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New Insights into the Pharmacology of Dexmedetomidine and Open Issues for Neurosurgical Procedures

  • Mariantonietta Scafuro
  • Francesca Gargano
  • Marco Fiore
Protocol
Part of the Neuromethods book series (NM, volume 150)

Abstract

Patients undergoing neurosurgical procedures or requiring mechanical ventilation at the end of the neurosurgical procedure need analgosedation to reduce the anxiety and discomfort related to the intervention, as well as to minimize ventilator intolerance and desynchronizations. Dexmedetomidine is an alpha2-adrenergic agonist (C13H16HCl), as clonidine but more selective for alpha2-receptor. Dexmedetomidine has become increasingly popular for use in neurosurgical procedures and intensive care units (ICU) due to its proposed peculiarities for the management of systemic and cerebral hemodynamics, and the need for intraoperative cortical mapping.

Nowadays the approved therapeutic indication of the European Medical Agency for dexmedetomidine is the sedation of adult ICU patients, whereas the recommended use of the Food and Drug Administration, besides the sedation of adult ICU patients, is the sedation of non-ICU patients prior or during surgical and interventional procedures. However, in many studies, dexmedetomidine is used off-label.

This chapter would be a quick overview of the dexmedetomidine use in neurosurgical procedures, providing new insights into its pharmacology.

Key words

Dexmedetomidine Neurosurgery Neuroanesthesia Sedation Intensive care unit Chronic subdural hematoma Awake craniotomy 

References

  1. 1.
    Belleville JP, Ward DS, Bloor BC et al (1992) Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 77:1125–1133CrossRefGoogle Scholar
  2. 2.
    Virtanen R, Savola JM, Saano V et al (1988) Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol 150:9–14CrossRefGoogle Scholar
  3. 3.
  4. 4.
    Sessler CN, Mark S et al (2002) The Richmond agitation–sedation scale. Am J Respir Crit Care Med 166:1338–1344CrossRefGoogle Scholar
  5. 5.
    Food and Drug Administration. Highlights on dexmedetomidine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021038s021lbl.pdf. Accessed 22 May 2019
  6. 6.
    Anttila M, Penttilä J, Helminen A et al (2003) Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 56:691–693CrossRefGoogle Scholar
  7. 7.
    Li BL, Zhang N, Huang JX et al (2016) A comparison of intranasal dexmedetomidine for sedation in children administered either by atomiser or by drops. Anaesthesia 71:522–528CrossRefGoogle Scholar
  8. 8.
    Zhong W, Zhang Y, Zhang MZ et al (2018) Pharmacokinetics of dexmedetomidine administered to patients with end-stage renal failure and secondary hyperparathyroidism undergoing general anaesthesia. J Clin Pharm Ther 43:414–421CrossRefGoogle Scholar
  9. 9.
  10. 10.
    Valitalo PA, Ahtola-Satila T, Wighton A et al (2013) Population pharmacokinetics of dexmedetomidine in critically ill patients. Clin Drug Investig 33:579–587CrossRefGoogle Scholar
  11. 11.
    Iirola T, Aantaa R, Laitio R et al (2011) Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients. Crit Care 15:R257CrossRefGoogle Scholar
  12. 12.
    Dutta S, Lal R, Karol MD et al (2000) Influence of cardiac output on dexmedetomidine pharmacokinetics. J Pharm Sci 89:519–527CrossRefGoogle Scholar
  13. 13.
    Karol MD, Maze M (2000) Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans. Best Pract Res Clin Anaesthesiol 14:261–269CrossRefGoogle Scholar
  14. 14.
    Farag E, Argalious M, Abd-Elsayed A et al (2012) The use of dexmedetomidine in anesthesia and intensive care: a review. Curr Pharm Des 18:6257–6265CrossRefGoogle Scholar
  15. 15.
    Venn RM, Karol MD, Grounds RM (2002) Pharmacokinetics of dexmedetomidine infusions for sedation of post-operative patients requiring intensive care. Br J Anaesth 88:669–675CrossRefGoogle Scholar
  16. 16.
    Zhang T, Deng Y, He P et al (2015) Effects of mild hypoalbuminemia on the pharmacokinetics and pharmacodynamics of dexmedetomidine in patients after major abdominal or thoracic surgery. J Clin Anesth 27:632–637CrossRefGoogle Scholar
  17. 17.
    Panzer O, Moitra V, Sladen RN (2011) Pharmacology of sedative analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol Clin 29:587–605CrossRefGoogle Scholar
  18. 18.
    Zhang Z, Ferretti V, Guntan I et al (2015) Neuronal ensembles sufficient for recovery sleep and the sedative actions of a2 adrenergic agonists. Nat Neurosci 18:553–561CrossRefGoogle Scholar
  19. 19.
    Nelson LE, Lu J, Guo T et al (2003) The a2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 98:428–436CrossRefGoogle Scholar
  20. 20.
    European Medicines Agency (2015) Dexdor (dexmedetomidine): EU summary of product characteristics. http://www.ema.europa.eu/. Accessed 4 May 2015
  21. 21.
    Miller RD, Cohen NH, Eriksson LI et al (2015) Miller’s anesthesia, 8th edn. Elsevier, Amsterdam, pp 854–859Google Scholar
  22. 22.
    Angst MS, Ramaswamy B, Davies MF et al (2004) Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans. Anesthesiology 101:744–752CrossRefGoogle Scholar
  23. 23.
    Weerink MAS, Struys MMRF, Hannivoort L et al (2017) Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet 56:893–913CrossRefGoogle Scholar
  24. 24.
    Alfieri A, Passavanti MB, Di Franco S et al (2019) Dexmedetomidine in the management of awake fiberoptic intubation. Open Anesth J 13:1–5CrossRefGoogle Scholar
  25. 25.
    Hsu Y-W, Cortinez LI, Robertson KM et al (2004) Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 101:1066–1076CrossRefGoogle Scholar
  26. 26.
    Ho AM-H (2005) Central apnoea after balanced general anaesthesia that included dexmedetomidine. Br J Anaesth 95:773–775CrossRefGoogle Scholar
  27. 27.
    Ebert TJ, Hall JE, Barney JA et al (2000) The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93:382–394CrossRefGoogle Scholar
  28. 28.
    Talke P, Lobo E, Brown R (2003) Systemically administered alpha2-agonist-induced peripheral vasoconstriction in humans. Anesthesiology 99:65–70CrossRefGoogle Scholar
  29. 29.
    Shehabi Y, Ruettimann U, Adamson H et al (2004) Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med 30:2188–2196CrossRefGoogle Scholar
  30. 30.
    Prielipp RC, Wall MH, Tobin JR et al (2002) Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow. Anesth Analg 95:1052–1059PubMedGoogle Scholar
  31. 31.
    Das S, Ghosh S (2015) Monitored anesthesia care: an overview. J Anaesthesiol Clin Pharmacol 31:27–29CrossRefGoogle Scholar
  32. 32.
    Wang W, Feng L, Bai F et al (2016) The safety and efficacy of dexmedetomidine vs. sufentanil in monitored anesthesia care during Burr-Hole surgery for chronic subdural hematoma: a retrospective clinical trial. Front Pharmacol 7:410PubMedPubMedCentralGoogle Scholar
  33. 33.
    Surve RM, Bansal S, Reddy M et al (2017) Use of dexmedetomidine along with local infiltration versus general anesthesia for Burr Hole and evacuation of chronic subdural hematoma (CSDH). J Neurosurg Anesthesiol 29:274–280CrossRefGoogle Scholar
  34. 34.
    Bishnoi V, Kumar B, Bhagat H et al (2016) Comparison of dexmedetomidine versus midazolam-fentanyl combination for monitored anesthesia care during burr-hole surgery for chronic subdural hematoma. J Neurosurg Anesthesiol 28:141–146CrossRefGoogle Scholar
  35. 35.
    Meng L, McDonagh DL, Berger MS et al (2017) Anesthesia for awake craniotomy: a how-to guide for the occasional practitioner. Can J Anaesth 64:517–529CrossRefGoogle Scholar
  36. 36.
    Carbone D, Lubrano G, Muzio MR et al (2019) Anesthetic management and psychological approaches for excision in awake craniotomy of lesions located within or near eloquent language areas. J Surg Forecast 2:1019Google Scholar
  37. 37.
    Eseonu CI, ReFaey K, Garcia O et al (2017) Awake craniotomy anesthesia: a comparison of the monitored anesthesia care and asleep-awake-asleep techniques. World Neurosurg 104:679–686CrossRefGoogle Scholar
  38. 38.
    Suero Molina E, Schipmann S, Mueller I et al (2018) Conscious sedation with dexmedetomidine compared with asleep-awake-asleep craniotomies in glioma surgery: an analysis of 180 patients. J Neurosurg 129:1223–1230CrossRefGoogle Scholar
  39. 39.
    Elbakry AE, Ibrahim E (2017) Propofol-dexmedetomidine versus propofol-remifentanil conscious sedation for awake craniotomy during epilepsy surgery. Minerva Anestesiol 83:1248–1254PubMedGoogle Scholar
  40. 40.
    Goettel N, Bharadwaj S, Venkatraghavan L et al (2016) Dexmedetomidine vs propofol-remifentanil conscious sedation for awake craniotomy: a prospective randomized controlled trial. Br J Anaesth 116:811–821CrossRefGoogle Scholar
  41. 41.
    Garavaglia MM, Das S, Cusimano MD et al (2014) Anesthetic approach to high-risk patients and prolonged awake craniotomy using dexmedetomidine and scalp block. J Neurosurg Anesthesiol 26:226–233CrossRefGoogle Scholar
  42. 42.
    Lin N, Han R, Zhou J, Gelb AW (2016) Mild sedation exacerbates or unmasks focal neurologic dysfunction in neurosurgical patients with supratentorial brain mass lesions in a drug-specific manner. Anesthesiology 124:598–607CrossRefGoogle Scholar
  43. 43.
    Lee JM, Lee SK, Lee SJ et al (2016) Comparison of remifentanil with dexmedetomidine for monitored anaesthesia care in elderly patients during vertebroplasty and kyphoplasty. J Int Med Res 44:307–316CrossRefGoogle Scholar
  44. 44.
    Peng K, Liu HY, Liu SL et al (2016) Dexmedetomidine-fentanyl compared with midazolam-fentanyl for conscious sedation in patients undergoing lumbar disc surgery. Clin Ther 38:192–201CrossRefGoogle Scholar
  45. 45.
    Srivastava VK, Agrawal S, Kumar S et al (2014) Comparison of dexmedetomidine, propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients. J Clin Diagn Res 8:GC04–GC07PubMedPubMedCentralGoogle Scholar
  46. 46.
    Luo X, Zheng X, Huang H (2016) Protective effects of dexmedetomidine on brain function of glioma patients undergoing craniotomy resection and its underlying mechanism. Clin Neurol Neurosurg 146:105–108CrossRefGoogle Scholar
  47. 47.
    Kim H, Min KT, Lee JR et al (2016) Comparison of dexmedetomidine and remifentanil on airway reflex and hemodynamic changes during recovery after craniotomy. Yonsei Med J 57:980–986CrossRefGoogle Scholar
  48. 48.
    Tanskanen PE, Kytta JV, Randell TT et al (2006) Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled study. Br J Anaesth 97:658–665CrossRefGoogle Scholar
  49. 49.
    Peng K, Jin XH, Liu SL et al (2015) Effect of intraoperative dexmedetomidine on post-craniotomy pain. Clin Ther 37:1114–1121CrossRefGoogle Scholar
  50. 50.
    Zhao LH, Shi ZH, Chen GQ et al (2017) Use of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy: a randomized controlled trial. J Neurosurg Anesthesiol 29:132–139CrossRefGoogle Scholar
  51. 51.
    Rajan S, Hutcherson MT, Sessler DI et al (2016) The effects of dexmedetomidine and remifentanil on hemodynamic stability and analgesic requirement after craniotomy: a randomized controlled trial. J Neurosurg Anesthesiol 28:282–290CrossRefGoogle Scholar
  52. 52.
    Goodwin H, Lewin JJ, Mirski MA (2012) ‘Cooperative sedation’: optimizing comfort while maximizing systemic and neurological function. Crit Care 16:217CrossRefGoogle Scholar
  53. 53.
    Cascella M, Fusco R, Caliendo D et al (2017) Anesthetic dreaming, anesthesia awareness and patient satisfaction after deep sedation with propofol target controlled infusion: a prospective cohort study of patients undergoing day case breast surgery. Oncotarget 8:79248–79256PubMedPubMedCentralGoogle Scholar
  54. 54.
    Cascella M, Bimonte S (2017) The role of general anesthetics and the mechanisms of hippocampal and extra-hippocampal dysfunctions in the genesis of postoperative cognitive dysfunction. Neural Regen Res 12:1780–1785CrossRefGoogle Scholar
  55. 55.
    Fiore M, Torretta G, Passavanti MB et al (2019) Effectiveness of dexmedetomidine as adjunctive therapy, compared to the standard of care in the treatment of alcohol withdrawal syndrome: a systematic review protocol. JBI Database System Rev Implement Rep 2019.  https://doi.org/10.11124/JBISRIR-2017-003949
  56. 56.
    Wang Y, Han R, Zuo Z (2016) Dexmedetomidine-induced neuroprotection: is it translational? Transl Perioper Pain Med 1:15–19PubMedPubMedCentralGoogle Scholar
  57. 57.
    Wang X, Ji J, Fen L, Wang A (2013) Effects of dexmedetomidine on cerebral blood flow in critically ill patients with or without traumatic brain injury: a prospective controlled trial. Brain Inj 27:1617–1622CrossRefGoogle Scholar
  58. 58.
    Schomer KJ, Sebat CM, Adams JY et al (2019) Dexmedetomidine for refractory intracranial hypertension. J Intensive Care Med 34:62–66CrossRefGoogle Scholar
  59. 59.
    Lee SH, Choi YS, Hong GR, Oh YJ (2015) Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia. Anaesthesia 70:1052–1059CrossRefGoogle Scholar
  60. 60.
    Erdman MJ, Doepker BA, Gerlach AT et al (2014) A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. Crit Care Med 42:1696–1702CrossRefGoogle Scholar
  61. 61.
    Yokota H, Yokoyama K, Noguchi H et al (2011) Post-operative dexmedetomidine-based sedation after uneventful intracranial surgery for unruptured cerebral aneurysm: comparison with propofol-based sedation. Neurocrit Care 14:182–187CrossRefGoogle Scholar
  62. 62.
    Kido H, Komasawa N, Fujiwara S et al (2014) Gasserian ganglion block for trigeminal neuralgia under dexmedetomidine sedation. Masui 63:901–913PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Mariantonietta Scafuro
    • 1
  • Francesca Gargano
    • 2
  • Marco Fiore
    • 1
  1. 1.Department of Women, Child and General and Specialized SurgeryUniversity of Campania “Luigi Vanvitelli”NaplesItaly
  2. 2.Unit of Anesthesia, Intensive Care and Pain Management, Department of MedicineUniversity Campus Bio-Medico of RomeRomeItaly

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