Skip to main content
Download PDF

Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials

European Journal of Medical Research volume 29, Article number: 239 (2024) Cite this article

Abstract

Background

Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction.

Methods

A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler.

Main results

This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81–2.24, p = 0.25, I2 = 0%).

Conclusion

Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

Background

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are postoperative phenomena linked to a range of surgical complications. While some individuals argue that both POD and POCD can be collectively referred to as ‘postoperative cerebral dysfunction’, others distinguish POCD as a distinct condition from POD. Delirium, recognised as a common and severe acute neuropsychiatric syndrome, is primarily characterised by cognitive deficits and inattention. It also presents with alterations in arousal, disruptions in sleep–wake patterns, and other variations in mental state [1]. In a meta-analysis, the incidence of POD ranged from 8.4–18.1% in patients with total hip replacement and slightly higher 12.8–30.5% after total knee arthroplasty, depending on the patient population and the assessment means [2]. In a study conducted in a tertiary care centre in Taipei, China, the prevalence of delirium was 5.1% among 701 patients (aged > 65 years) undergoing elective orthopaedic or urologic surgery [3]. Likewise, elderly patients who have undergone non-cardiac surgery frequently encounter POCD, which is frequently accompanied by a decline in cognitive function and an elevated risk of mortality. POD and POCD are significantly associated with adverse clinical outcomes, including higher mortality rates and increased complications. The research findings indicated that POD patients experienced a significantly higher mortality rate within one-year post-surgery compared to patients undergoing similar procedures. Specifically, the mortality rate among POD patients ranges from 17.4% to 22.7%, whereas the mortality rate for patients undergoing similar surgeries was only in the range of 7.5% to 8.4% [4, 5]. These conditions can inflict distress upon patients and their families, potentially leading to psychological challenges. Further, they can prolong hospital stays and result in escalated medical expenses. The association between POD and increased mortality may involve various mechanisms, including inflammatory response and immune system dysregulation, cognitive impairment, physical and psychological stress, neuroinflammatory changes, and the impact of sedatives and anaesthesia. These mechanisms are likely intertwined, collectively contributing to the occurrence of POD and heightened mortality risk. Monk’s study reported that among patients aged 60 and above who underwent non-cardiac surgery, the incidence of POCD was 41.4% on leaving the hospital and 12.7% at 3 months [6]. Several independent risk factors for early POCD were identified, including increased age, lower levels of education, longer duration of anaesthesia, postoperative infections, a history of previous surgery, and respiratory complications. Notably, only age was found to be a significant factor in long-term cognitive impairment following surgery [7]. POD is typically assessed using the Confusion Assessment Method (CAM). In contrast to POD, there is currently no universally accepted and standardised method for evaluating POCD within the medical community [8]. The Mini-Mental State Examination (MMSE) serves as a valuable tool for quantitatively assessing the extent of cognitive impairment and monitoring alterations in cognitive function. MMSE scores exhibit a positive correlation with the patient's cognitive capabilities [9].

Dexmedetomidine (DEX) is an alpha2-adrenergic agonist with high selectivity. It possesses the ability to suppress sympathetic excitability, enhance vagal excitability, lower blood pressure, reduce heart rate, and diminish myocardial oxygen consumption. Additionally, DEX exhibits sedative, analgesic, anxiolytic, hypnotic, amnesic, and narcotic effects. It reduces pain and anxiety by inhibiting neuronal firing, thereby achieving sedation. The pharmacological properties of dexmedetomidine include swift absorption, rapid distribution, quick metabolism, and prompt excretion. In clinical practice, dexmedetomidine can be used for sedation, analgesia and tranquillisation, as well as intra- and post-operative sedation and analgesia. Moreover, dexmedetomidine also inhibits the activity of the central nervous system, thereby reducing the patient’s pain. Several studies have reported a neuroprotective effect of DEX [10,11,12]. Despite previous studies having examined the impact of DEX on POD or POCD, owing to the lack of exclusion of confounding factors such as the type of surgery and anaesthesia protocol, the results have not always been applicable to clinical practice. As such, in the present study, a meta-analysis was conducted to evaluate the effectiveness of DEX in reducing the incidence of POD and POCD in patients undergoing non-cardiac surgery and non-neurosurgery. Further, a subgroup analysis was conducted based on the type of anaesthesia administered to account for any potential variations in results. As a secondary outcome, efforts were made to determine if dexmedetomidine affected the stability of the circulatory system.

Methods

Search strategy

A systematic search was conducted in the databases of PubMed, Embase, and The Cochrane Library to identify all relevant studies, spanning from their inception to February 10, 2023. Supplementary data were acquired from sources such as reference lists of the included articles or grey literature; however, no suitable literature was found for inclusion. The PubMed basic search strategy was as follows: (("delirium"[MeSH Terms] OR "delirium"[All Fields] OR ("Postoperative Cognitive Complications"[MeSH Terms] OR "Postoperative Cognitive Complications"[All Fields])) AND ("dexmedetomidine"[MeSH Terms] OR "dexmedetomidine"[All Fields])). The search strategy only included randomised controlled trials (RCTs), and the language was limited to English and Chinese. Species restriction was limited to human subjects. Di Wang, Wenhui Zhang, and Zhi Liu each performed independent literature searches, data extraction, and conducted bias and GRADE evaluation. In the event of any disagreements, the matter would be referred to the corresponding author for discussion and resolution. The present meta-analysis was prospectively registered in the PROSPERO database with the registration number CRD42023402004.

Study selection

The inclusion criteria and requirements for the studies incorporated into this meta-analysis were as follows: (1) they were designed as randomised controlled trials (RCTs); (2) they were published in English or Chinese; (3) they involved patients undergoing non-cardiac surgery and non-neurosurgery procedures; and (4) the intervention included intravenous infusion of dexmedetomidine or the drugs used in the control group during the surgical procedure. The following were excluded from consideration: reviews, study protocols, observational studies, studies where the outcomes or adverse effects did not pertain to POD and POCD, studies involving critically ill patients or sedated patients in the ICU(ICU patients need complex care; multiple diseases, diverse medications, and interventions may complicate research reliability by confounding intervention effectiveness), studies where DEX was administered to patients through other routes, and duplicate or redundant reports.

Endpoints

The primary outcome was the occurrence of POD and POCD during the seventh post-operative day, and the secondary outcomes were the occurrence of hypertension, hypotension, and bradycardia during the surgery.

Data extraction

Data were extracted according to the standard forms, and any uncertainties or discrepancies were resolved through discussions with the corresponding author. The extracted data included the following: first author, publication year and country, experiment design, the sample size of the intervention and comparison groups, age range, and ASA Grade, anaesthetic type, surgery procedure, drugs applied in the control group, the anaesthesia depth monitoring, the strategy of DEX infusion, cognitive problem and the assessment method.

Assessment of trial quality

The risk of bias was assessed using the risk bias assessment tool RoB2 (revised version 2019) for RCTs in six areas: the process of randomisation, departures from the intended interventions, lack of outcome data, measurement of the outcome, selection of the reported outcome, and overall risk of bias [13].

Statistical analysis

For statistical analysis and graphing, Review Manager software (RevMan version 5.4.1), STATA software (Version 12.0), and GRADE profiler were used. Dichotomous data were analysed by using risk ratios (RR) with 95% confidence interval (CI). There were three levels of heterogeneity determined by the I2 statistics: low (I2 < 50%), moderate (50% ≤ I2 ≤ 75%), and high (I2 > 75%) [14]. When I2 < 50%, the fixed effect model was selected to pool the data; conversely, if a study was found to have moderate or high heterogeneity, the random effect model was selected to pool the data, and subgroup analysis was conducted to identify sources of heterogeneity. Publication bias was assessed by examining funnel plots and conducting Egger's test, with p-values greater than 0.05 indicating no significant publication bias. Additionally, a sensitivity analysis was performed to evaluate the stability of the results. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) technique was utilised to classify the major results of the degree of certainty.

Results

Search results

The process for searching and including literature in the database is illustrated in Fig. 1. After searching using the previously defined search strategy, a total of 436 articles were identified through the database search, while no additional articles were found through other sources. A total of 319 articles were retrieved after duplicated records were taken out. According to titles and abstracts, 227 of them were later excluded, mainly because of the low correlation between these studies and the aim of the meta-analysis. A full read-through of the other 92 articles was performed, and a further 67 articles were eliminated, as shown in Fig. 1. Ultimately, a total of 24 RCTs fully satisfied the inclusion criteria and were subsequently included in the meta-analysis (Fig. 1).

Fig. 1
figure 1

Flow diagram showing results of search and reasons for exclusion of studies

Full size image

Characteristics of trials

The present meta-analysis included trials published from 2014 to 2023, involving 5207 participants (2638 patients received intraoperative intravenous DEX for sedation and 2569 patients received other medication for sedation or saline as a control group). Notably, two studies [15, 16] evaluated both POD and POCD, and one study [17] employed two distinct methods to assess POCD, yielding different conclusions. Thus, these studies were included as two separate outcomes in the analysis. A total of 23 studies were reported in English and one study was published in Chinese. Among the included studies, there were 17 experiments conducted in China, 3 in Korea, 1 in Egypt, 1 in Japan, and 2 in India. In the present meta-analysis, a comprehensive examination involving 20 studies, with a total of 4304 patients, was conducted to investigate whether there exists an association between the use of DEX and a decrease in the incidence of POD. In addition, 7 studies, comprising 690 participants, were included to explore the potential impact of DEX on the incidence of POCD. In Table 1, detailed descriptions of the included trials are provided. All patients included in the study were over the age of 18 and drugs used in the control group included saline, midazolam and propofol. Table 1 also shows that the DEX doses and administration times were different. Although POCD evaluation instruments varied, the process for evaluating POD was generally consistent.

Table 1 The characteristics of the included studies
Full size table

Risk of bias in included studies

Based on the main results, RoB 2.0 was used to assess 24 RCTs. The assessment revealed that 5 trials were determined to have ‘some concerns’, 19 trials were categorised as having a ‘low risk of bias’, and none of the trials were deemed to have a 'high risk of bias' (Fig. 2).

Fig. 2
figure 2

Quality assessment of each study included in the meta-analysis

Full size image

Meta‐analysis for the studies on cognitive impairment

The occurrence of POD

Twenty studies [15, 16, 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], with a total of 4304 patients, investigated the incidence of POD. There was no statistical heterogeneity between these studies (P = 0.43, I2 = 2%). A fixed-effects model was used for analysis, and the results indicated a statistically significant association. Specifically, in the context of non-cardiac surgery and non-neurosurgery procedures, the use of DEX was significantly linked to a reduced incidence of POD compared to the control group (19 trials, RR: 0.54; 95% CI 0.46 to 0.64; p < 0.0001) (Fig. 3).

Fig. 3
figure 3

Forest plot of comparison: DEX vs control, outcome: incidence of POD

Full size image

The occurrence of POCD

Six studies [15,16,17, 36,37,38] reported the occurrence of POCD on the seventh postoperative day. Various neuropsychological tests, including the Stroop colour word interference test, Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE), were utilised as evaluation methods in these studies. One study [17] adopted two different methods for assessing POCD and reached different conclusions, and thus, were included in the analysis as two separate outcomes. The results of meta-analyses using a random-effects model revealed statistical differences in preventing POCD undergoing non-cardiac surgery and non-neurosurgery compared with the control group (7 trials, RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03) with moderate heterogeneity (P = 0.02, I2 = 60%) (Fig. 4).

Fig. 4
figure 4

Forest plot of comparison: DEX vs control, outcome: incidence of POCD at 7 days after surgery

Full size image

Secondary outcomes

Four studies [22, 25, 30, 35] with 694 participants (DEX group: 349 patients; control group: 345 patients) reported the occurrence of hypertension during surgery. The fixed effect model was applied, and no statistical heterogeneity was identified between studies (P = 0.70, I2 = 0%) in the present analysis. There was no significantly higher occurrence of hypertension in the DEX groups in the included studies (RR = 1.35, 95% CI 0.81–2.24, p = 0.25) (Fig. 5). Moreover, seven studies [15, 16, 22, 25, 30, 34, 35] with 994 patients (DEX group: 519 patients; control group: 475 patients) examined the occurrence of hypotension. These studies demonstrated that intravenous infusion of DEX for sedation led to intraoperative hypotension in patients when compared to the group that received other sedatives or normal saline, with low heterogeneity (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) (Fig. 6). Likewise, these seven studies [15, 16, 22, 25, 30, 34, 35] also examined the occurrence of bradycardia. They revealed that intravenous infusion of DEX for sedation led to intraoperative bradycardia in patients when compared to the group that received other sedatives or normal saline, with low heterogeneity (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) (Fig. 7).

Fig. 5
figure 5

Forest plot of comparison: DEX vs control, outcome: incidence of hypertension

Full size image
Fig. 6
figure 6

Forest plot of comparison: DEX vs control, outcome: incidence of hypotension

Full size image
Fig. 7
figure 7

Forest plot of comparison: DEX vs control, outcome: incidence of bradycardia

Full size image

Subgroup analysis

The studies on the incidence of POD were categorised into two subgroups according to the type of anaesthesia. Fourteen studies were conducted with patients only receiving general anaesthesia, and four studies were tested under non-general anaesthesia plus sedation and assessed the effect on POD. Notably, regardless of the type of anaesthesia, DEX significantly reduced the prevalence of POD with low heterogeneity (Fig. 8).

Fig. 8
figure 8

Forest plot of POD by subgroup based on the type of anaesthesia

Full size image

For POCD, subgroups were also assigned according to the type of anaesthesia. Five studies were conducted with patients exclusively receiving general anaesthesia, while two studies were conducted under regional anaesthesia plus sedation. These studies assessed the preventive effect of dexmedetomidine on the incidence of POCD. Compared with regional anaesthesia plus sedation, continuous intravenous injection of DEX during general anaesthesia (5 trials, RR: 0.50; 95% CI 0.34 to 0.74, p = 0.0005, I2 = 31%) may be more beneficial in reducing the risk of POCD (2 trials, RR: 0.84; 95% CI 0.60 to 1.19, p = 0.03, I2 = 80%) (Fig. 9). The type of anaesthesia was considered to be a source of obvious heterogeneity (I2 = 74.4%).

Fig. 9
figure 9

Forest plot of POCD at 7 days after surgery by subgroup based on the type of anaesthesia

Full size image

Level of certainty for outcomes (GRADE)

GRADE profiler was used to assess the level of certainty in the outcomes of the meta-analysis, following the GRADE methodology. The results were categorised and ranked, ranging from low to high certainty, as presented in Table 2.

Table 2 Summary of findings table with GRADE assessment quality of evidence
Full size table

Publication bias and sensitivity analysis

The funnel plots (Fig. 10 and 11) and Egger’s tests (with a P value of 0.448 for POD and 0.098 for POCD) suggest that there was no significant publication bias in the studies that investigated the effects of DEX on both POD and POCD. Further, sensitivity analysis was conducted to assess the impact of each individual study on the overall meta-analysis. By excluding one study at a time from the included research, findings were made that the overall outcome regarding POD remained robust (Fig. 12). In the studies on POCD, the exclusion of a particular study [37] significantly altered the results (Fig. 13), and thus was regarded as a source of heterogeneity.

Fig. 10
figure 10

Funnel plot of the incidence of POD

Full size image
Fig. 11
figure 11

Funnel plot of the incidence of POCD at 7 days after surgery

Full size image
Fig. 12
figure 12

Sensitivity analysis for POD

Full size image
Fig. 13
figure 13

Sensitivity analysis for POCD

Full size image

Discussion

By analysing all available RCTs, intraoperative intravenous DEX infusion was found to reduce the incidence of POD and POCD compared to other sedatives or normal saline. At the same time, the subgroup analysis showed that DEX had a consistent preventive effect on POD in patients undergoing non-cardiac or non-neurosurgery, regardless of the type of anaesthesia used. Meanwhile, another subgroup analysis also suggested that continuous intravenous injection of DEX during general anaesthesia appeared to be more effective in reducing the risk of POCD compared to regional anaesthesia. Despite such results, in contrast to the control group receiving normal saline or other sedatives, patients receiving DEX during surgery were more prone to experiencing hypotension and bradycardia, whereas the occurrence of hypertension during surgery did not differ significantly between the two groups.

DEX demonstrates effectiveness in preventing POD and POCD across various surgical and anaesthesia types. Continuous intravenous DEX administration during general anaesthesia appears to be more effective in reducing the risk of POCD compared to regional anaesthesia. However, clinicians should exercise caution and closely monitor patients for potential side effects when using DEX, without excessive concern for hypertension.

POD and POCD have become major concerns in clinical practice because of their potential to cause prolonged hospital stays, higher medical expenses and lower quality of life for patients. Risk factors for these complications include advanced age, pain, anaemia, and hypoxemia [39]. The use of certain anaesthetic drugs has also been implicated as a risk factor for POD [40,41,42]. Proposed mechanisms for these complications include the disruption of normal neurotransmitter function, alterations in tau protein, inflammatory responses, disruptions in calcium homeostasis, and impairment of mitochondrial function. Moreover, POD has been recognised as a significant risk factor for adverse outcomes in hip fracture patients. Patients with either POCD or POD have been observed to experience a twofold increase in the risk of mortality [43] Thus, it is crucial to recognise patients who are susceptible to POD and POCD and take preventive measures to mitigate their incidence.

Fortunately, it has been suggested that 40% of POD cases can be prevented [44]. One method of prevention involves administering DEX during the perioperative period. DEX is a highly selective alpha-2 adrenergic receptor agonist known for its neuroprotective effects. DEX does not interact with gamma-aminobutyric acid receptors, lacks anticholinergic activity, and has been demonstrated to promote natural sleep patterns, which could contribute to its potential anti-delirium effects [45]. Several interventions, including multimodal analgesia techniques, cognitive stimulation programs, and early mobilisation, have also been proposed for the prevention of POD and POCD [44].

Two meta-analyses published in 2019 [46] and 2022 [47] were conducted to investigate the impact of DEX on the postoperative neurocognitive function of elderly patients who underwent non-cardiac surgery. Concerning elderly patients who underwent non-cardiac surgery, both studies concluded that administering DEX during the perioperative period was more effective than other sedatives in preserving cognitive function after the surgical procedure. Simultaneously, Zeng H et al. found that DEX also leads to an increased incidence of hypotension and bradycardia. The results of our study are generally consistent with these research findings. However, these meta-analyses only included the elderly population and did not apply to all patients. Although POD and POCD are more common in older patients, they can still occur in relatively young patients and middle-aged people after major surgery. Further, neither meta-analysis included a subgroup analysis based on anaesthetic modality to assess whether the efficacy of DEX in preventing POD and POCD was influenced by differences in the type of anaesthesia. This is a crucial consideration because various anaesthesia types can exert distinct impacts on neurocognitive function. As such, a new meta-analysis was undertaken to overcome these limitations and offer a more comprehensive analysis of the influence of DEX on POD and POCD.

The heterogeneity observed in the analysis of POCD can be primarily attributed to this particular study. An assumption could be made that this heterogeneity may be linked to factors such as the small sample size, a high rate of loss to follow-up, variations in drug administration protocols within the study, and differences in the assessment method for POCD compared to other studies.

In this new meta-analysis, databases were added for up-to-date literature searches, resulting in a considerably larger number of included RCTs and patients compared to previous studies. Additionally, a subgroup analysis was conducted to evaluate the influence of DEX on POD and POCD under different types of anaesthesia. The focus of the meta-analysis was on evaluating the effect of continuous intravenous infusion of DEX during surgery on the prevention of POD and POCD in patients of all age groups, providing a more comprehensive and reliable analysis of the neuroprotective effects of DEX.

The present meta-analysis supports previous findings that the administration of DEX to patients undergoing non-cardiac and non-neurosurgical procedures has a significant beneficial effect on postoperative cognitive function. In parallel, the analysis demonstrates that a continuous intraoperative infusion of DEX is effective in preventing both POD and POCD. The subgroup analysis revealed that DEX had a consistent preventive effect on POD regardless of anaesthesia type, and continuous intravenous injection of DEX during general anaesthesia was more effective in reducing the risk of POCD than regional anaesthesia. These results suggest that DEX could serve as a valuable resource in perioperative care for this patient population. Further research is warranted to explore its potential benefits in future studies.

However, the present meta-analysis demonstrates that DEX leads to bradycardia, hypertension and hypotension, which can be attributed to its activity as an α2-adrenoreceptor agonist. When DEX is administered, it produces a distinct two-phase haemodynamic response, whereby lower plasma concentrations lead to a reduction in blood pressure, while higher plasma concentrations result in an increase in blood pressure [48]. Notably, the hypotension and bradycardia associated with DEX are primarily observed as intraoperative adverse effects. Moreover, there is a paucity of sufficient studies to establish a clear link between these intraoperative adverse effects and long-term postoperative adverse outcomes in patients. It is possible that there may be a superior medication or a novel drug administration strategy that can effectively prevent both POD and POCD while also improving the haemodynamic stability of patients [49]. Further research and development in this area may lead to advancements in perioperative care.

The present study had several limitations and shortcomings. Firstly, it should be emphasised that there was considerable heterogeneity in both the assessment measures employed to evaluate POCD and the types of drugs administered to the control group among the studies incorporated in the analysis. Secondly, more precise studies are needed to determine if there is an optimal dosing regimen and dosage to protect the patient's cognitive function with less haemodynamic impact on the patient. Thirdly, the accuracy of the results was compromised by the under-representation of certain groups of studies. Therefore, in the future, clinicians may conduct more RCTs, with particular focus on various drug administration strategies and the timing of DEX infusion, in order to confirm the impact of different administration methods on POD and POCD.

Conclusion

Intravenous DEX infusion during surgery reduces POD and POCD risk in elderly non-cardiac, non-neurosurgery patients. Continuous DEX infusion in general anaesthesia is more effective for POCD prevention than regional anaesthesia. DEX is equally effective in POD reduction regardless of anaesthesia type. However, intraoperative hypotension and bradycardia may occur. There might exist an advanced medication or innovative drug delivery approach capable of preventing both POD and POCD while enhancing patients' haemodynamic stability.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

References

  1. MacLullich AMJ, Ferguson KJ, Miller T, de Rooij SEJA, Cunningham C. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008;65(3):229–38.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Scott JE, Mathias JL, Kneebone AC. Incidence of delirium following total joint replacement in older adults: a meta-analysis. Gen Hosp Psychiatry. 2015;37(3):223–9.

    Article  CAS  PubMed  Google Scholar 

  3. Dai YT, Lou MF, Yip PK, Huang GS. Risk factors and incidence of postoperative delirium in elderly chinese patients. GER. 2000;46(1):28–35.

    CAS  Google Scholar 

  4. Pipanmekaporn T, Punjasawadwong Y, Wongpakaran N, Wongpakaran T, Suwannachai K, Chittawatanarat K, et al. Risk factors and adverse clinical outcomes of postoperative delirium in Thai elderly patients: a prospective cohort study. Perspect Psychiatr Care. 2021;57:1073–82.

    Article  PubMed  Google Scholar 

  5. Janssen TL, Steyerberg EW, van Hoof-de LCCHA, Seerden TCJ, de Lange DC, Wijsman JH, et al. Long-term outcomes of major abdominal surgery and postoperative delirium after multimodal prehabilitation of older patients. Surg Today. 2020;50:1461–70.

    Article  PubMed  Google Scholar 

  6. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008;108(1):18–30.

    Article  PubMed  Google Scholar 

  7. Biedler A, Juckenhöfel S, Larsen R, Radtke F, Stotz A, Warmann J, et al. Postoperative Störungen der kognitiven Leistungsfähigkeit bei älteren Patienten Die Ergebnisse der „International Study of Postoperative Cognitive Dysfunction” (ISPOCD 1). Anaesthesist. 1999;48(12):884–95.

    Article  CAS  PubMed  Google Scholar 

  8. Steinmetz J, Rasmussen LS. Peri-operative cognitive dysfunction and protection. Anaesthesia. 2016;71(S1):58–63.

    Article  PubMed  Google Scholar 

  9. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.

    Article  CAS  PubMed  Google Scholar 

  10. Nguyen V, Tiemann D, Park E, Salehi A. Alpha-2 agonists. Anesthesiol Clin. 2017;35(2):233–45.

    Article  PubMed  Google Scholar 

  11. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia. 1999;54(12):1136–42.

    Article  CAS  PubMed  Google Scholar 

  12. Huang R, Chen Y, Yu AC, Hertz L. Dexmedetomidine-induced stimulation of glutamine oxidation in astrocytes: a possible mechanism for its neuroprotective activity. J Cereb Blood Flow Metab. 2000;20(6):895–8.

    Article  CAS  PubMed  Google Scholar 

  13. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;28(366): l4898.

    Article  Google Scholar 

  14. Melsen WG, Bootsma MCJ, Rovers MM, Bonten MJM. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect. 2014;20(2):123–9.

    Article  CAS  PubMed  Google Scholar 

  15. Tang Y, Wang Y, Kong G, Zhao Y, Wei L, Liu J. Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022;47(2):219–25.

    PubMed  Google Scholar 

  16. Shi H, Du X, Wu F, Hu Y, Xv Z, Mi W. Dexmedetomidine improves early postoperative neurocognitive disorder in elderly male patients undergoing thoracoscopic lobectomy. Exp Ther Med. 2020;20(4):3868–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Mohamed S, Shaaban AR. The effect of Dexmedetomidine on the incidence of postoperative cognitive dysfunction in elderly patients after prolonged abdominal surgery. Egypt J Anaesth. 2014;30(4):331–8.

    Article  Google Scholar 

  18. Wu Y, Miao Y, Chen X, Wan X. A randomised placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery. BMC Anesthesiol. 2022;22(1):172.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kim JA, Ahn HJ, Yang M, Lee SH, Jeong H, Seong BG. Intraoperative use of dexmedetomidine for the prevention of emergence agitation and postoperative delirium in thoracic surgery: a randomised-controlled trial. Can J Anaesth. 2019;66(4):371–9.

    Article  CAS  PubMed  Google Scholar 

  20. Chen PH, Tsuang FY, Lee CT, Yeh YC, Cheng HL, Lee TS, et al. Neuroprotective effects of intraoperative dexmedetomidine versus saline infusion combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery: a randomised controlled trial. Eur J Anaesthesiol. 2021;38(12):1262–71.

    Article  CAS  PubMed  Google Scholar 

  21. Cheng XQ, Cheng J, Zhou YN, Zuo YM, Liu XS, Gu EW, et al. Anti-nociceptive effects of dexmedetomidine infusion plus modified intercostal nerve block during single-port thoracoscopic lobectomy: a double-blind randomised controlled trial. Pain Physician. 2021;24(5):E565–72.

    PubMed  Google Scholar 

  22. Hu J, Zhu M, Gao Z, Zhao S, Feng X, Chen J, et al. Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: a double-blind, randomised clinical trial. Eur J Anaesthesiol. 2021;38:9.

    Article  Google Scholar 

  23. Lee C, Lee CH, Lee G, Lee M, Hwang J. The effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery: a double blind randomised controlled study. J Clin Anesth. 2018;47:27–32.

    Article  CAS  PubMed  Google Scholar 

  24. Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, et al. Randomised clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg. 2020;107(2):e123–32.

    Article  CAS  PubMed  Google Scholar 

  25. Liu T, Tuo J, Wei Q, Sun X, Zhao H, Zhao X, et al. Effect of perioperative dexmedetomidine infusion on postoperative delirium in elderly patients undergoing oral and maxillofacial surgery: a randomised controlled clinical trial. Int J Gen Med. 2022;15:6105–13.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Liu Y, Ma L, Gao M, Guo W, Ma Y. Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. Aging Clin Exp Res. 2016;28(4):729–36.

    Article  PubMed  Google Scholar 

  27. Lu Y, Fang PP, Yu YQ, Cheng XQ, Feng XM, Wong GTC, et al. Effect of intraoperative dexmedetomidine on recovery of gastrointestinal function after abdominal surgery in older adults: a randomised clinical trial. JAMA Netw Open. 2021;4(10): e2128886.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mei B, Meng G, Xu G, Cheng X, Chen S, Zhang Y, et al. Intraoperative sedation with dexmedetomidine is superior to propofol for elderly patients undergoing hip arthroplasty: a prospective randomised controlled study. Clin J Pain. 2018;34(9):811–7.

    Article  PubMed  Google Scholar 

  29. Mei B, Xu G, Han W, Lu X, Liu R, Cheng X, et al. The benefit of dexmedetomidine on postoperative cognitive function is unrelated to the modulation on peripheral inflammation: a single-center, prospective randomised study. Clin J Pain. 2020;36(2):88–95.

    Article  PubMed  Google Scholar 

  30. Mishina T, Aiba T, Hiramatsu K, Shibata Y, Yoshihara M, Aoba T, et al. Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomised controlled trial. Hernia. 2018;22(3):471–8.

    Article  CAS  PubMed  Google Scholar 

  31. Shin HJ, Woo Nam S, Kim H, Yim S, Han SH, Hwang JW, et al. Postoperative delirium after dexmedetomidine versus propofol sedation in healthy older adults undergoing orthopedic lower limb surgery with spinal anesthesia: a randomised controlled trial. Anesthesiology. 2023;138(2):164–71.

    Article  CAS  PubMed  Google Scholar 

  32. Tang CL, Li J, Zhang ZT, Zhao B, Wang SD, Zhang HM, et al. Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization. Neural Regen Res. 2018;13(2):280–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wu CY, Lu YF, Wang ML, Chen JS, Hsu YC, Yang FS, et al. Effects of dexmedetomidine infusion on inflammatory responses and injury of lung tidal volume changes during one-lung ventilation in thoracoscopic surgery: a randomised controlled trial. Mediators Inflamm. 2018;2018:2575910.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Xin X, Chen J, Hua W, Wang H. Intraoperative dexmedetomidine for prevention of postoperative delirium in elderly patients with mild cognitive impairment. Int J Geriatr Psychiatry. 2021;36(1):143–51.

    Article  PubMed  Google Scholar 

  35. Zhang W, Wang T, Wang G, Yang M, Zhou Y, Yuan Y. Effects of dexmedetomidine on postoperative delirium and expression of IL-1β, IL-6, and TNF-α in elderly patients after hip fracture operation. Front Pharmacol. 2020;11:678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chawdhary AA, Kulkarni A, Nozari A. Substitution of propofol for dexmedetomidine in the anaesthetic regimen does not ameliorate the post-operative cognitive decline in elderly patients. Indian J Anaesth. 2020;64(10):880–6.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Li WX, Luo RY, Chen C, Li X, Ao JS, Liu Y, et al. Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: a randomised controlled preliminary trial. Chin Med J (Engl). 2019;132(4):437–45.

    Article  CAS  PubMed  Google Scholar 

  38. Nag DDS. Effect of intraoperative dexmedetomidine infusion on early postoperative cognitive dysfunction (POCD) in geriatric patients undergoing hip surgery under spinal anaesthesia. clinicaltrials.gov; 2020. Report No.: study/NCT03793751. 2020. https://clinicaltrials.gov/ct2/show/study/NCT03793751. Accessed 9 Mar 2023.

  39. Müller A, Lachmann G, Wolf A, Mörgeli R, Weiss B, Spies C. Peri- and postoperative cognitive and consecutive functional problems of elderly patients. Curr Opin Crit Care. 2016;22(4):406.

    Article  PubMed  Google Scholar 

  40. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911–22.

    Article  PubMed  Google Scholar 

  41. Bilotta F, Lauretta MP, Borozdina A, Mizikov VM, Rosa G. Postoperative delirium: risk factors, diagnosis and perioperative care. Minerva Anestesiol. 2013;79(9):1066–76.

    CAS  PubMed  Google Scholar 

  42. Belrose JC, Noppens RR. Anesthesiology and cognitive impairment: a narrative review of current clinical literature. BMC Anesthesiol. 2019;19(1):241.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ruggiero C, Bonamassa L, Pelini L, Prioletta I, Cianferotti L, Metozzi A, et al. Early post-surgical cognitive dysfunction is a risk factor for mortality among hip fracture hospitalized older persons. Osteoporos Int. 2017;28(2):667–75.

    Article  CAS  PubMed  Google Scholar 

  44. Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669–76.

    Article  CAS  PubMed  Google Scholar 

  45. Mo Y, Zimmermann AE. Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Ann Pharmacother. 2013;47(6):869–76.

    Article  PubMed  Google Scholar 

  46. Zeng H, Li Z, He J, Fu W. Dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing noncardiac surgery: a meta-analysis of randomised controlled trials. PLoS ONE. 2019;14(8): e0218088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yu H, Kang H, Fan J, Cao G, Liu B. Influence of dexmedetomidine on postoperative cognitive dysfunction in the elderly: a meta-analysis of randomised controlled trials. Brain Behav. 2022;12(8): e2665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Javaherforooshzadeh F, Dezfoli AB, Malehi AS, Gholizadeh B. The efficacy of dexmedetomidine alone or with melatonin on delirium after coronary artery bypass graft surgery a randomized clinical trial. Anesth Pain Med. 2023;13: e138317.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, Dalian Municipal Central Hospital Affiliated to Dalian University of Technology, Dalian, Liaoning, China

    Di Wang, Zhi Liu, Wenhui Zhang, He Tao & Congjie Bi

  2. China Medical University, Shenyang, China

    Zhi Liu & Wenhui Zhang

  3. Dalian Medical University, Dalian, China

    Di Wang

  4. Department of Gastroenterology, Dalian Municipal Central Hospital Affiliated to Dalian University of Technology, Dalian, Liaoning, China

    Guo Zu

Authors
  1. Di Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenhui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guo Zu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. He Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Congjie Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Di Wang participated in the design, collected the data, performed the quality assessment, statistical analyses and draft the manuscript. Congjie Bi participated in the design and draft the manuscript. Wenhui Zhang and Zhi Liu collected the data and performed the quality assessment. Guo Zu, He Tao helped to perform statistical analyses and search strategy. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Congjie Bi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, D., Liu, Z., Zhang, W. et al. Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials. Eur J Med Res 29, 239 (2024). https://doi.org/10.1186/s40001-024-01838-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-024-01838-z

Keywords

European Journal of Medical Research

ISSN: 2047-783X

Contact us