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. 2020 Jan 3;99(1):e18538. doi: 10.1097/MD.0000000000018538

Pain relieving effect of dexmedetomidine in patients undergoing total knee or hip arthroplasty

A meta-analysis

Qi Yang a,b, Yi Ren a, Bin Feng a,∗, Xisheng Weng a,∗
Editor: Eric Bush
PMCID: PMC6946532  PMID: 31895790

Abstract

Background

To evaluate the safety and efficacy of dexmedetomidine in patients undergoing total knee and hip arthroplasty for postoperative pain control.

Methods

An updated systematic review and meta-analysis of randomized controlled trials (RCTs) identified in systematic searches of MEDLINE, EMBASE, Google Scholar, the Cochrane Database and the Chinese SinoMed Database.

Results

Fourteen RCTs with a total of 1220 patients were included. Overall, dexmedetomidine therapy was associated with significantly decreased pain scores 24 hours after surgery (WMD, −0.36; 95% CI, −0.49 to −0.22; I2 = 90.0%, P < .001) compared with scores in the control group after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Furthermore, the rate of postoperative delirium was also markedly decreased with dexmedetomidine therapy (RR, 0.38; 95% CI, 0.24 to 0.59; I2 = 0.0%, P < .001). Moreover, compared with the control group, dexmedetomidine treatment was associated with a decreased risk of postoperative nausea and vomiting in patients undergoing TKA (RR, 0.34; 95% CI, 0.15 to 0.79; I2 = 0.0%, P = .012), and there was a similar risk of hypotension (RR, 1.03; 95% CI, 0.72 to 1.49; I2 = 24.4%, P = .87) regardless of whether patients underwent TKA or THA. However, the rate of bradycardia was significantly increased with dexmedetomidine treatment in those undergoing TKA (RR, 6.11; 95% CI, 2.35 to 15.91; I2 = 0.0%, P < .001).

Conclusions

Dexmedetomidine therapy seems to be an effective treatment for pain control and postoperative delirium in patients undergoing TKA/THA. However, the incidence of bradycardia is markedly increased in patients undergoing TKA. Hence, much larger prospective clinical studies are warranted to confirm these findings.

Keywords: delirium, dexmedetomidine, meta-analysis, pain management, total hip arthroplasty, total knee arthroplasty

1. Introduction

Patients who undergo total knee or hip arthroplasty are associated with significant postoperative pain,[1,2] which may be underestimated. Previous studies have found that postoperative pain can affect early mobilization and psychological state and can delay patient discharge and early rehabilitation in patients with knee arthroplasty.[3,4] Therefore, adequate pain management is very important to reduce morbidity and promote recovery.[5]

Many agents have been used to provide effective postoperative pain control, including local anesthetics such as lidocaine and bupivacaine, opioids such as morphine, and α2-adrenergic receptor agonists such as clonidine.[5] However, none of these anesthetics are free from limitations such as the need for special equipment and monitoring or the risk of complications that may delay discharge or cause readmission.

Dexmedetomidine is a highly selective, specific, and potent α2-adrenergic receptor agonist.[6] Many studies have demonstrated that dexmedetomidine can significantly decrease pain scores and postoperative diclofenac sodium consumption and can improve the duration of the analgesic effect.[7,8] Furthermore, the incidence of postoperative delirium[9] and postoperative nausea and vomiting (PONV)[10] decreases with the use of dexmedetomidine therapy. However, several studies have shown that dexmedetomidine administration is associated with an increased risk of hypotension[11] and bradycardia requiring atropine.[12] Therefore, the safety and efficacy of dexmedetomidine therapy in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA) is still debatable. Moreover, previous studies are limited by a small size and low quality. Therefore, as the amount of evidence has been recently increasing, we performed a meta-analysis to evaluate the safety and efficacy of dexmedetomidine therapy in patients with TKA/THA.

2. Materials and methods

2.1. Data sources and search strategies

We searched MEDLINE (source, PubMed from 2005 to April 2018), EMBASE (2005 to April 2018), the Cochrane Controlled Clinical Trials Register Database (to April 2018), and the ClinicalTrials.gov website (to April 2018) using the terms “total knee arthroplasty”, “total hip arthroplasty”, “dexmedetomidine”, “pain intensity”, “pain score”, “delirium”, and “randomized trial” in each database. Manual reference checking of the bibliographies of all relevant articles was performed. The reference list of relevant studies was additionally screened. No language restrictions were applied. There is no need for an approval from ethics committee because our study belongs to a retrospective type focusing on literature review.

2.2. Study selection

We first conducted an initial screening of titles and abstracts; the second evaluation was based on a full-text review. Trials were considered eligible if they met the following criteria:

  • 1)

    the study was a prospective randomized controlled trial (RCT);

  • 2)

    the intervention consisted of dexmedetomidine treatment; and

  • 3)

    the primary outcome of interest was the change in pain intensity.

The exclusion criteria were

  • 1)

    non-RCTs and

  • 2)

    duplicate data.

2.3. Data extraction

Two reviewers (QY and YR) extracted data concerning patient characteristics, dexmedetomidine use, study quality, and clinical outcomes using a standard data-collection form. Disagreements were resolved via discussion by 2 reviewers (QY and YR) and the corresponding author (XSW).

The primary outcome was the change in pain intensity at rest and upon movement 24 hours postoperatively. The secondary outcomes were the rate of postoperative delirium, dose of opioid consumption, duration of the analgesic effect, and time to first analgesic request. Adverse events included PONV, hypotension, bradycardia, and somnolence.

2.4. Quality assessment

The Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) statement[13] was followed. Two reviewers (QY and YR) assessed the quality of the selected trials based on the Jadad Scale[14] and the Cochrane Collaboration method.[15] The components used for quality assessment were randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points).

2.5. Data synthesis and analysis

The results were analyzed quantitatively with STATA 14.0 software (Stata Corp, CA) using the random-effects model[16] in consultation with one statistician. We calculated the pooled relative risk (RR) for dichotomous outcomes and the weighted mean difference (WMD) for continuous data with 95% confidence intervals (CIs).

Heterogeneity was examined with the I2 statistic and the chi-squared test. A value of I2 > 50% was considered a substantial level of heterogeneity.[17] Once heterogeneity was noted, publication bias was assessed quantitatively using Egger regression test (P ≤ .10)[18] and qualitatively with the visual inspection of funnel plots of the logarithm of RRs versus their standard errors.[19] Sensitivity analyses were conducted to determine the influence of individual trials on the overall pooled results. All analyses were performed according to the intention-to-treat principle. Statistical significance was set at P < .05.

3. Results

3.1. Search results

We initially identified 223 potentially relevant articles. Sixty-five studies were considered to be of interest and were retrieved for full-text review. Fifty-one articles were excluded due to duplication (n = 9), reviews (n = 24), incorrect comparisons (n = 13) and a lack of primary clinical outcomes (n = 5). Therefore, 14 randomized trials including 1 study identified in the references were finally included in the analysis. Figure 1 is a flow chart showing the study selection process.

Figure 1.

Figure 1

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Flow chart.

3.2. Study characteristics

Fourteen[20–33] published RCTs with a total of 1220 patients were included. The total number of patients in each study ranged from 40 to 296. The participants’ ages ranged from 72.3 ± 12.5 years. Most patients were male, with a percentage of 64.3%. The mean duration of surgery was 78.6 minutes. All patients in the treatment group were treated with dexmedetomidine alone (0.5–2 ug/kg) or in combination with ropivacaine, bupivacaine, or propofol. Patients in the control group were treated with saline, ropivacaine, bupivacaine or propofol. Two studies had thee comparisons because of different dexmedetomidine concentrations. The Jadad scores of all included studies varied from 3 to 5; all 14 studies were considered to be of high quality according to the quality assessment (Table 1, Figs. 2 and 3).

Table 1.

Characteristics of patients with dexmedetomidine therapy in knee or hip arthroplasty.

3.2.

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Figure 2.

Figure 2

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Risk of bias.

Figure 3.

Figure 3

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Risk of bias evaluation.

3.3. Efficacy of postoperative pain management

Overall, 10 of 14 trials[21,23–27,29–32] provided data about pain intensity 24 hours postoperatively, with 642 patients in the dexmedetomidine group and 647 patients in the control group. Compared with the control group, dexmedetomidine therapy was associated with significantly decreased pain scores 24 hours after surgery (WMD, −0.36; 95% CI, −0.49 to −0.22; I2 = 90.0%, P < .001), regardless of whether the patients underwent THA (WMD, −0.26; 95% CI, −0.44 to −0.08; I2 = 94.1%, P < .01) or TKA (WMD, −0.49; 95% CI, −0.70 to −0.27; I2 = 83.3%, P < .001) (Fig. 4). However, there was a high level of heterogeneity (I2 = 90.0%). The funnel plot showed marked asymmetry according to Begg's test (P = .03) and Egger test (P = .02). However, sensitivity analysis was performed by removing each of the trials one at a time, which did not detect any influence on the change in pain intensity (Fig. 5).

Figure 4.

Figure 4

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Change of pain intensity evaluated by VAS after dexmedetomidine treatment.

Figure 5.

Figure 5

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Sensitivity analysis.

3.4. Safety and side effects

The rate of postoperative delirium[22,24,25,28,31,33] was markedly decreased with dexmedetomidine therapy (RR, 0.38; 95% CI, 0.24 to 0.59; I2 = 0.0%, P < .001), regardless of whether the patients underwent THA (RR, 0.39; 95% CI, 0.21 to 0.73; I2 = 0.0%, P < .01) or TKA (RR, 0.36; 95% CI, 0.19 to 0.69; I2 = 25.5%, P < .01) (Fig. 6). Furthermore, dexmedetomidine treatment was associated with a decreased risk of postoperative nausea and vomiting[24,26,27,29,30] in patients undergoing TKA (RR, 0.34; 95% CI, 0.15 to 0.79; I2 = 0.0%, P < .01), and this result was comparable in patients undergoing THA (RR, 0.29; 95% CI, 0.06 to 1.26; P < .01) (Fig. 7).

Figure 6.

Figure 6

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Risk of delirium after dexmedetomidine treatment.

Figure 7.

Figure 7

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Risk of PONV after dexmedetomidine treatment.

The incidence of hypotension[20,22,24,27,30] was similar between the dexmedetomidine group and control group (RR, 1.03; 95% CI, 0.72 to 1.49; I2 = 24.4%, P = .87), regardless of whether the patients underwent THA (RR, 0.73; 95% CI, 0.37 to 1.47; I2 = 53.0%, P = .38) or TKA (RR, 1.29; 95% CI, 0.86 to 1.94; I2 = 0.0%, P = .21) (Fig. 8). Nevertheless, the rate of bradycardia[20,22,24–27,30] was significantly increased with dexmedetomidine treatment in those undergoing TKA (RR, 6.11; 95% CI, 2.35 to 15.91; I2 = 0.0%, P < .001), and this result was comparable in patients undergoing THA (RR, 1.70; 95% CI, 0.85 to 3.41; I2 = 0.0%, P = .14) (Fig. 9).

Figure 8.

Figure 8

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Risk of hypotension after dexmedetomidine treatment.

Figure 9.

Figure 9

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Risk of bradycardia after dexmedetomidine treatment.

4. Discussion

Our meta-analysis of 14 highly qualified randomized controlled clinical trials showed that dexmedetomidine therapy could significantly decrease pain scores compared with placebo in patients undergoing TKA/THA. Furthermore, the risk of postoperative delirium was markedly decreased in the dexmedetomidine group. Moreover, the incidence of PONV was significantly lower in patients undergoing TKA with dexmedetomidine treatment, and the rate of hypotension was similar between the groups. However, the incidence of bradycardia was markedly increased in those undergoing TKA and administered dexmedetomidine.

Postoperative pain is one of the most commonly reported discomforts after TKA/THA surgery and is described as severe by more than half of patients.[1] Although many pain-relieving remedies have been employed as regular measures, it is still a challenge to optimize postoperative pain control. Opioids typically play a large role in the treatment of postoperative pain after TKA, which may result in a high risk of respiratory depression in patients.[35,36] Compared with the opioid-only pain management strategy, a combination of dexmedetomidine with opioids is conducive to decreasing postoperative pain and simultaneously reducing opioid requirements and opioid-related adverse events.[37] Furthermore, dexmedetomidine therapy alone has also yielded promising results.[38,39] In addition, our study confirmed that dexmedetomidine could decrease pain scores in the first 24 hours, which suggests that the analgesic benefits of dexmedetomidine extend beyond its biological half-life of 2 hours. However, the mechanism underlying this long-term analgesic effect remains unclear. A previous study suggested the existence of different action pathways between the sedation and analgesic effects of dexmedetomidine as a possible mechanism.[40] While the effect of dexmedetomidine is mediated by the ascending noradrenergic pathway in the locus coeruleus, the analgesic effect occurs via an α2- adrenergic receptor-dependent descending pathway in the spinal cord.[40] However, the comparison of dexmedetomidine vs opioids for postoperative pain management remains unclear due to limited data.

Of the postoperative complications, delirium is common among elderly patients and is associated with poor clinical outcomes.[41] Many risk factors are related to postoperative delirium, such as exposure to general anesthetics, pain and the postoperative inflammatory response.[42] Preclinical and clinical studies have found that dexmedetomidine attenuates neurotoxicity induced by general anesthetics, improves postoperative analgesia and inhibits the inflammatory response after surgery.[34,43] Several studies have found that the intraoperative use of dexmedetomidine can prevent postoperative delirium, but the data are inconsistent. In pediatric patients undergoing tonsillectomy and cardiac surgery, intraoperative infusion of dexmedetomidine lowers the incidence of emergent delirium.[44,45] For adult patients undergoing cardiac surgery and microvascular free flap surgery, intraoperative dexmedetomidine slightly decreased the incidence of delirium compared with normal saline, although the differences were not statistically significant between the 2 groups, possibly due to the underpowered sample size.[46] Su et al found that prophylactic low-dose dexmedetomidine significantly decreased the occurrence of delirium during the first 7 days after noncardiac surgery.[47] For elderly patients undergoing joint replacement, several studies confirmed that dexmedetomidine treatment during surgery significantly reduced the incidence of postoperative delirium.[31,48,49] Inconsistent with previous studies, our pooled data indicated that dexmedetomidine could markedly lower the risk of postoperative delirium in patients undergoing TKA/THA. However, in a recent study, the use of dexmedetomidine during general anesthesia did not reduce delirium after major noncardiac surgery, including arthroplasty, in elderly patients.[50] Therefore, more studies are warranted to confirm the effect on postoperative delirium.

The present study has a few limitations. First, our study is based on study-level data and as such shares the flaws of original studies. Notwithstanding the value of patient-level meta-analyses, we believe that a meta-analysis of aggregate data can answer this question. Second, our study enrolled patients with different dexmedetomidine concentrations, which are associated with different safeties and efficacies that can impact the therapeutic potential. Moreover, although the inclusion criteria were broad across all 14 studies, slight differences remained in terms of the characteristics of patients and the doses of dexmedetomidine used. We cannot exclude geographical variations. Third, the sample size was inadequate for excluding small differences in outcome between the 2 groups. Therefore, the power of the studies selected was not high. In this sense, our meta-analysis is just a possible indication, and future studies will require larger numbers of patients and careful matching of key clinical and technical variables to definitively quantify the potential effects of dexmedetomidine therapy in patients undergoing TKA/THA.

Given the clinical data, dexmedetomidine therapy appears to provide clinical benefits with respect to postoperative pain control and delirium prevention for patients with TKA/THA. More studies are needed to evaluate the safety of dexmedetomidine treatment for TKA/THA.

5. Conclusion

In summary, dexmedetomidine is effective for postoperative pain control, and there is a decreased risk of postoperative delirium in patients undergoing TKA/THA. However, an increased risk of bradycardia is among the side effects of dexmedetomidine.

Author contributions

Data curation: Yi Ren, Xisheng Weng.

Formal analysis: Qi Yang, Yi Ren.

Investigation: Qi Yang.

Methodology: Qi Yang, Bin Feng.

Resources: Xisheng Weng, Bin Feng.

Software: Qi Yang.

Supervision: Xisheng Weng, Bin Feng.

Validation: Xisheng Weng, Bin Feng.

Visualization: Xisheng Weng.

Writing – original draft: Qi Yang, Yi Ren.

Writing – review & editing: Yi Ren, Bin Feng.

Footnotes

Abbreviations: PONV = postoperative nausea and vomiting, RCT = randomized controlled trial, THA = total hip arthroplasty, TKA = total knee arthroplasty.

How to cite this article: Yang Q, Ren Y, Feng B, Weng X. Pain relieving effect of dexmedetomidine in patients undergoing total knee or hip arthroplasty: a meta-analysis. Medicine. 2020;99:1(e18538).

QY and YR contributed equally to this work and should be considered as co-first author.

This study was financially supported by the National Natural Science Foundation in China (No. 81871740).

All authors state that there are no conflicts of interest.

All the data and related protocols in this article are available to Editorial Board Members and every reader.

References

  • [1].Grosu I, Lavand’homme P, Thienpont E. Pain after knee arthoplasty: an unresolved issue. Knee Surg Sports Traumatol Arthosc 2014;22:1744–58. [DOI] [PubMed] [Google Scholar]
  • [2].Robinson KP, Wagstaff KJ, Sanghera S, et al. Postoperative pain following primary lower limb arthoplasty and enhanced recovery pathway. Ann R Coll Surg Engl 2014;96:302–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Aveline C, Roux AL, Hetet HL, et al. Pain and recovery after total knee arthoplasty: a 12-month follow-up after a prospective randomized study evaluating Nefopam and Ketamine for early rehabilitation. Clin J Pain 2014;30:749–54. [DOI] [PubMed] [Google Scholar]
  • [4].Lindberg MF, Miaskowski C, RustøEn T, et al. Factors that can predict pain with walking, 12 months after total knee arthoplasty. Acta Orthop 2016;87:600–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Correll D. Chonic postoperative pain: recent findings in understanding and management. F1000Res 2017;6:1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Gertler R, Brown HC, Mitchell DH, et al. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Arain SR, Ebert TJ. The efficacy, side effects, and recovery char- acteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg 2002;95:461–6. [DOI] [PubMed] [Google Scholar]
  • [8].Chan IA, Maslany JG, Gorman KJ, et al. Dexmedetomidine during total knee arthoplasty performed under spinal anesthesia decreases opioid use: a randomized- controlled trial. Can J Anaesth 2016;63:569–76. [DOI] [PubMed] [Google Scholar]
  • [9].Pasin L, Landoni G, Nardelli P, et al. Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth 2014;28:1459–66. [DOI] [PubMed] [Google Scholar]
  • [10].Bakri MH, Ismail EA, Ibrahim A. Comparison of dexmedetomidine and dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Korean J Anesthesiol 2015;68:254–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].MacLaren R, Preslaski CR, Mueller SW, et al. A randomized, double-blind pilot study of dexmedetomidine versus midazolam for intensive care unit sedation: patient recall of their experiences and short-term psychological outcomes. J Intensive Care Med 2015;30:167–75. [DOI] [PubMed] [Google Scholar]
  • [12].Niu XY, Ding XB, Guo T, et al. Effects of intravenous and intrathecal dexmedetomidine in spinal anesthesia: a meta-analysis. CNS Neurosci Ther 2013;19:897–904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Moher D, Liberati A, Tetzlaff J, et al. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol 2009;62:1006–12. [DOI] [PubMed] [Google Scholar]
  • [14].Clark HD, Wells GA, Huët C, et al. Assessing the quality of randomized trials: reliability of the Jadad scale. Control Clin Trials 1999;20:448–52. [DOI] [PubMed] [Google Scholar]
  • [15].Higgins JP, Green S. Cochane handbook for systematic reviews of interventions; http://handbook.cochane.org 2014. [Google Scholar]
  • [16].DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88. [DOI] [PubMed] [Google Scholar]
  • [17].Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Easterbrook PJ, Berlin JA, Gopalan R, et al. Publication bias in clinical research. Lancet 1991;337:867–72. [DOI] [PubMed] [Google Scholar]
  • [20].Cui YK, Tian B, Wang J, et al. Efficacy of dexmedetomidine used to supplement lumbar plexus combined with sciatic nerve block for total hip arthoplasty in elderly patients. Chin J Anesthesiol 2012;32:1449–52. [Google Scholar]
  • [21].Wang ML, Luo F, Zhang Q. Application of dexmedetomidine in elderly patients with arthoplasty. Chin J Post Med 2013;36:69–71. [Google Scholar]
  • [22].Xia Q, Wang SD, Huang H, et al. Comparative study of efficacy and safety between dexmedetomidine and propofol for sedation in elderly undergoing hip arthoplasty. Chin J Clin (Electronic Edition) 2013;7:1779–80. [Google Scholar]
  • [23].Zhou XD, Mao HJ. Influence of dexmedetomidine on hemodynamic, cerebral state index and awakening quality in elderly patients after total hip replacement. Chin J Postgrad Med 2013;36:23–6. [Google Scholar]
  • [24].Yang YQ. The effect of dexmedetomidine on low-dose bupivacaine spinal anesthesia in elderly patients after total hip arthoplasty. Chin J Clin (Electronic Edition) 2015;9:2516–20. [Google Scholar]
  • [25].Xue LJ, Li JZ, Gao YD, et al. Sedative effect of dexmedetomidine in patients undergoing knee arthoplasty under sciatic nerve combined with femoral nerve block anesthesia. China Med 2016;11:874–6. [Google Scholar]
  • [26].Zhang JN, Liu J, Xu MY, et al. Effect of dexmedetomidine-assisted continuous femoral nerve block analgesia after total knee arthoplasty (TKA). J Chin Physic 2016;18:501–4. [Google Scholar]
  • [27].Chan IA, Maslany JG, Gorman KJ, et al. Dexmedetomidine during total knee arthoplasty performed under spinal anesthesia decreases opioid use: a randomized-controlled trial. Can J Anesth 2016;63:569–76. [DOI] [PubMed] [Google Scholar]
  • [28].Teng CL, Zhao Y, Lyu DZ. Effect of dexmedetomidine combined with edaravone on postoperative delirium in elderly patients after total hip arthoplasty. China Med 2017;12:1235–8. [Google Scholar]
  • [29].Goyal R, Mittal G, Yadav AK, et al. Adductor canal block for post-operative analgesia after simultaneous bilateral total knee replacement: a randomized controlled trial to study the effect of addition of dexmedetomidine to ropivacaine. Indian J Anaesth 2017;61:903–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Packiasabapathy SP, Kashyap L, Arora MK, et al. Effect of dexmedetomidine as an adjuvant to bupivacaine in femoral nerve block for perioperative analgesia in patients undergoing total knee replacement arthoplasty: a dose-response study. Saudi J Anaesth 2017;11:293–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Mei B, Meng G, Xu GH, et al. Intraoperative sedation with dexmedetomidine is superior to Propofol for elderly patients undergoing hip arthoplasty: a prospective randomized controlled study. Clin J Pain 2018;34:811–7. [DOI] [PubMed] [Google Scholar]
  • [32].Shin HJ, Do SH, Lee JS, et al. Comparison of intraoperative sedation with dexmedetomidine versus Propofol on acute postoperative pain in total knee arthoplasty under spinal anesthesia: a randomized trial. Anesth Analg 2019;129:1512–8. [DOI] [PubMed] [Google Scholar]
  • [33].Wang XL, Wang J, Mu DL, et al. Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthoplasty. Natl Med J Chin 2018;98:728–32. [DOI] [PubMed] [Google Scholar]
  • [34].Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol 2008;21:457–61. [DOI] [PubMed] [Google Scholar]
  • [35].Lee LA, Caplan RA, Stephens LS, et al. Postoperative opioid- induced respiratory depression: a closed claims analysis. Anesthesiology 2015;122:659–65. [DOI] [PubMed] [Google Scholar]
  • [36].Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain PhysicianV 11 2008;2 Suppl: S105–20. 26. Pattinson KT. Opioids and the control of respiration. Br J Anaesth 2008;100:747-758. [PubMed] [Google Scholar]
  • [37].Peng K, Zhang J, Meng XW, et al. Optimization of postoperative intravenous patient-controlled analgesia with opioid-dexmedetomidine combinations: an updated meta-analysis with trial sequential analysis of randomized controlled trials. Pain Physician 2017;20:569–96. [PubMed] [Google Scholar]
  • [38].Ge DJ, Qi B, Tang G, et al. Intraoperative dexmedetomidine promotes postoperative analgesia and recovery in patients after abdominal hysterectomy: a double-blind, randomized clinical trial. Sci Rep 2016;6:21514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Schnabel A, Meyer-Frießem CH, Reichl SU, et al. Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. Pain 2013;154:1140–9. [DOI] [PubMed] [Google Scholar]
  • [40].Tang C, Xia Z. Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic. J Pain Res 2017;10:1899–904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Petersen PB, Jørgensen CC, Kehlet H. Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Collaborative Group. Delirium after fast-track hip and knee arthoplasty - a cohort study of 6331 elderly patients. Acta Anaesthesiol Scand 2017;61:767–72. [DOI] [PubMed] [Google Scholar]
  • [42].de Castro SM, Ünlü Ç, Tuynman JB, et al. Incidence and risk factors of delirium in the elderly general surgical patient. Am J Surg 2014;208:26–32. [DOI] [PubMed] [Google Scholar]
  • [43].Altshuler J, Spoelhof B. Pain, agitation, delirium, and neuromuscular blockade: a review of basic pharmacology, assessment, and monitoring. Crit Care Nurs Q 2013;36:356–69. [DOI] [PubMed] [Google Scholar]
  • [44].Cao JL, Pei YP, Wei JQ, et al. Effects of intraoperative dexmedetomidine with intravenous anesthesia on postoperative emergence agitation/delirium in pediatric patients undergoing tonsillectomy with or without adenoidectomy: a CONSORT- prospective, randomized, controlled clinical trial. Medicine 2016;95:e5566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Sun Y, Liu J, Yuan X, et al. Effects of dexmedetomidine on emergence delirium in pediatric cardiac surgery. Minerva Pediatr 2017;69:165–73. [DOI] [PubMed] [Google Scholar]
  • [46].Li X, Yang J, Nie XL, et al. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: a randomized controlled trial. PLoS One 2017;12:e0170757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [47].Deiner S, Luo X, Lin HM, et al. Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial. JAMA Surg 2017;152:e171505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Liu Y, Ma L, Gao M, et al. Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. Aging Clin Exp Res 2016;28:729–36. [DOI] [PubMed] [Google Scholar]
  • [49].Wang XL, Wang J, Mu DL, et al. Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthoplasty. Zhonghua Yi Xue Za Zhi 2018;98:728–32. [DOI] [PubMed] [Google Scholar]
  • [50].Su X, Meng ZT, Wu XH, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 2016;388:1893–902. [DOI] [PubMed] [Google Scholar]

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