Efficacy of Dexmedetomidine in Preventing Postoperative Delirium in Patients Undergoing Brain Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Efficacy of Dexmedetomidine in Preventing Postoperative Delirium in Patients Undergoing Brain Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of Dexmedetomidine in Preventing Postoperative Delirium in Patients Undergoing Brain Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials Maria Angélica Otero de Melo dos Reis, Eloisa Assis, Harshada Kalaiarasan Swamy, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7474988/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction: Dexmedetomidine (DEX), a selective alpha-2 adrenergic receptor agonist, is widely used in various surgical settings, including cardiac and general surgeries, for its sedative, analgesic, and neuroprotective properties. Patients undergoing brain surgery are particularly susceptible to postoperative delirium (POD). Given the established benefits of dexmedetomidine in other surgical fields, its potential to mitigate delirium in neurosurgery warrants focused investigation. Methods A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted from inception to January 2025 and updated in April 2025 per PRISMA guidelines. Risk of bias was assessed, and a meta-analysis was performed using Review Manager 5.4.1. This systematic review and meta-analysis included five randomised controlled trials that met the inclusion criteria and evaluated the efficacy of DEX in preventing postoperative delirium among adult patients undergoing brain surgery. Results A total of 752 patients were analysed, with DEX administered with a loading dose ranging from 0.5 to 1 µg/kg over 10 minutes, followed by a maintenance infusion rate of 0.1 to 0.5 µg/kg/hour during the surgical procedure. The pooled risk ratio (RR) for POD with DEX was 0.47 (95% CI: 0.35–0.63; p < 0.00001); this corresponds to a 53% reduction in the risk of postoperative delirium, with no observed heterogeneity (χ² = 2.09, df = 4, p = 0.72; I² = 0%), indicating a consistent effect size across trials. In the brain-tumour resection subgroup (n = 319; 160 DEX, 159 control), DEX conferred a 53% risk reduction (RR 0.47; 95% CI 0.33–0.68; Z = 3.98; p < 0.0001; χ² = 0.13, df = 1, p = 0.72; I² = 0%). In the various cranial‑surgery subgroups (n = 322; 162 DEX, 160 control), DEX was associated with a 53% risk reduction (RR 0.47; 95% CI 0.29–0.76; Z = 3.10; p = 0.002; τ² = 0.00, χ² = 1.99, df = 2, p = 0.37; I² = 0%). With no observed heterogeneity in both subgroups. The incidence of adverse events was comparable between the DEX and control groups, and the reported adverse effects were generally mild and effectively managed with standard interventions. Conclusion This meta-analysis demonstrates that in the included studies DEX was associated with a significant reduction in postoperative delirium risk in brain surgery patients, suggesting potential benefits for POD control. However, further studies are needed to optimise dosing and the timing of application. Dexmedetomidine Postoperative Delirium Brain Surgery Neurosurgery Randomised Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION Postoperative delirium (POD) is an acute and fluctuating disturbance of consciousness and attention, typically associated with cognitive impairment and caused by an underlying medical condition or physiological disturbance. It is a common postoperative complication in older adults and is associated with increased morbidity, prolonged hospital stay, and higher mortality [ 11 ]. Following intracranial procedures, reported POD incidence ranges from 12–26%, while broader surgical cohorts demonstrate rates of 10–50%, reflecting variability in patient vulnerabilities and surgical complexity [ 13 , 2 ]. Neurosurgical patients face elevated risk of POD due to neural manipulation, neuroinflammation, and anaesthetic exposure, and despite that, effective prevention remains limited [ 13 ]. Dexmedetomidine (DEX) is a highly selective α₂‑adrenergic receptor agonist whose pharmacodynamic profile attenuates sympathetic outflow, elevation of vagal tone, and consequent reduction in heart rate, blood pressure, and myocardial oxygen consumption. In addition, DEX provides sedative, analgesic, anxiolytic, sleep-promoting, and memory-modulating properties [ 23 ][ 33 ]. Such a combination of actions makes DEX especially well suited for sedation and anaesthesia in neurosurgical settings, where maintenance of neurologic integrity is critical. Moreover, compared with traditional sedatives, DEX uniquely supports neuroprotection by modulating neurotransmitter metabolism, by attenuating the presynaptic norepinephrine release, reducing noradrenergic excitotoxic stress, disrupting PSD95–NMDA receptor (Postsynaptic density protein 95 of N-Methyl-D-Aspartate receptor) coupling, limiting glutamate-induced Ca²⁺ influx and oxidative damage and activating α₂A-ERK1/2-CREB (α₂A-adrenergic receptor, extracellular signal–regulated kinases 1 and 2, and cAMP response element–binding protein) signaling to upregulate BDNF, promoting synaptic repair and functional recovery, and has been shown to prevent or attenuate the incidence of postoperative delirium. Unlike traditional sedatives such as benzodiazepines or propofol, DEX induces a natural sleep-like state and attenuates sympathetic nervous system activity and systemic inflammation, two key contributors to delirium [ 10 ][ 35 ]. Previous studies in non-neurosurgical populations have shown that intraoperative and postoperative administration of DEX significantly reduces the risk of POD. However, its role in neurosurgical settings has not been thoroughly investigated. Given the high burden and clinical consequences of POD in brain surgery patients, this study aims to systematically assess the effectiveness of DEX in preventing postoperative delirium in adults undergoing neurosurgical procedures. METHODS This systematic review and meta-analysis was performed and reported in accordance with the Cochrane Collaboration Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement Guidelines. The study was prospectively registered in the “International Prospective Register of Systematic Reviews” (PROSPERO) in 2025 under the identification CRD42025649703. Search Strategy We systematically searched PubMed, Scopus, Web of Science, and Embase from inception to March 2025 with the following research strategy: ("brain tumor resection" OR "neurosurgery" OR “craniotomy" OR “intracranial surgery” OR “intracranial" OR TBI OR “Traumatic Brain Injury") AND ("dexmedetomidine" OR "alpha-2 adrenergic agonist" OR "sedation") AND ("delirium" OR "postoperative delirium" OR "delirium prevention"). The search was carried out in January 2025 and was updated in April 2025. The references from all included studies, previous systematic reviews, and meta-analyses were also searched manually for any additional studies. Selection Procedure and Data Extraction The triage of studies was done manually by two authors (M.A.O.M.R. and E.B.T.A.), with any disagreement resolved through discussion with the senior author (A.D.P.). Eligibility Criteria Inclusion in this meta-analysis was restricted to studies that met all the following criteria: (1) randomised clinical trials (2) of patients undergoing brain surgery, defined as any neurosurgical procedure involving craniotomy, which encompasses elective procedures (brain tumour resection) as well as emergent procedures (craniotomy haematoma removal, Intracranial aneurysm embolisation, and others), with use of DEX intraoperatively and/or postoperatively compared to placebo interventions, interventions that do not include DEX or standard sedation protocols (3) that reported the occurrence of postoperative delirium amongst the patients. Subgroup analyses were conducted based on specific neurosurgical characteristics, if reported. Exclusion criteria included observational studies, preclinical investigations, studies assessing the use of DEX for postoperative delirium not involving brain surgery, and studies not published in English. There were no restrictions in terms of year of publication. End Points and Definitions The primary endpoint assessed in this review was the incidence of postoperative delirium (POD), as defined by each included study using validated diagnostic tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Secondary endpoints included adverse events related to DEX administration, such as bradycardia, hypotension, and oversedation. For consistency across studies, POD was considered present when diagnosed within the first seven postoperative days. DEX dosing regimens varied slightly among studies but generally included a loading dose of 0.5–1 µg/kg over 10 minutes, followed by a maintenance infusion of 0.1–0.5 µg/kg/hour during surgery. Statistical Analysis We computed pooled risk ratios (RR) with 95% confidence intervals (CIs) primarily for the occurrence of POD between patients that used DEX before, during, and/or after surgery compared to placebo interventions, interventions that do not include DEX, or standard sedation protocols. Subgroup analyses were performed to explore the consistency of the effect of DEX across different neurosurgical procedures. Studies were grouped based on the type of neurosurgical procedure, including one subgroup for cranial surgeries and another specific to brain tumour resections. These analyses aimed to assess whether the efficacy of DEX in preventing postoperative delirium varied across surgical contexts. A random-effects model was applied for data pooling to account for potential heterogeneity. Statistical analysis was performed using Review Manager version 5.4.1 (Cochrane Center, The Cochrane Collaboration). Statistical significance was defined as p-values < 0.05. Sensitivity Analyses To assess the robustness of the pooled estimates, a sensitivity analysis was performed. Which included repeating the meta-analysis using a fixed-effect model, given the absence of statistical heterogeneity among studies. The results of this analysis were compared with the main random-effects model to identify any significant deviations. Heterogeneity Heterogeneity was examined with I² statistics, and P values inferior to 0.10 or I² >25% were considered statistically significant for heterogeneity, based on Cochrane’s Handbook for Systematic Reviews of Interventions thresholds. Quality Assessment The Cochrane Risk of Bias 2 (RoB 2) tool was used. This tool evaluates risk of bias in five domains: bias arising from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Studies are categorised as having low risk, some concerns, or high risk of bias in each domain, as well as overall. RESULTS Study Selection and baseline characteristics The initial search yielded 1081 results, of which 471 were excluded as duplicates, and another 567 were excluded during screening based on title and abstract. From those studies, 43 remained and were fully reviewed based on inclusion criteria. Of these, a total of 5 studies were included, comprising 752 patients from 5 randomised controlled trials (RCTs) (Fig. 1 ). Study characteristics, including patient demographics, types of surgery, anaesthetic regimens, and DEX protocols, are summarised in Table 1 . A total of 430 patients (approximately 57%) received DEX intervention, and 322 patients (approximately 43%) received placebo, no intervention, or standard sedation. Study characteristics are reported in Table 1 . Four studies included the use of DEX only intraoperatively; one study included the intraoperative and postoperative use. Figure 1 . Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study screening and selection. The studies included in the meta-analysis were five randomised controlled trials with the geographic distribution predominantly concentrated in China and Taiwan. Patient ages ranged broadly from mid-40s to early 60s. Surgical indications included brain tumour resection, haematoma removal, and intracranial aneurysm embolisation. Most patients received balanced general anaesthesia, with some protocols incorporating total intravenous anaesthesia or regional blocks. DEX was administered with varying regimens, typically involving a loading dose of 0.5–1 µg/kg followed by a continuous infusion of 0.1–0.5 µg/kg/h, given intraoperatively, postoperatively, or both. Postoperative delirium incidence was the primary outcome assessed across all studies. Table 1 Description of the selected studies Study ID Location Design n (DEX) n (CONTROL) Age Dex Age Control Surgical Procedure Anaesthetic regimen Strategy of DEX Time of Administration Control He 2021 China RCT 30 30 48 ± 11 51 ± 11 Brain Tumour Resection Balanced General anaesthesia Continuous infusion at 0.1 µg/kg/h from the day of surgery until 08:00 AM on postoperative day 1 Intraoperative and Postoperative use Saline Li 2023 China RCT 130 130 45 (34–53) 45 (36–53) Brain Tumour Resection Balanced general anaesthesia with a complementary regional block Loading dose of 0.6 µg/kg over 10 min followed by infusion at 0.4 µg/kg/h Intraoperative use Saline Feng 2022 China RCT 30 30 44.7 ± 11.3 44.7 ± 11.3 Craniotomy haematoma removal TIVA Loading dose of 1 µg/kg over 10 min followed by infusion at 0.5 µg/kg/h Intraoperative use Saline Chen 2021 Taiwan RCT 80 80 59 (47–66) 56 (43–65) Cranial Surgery TIVA with Complementary Regional Blockade Continuous infusion at 0.5 µg/kg/h Intraoperative use Saline Tang 2017 China RCT 54 52 62.0 ± 7.3 61.1 ± 8.5 Intracranial aneurysm embolisation Balanced general anaesthesia with LMA Loading dose of 1 µg/kg over 15 min followed by 0.3 µg/kg/h Intraoperative use Saline Delirium Assessment Methods The methods used to assess postoperative delirium varied across the included studies. Three studies employed validated tools, including the Confusion Assessment Method for the ICU (CAM-ICU), the Intensive Care Delirium Screening Checklist (ICDSC), and the CAM Short version (CAM-S). One study used dual screening protocols depending on the care setting (CAM-ICU in the ICU and 3D-CAM in the ward). Three studies involved blinded, trained assessors. However, one study relied solely on agitation scoring, which may not comprehensively capture delirium. The frequency and the duration of assessments also varied, ranging from a single time point to twice-daily evaluations over five days. A full summary of POD assessment approaches is provided in Table 2 . Table 2 Postoperative Delirium Assessment Methods Study ID Tool Used Frequency/Duration Blinded Assessors Assessment Details He 2021 CAM-ICU 2 x daily for 5 days Yes RASS ≥ − 3 Li 2023 CAM-ICU/ 3D CAM 2 x daily for 5 days Yes Dual screening Feng 2022 Riker SAS 6 x over 2 hours post-extubation N/A - Chen 2021 ICDSC ≥ 2 x daily Yes Included subsyndromal delirium Tang 2017 CAM-S Once at 24 hours N/A Severity categorised (mild-severe) Pooled Analysis of all included studies The meta-analysis included five studies that assessed the effectiveness of DEX in reducing the incidence of postoperative delirium (POD) in adult patients undergoing brain surgery. These studies encompassed a total of 752 patients, with 430 individuals receiving DEX as part of their perioperative management and 322 allocated to a control group, which included placebo, standard sedation protocols, or no DEX administration. The primary outcome analysed across all studies was the occurrence of POD, a frequent and clinically significant complication following neurosurgical procedures known to be associated with increased morbidity, longer hospital stays, and worse functional and neurological outcomes. The pooled analysis demonstrated that DEX was associated with a statistically significant reduction in the risk of POD when compared to the control conditions. The overall risk ratio (RR) was 0.47 (95% CI: 0.35–0.63; p < 0.00001), representing a 53% reduction of risk in the occurrence of delirium among patients who received DEX. This finding indicates that DEX may exert a meaningful protective effect in the neurosurgical setting, potentially due to its sedative, anxiolytic, and anti-inflammatory properties, all of which have been proposed as mechanisms involved in the prevention of delirium. Pooled RR of all included Studies Subgroup Analyses To analyse whether the observed effect persisted across different neurosurgical procedures, two subgroup analyses were conducted considering brain tumour resection surgeries and Cranial Surgery approaches (cranial surgery, Intracranial aneurysm embolisation, and craniectomy for haematoma removal). Subgroup Analysis of Brain Tumour Resection Among the studies that exclusively investigated patients undergoing brain tumour resection (n = 319; 160 in the DEX arm and 159 in the control arm), DEX reduced the incidence of postoperative delirium by 53%, with a pooled RR of 0.47 (95% CI 0.33–0.68; Z = 3.98; p < 0.0001). There was no evidence of statistical heterogeneity (Tau² = 0.00; χ² = 0.13, df = 1, p = 0.72; I² = 0%), suggesting that the benefit of DEX remains stable even when the analysis is restricted to a specific neurosurgical subgroup. Subgroup Analysis of Cranial Surgery Likewise, in the subgroup of patients undergoing various craniotomies (n = 322; 162 in the DEX arm and 160 in the control arm), the random-effects pooled RR for postoperative delirium was 0.47 (95% CI 0.29–0.76; Z = 3.10; p = 0.002), corresponding to a 53% relative risk reduction. There was no evidence of statistical heterogeneity (Tau² = 0.00; χ² = 1.99, df = 2, p = 0.37; I² = 0%). Adverse Events Adverse events related to DEX, such as hypotension and bradycardia, were reported among the studies but were mild, transient, and manageable with standard clinical interventions. No study reported serious or irreversible adverse effects attributable to DEX. Sensitivity Analysis A sensitivity analysis was conducted to evaluate the robustness of the primary findings by applying a fixed-effect model, as opposed to the random-effects model used in the main analysis. This approach was justified by the absence of heterogeneity across studies and aimed to test whether the statistical model influenced the effect estimate. Under the DerSimonian–Laird random-effects model, DEX reduced the risk of postoperative delirium by 53% compared with placebo or standard therapy (pooled RR 0.47; 95% CI 0.35–0.63; p < 0.00001; I² = 0%; n = 322 DEX vs. 319 control). Study weights ranged from 1.0% (Feng 2022) to 59.6% (Li 2023), reflecting varying sample sizes and event rates. Applying a fixed-effect model yielded virtually identical results (pooled RR 0.46; 95% CI 0.34–0.62; p < 0.00001; I² = 0%; n = 322 vs. 319) (Fig. 2 ). The distribution of study weights shifted only slightly, with Li 2023 remaining the largest contributor (55.2%), while Feng 2022 (5.1%) and He 2021 (2.8%) remained the smallest. The absence of heterogeneity (χ² = 2.09, df = 4, p = 0.72; I² = 0%) confirms consistency across studies. This consistency across analytical models confirms the reliability and robustness of the effect of DEX on reducing the incidence of POD in the population of interest. Pooled RR - Fixed Effect of all included Studies QUALITY ASSESSMENT We used the Cochrane Risk of Bias 2 (RoB 2). The five randomised studies were deemed to have a low risk, according to the five evaluated domains. The graphical representation of these risk assessments for non-randomised studies is shown in Fig. 2 :(A) Summary Plot and (B) Traffic Light Plot. DISCUSSION This meta-analysis demonstrated a protective effect of dexmedetomidine (DEX) on postoperative delirium (POD) with a risk ratio of 0.47 (95% CI: 0.35–0.63; p < 0.00001) for neurosurgical patients and the brain tumour subgroup, representing a 53% reduction of risk in the occurrence of delirium among patients who received DEX. A halving of delirium risk in this high-vulnerability cohort far exceeds the modest risk reductions (often 10–20%) typically reported with other sedative regimens (e.g., benzodiazepine‐sparing protocols or propofol‐based strategies). Such a pronounced magnitude suggests that DEX’s mechanisms, modulation of noradrenergic tone, attenuation of glutamate‐driven excitotoxicity, and enhancement of neurotrophic signalling translate into clinically meaningful delirium prevention rather than merely statistical significance. Clinically, a 53% reduction in POD could translate to shorter ICU stays, decreased need for antipsychotic rescue medications, and potentially lower long-term cognitive sequelae, outcomes that have been linked to even smaller shifts in delirium incidence in prior trials. Moreover, subgroup analyses revealed consistently large effects across dosages ranging from 0.2 to 0.7 µg·kg⁻¹·h⁻¹, indicating that the magnitude of benefit is robust to infusion rate and timing variations. This robustness underscores DEX’s unique pharmacodynamic profile in neurosurgical settings, where standard sedatives frequently fail to curb neuroinflammation and neurotransmitter dysregulation to a comparable extent. POD is frequently observed following surgical procedures performed under general anaesthesia, particularly among vulnerable patient groups. Although extensively investigated, its underlying pathophysiology remains incompletely understood. The condition typically emerges within the first 48 to 72 hours after surgery and is characterised by acute disturbances in attention, cognition, and orientation, with some patients experiencing perceptual changes or fluctuating levels of consciousness. These manifestations can interfere with postoperative recovery and are associated with increased morbidity, prolonged hospital stay, and long-term cognitive impairment [ 8 ]. These complications are also associated with several risk factors, including patients of advanced age, pre-existing dementia conditions, hearing loss or visual impairment, impaired cognitive function, and metabolic/physiological disruptions [ 5 ]. The aetiology of postoperative delirium remains to be elucidated, although several possible mechanisms have been postulated, including neurotransmitter theory, neuroinflammatory mechanisms, stress mechanisms, cerebral blood supply, and metabolic disorders. Risk factors for development include trauma, stress, postoperative pain, renal dysfunction, diabetes, and sleep cycle disorders [ 8 , 22 ]. While DEX has primarily been studied in the context of cardiac surgery and other non-cardiac surgeries, given the high-risk nature of neurosurgical procedures and patients who are inherently at higher risk due to the nature of brain manipulation, anaesthetic exposure, and ICU-level care, the prevention of postoperative delirium becomes particularly important, and the identification of effective preventive strategies, such as the use of DEX, holds substantial clinical value. Beyond reducing the immediate burden of delirium, targeted prevention may also minimise complications, shorten hospital stays, and support better neurological recovery in patients undergoing brain surgery. In this context, the use of validated, structured diagnostic tools plays a pivotal role in ensuring accurate recognition and timely management of delirium. Among the studies included in this meta-analysis, several employed robust assessment instruments such as the Confusion Assessment Method for the ICU (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Intensive Care Delirium Screening Checklist (ICDSC), all of which have demonstrated strong validity and reliability in critically ill populations. A subset of studies further improved detection accuracy by utilising dual screening strategies, applying CAM-ICU in intensive care settings, and applying 3D-CAM in ward environments. However, not all studies adhered to these standards; some relied solely on agitation scores, such as the Riker Sedation-Agitation Scale, which may have limited their ability to capture hypoactive or fluctuating presentations of delirium. These discrepancies not only highlight a source of potential detection bias but also reinforce the need for standardised, validated approaches in both research and clinical care when evaluating POD in neurosurgical populations. The potential link between the prevention of POD may be associated with the distinct characteristics of DEX. As an α₂-adrenoceptor agonist, it can mitigate delirium by targeting the possible underlying pathophysiology of delirium and by providing analgesia [ 3 , 17 , 39 ]. Studies have proposed that all α₂-adrenoceptor agonists possess an intrinsic “delirium-sparing” effect due to their minimal impact on cognition [ 17 ]. They further suggest that DEX reduces both the incidence and severity of delirium by decreasing the requirement for γ-aminobutyric acid (GABA)ergic sedatives, benzodiazepines, and opioids typically used for sedation and analgesia [ 16 , 25 ]. Additionally, DEX exerts limited influence on the cholinergic system, which is crucial for cognitive function and implicated in delirium development. Its neuroprotective profile extends beyond these anti-inflammatory and anti-apoptotic effects to include modulation of key neurotransmitter pathways: as a highly selective α₂-adrenergic agonist, DEX attenuates presynaptic norepinephrine release, reducing noradrenergic excitotoxic stress; it disrupts PSD95–NMDA receptor coupling, limiting glutamate-induced Ca²⁺ influx and oxidative damage; and through α₂A-ERK1/2-CREB signalling, it upregulates BDNF to foster synaptic repair and functional recovery [ 10 ]. Moreover, the sympatholytic action of DEX confers greater intraoperative haemodynamic stability, attenuating tachycardia and hypertension without causing clinically significant hypotension, particularly when compared with saline infusion under goal-directed therapy in cranial surgery [ 4 ]. This haemodynamic stability represents an important clinical benefit not only in the surgical setting but also during sedation in intensive care units and diagnostic procedures, where fluctuations in blood pressure and heart rate can have detrimental effects on vulnerable patients. By improving pain control, an independent risk factor for the development of delirium, DEX may further contribute to reducing delirium rates [ 16 , 32 ]. Research also shows that DEX supports the maintenance of physiological sleep patterns [ 21 ], an important factor in neurological and immunological recovery, and exerts anti-inflammatory effects through reductions in interleukin-6, interleukin-8, and TNF-α levels [ 14 ]. It is worth noting that the protective effects of DEX remain consistent across different anaesthetic techniques, underscoring its versatility and applicability in diverse clinical scenarios. The studies included in this meta-analysis employed a range of anaesthetic techniques, including total intravenous anaesthesia (TIVA), inhalational anaesthesia, and balanced anaesthesia approaches. This variability reflects real-world clinical practice and enhances the generalisability of our findings. Despite these differences, the protective effect of DEX against postoperative delirium remained consistent across anaesthetic strategies. Several recent meta-analyses have shown similar reductions in delirium and cognitive dysfunction among patients undergoing non-cardiac surgery [ 19 , 24 , 28 , 40 ], including a study by Govêia et al. (2021), which reported improvements in both cognitive and behavioural outcomes in patients receiving general anaesthesia. Comparable results have also been observed in cardiac surgery [ 27 , 29 , 34 , 38 , 42 ], orthopaedic procedures [ 30 , 37 ], and among vulnerable populations such as the elderly [ 12 ] and paediatric patients [ 1 , 26 ]. Despite this variability, the overall reduction in POD remained robust, indicating that the efficacy of DEX is not significantly influenced by the choice of anaesthetic technique or surgical context. Notably, the sensitivity analysis in our meta-analysis, under a fixed-effect model, produced a virtually identical pooled risk ratio (RR 0.46 vs. 0.47), and both models yielded I² = 0%, confirming that our findings are robust to differing assumptions about between‐study variance. These findings enhance the external validity of our results and support the broad applicability of DEX in neurosurgical perioperative care. Adverse events related to DEX, such as hypotension and bradycardia, were reported among the studies but were mild, transient, and manageable with standard clinical interventions. No study reported serious or irreversible adverse effects attributable to DEX; however, it should be noted that DEX carries a higher risk of reducing heart rate than normal saline. Therefore, it is necessary to closely monitor heart rate when using DEX and discontinue the drug promptly if necessary. This study has certain limitations. Although the pooled results consistently demonstrated a protective effect of DEX against postoperative delirium, the limited number of included studies (n = 5) reduces the overall statistical power and generalisability of the findings. In addition, despite the absence of statistical heterogeneity, methodological variability was observed across studies, particularly in dosing regimens, timing of administration (intraoperative and postoperative versus intraoperative), and anaesthetic protocols, which may have influenced outcomes. Moreover, although subgroup analyses offered valuable insights, the relatively small sample sizes within each subgroup may have compromised the robustness of those findings. Furthermore, most studies were conducted in a single geographical region (primarily East Asia), potentially introducing population-specific bias and limiting external validity. Lastly, assessment methods for POD varied across studies, with some employing validated, structured tools and blinded assessors, while others lacked standardised criteria or relied solely on agitation scoring, potentially introducing variability and detection bias in the reported outcomes. Future research should prioritise well-powered, multicentre randomised controlled trials involving diverse populations to confirm these findings and to establish optimal strategies for DEX use in neurosurgical care, including standardisation of dosage, timing of administration, and infusion protocols. CONCLUSION Our meta-analysis affirms previous research by demonstrating that the administration of DEX to patients undergoing neurosurgical procedures significantly reduces the incidence of POD and also may improve postoperative cognitive function. Subgroup analysis shows consistent preventive effects of DEX on POD, regardless of the type of neurosurgical procedure, the choice of anaesthetic technique, or the regimen of administration of DEX. This magnitude of effect, far greater than that reported for other sedatives, underscores DEX’s unique pharmacologic profile in attenuating noradrenergic excitotoxicity, glutamatergic injury, and neuroinflammation. Moving forward, standardised multicentre trials should refine optimal infusion regimens (loading versus continuous infusion, intraoperative versus postoperative initiation) and employ uniform delirium-assessment scales, as well as extend follow-up to capture long-term cognitive and functional outcomes. Meanwhile, incorporation of DEX into neurosurgical sedation pathways, with attention to individualised, risk-stratified dosing and vigilant haemodynamic monitoring, offers a clinically meaningful strategy to reduce POD and improve postoperative recovery in this vulnerable population. Abbreviations CAM-ICU – Confusion Assessment Method for the Intensive Care Unit CAM-S – Confusion Assessment Method – Short version CI – Confidence Interval DEX – Dexmedetomidine df – Degrees of Freedom ICDSC – Intensive Care Delirium Screening Checklist I² – Inconsistency Index IL-6 – interleukin-6 IL-8 – interleukin-8 LMA – Laryngeal Mask Airway POD – Postoperative Delirium PRISMA – Preferred Reporting Items for Systematic Reviews and Meta-Analyses PROSPERO – International Prospective Register of Systematic Reviews PSD95–NMDA – Postsynaptic density protein 95 of N-Methyl-D-Aspartate receptor RCT – Randomised Controlled Trial RoB 2 – Risk of Bias 2 Tool RR – Risk Ratio TIVA – Total Intravenous Anaesthesia TNF - tumour necrosis factor-alpha χ² – Chi-Square τ² – Between-study variance α₂A-ERK1/2-CREB – α₂A-adrenergic receptor, extracellular signal–regulated kinases 1 and 2, and cAMP response element–binding protein Declarations Funding No specific funding was received for this study. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request. PRISMA Checklist A completed PRISMA 2020 checklist was used to guide the conduct and reporting of this review and is available from the corresponding author upon request. References Alassaf, H. M., Sobahi, A. M., & Alshahrani, N. S. (2022). The efficacy and safety of dexmedetomidine in preventing emergence delirium in paediatric patients following ophthalmic surgery: a systematic review and meta-analysis of randomised controlled trials. Journal of anesthesia, analgesia and critical car e, 2(1), 48. https://doi.org/10.1186/s44158-022-00079-y Aldecoa, C., Bettelli, G., Bilotta, F., Sanders, R. D., & Valerio, M. (2017). European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. 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Perioperative dexmedetomidine reduces delirium after cardiac surgery: A meta-analysis of randomized controlled trials. Journal of clinical anesthesia , 50 , 33–42. https://doi.org/10.1016/j.jclinane.2018.06.045 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 07 Oct, 2025 Reviewers invited by journal 06 Oct, 2025 Editor invited by journal 01 Sep, 2025 Editor assigned by journal 29 Aug, 2025 First submitted to journal 29 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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18:19:04","extension":"png","order_by":41,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23298,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/b5a5725e244adf98c8c0a4c1.png"},{"id":93806388,"identity":"9084a07c-7e3e-4c60-8190-ed0b1c599ec5","added_by":"auto","created_at":"2025-10-17 18:11:04","extension":"png","order_by":42,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86543,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/f1a3070e0d400743eea2dba4.png"},{"id":93806384,"identity":"f5c99900-8034-42cd-8d72-50268aca7854","added_by":"auto","created_at":"2025-10-17 18:11:04","extension":"xml","order_by":43,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":157758,"visible":true,"origin":"","legend":"","description":"","filename":"NECAD25009170structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/116484f7bd028afb52c77a3d.xml"},{"id":93805791,"identity":"59a472f0-5b60-4874-a0da-532db2fd9d40","added_by":"auto","created_at":"2025-10-17 18:03:04","extension":"html","order_by":44,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":174038,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/68e3ff83303752116d8a29fd.html"},{"id":93806365,"identity":"f06536ba-cea0-4e7d-bfed-b3f380dc1c4d","added_by":"auto","created_at":"2025-10-17 18:11:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":186285,"visible":true,"origin":"","legend":"\u003cp\u003ePreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study screening and selection.\u003c/p\u003e","description":"","filename":"01.figure1DEX.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/874a60a346b8dea4979d0e96.png"},{"id":93805742,"identity":"15c4e714-a7b5-4fff-a24c-25dcf7833e61","added_by":"auto","created_at":"2025-10-17 18:03:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":180223,"visible":true,"origin":"","legend":"\u003cp\u003ePooled risk ratio (RR) for postoperative delirium in all included studies (random-effects model).\u003c/p\u003e\n\u003cp\u003e(RR 0.47; 95% CI: 0.35–0.63; p \u0026lt; 0.00001; I² = 0%)\u003c/p\u003e","description":"","filename":"02.PooledRRofallincludedStudies.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/8fe4245d264aea9afd448951.png"},{"id":93805743,"identity":"215245fc-5da4-4fbb-872b-898e0ac07725","added_by":"auto","created_at":"2025-10-17 18:03:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":136188,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of brain tumour resection patients (pooled RR for postoperative delirium).\u003c/p\u003e\n\u003cp\u003e(RR 0.47; 95% CI: 0.33–0.68; p \u0026lt; 0.00001; I² = 0%)\u003c/p\u003e","description":"","filename":"03.SABrainTumour.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/2742aa95b205d611a1557a32.png"},{"id":93807047,"identity":"b49ade50-d1d5-4084-86fe-ec06034a7df4","added_by":"auto","created_at":"2025-10-17 18:27:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":152262,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of cranial surgery patients (pooled RR for postoperative delirium).\u003c/p\u003e\n\u003cp\u003e(RR 0.47; 95% CI 0.29–0.76; p = 0.002; I² = 0%)\u003c/p\u003e","description":"","filename":"04.SAcranialsurgery.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/f3ca6b42eef0aa989d70c775.png"},{"id":93805750,"identity":"c848512b-54e3-4678-9213-e69f6963f5c8","added_by":"auto","created_at":"2025-10-17 18:03:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":180490,"visible":true,"origin":"","legend":"\u003cp\u003ePooled risk ratio (RR) for postoperative delirium in all included studies (fixed-effect model).\u003c/p\u003e\n\u003cp\u003e(RR 0.46; 95% CI: 0.34–0.62; p \u0026lt; 0.00001; I² = 0%)\u003c/p\u003e","description":"","filename":"05.FixedEffectofallincludedStudies.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/ce3791bd382934de3c7e5568.png"},{"id":93805745,"identity":"4bc4a95e-93a3-4b90-88f0-7e79044c7c51","added_by":"auto","created_at":"2025-10-17 18:03:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":98929,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 6.1: (A) Summary Plot.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRisk of bias assessment using the Cochrane RoB 2 tool: (A) Summary plot\u003c/p\u003e","description":"","filename":"06.RiskofBias1.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/02b66fb85c982ad7cba5dada.png"},{"id":93805753,"identity":"988ced9f-1762-4b21-ade4-d6036fc62cfe","added_by":"auto","created_at":"2025-10-17 18:03:03","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":262433,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 6.2: (B) Traffic Light Plot.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRisk of bias assessment using the Cochrane RoB 2 tool: (B) Traffic light plot.\u003c/p\u003e","description":"","filename":"07.Riskofbias2.png","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/61539c431b09161cff0ee9e9.png"},{"id":93807430,"identity":"a75f429f-3150-40d9-928d-f2722447c2d0","added_by":"auto","created_at":"2025-10-17 18:35:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1965250,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7474988/v1/530b7224-62c9-4e09-9662-438910564c7c.pdf"}],"financialInterests":"","formattedTitle":"Efficacy of Dexmedetomidine in Preventing Postoperative Delirium in Patients Undergoing Brain Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePostoperative delirium (POD) is an acute and fluctuating disturbance of consciousness and attention, typically associated with cognitive impairment and caused by an underlying medical condition or physiological disturbance. It is a common postoperative complication in older adults and is associated with increased morbidity, prolonged hospital stay, and higher mortality [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Following intracranial procedures, reported POD incidence ranges from 12\u0026ndash;26%, while broader surgical cohorts demonstrate rates of 10\u0026ndash;50%, reflecting variability in patient vulnerabilities and surgical complexity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Neurosurgical patients face elevated risk of POD due to neural manipulation, neuroinflammation, and anaesthetic exposure, and despite that, effective prevention remains limited [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDexmedetomidine (DEX) is a highly selective α₂‑adrenergic receptor agonist whose pharmacodynamic profile attenuates sympathetic outflow, elevation of vagal tone, and consequent reduction in heart rate, blood pressure, and myocardial oxygen consumption. In addition, DEX provides sedative, analgesic, anxiolytic, sleep-promoting, and memory-modulating properties [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e][\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Such a combination of actions makes DEX especially well suited for sedation and anaesthesia in neurosurgical settings, where maintenance of neurologic integrity is critical. Moreover, compared with traditional sedatives, DEX uniquely supports neuroprotection by modulating neurotransmitter metabolism, by attenuating the presynaptic norepinephrine release, reducing noradrenergic excitotoxic stress, disrupting PSD95\u0026ndash;NMDA receptor (Postsynaptic density protein 95 of N-Methyl-D-Aspartate receptor) coupling, limiting glutamate-induced Ca\u0026sup2;⁺ influx and oxidative damage and activating α₂A-ERK1/2-CREB (α₂A-adrenergic receptor, extracellular signal\u0026ndash;regulated kinases 1 and 2, and cAMP response element\u0026ndash;binding protein) signaling to upregulate BDNF, promoting synaptic repair and functional recovery, and has been shown to prevent or attenuate the incidence of postoperative delirium. Unlike traditional sedatives such as benzodiazepines or propofol, DEX induces a natural sleep-like state and attenuates sympathetic nervous system activity and systemic inflammation, two key contributors to delirium [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Previous studies in non-neurosurgical populations have shown that intraoperative and postoperative administration of DEX significantly reduces the risk of POD. However, its role in neurosurgical settings has not been thoroughly investigated. Given the high burden and clinical consequences of POD in brain surgery patients, this study aims to systematically assess the effectiveness of DEX in preventing postoperative delirium in adults undergoing neurosurgical procedures.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e This systematic review and meta-analysis was performed and reported in accordance with the Cochrane Collaboration Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement Guidelines. The study was prospectively registered in the \u0026ldquo;International Prospective Register of Systematic Reviews\u0026rdquo; (PROSPERO) in 2025 under the identification CRD42025649703.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSearch Strategy\u003c/h2\u003e\u003cp\u003eWe systematically searched PubMed, Scopus, Web of Science, and Embase from inception to March 2025 with the following research strategy: (\"brain tumor resection\" OR \"neurosurgery\" OR \u0026ldquo;craniotomy\" OR \u0026ldquo;intracranial surgery\u0026rdquo; OR \u0026ldquo;intracranial\" OR TBI OR \u0026ldquo;Traumatic Brain Injury\") AND (\"dexmedetomidine\" OR \"alpha-2 adrenergic agonist\" OR \"sedation\") AND (\"delirium\" OR \"postoperative delirium\" OR \"delirium prevention\"). The search was carried out in January 2025 and was updated in April 2025. The references from all included studies, previous systematic reviews, and meta-analyses were also searched manually for any additional studies.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSelection Procedure and Data Extraction\u003c/h3\u003e\n\u003cp\u003eThe triage of studies was done manually by two authors (M.A.O.M.R. and E.B.T.A.), with any disagreement resolved through discussion with the senior author (A.D.P.).\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eInclusion in this meta-analysis was restricted to studies that met all the following criteria: (1) randomised clinical trials (2) of patients undergoing brain surgery, defined as any neurosurgical procedure involving craniotomy, which encompasses elective procedures (brain tumour resection) as well as emergent procedures (craniotomy haematoma removal, Intracranial aneurysm embolisation, and others), with use of DEX intraoperatively and/or postoperatively compared to placebo interventions, interventions that do not include DEX or standard sedation protocols (3) that reported the occurrence of postoperative delirium amongst the patients. Subgroup analyses were conducted based on specific neurosurgical characteristics, if reported. Exclusion criteria included observational studies, preclinical investigations, studies assessing the use of DEX for postoperative delirium not involving brain surgery, and studies not published in English. There were no restrictions in terms of year of publication.\u003c/p\u003e\n\u003ch3\u003eEnd Points and Definitions\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint assessed in this review was the incidence of postoperative delirium (POD), as defined by each included study using validated diagnostic tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Secondary endpoints included adverse events related to DEX administration, such as bradycardia, hypotension, and oversedation. For consistency across studies, POD was considered present when diagnosed within the first seven postoperative days. DEX dosing regimens varied slightly among studies but generally included a loading dose of 0.5\u0026ndash;1 \u0026micro;g/kg over 10 minutes, followed by a maintenance infusion of 0.1\u0026ndash;0.5 \u0026micro;g/kg/hour during surgery.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eWe computed pooled risk ratios (RR) with 95% confidence intervals (CIs) primarily for the occurrence of POD between patients that used DEX before, during, and/or after surgery compared to placebo interventions, interventions that do not include DEX, or standard sedation protocols. Subgroup analyses were performed to explore the consistency of the effect of DEX across different neurosurgical procedures. Studies were grouped based on the type of neurosurgical procedure, including one subgroup for cranial surgeries and another specific to brain tumour resections. These analyses aimed to assess whether the efficacy of DEX in preventing postoperative delirium varied across surgical contexts. A random-effects model was applied for data pooling to account for potential heterogeneity. Statistical analysis was performed using Review Manager version 5.4.1 (Cochrane Center, The Cochrane Collaboration). Statistical significance was defined as p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSensitivity Analyses\u003c/h2\u003e\u003cp\u003eTo assess the robustness of the pooled estimates, a sensitivity analysis was performed. Which included repeating the meta-analysis using a fixed-effect model, given the absence of statistical heterogeneity among studies. The results of this analysis were compared with the main random-effects model to identify any significant deviations.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eHeterogeneity\u003c/h3\u003e\n\u003cp\u003eHeterogeneity was examined with I\u0026sup2; statistics, and P values inferior to 0.10 or I\u0026sup2; \u0026gt;25% were considered statistically significant for heterogeneity, based on Cochrane\u0026rsquo;s Handbook for Systematic Reviews of Interventions thresholds.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eThe Cochrane Risk of Bias 2 (RoB 2) tool was used. This tool evaluates risk of bias in five domains: bias arising from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Studies are categorised as having low risk, some concerns, or high risk of bias in each domain, as well as overall.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eStudy Selection and baseline characteristics\u003c/h2\u003e\u003cp\u003eThe initial search yielded 1081 results, of which 471 were excluded as duplicates, and another 567 were excluded during screening based on title and abstract. From those studies, 43 remained and were fully reviewed based on inclusion criteria. Of these, a total of 5 studies were included, comprising 752 patients from 5 randomised controlled trials (RCTs) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Study characteristics, including patient demographics, types of surgery, anaesthetic regimens, and DEX protocols, are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 430 patients (approximately 57%) received DEX intervention, and 322 patients (approximately 43%) received placebo, no intervention, or standard sedation. Study characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Four studies included the use of DEX only intraoperatively; one study included the intraoperative and postoperative use.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study screening and selection.\u003c/p\u003e\u003cp\u003eThe studies included in the meta-analysis were five randomised controlled trials with the geographic distribution predominantly concentrated in China and Taiwan. Patient ages ranged broadly from mid-40s to early 60s. Surgical indications included brain tumour resection, haematoma removal, and intracranial aneurysm embolisation. Most patients received balanced general anaesthesia, with some protocols incorporating total intravenous anaesthesia or regional blocks. DEX was administered with varying regimens, typically involving a loading dose of 0.5\u0026ndash;1 \u0026micro;g/kg followed by a continuous infusion of 0.1\u0026ndash;0.5 \u0026micro;g/kg/h, given intraoperatively, postoperatively, or both. Postoperative delirium incidence was the primary outcome assessed across all studies.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescription of the selected studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy ID\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLocation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDesign\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003en (DEX)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003en (CONTROL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAge Dex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAge Control\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSurgical Procedure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAnaesthetic regimen\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eStrategy of DEX\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTime of Administration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHe 2021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBrain Tumour Resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBalanced General anaesthesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous infusion at 0.1 \u0026micro;g/kg/h from the day of surgery until 08:00 AM on postoperative day 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eIntraoperative and Postoperative use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSaline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLi 2023\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45 (34\u0026ndash;53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e45 (36\u0026ndash;53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBrain Tumour Resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBalanced general anaesthesia with a complementary regional block\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLoading dose of 0.6 \u0026micro;g/kg over 10 min followed by infusion at 0.4 \u0026micro;g/kg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eIntraoperative use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSaline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFeng 2022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCraniotomy haematoma removal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTIVA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLoading dose of 1 \u0026micro;g/kg over 10 min followed by infusion at 0.5 \u0026micro;g/kg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eIntraoperative use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSaline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChen 2021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTaiwan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e59 (47\u0026ndash;66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e56 (43\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCranial Surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTIVA with Complementary Regional Blockade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eContinuous infusion at 0.5 \u0026micro;g/kg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eIntraoperative use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSaline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTang 2017\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e61.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eIntracranial aneurysm\u003c/p\u003e\u003cp\u003eembolisation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBalanced general anaesthesia with LMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eLoading dose of 1 \u0026micro;g/kg over 15 min followed by 0.3 \u0026micro;g/kg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eIntraoperative use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSaline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eDelirium Assessment Methods\u003c/h2\u003e\u003cp\u003eThe methods used to assess postoperative delirium varied across the included studies. Three studies employed validated tools, including the Confusion Assessment Method for the ICU (CAM-ICU), the Intensive Care Delirium Screening Checklist (ICDSC), and the CAM Short version (CAM-S). One study used dual screening protocols depending on the care setting (CAM-ICU in the ICU and 3D-CAM in the ward). Three studies involved blinded, trained assessors. However, one study relied solely on agitation scoring, which may not comprehensively capture delirium. The frequency and the duration of assessments also varied, ranging from a single time point to twice-daily evaluations over five days. A full summary of POD assessment approaches is provided in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePostoperative Delirium Assessment Methods\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy ID\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTool Used\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrequency/Duration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBlinded Assessors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAssessment Details\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHe 2021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCAM-ICU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 x daily for 5 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRASS \u0026ge; \u0026minus;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLi 2023\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCAM-ICU/ 3D CAM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 x daily for 5 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDual screening\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFeng 2022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRiker SAS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 x over 2 hours post-extubation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChen 2021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eICDSC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;2 x daily\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIncluded subsyndromal delirium\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTang 2017\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCAM-S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOnce at 24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSeverity categorised (mild-severe)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePooled Analysis of all included studies\u003c/h2\u003e\u003cp\u003eThe meta-analysis included five studies that assessed the effectiveness of DEX in reducing the incidence of postoperative delirium (POD) in adult patients undergoing brain surgery. These studies encompassed a total of 752 patients, with 430 individuals receiving DEX as part of their perioperative management and 322 allocated to a control group, which included placebo, standard sedation protocols, or no DEX administration. The primary outcome analysed across all studies was the occurrence of POD, a frequent and clinically significant complication following neurosurgical procedures known to be associated with increased morbidity, longer hospital stays, and worse functional and neurological outcomes.\u003c/p\u003e\u003cp\u003eThe pooled analysis demonstrated that DEX was associated with a statistically significant reduction in the risk of POD when compared to the control conditions. The overall risk ratio (RR) was 0.47 (95% CI: 0.35\u0026ndash;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), representing a 53% reduction of risk in the occurrence of delirium among patients who received DEX. This finding indicates that DEX may exert a meaningful protective effect in the neurosurgical setting, potentially due to its sedative, anxiolytic, and anti-inflammatory properties, all of which have been proposed as mechanisms involved in the prevention of delirium.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003ePooled RR of all included Studies\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eSubgroup Analyses\u003c/h2\u003e\u003cp\u003eTo analyse whether the observed effect persisted across different neurosurgical procedures, two subgroup analyses were conducted considering brain tumour resection surgeries and Cranial Surgery approaches (cranial surgery, Intracranial aneurysm embolisation, and craniectomy for haematoma removal).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eSubgroup Analysis of Brain Tumour Resection\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAmong the studies that exclusively investigated patients undergoing brain tumour resection (n\u0026thinsp;=\u0026thinsp;319; 160 in the DEX arm and 159 in the control arm), DEX reduced the incidence of postoperative delirium by 53%, with a pooled RR of 0.47 (95% CI 0.33\u0026ndash;0.68; Z\u0026thinsp;=\u0026thinsp;3.98; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). There was no evidence of statistical heterogeneity (Tau\u0026sup2; = 0.00; χ\u0026sup2; = 0.13, df\u0026thinsp;=\u0026thinsp;1, p\u0026thinsp;=\u0026thinsp;0.72; I\u0026sup2; = 0%), suggesting that the benefit of DEX remains stable even when the analysis is restricted to a specific neurosurgical subgroup.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eSubgroup Analysis of Cranial Surgery\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eLikewise, in the subgroup of patients undergoing various craniotomies (n\u0026thinsp;=\u0026thinsp;322; 162 in the DEX arm and 160 in the control arm), the random-effects pooled RR for postoperative delirium was 0.47 (95% CI 0.29\u0026ndash;0.76; Z\u0026thinsp;=\u0026thinsp;3.10; p\u0026thinsp;=\u0026thinsp;0.002), corresponding to a 53% relative risk reduction. There was no evidence of statistical heterogeneity (Tau\u0026sup2; = 0.00; χ\u0026sup2; = 1.99, df\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;=\u0026thinsp;0.37; I\u0026sup2; = 0%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eAdverse Events\u003c/h2\u003e\u003cp\u003eAdverse events related to DEX, such as hypotension and bradycardia, were reported among the studies but were mild, transient, and manageable with standard clinical interventions. No study reported serious or irreversible adverse effects attributable to DEX.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eSensitivity Analysis\u003c/h2\u003e\u003cp\u003eA sensitivity analysis was conducted to evaluate the robustness of the primary findings by applying a fixed-effect model, as opposed to the random-effects model used in the main analysis. This approach was justified by the absence of heterogeneity across studies and aimed to test whether the statistical model influenced the effect estimate.\u003c/p\u003e\u003cp\u003eUnder the DerSimonian\u0026ndash;Laird random-effects model, DEX reduced the risk of postoperative delirium by 53% compared with placebo or standard therapy (pooled RR 0.47; 95% CI 0.35\u0026ndash;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001; I\u0026sup2; = 0%; n\u0026thinsp;=\u0026thinsp;322 DEX vs. 319 control). Study weights ranged from 1.0% (Feng 2022) to 59.6% (Li 2023), reflecting varying sample sizes and event rates. Applying a fixed-effect model yielded virtually identical results (pooled RR 0.46; 95% CI 0.34\u0026ndash;0.62; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001; I\u0026sup2; = 0%; n\u0026thinsp;=\u0026thinsp;322 vs. 319) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The distribution of study weights shifted only slightly, with Li 2023 remaining the largest contributor (55.2%), while Feng 2022 (5.1%) and He 2021 (2.8%) remained the smallest. The absence of heterogeneity (χ\u0026sup2; = 2.09, df\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;=\u0026thinsp;0.72; I\u0026sup2; = 0%) confirms consistency across studies. This consistency across analytical models confirms the reliability and robustness of the effect of DEX on reducing the incidence of POD in the population of interest.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003ePooled RR - Fixed Effect of all included Studies\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eQUALITY ASSESSMENT\u003c/h2\u003e\u003cp\u003eWe used the Cochrane Risk of Bias 2 (RoB 2). The five randomised studies were deemed to have a low risk, according to the five evaluated domains. The graphical representation of these risk assessments for non-randomised studies is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e:(A) Summary Plot and (B) Traffic Light Plot.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis meta-analysis demonstrated a protective effect of dexmedetomidine (DEX) on postoperative delirium (POD) with a risk ratio of 0.47 (95% CI: 0.35\u0026ndash;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) for neurosurgical patients and the brain tumour subgroup, representing a 53% reduction of risk in the occurrence of delirium among patients who received DEX. A halving of delirium risk in this high-vulnerability cohort far exceeds the modest risk reductions (often 10\u0026ndash;20%) typically reported with other sedative regimens (e.g., benzodiazepine‐sparing protocols or propofol‐based strategies). Such a pronounced magnitude suggests that DEX\u0026rsquo;s mechanisms, modulation of noradrenergic tone, attenuation of glutamate‐driven excitotoxicity, and enhancement of neurotrophic signalling translate into clinically meaningful delirium prevention rather than merely statistical significance.\u003c/p\u003e\u003cp\u003eClinically, a 53% reduction in POD could translate to shorter ICU stays, decreased need for antipsychotic rescue medications, and potentially lower long-term cognitive sequelae, outcomes that have been linked to even smaller shifts in delirium incidence in prior trials. Moreover, subgroup analyses revealed consistently large effects across dosages ranging from 0.2 to 0.7 \u0026micro;g\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;, indicating that the magnitude of benefit is robust to infusion rate and timing variations. This robustness underscores DEX\u0026rsquo;s unique pharmacodynamic profile in neurosurgical settings, where standard sedatives frequently fail to curb neuroinflammation and neurotransmitter dysregulation to a comparable extent.\u003c/p\u003e\u003cp\u003ePOD is frequently observed following surgical procedures performed under general anaesthesia, particularly among vulnerable patient groups. Although extensively investigated, its underlying pathophysiology remains incompletely understood. The condition typically emerges within the first 48 to 72 hours after surgery and is characterised by acute disturbances in attention, cognition, and orientation, with some patients experiencing perceptual changes or fluctuating levels of consciousness. These manifestations can interfere with postoperative recovery and are associated with increased morbidity, prolonged hospital stay, and long-term cognitive impairment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These complications are also associated with several risk factors, including patients of advanced age, pre-existing dementia conditions, hearing loss or visual impairment, impaired cognitive function, and metabolic/physiological disruptions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The aetiology of postoperative delirium remains to be elucidated, although several possible mechanisms have been postulated, including neurotransmitter theory, neuroinflammatory mechanisms, stress mechanisms, cerebral blood supply, and metabolic disorders. Risk factors for development include trauma, stress, postoperative pain, renal dysfunction, diabetes, and sleep cycle disorders [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile DEX has primarily been studied in the context of cardiac surgery and other non-cardiac surgeries, given the high-risk nature of neurosurgical procedures and patients who are inherently at higher risk due to the nature of brain manipulation, anaesthetic exposure, and ICU-level care, the prevention of postoperative delirium becomes particularly important, and the identification of effective preventive strategies, such as the use of DEX, holds substantial clinical value. Beyond reducing the immediate burden of delirium, targeted prevention may also minimise complications, shorten hospital stays, and support better neurological recovery in patients undergoing brain surgery. In this context, the use of validated, structured diagnostic tools plays a pivotal role in ensuring accurate recognition and timely management of delirium.\u003c/p\u003e\u003cp\u003eAmong the studies included in this meta-analysis, several employed robust assessment instruments such as the Confusion Assessment Method for the ICU (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Intensive Care Delirium Screening Checklist (ICDSC), all of which have demonstrated strong validity and reliability in critically ill populations. A subset of studies further improved detection accuracy by utilising dual screening strategies, applying CAM-ICU in intensive care settings, and applying 3D-CAM in ward environments. However, not all studies adhered to these standards; some relied solely on agitation scores, such as the Riker Sedation-Agitation Scale, which may have limited their ability to capture hypoactive or fluctuating presentations of delirium. These discrepancies not only highlight a source of potential detection bias but also reinforce the need for standardised, validated approaches in both research and clinical care when evaluating POD in neurosurgical populations.\u003c/p\u003e\u003cp\u003eThe potential link between the prevention of POD may be associated with the distinct characteristics of DEX. As an α₂-adrenoceptor agonist, it can mitigate delirium by targeting the possible underlying pathophysiology of delirium and by providing analgesia [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Studies have proposed that all α₂-adrenoceptor agonists possess an intrinsic \u0026ldquo;delirium-sparing\u0026rdquo; effect due to their minimal impact on cognition [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. They further suggest that DEX reduces both the incidence and severity of delirium by decreasing the requirement for γ-aminobutyric acid (GABA)ergic sedatives, benzodiazepines, and opioids typically used for sedation and analgesia [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Additionally, DEX exerts limited influence on the cholinergic system, which is crucial for cognitive function and implicated in delirium development. Its neuroprotective profile extends beyond these anti-inflammatory and anti-apoptotic effects to include modulation of key neurotransmitter pathways: as a highly selective α₂-adrenergic agonist, DEX attenuates presynaptic norepinephrine release, reducing noradrenergic excitotoxic stress; it disrupts PSD95\u0026ndash;NMDA receptor coupling, limiting glutamate-induced Ca\u0026sup2;⁺ influx and oxidative damage; and through α₂A-ERK1/2-CREB signalling, it upregulates BDNF to foster synaptic repair and functional recovery [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMoreover, the sympatholytic action of DEX confers greater intraoperative haemodynamic stability, attenuating tachycardia and hypertension without causing clinically significant hypotension, particularly when compared with saline infusion under goal-directed therapy in cranial surgery [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This haemodynamic stability represents an important clinical benefit not only in the surgical setting but also during sedation in intensive care units and diagnostic procedures, where fluctuations in blood pressure and heart rate can have detrimental effects on vulnerable patients. By improving pain control, an independent risk factor for the development of delirium, DEX may further contribute to reducing delirium rates [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Research also shows that DEX supports the maintenance of physiological sleep patterns [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], an important factor in neurological and immunological recovery, and exerts anti-inflammatory effects through reductions in interleukin-6, interleukin-8, and TNF-α levels [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It is worth noting that the protective effects of DEX remain consistent across different anaesthetic techniques, underscoring its versatility and applicability in diverse clinical scenarios.\u003c/p\u003e\u003cp\u003eThe studies included in this meta-analysis employed a range of anaesthetic techniques, including total intravenous anaesthesia (TIVA), inhalational anaesthesia, and balanced anaesthesia approaches. This variability reflects real-world clinical practice and enhances the generalisability of our findings. Despite these differences, the protective effect of DEX against postoperative delirium remained consistent across anaesthetic strategies. Several recent meta-analyses have shown similar reductions in delirium and cognitive dysfunction among patients undergoing non-cardiac surgery [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], including a study by Gov\u0026ecirc;ia et al. (2021), which reported improvements in both cognitive and behavioural outcomes in patients receiving general anaesthesia. Comparable results have also been observed in cardiac surgery [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], orthopaedic procedures [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], and among vulnerable populations such as the elderly [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and paediatric patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite this variability, the overall reduction in POD remained robust, indicating that the efficacy of DEX is not significantly influenced by the choice of anaesthetic technique or surgical context. Notably, the sensitivity analysis in our meta-analysis, under a fixed-effect model, produced a virtually identical pooled risk ratio (RR 0.46 vs. 0.47), and both models yielded I\u0026sup2; = 0%, confirming that our findings are robust to differing assumptions about between‐study variance. These findings enhance the external validity of our results and support the broad applicability of DEX in neurosurgical perioperative care. Adverse events related to DEX, such as hypotension and bradycardia, were reported among the studies but were mild, transient, and manageable with standard clinical interventions. No study reported serious or irreversible adverse effects attributable to DEX; however, it should be noted that DEX carries a higher risk of reducing heart rate than normal saline. Therefore, it is necessary to closely monitor heart rate when using DEX and discontinue the drug promptly if necessary.\u003c/p\u003e\u003cp\u003eThis study has certain limitations. Although the pooled results consistently demonstrated a protective effect of DEX against postoperative delirium, the limited number of included studies (n\u0026thinsp;=\u0026thinsp;5) reduces the overall statistical power and generalisability of the findings. In addition, despite the absence of statistical heterogeneity, methodological variability was observed across studies, particularly in dosing regimens, timing of administration (intraoperative and postoperative versus intraoperative), and anaesthetic protocols, which may have influenced outcomes. Moreover, although subgroup analyses offered valuable insights, the relatively small sample sizes within each subgroup may have compromised the robustness of those findings. Furthermore, most studies were conducted in a single geographical region (primarily East Asia), potentially introducing population-specific bias and limiting external validity. Lastly, assessment methods for POD varied across studies, with some employing validated, structured tools and blinded assessors, while others lacked standardised criteria or relied solely on agitation scoring, potentially introducing variability and detection bias in the reported outcomes. Future research should prioritise well-powered, multicentre randomised controlled trials involving diverse populations to confirm these findings and to establish optimal strategies for DEX use in neurosurgical care, including standardisation of dosage, timing of administration, and infusion protocols.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eOur meta-analysis affirms previous research by demonstrating that the administration of DEX to patients undergoing neurosurgical procedures significantly reduces the incidence of POD and also may improve postoperative cognitive function. Subgroup analysis shows consistent preventive effects of DEX on POD, regardless of the type of neurosurgical procedure, the choice of anaesthetic technique, or the regimen of administration of DEX. This magnitude of effect, far greater than that reported for other sedatives, underscores DEX\u0026rsquo;s unique pharmacologic profile in attenuating noradrenergic excitotoxicity, glutamatergic injury, and neuroinflammation. Moving forward, standardised multicentre trials should refine optimal infusion regimens (loading versus continuous infusion, intraoperative versus postoperative initiation) and employ uniform delirium-assessment scales, as well as extend follow-up to capture long-term cognitive and functional outcomes. Meanwhile, incorporation of DEX into neurosurgical sedation pathways, with attention to individualised, risk-stratified dosing and vigilant haemodynamic monitoring, offers a clinically meaningful strategy to reduce POD and improve postoperative recovery in this vulnerable population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAM-ICU \u0026ndash; Confusion Assessment Method for the Intensive Care Unit\u003c/p\u003e\n\u003cp\u003eCAM-S \u0026ndash; Confusion Assessment Method \u0026ndash; Short version\u003c/p\u003e\n\u003cp\u003eCI \u0026ndash; Confidence Interval\u003c/p\u003e\n\u003cp\u003eDEX \u0026ndash; Dexmedetomidine\u003c/p\u003e\n\u003cp\u003edf \u0026ndash; Degrees of Freedom\u003c/p\u003e\n\u003cp\u003eICDSC \u0026ndash; Intensive Care Delirium Screening Checklist\u003c/p\u003e\n\u003cp\u003eI\u0026sup2; \u0026ndash; Inconsistency Index\u003c/p\u003e\n\u003cp\u003eIL-6\u0026nbsp;\u0026ndash; interleukin-6\u003c/p\u003e\n\u003cp\u003eIL-8\u0026nbsp;\u0026ndash; interleukin-8\u003c/p\u003e\n\u003cp\u003eLMA \u0026ndash; Laryngeal Mask Airway\u003c/p\u003e\n\u003cp\u003ePOD \u0026ndash; Postoperative Delirium\u003c/p\u003e\n\u003cp\u003ePRISMA \u0026ndash; Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e\n\u003cp\u003ePROSPERO \u0026ndash; International Prospective Register of Systematic Reviews\u003c/p\u003e\n\u003cp\u003ePSD95\u0026ndash;NMDA \u0026ndash; Postsynaptic density protein 95 of N-Methyl-D-Aspartate receptor\u003c/p\u003e\n\u003cp\u003eRCT \u0026ndash; Randomised Controlled Trial\u003c/p\u003e\n\u003cp\u003eRoB 2 \u0026ndash; Risk of Bias 2 Tool\u003c/p\u003e\n\u003cp\u003eRR \u0026ndash; Risk Ratio\u003c/p\u003e\n\u003cp\u003eTIVA \u0026ndash; Total Intravenous Anaesthesia\u003c/p\u003e\n\u003cp\u003eTNF - tumour necrosis factor-alpha\u003c/p\u003e\n\u003cp\u003e\u0026chi;\u0026sup2; \u0026ndash; Chi-Square\u003c/p\u003e\n\u003cp\u003e\u0026tau;\u0026sup2; \u0026ndash; Between-study variance\u003c/p\u003e\n\u003cp\u003e\u0026alpha;₂A-ERK1/2-CREB \u0026ndash; \u0026alpha;₂A-adrenergic receptor, extracellular signal\u0026ndash;regulated kinases 1 and 2, and cAMP response element\u0026ndash;binding protein\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this study.\u003c/p\u003e\n\n\u003cp\u003eConflicts of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\n\u003cp\u003eData Availability Statement\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\n\u003cp\u003ePRISMA Checklist \u003c/p\u003e\n\u003cp\u003eA completed PRISMA 2020 checklist was used to guide the conduct and reporting of this review and is available from the corresponding author upon request.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAlassaf, H. 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Perioperative dexmedetomidine reduces delirium after cardiac surgery: A meta-analysis of randomized controlled trials. \u003cem\u003eJournal of clinical anesthesia\u003c/em\u003e, \u003cem\u003e50\u003c/em\u003e, 33–42. https://doi.org/10.1016/j.jclinane.2018.06.045\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Dexmedetomidine, Postoperative Delirium, Brain Surgery, Neurosurgery, Randomised, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-7474988/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7474988/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003eDexmedetomidine (DEX), a selective alpha-2 adrenergic receptor agonist, is widely used in various surgical settings, including cardiac and general surgeries, for its sedative, analgesic, and neuroprotective properties. Patients undergoing brain surgery are particularly susceptible to postoperative delirium (POD). Given the established benefits of dexmedetomidine in other surgical fields, its potential to mitigate delirium in neurosurgery warrants focused investigation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted from inception to January 2025 and updated in April 2025 per PRISMA guidelines. Risk of bias was assessed, and a meta-analysis was performed using Review Manager 5.4.1. This systematic review and meta-analysis included five randomised controlled trials that met the inclusion criteria and evaluated the efficacy of DEX in preventing postoperative delirium among adult patients undergoing brain surgery.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 752 patients were analysed, with DEX administered with a loading dose ranging from 0.5 to 1 \u0026micro;g/kg over 10 minutes, followed by a maintenance infusion rate of 0.1 to 0.5 \u0026micro;g/kg/hour during the surgical procedure. The pooled risk ratio (RR) for POD with DEX was 0.47 (95% CI: 0.35\u0026ndash;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001); this corresponds to a 53% reduction in the risk of postoperative delirium, with no observed heterogeneity (χ\u0026sup2; = 2.09, df\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;=\u0026thinsp;0.72; I\u0026sup2; = 0%), indicating a consistent effect size across trials. In the brain-tumour resection subgroup (n\u0026thinsp;=\u0026thinsp;319; 160 DEX, 159 control), DEX conferred a 53% risk reduction (RR 0.47; 95% CI 0.33\u0026ndash;0.68; Z\u0026thinsp;=\u0026thinsp;3.98; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; χ\u0026sup2; = 0.13, df\u0026thinsp;=\u0026thinsp;1, p\u0026thinsp;=\u0026thinsp;0.72; I\u0026sup2; = 0%). In the various cranial‑surgery subgroups (n\u0026thinsp;=\u0026thinsp;322; 162 DEX, 160 control), DEX was associated with a 53% risk reduction (RR 0.47; 95% CI 0.29\u0026ndash;0.76; Z\u0026thinsp;=\u0026thinsp;3.10; p\u0026thinsp;=\u0026thinsp;0.002; τ\u0026sup2; = 0.00, χ\u0026sup2; = 1.99, df\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;=\u0026thinsp;0.37; I\u0026sup2; = 0%). With no observed heterogeneity in both subgroups. The incidence of adverse events was comparable between the DEX and control groups, and the reported adverse effects were generally mild and effectively managed with standard interventions.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis meta-analysis demonstrates that in the included studies DEX was associated with a significant reduction in postoperative delirium risk in brain surgery patients, suggesting potential benefits for POD control. However, further studies are needed to optimise dosing and the timing of application.\u003c/p\u003e","manuscriptTitle":"Efficacy of Dexmedetomidine in Preventing Postoperative Delirium in Patients Undergoing Brain Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 18:02:58","doi":"10.21203/rs.3.rs-7474988/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-10-07T17:25:50+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-06T22:41:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Neurocritical Care","date":"2025-09-01T17:37:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-29T18:04:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurocritical Care","date":"2025-08-29T09:12:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"57d9d85b-25fb-403b-a9f5-7dec65d1f24c","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-08T12:19:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 18:02:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7474988","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7474988","identity":"rs-7474988","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}