedures with the Retardate: An Overview of Laboratory Research · 1971 · DOI

  • Previous randomized studies have largely focused on the induction phase or the incidence of hypotension, with limited data on continuous intraoperative hemodynamic changes during laparoscopic gynecologic surgery.

    Comparison of intraoperative hemodynamic parameters between propofol- and remimazolam-based total intravenous anesthesia in patients undergoing robotic gynecologic surgery: a randomized controlled trial protocol · 2026 · DOI

  • Despite established treatment protocols, the extent of clinician awareness and institutional preparedness across surgical specialties remains poorly characterized.

    Awareness and preparedness for local anesthetic systemic toxicity among surgical clinicians: a multi-center cross-sectional survey study · 2026 · DOI

  • Although remimazolam has been studied as a sole agent for anaesthesia in day case gynaecological surgery, studies assessing its use in combination with other anaesthetics remain scarce.

    The Effects of Low-Dose Remimazolam Adjunct on Propofol–Remifentanil Anaesthesia in Day Case Gynaecological Surgery: A Retrospective Cohort Study · 2026 · DOI

  • Abstract Background Remimazolam is a novel ultra-short-acting benzodiazepine sedative, but its clinical positioning, delirium risk profile, and comparative efficacy against standard-of-care sedatives remain incompletely defined.

    Multidimensional clinical evaluation of remimazolam versus propofol and dexmedetomidine: two systematic reviews and meta-analyses based on differentiated endpoints · 2026 · DOI

  • Whether multimodal analgesic strategies incorporating dexmedetomidine and esketamine would benefit high-risk parturients after vaginal delivery remains unknown and warrants prospective evaluation. Exploratory biomarker analyses were limited to a non-systematic subset.

    Association of multimodal analgesic protocol with postpartum depression incidence and sleep quality in high-risk parturients · 2026 · DOI

  • Furthermore, another important limitation of this study is the substantial heterogeneity in both the study populations and the respiratory conditions in both pediatric and adult studies, which limited the ability to draw firm conclusions.

    Dexmedetomidine for acute respiratory conditions requiring non-invasive respiratory support in pediatric and adult patients: systematic review and meta-analysis of the literature · 2026 · DOI

  • STUDY OBJECTIVE: Remimazolam's benefits for patients undergoing painless flexible fiberoptic bronchoscopy remain uncertain.

    Efficacy and safety of remimazolam versus dexmedetomidine for patients undergoing flexible fiberoptic bronchoscopy: A randomized, clinical trial · 2024 · DOI

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46 open questions have been extracted from the limitations and future-work passages of 687 Anesthesia and Sedative Agents papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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