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Dexmedetomidine as a sedative and analgesic adjuvant in spine surgery: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Purpose

This systematic review and meta-analysis appraise the clinical evidence on efficacy and safety of dexmedetomidine (DEX), as a sedative and analgesic adjunct in adult patients undergoing spine surgery.

Methods

A database search was conducted to identify randomized clinical trials (RCTs) pertinent to the perioperative use of DEX in spine surgery. Sedative and analgesic efficacy of DEX constituted the primary outcomes, whilst the incidence of hemodynamic changes, quality of recovery and occurrence of adverse events served as secondary ones.

Results

Fifteen studies enrolling a total of 913 patients were selected for qualitative analysis, among which eight RCTs incorporating a placebo comparison group were included in the meta-analysis. Most of the retrieved studies were of moderate to good quality and demonstrated an acceptable risk of bias. DEX-treated patients showed a significant reduction of both propofol [mean difference (MD), −214.47 mg; 95%CI, −253.16 to −175.78; P < 0.001] and morphine equivalents consumption both intraoperatively and postoperatively (MD, −2.69; 95% CI, −3.05 to −2.33; P < 0.001 and MD, −4.36 mg; 95%CI, −6.93 to −1.79; P < 0.001, respectively) compared to those assigned to placebo. Postoperative nausea and vomiting incidence were comparable between DEX and placebo groups, whilst other adverse events were not consistently reported.

Conclusions

DEX emerges as an attractive alternative to standard sedative and analgesic modalities applied in spine surgery, by attaining a notable sedative and opioid-sparing effect, which goes with an enhanced safety profile. Yet, no definite conclusion can be drawn due to the considerable heterogeneity of available data.

Trial registration

PROSPERO CRD42015029537.

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References

  1. Edgcombe H, Carter K, Yarrow S (2008) Anesthesia in the prone position. Br J Anaesth 100:165–183

    Article  CAS  PubMed  Google Scholar 

  2. Willner D, Spennati V, Stohl S, Tosti G, Aloisio S, Bilotta F (2016) Sa pine surgery and blood loss: systematic review of clinical evidence. Anesth Analg 123:1307–1315

    Article  CAS  PubMed  Google Scholar 

  3. Sharma S, Balireddy RK, Vorenkamp KE, Durieux ME (2012) Beyond opioid patient-controlled analgesia: a systematic review of analgesia after major spine surgery. Reg Anesth Pain Med 37:79–98

    Article  CAS  PubMed  Google Scholar 

  4. Sekimoto K, Nishikawa K, Ishizeki J, Kubo K, Saito S, Goto F (2006) The effects of volatile anesthetics on intraoperative monitoring of myogenic motor-evoked potentials to transcranial electrical stimulation and on partial neuromuscular blockade during propofol/fentanyl/nitrous oxide anesthesia in humans. J Neurosurg Anesthesiol 18:106–111

    Article  PubMed  Google Scholar 

  5. Mathiesen O, Dahl B, Thomsen BA, Kitter B, Sonne N, Dahl JB, Kehlet H (2013) A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery. Eur Spine J 22:2089–2096

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zheng Y, Cui S, Liu Y, Zhang J, Zhang W, Zhang J, Gu X, Ma Z (2012) Dexmedetomidine prevents remifentanil-induced postoperative hyperalgesia and decreases spinal tyrosine phosphorylation of N-methyl-d-aspartate receptor 2B subunit. Brain Res Bull 87:427–431

    Article  CAS  PubMed  Google Scholar 

  7. Lee C, Kim YD, Kim JN (2013) Antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia. Korean J Anesthesiol 64:301–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kang WS, Kim SY, Son JC, Kim JD, Muhammad HB, Kim SH, Yoon TG, Kim TY (2012) The effect of dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics during remifentanil-based anesthesia. Korean J Anesthesiol 62:113–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Grewal A (2011) Dexmedetomidine: new avenues. J Anaesthesiol Clin Pharmacol 27:297–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Blaudszun G, Lysakowski C, Elia N, Tramèr MR (2012) Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology 116:1312–1322

    Article  CAS  PubMed  Google Scholar 

  11. Tsaousi GG, Lamperti M, Bilotta F (2016) Role of Dexmedetomidine for sedation in neurocritical care patients: a qualitative systematic review and meta-analysis of current evidence. Clin Neuropharmacol 39:144–151

    Article  CAS  PubMed  Google Scholar 

  12. Schnabel A, Meyer-Friessem CH, Reichl SU, Zahn PK, Pogatzki-Zahn EM (2013) Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. Pain 154:1140–1149

    Article  CAS  PubMed  Google Scholar 

  13. Peng K, Wu S, Liu H, Ji F (2014) Dexmedetomidine as an anesthetic adjuvant for intracranial procedures: meta-analysis of randomized controlled trials. J Clin Neurosci 21:1951–1958

    Article  CAS  PubMed  Google Scholar 

  14. McQueen-Shadfar LA, Megalla SA, White WD, Olufolabi AJ, Jones CA, Habib AS (2011) Impact of intraoperative dexmedetomidine on postoperative analgesia following gynecologic surgery. Curr Med Res Opin 27:2091–2097

    Article  CAS  PubMed  Google Scholar 

  15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339. https://doi.org/10.1136/bmj.b2700

    Article  PubMed  PubMed Central  Google Scholar 

  16. Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration, http://handbook.cochrane.org

  17. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  CAS  PubMed  Google Scholar 

  18. Higgins JP, Altman DG, Gotzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods Group; Cochrane Statistical Methods Group (2011) The Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials. BMJ 343:d5928

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kontopantelis E, Springate DA, Reeves D (2013) A re-analysis of the Cochrane library data: the dangers of unobserved heterogeneity in meta-analysis. PLoS One 8:e69930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bojaraaj DRK, Senthilkumar S, Vijayaragavan S, Gnanavelrajan A (2016) Effect of intravenous use of dexmedetomidine on anesthetic requirements in patients undergoing elective spine surgery: A double-blinded randomized controlled trial. International J Scientific Study 4:251–255

    Google Scholar 

  21. Naik BI, Nemergut EC, Kazemi A, Fernández L, Cederholm SK, McMurry TL, Durieux ME (2016) The effect of dexmedetomidine on postoperative opioid consumption and pain after major spine surgery. Anesth Analg 122:1646–1653

    Article  CAS  PubMed  Google Scholar 

  22. Ozkose Z, Demir FS, Pampal K, Yardim S (2006) Hemodynamic and anesthetic advantages of dexmedetomidine, an alpha 2-agonist, for surgery in prone position. Tohoku J Exp Med 210:153–160

    Article  CAS  PubMed  Google Scholar 

  23. Rozet I, Metzner J, Brown M, Treggiari MM, Slimp JC, Kinney G, Sharma D, Lee LA, Vavilala MS (2015) Dexmedetomidine does not affect evoked potentials during spine surgery. Anesth Analg 121:492–501

    Article  CAS  PubMed  Google Scholar 

  24. Chen Z, Lin S, Shao W (2015) Effects on somatosensory and motor evoked potentials of senile patients using different doses of dexmedetomidine during spine surgery. Ir J Med Sci 184:813–818

    Article  CAS  PubMed  Google Scholar 

  25. Srivastava VK, Mishra A, Agrawal S, Kumar S, Sharma S, Kumar R (2016) Comparative evaluation of dexmedetomidine and magnesium sulphate on propofol consumption, hemodynamics and postoperative recovery in spine surgery: a prospective, randomized, placebo-controlled, double-blind study. Adv Pharm Bull 6:75–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gandhi KA, Panda NB, Vellaichamy A, Mathew PJ, Sahni N, Batra YK (2017) Intraoperative and postoperative administration of dexmedetomidine reduces anesthetic and postoperative analgesic requirements in patients undergoing cervical spine surgeries. J Neurosurg Anesthesiol 29:258–263

    Article  PubMed  Google Scholar 

  27. Hwang W, Lee J, Park J, Joo J (2015) Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled study. BMC Anesthesiol 15:21

    Article  PubMed  PubMed Central  Google Scholar 

  28. Peng K, Liu HY, Liu SL, Ji FH (2016) Dexmedetomidine-fentanyl compared with midazolam-fentanyl for conscious sedation in patients undergoing lumbar disc surgery. Clin Ther 38:192–201

    Article  CAS  PubMed  Google Scholar 

  29. Turgut N, Turkmen A, Gökkaya S, Altan A, Hatiboglu MA (2008) Dexmedetomidine-based versus fentanyl-based total intravenous anesthesia for lumbar laminectomy. Minerva Anestesiol 74:469–474

    CAS  PubMed  Google Scholar 

  30. Lin S, Dai N, Cheng Z, Shao W, Fu Z (2014) Effect of dexmedetomidine-etomidate-fentanyl combined anesthesia on somatosensory- and motor-evoked potentials in patients undergoing spinal surgery. Exp Ther Med 7:1383–1387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mariappan R, Ashokkumar H, Kuppuswamy B (2014) Comparing the effects of oral clonidine premedication with intraoperative dexmedetomidine infusion on anesthetic requirement and recovery from anesthesia in patients undergoing major spine surgery. J Neurosurg Anesthesiol 26:192–197

    Article  PubMed  Google Scholar 

  32. Garg N, Panda NB, Gandhi KA, Bhagat H, Batra YK, Grover VK, Chhabra R (2016) Comparison of small dose ketamine and dexmedetomidine infusion for postoperative analgesia in spine surgery - a prospective randomized double-blind placebo controlled study. J Neurosurg Anesthesiol 28:27–31

    Article  PubMed  Google Scholar 

  33. Song Y, Shim JK, Song JW, Kim EK, Kwak YL (2016) Dexmedetomidine added to an opioid-based analgesic regimen for the prevention of postoperative nausea and vomiting in highly susceptible patients: a randomised controlled trial. Eur J Anaesthesiol 33:75–83

    Article  CAS  PubMed  Google Scholar 

  34. Terao Y, Ichinomiya T, Higashijima U, Tanise T, Miura K, Fukusaki M, Sumikawa K (2012) Comparison between propofol and dexmedetomidine in postoperative sedation after extensive cervical spine surgery. J Anesth 26:179–186

    Article  PubMed  Google Scholar 

  35. Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M (2013) The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. J Neurosurg Anesthesiol 25:16–24

    Article  PubMed  PubMed Central  Google Scholar 

  36. Jamaliya RH, Chinnachamy R, Maliwad J, Deshmukh VP, Shah BJ, Chadha IA (2014) The efficacy and hemodynamic response to Dexmedetomidine as a hypotensive agent in posterior fixation surgery following traumatic spine injury. J Anaesthesiol Clin Pharmacol 30:203–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M (2003) The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 98:428–436

    Article  CAS  PubMed  Google Scholar 

  38. Kaskinoro K, Maksimow A, Långsjӧ J, Aantaa R, Jääskeläinen S, Kaisti K, Särkelä M, Scheinin H (2011) Wide inter-individual variability of bispectral index and spectral entropy at loss of consciousness during increasing concentrations of dexmedetomidine, propofol, and sevoflurane. Br J Anaesth 107:573–580

    Article  CAS  PubMed  Google Scholar 

  39. Lobo FA, Schraag S (2011) Limitations of anaesthesia depth monitoring. Curr Opin Anaesthesiol 24:657–664

    Article  PubMed  Google Scholar 

  40. Yu L, Ran B, Li M, Shi Z (2013) Gabapentin and pregabalin in the management of postoperative pain after lumbar spinal surgery: a systematic review and meta-analysis. Spine (Phila Pa 1976) 38:1947–1952

    Article  Google Scholar 

  41. Boezaart AP, Davis G, Le-Wendling L (2012) Recovery after orthopedic surgery: techniques to increase duration of pain control. Curr Opin Anaesthesiol 25:665–672

    PubMed  Google Scholar 

  42. Dunn LK, Durieux ME, Nemergut EC (2016) Non-opioid analgesics: novel approaches to perioperative analgesia for major spine surgery. Best Pract Res Clin Anaesthesiol 30:79–89

    Article  PubMed  Google Scholar 

  43. Constantin JM, Momon A, Mantz J, Payen JF, De Jonghe B, Perbet S, Cayot S, Chanques G, Perreira B (2016) Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth Crit Care Pain Med 35:7–15

    Article  PubMed  Google Scholar 

  44. Bloor BC, Ward DS, Belleville JP, Maze M (1992) Effects of intravenous dexmedetomidine in humans: II. Hemodynamic changes. Anesthesiology 77:1134–1142

    Article  CAS  PubMed  Google Scholar 

  45. Ice CJ, Personett HA, Frazee EN, Dierkhising RA, Kashyap R, Oeckler RA (2016) Risk factors for Dexmedetomidine-associated hemodynamic instability in noncardiac intensive care unit patients. Anesth Analg 122:462–469

    Article  CAS  PubMed  Google Scholar 

  46. Erdman MJ, Doepker BA, Gerlach AT, Phillips GS, Elijovich L, Jones GM (2014) A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. Crit Care Med 42:1696–1702

    Article  CAS  PubMed  Google Scholar 

  47. Karlsson AK (1999) Autonomic dysreflexia. Spinal Cord 37:383–391

    Article  CAS  PubMed  Google Scholar 

  48. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J, Dexmedetomidine for Long-Term Sedation Investigators (2012) Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 307:1151–1160

    Article  CAS  PubMed  Google Scholar 

  49. Jones GM, Murphy CV, Gerlach AT, Goodman EM, Pell LJ (2011) High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety. Ann Pharmacother 45:740–747

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

1. Georgia Tsaousi: conception and design of the work; acquisition, analysis, and interpretation of data; wrote the paper; drafted the work or revised it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work.

2. Chryssa Pourzitaki: acquisition, analysis, and interpretation of data; wrote the paper; Drafted the work or revised it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work.

3. Simone Aloisio: acquisition and interpretation of data; Drafted the work or revised it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work.

4. Federico Bilotta: conception and design of the work; interpretation of data; drafted the work or revised it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work.

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Tsaousi, G.G., Pourzitaki, C., Aloisio, S. et al. Dexmedetomidine as a sedative and analgesic adjuvant in spine surgery: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 74, 1377–1389 (2018). https://doi.org/10.1007/s00228-018-2520-7

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