The use of Dexmedetomidine in patients with Spinal Cord Injury
Keywords:
Spinal Cord Injury, Dexmedetomidine, ICU, SurgeryAbstract
Traumatic Spinal Cord Injury (SCI) may often lead to significant disability in affected individuals and reduce quality of life.
Over 70% of SCI patients suffer from multiple injuries, concomitant with spinal cord trauma, contributing to the high rates of associated complications during the acute and long-term phases of care [1].
SCI impairs body’s autonomic and biomechanical performance by interrupting communications between the brain, organ systems, muscles and bones. This carries important implications on patients’ ability to perform basic daily-lifeactivities and reserve capacity to withstand illnesses and aging [2].
Dexmedetomidine, an imidazole compound, is a highly selective a2-adrenoreceptor agonist, even ten times more selective than Clonidine. It is a very versatile drug in anaesthesia practice, nowadays applied in increasing number of clinical scenarios. It is an analgesic with anaesthetic sparing effects, sympatholytic properties, applied for procedural sedation, displaying cardiovascular stabilizing properties. It reduces delirium and preserves respiratory function, adding benefits to its use [3].
The aim of this review is to present the evolving role of Dexmedetomidine in patients with Spinal Cord Injuries in anaesthesia and ICU sedation and discuss its limitations.
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References
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2. Ong B, Wilson JR, Henzel MK. Management of the Patient with Chronic Spinal Cord Injury. 2019, doi:10.1016/j.mcna.2019.1006
3. Naaz S.C. Dexmedetomidine in Current Anaesthesia Practice. A Review Journal of Clinical and Diagnostic Research 2014, doi:10.7860/JCDR/2014/9624.4946
4. Panzer O, Moitra V, Sladen RN. Pharmacology of sedative analgesic agents:dexmedetomidine, remifentanyl, ketamine,volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol.Clin. 2011;29(4):587-605
5. European Medicines Agency. Dexmedetomidine: assessment report. 2011.http//www ema.europa.eu/ Assessed 4 May 2015
6. US Food and Drug Administration. Precedex label. Available from:http//www.accessdata.fda.gov/drugsafda_docs/label/1999/21038lbl. Accessed 14 Nov 2016
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8. Weerink MS, Strugs RF, Hannivoort LN. Barends A.R. Absalom P. Colin, Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine, Clin. Pharmacokinetic 2017; 56:893-913
9. H. Yoo, T. Lirola, S. Vilo, T. Manner, R. Aantaa, M. Lahtinen, M. Scheinin, K.T. Olkkola, W.J. Jusco. Mechanism-based population pharmacokinetic and pharmacodynamics modeling of intravenous and intranasal dexmedetomidine in healthy subjects,Eur. J. Clin. Pharmacol. 2015;71:1197-1207
10. A.H.W. Tse, L. Ling, A. Lee, G.M. Joyut, Altered pharmacokinetics in prolonged infusions of sedatives and analgesics among adult critically ill patients: a systematic review, Clin.Ther. 2018;40:1598-1615,e2.
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A. Rlle, S. Paredes, L.I. Cortinez, B.J. Anderson, N. Quezada, S. Slari, F. Allende, J. Torres, D. Cabrera, V. Conteras, J. Cawona, C. Ramirez, A.M. Olivera, M. Ibacache, Dexmedetomidine metabolic clearance is not affected by fatmass in obese patients, Br. J. anaesth. 12092018)969-977
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21. Ebert TJ, Hall JE, Barney JA, et al. The effects of increasing plasma concentration of dexmedetomidine in humans. Anesthesiology. 2020;939(2):382-94
22. Hsu Y-W, Cortinez LI, Robertson KM, et al. Dexmedetomidine pharmacodynamics; part I. Crossover comparison of the respiratory effects of dexmedetomidine and remifentanyl in healthy volunteers. Anesthesiology 2004;(5):1066-76
23. Hall JC, Uhrich TD, Barney JA, et al. Sedative, amnestic and analgesic properties of small-dose dexmedetomidine infusions. Anesth. Analg. 2000;90(3):699:705
24. Shehabi Y, Ruettimann U, Adamson H, et al. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004;30(12);2188-96
25. Venn RM, Grounds RM. Comparison between Dexmedetomidine and propofol for sedation in the intensive care unit, patient and clinician perceptions. Br. J. Anaesth. 2001;87(5):684-90
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27. Venn RM, Newman PJ, Grounds RM. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. 2003;29(2):201-7
28. Nelson LE, Lu J, Guo T, et al. The a2-adrenoreceptor agonist dexmedetomidine conveges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003;98(2):428-36
29. Huupponen E, Maksimow A, Lapinlampi P, et al. Electroencephalogram Spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol. Scand.2008;52(2):289-94
30. Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanyl, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol. Clin. 2011;29(4):587-605
31. Bloor BC, Ward DS, Belleville JP, et al. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesilogy. 1992;77(6):1134-42
32. Kallio A, Scheinin M, Koulu M, et al. Effects of dexmedetomidne, a selective a2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther.1989;46(10:33-42
33. Talke P, Richardson CA, Scheinin M, et al. Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth. Analg. 1997;85(5):1136-42
34. MacMillan LB, Hein L, Smith M, et al. Central hypotensive effects of the alpha2 adrenergic receptor subtype. Science. 1996;273:801-3
35. Ebert T, Hall JE, Barney JA, et al. The effects of increasing plasma concentrations of dexmedetomdine in humans. Anesthesiology. 2000;93:382-94
36. Sulaiman S, Karthekeyan RB, Vakamudi M, et al. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Ann Card Anaesth. 2012;15:39-43
37. Kunisawa T, Ueno M, Kurosawa A, et al. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J Anesth. 2001;25:818-22
38. Yildiz M, Tavlan A, Tuncer S, et al. Effect of dexmedetomidine on hemodynamic responses to laryngoscopy and intubation: perioperative haemodynamics and anaesthetic requirements. Drugs R D. 2006;7:43-52
39. Tsaousi G, Lamperti M, Bilota F. Role of Dexmedetomidine for Sedation in Neurocritical Care Patients: A Qualitative Systematic Review and Meta-analysis of Current Evidence. Clin Neuropharm 2016;39:144-151
40. Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW (2005) Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 9:R375-R381
41. Shehabi Y, Ruettimann U, Adamson H, Innes R, Ickeringill m. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004;30:2188-96.doi:10.1007/s00134-004-2417-z
42. Marek A. Mirski et al. Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: The Acute Neurological ICU Sedation Trial (ANIST) (doi:10.1007/s00134-010-1874-9).
43. Reade MC, Eastwood GM, Bellomo R et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315:1460-1468
44. Srivastrava VK, Agrawal S, Kumar S, et al. Comparison of dexmedetomidine, propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients. J. Clin Diagn Res. 2014;8:GC04-GC07
45. Erdman MJ, Doepker BA, Gerlach AT. et al. A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. Crit Care Med. 2014;42:1696-1702
46. Zhao LH, Shi ZH, Chen GQ, et al. Use of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy; a randomized controlled trial. J. Neurosurg Anesthesiol. 2017;29:132-139
47. Edgcombe H, Carter K, Yarrow S 92008). Anesthesia in the prone position. Br J anaesth 100:165-183
48. Willner D, Spennativ V, Stohl S, Tosti G, Aloisio S, Bilotta F (2016) Spine surgery and blood loss: systematic review of clinical evidence. Anesth Analg 123:1307-1315
49. Sharma S, Balireddy RK, Vorenkamp KE, Durieux ME. Beyond opioid patient-controlled analgesia: a systematic review of of analgesia after major spine surgery. Reg Anesth Pain Med 2012;37:79-98
50. Sekimoto K, Nishikawa K, Ishizeki J, Kubo K, Sato S, Goto F. 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 2006;18:106-111
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2. Ong B, Wilson JR, Henzel MK. Management of the Patient with Chronic Spinal Cord Injury. 2019, doi:10.1016/j.mcna.2019.1006
3. Naaz S.C. Dexmedetomidine in Current Anaesthesia Practice. A Review Journal of Clinical and Diagnostic Research 2014, doi:10.7860/JCDR/2014/9624.4946
4. Panzer O, Moitra V, Sladen RN. Pharmacology of sedative analgesic agents:dexmedetomidine, remifentanyl, ketamine,volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol.Clin. 2011;29(4):587-605
5. European Medicines Agency. Dexmedetomidine: assessment report. 2011.http//www ema.europa.eu/ Assessed 4 May 2015
6. US Food and Drug Administration. Precedex label. Available from:http//www.accessdata.fda.gov/drugsafda_docs/label/1999/21038lbl. Accessed 14 Nov 2016
7. European Medicines Agency. European Public Assessment Report. 2016. Availablefrom:http//www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/002268/WC500115631.pdf.Accessed 14 Nov. 2016
8. Weerink MS, Strugs RF, Hannivoort LN. Barends A.R. Absalom P. Colin, Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine, Clin. Pharmacokinetic 2017; 56:893-913
9. H. Yoo, T. Lirola, S. Vilo, T. Manner, R. Aantaa, M. Lahtinen, M. Scheinin, K.T. Olkkola, W.J. Jusco. Mechanism-based population pharmacokinetic and pharmacodynamics modeling of intravenous and intranasal dexmedetomidine in healthy subjects,Eur. J. Clin. Pharmacol. 2015;71:1197-1207
10. A.H.W. Tse, L. Ling, A. Lee, G.M. Joyut, Altered pharmacokinetics in prolonged infusions of sedatives and analgesics among adult critically ill patients: a systematic review, Clin.Ther. 2018;40:1598-1615,e2.
11. T. Lirola, H. Ihmsen, R. Laitio, E. Kentala, R. Aantaa, J.P. Kurvinen, M. Scheinin, H. Schwilden, J. Schttler, K.T. Olkkola, Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients, Br. J. Anaesth. 2012;108:460-468
12. P.A. Valitalo, T. Ahtola-Satila, A. Wighton, T. Sarapohja, P. Pohjanjousi, C. Garratt, Population pharmacokinetics of dexmedetomidine in critically ill patients, Clin. Drug Investig. 2013;33:579-587
13. T. Lirola, R. Aantaa, R. Laitio, E. Kentala, M. Lahtinen, A. Wighton, C. Garratt, T. Ahtola-Satila, K.T. Olkkola, Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients. Crit.Care 2011:15
14. P.Talke, B.J.Anderson, Pharmacokinetics and pharmacodynamics of dexmedetimidine-indused vasoconstriction in healthy volunteers, Br. J. Clin. Pharmacol. 2018;84:1364-1372
15. Abbott Laboratories, Precedex Approval documents, 2019
16. S. Kaivosaari, P.Toivonen, O. aitio, I. Sipila, M. Kskinen, J.S. Salonen, M. Finel, Regio- and stereospecific N-glucoronidation of medetimidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2BI0 account for the complex kinetics of human liver microsomes, Drug Metab. Dispos. 2008;36:1529-1537
A. Rlle, S. Paredes, L.I. Cortinez, B.J. Anderson, N. Quezada, S. Slari, F. Allende, J. Torres, D. Cabrera, V. Conteras, J. Cawona, C. Ramirez, A.M. Olivera, M. Ibacache, Dexmedetomidine metabolic clearance is not affected by fatmass in obese patients, Br. J. anaesth. 12092018)969-977
17. Trauma: Spinal Cord Injury. Matthew J,Eckert et al. Surg Clin North Am. 2017 Oct;97(5):1031-1045 doi:10.1016/j.suc.2017.06.008
18. Gulsah Karatas, Neslihan Metli, Mufit Akyuz,et al. Sz 2020 Jan 30;73(1-2):27-34 doi:10.18071/isz.73.0027
19. Ong B, Wilson I.R, Henzel M.K (2019). Management of the patient with Chronic Spinal Cord Injury. Medical Clinics of North America. doi: 10.1016/j.mcna.2019.10.006
20. Belleville JP, Ward DS, Bloor BC, et al. Effects of intravenous dexmedetomidine in humans.I.Sedation, ventilatin, and metabolic rate. Anaesthesiology. 1992;77(0)1125-33
21. Ebert TJ, Hall JE, Barney JA, et al. The effects of increasing plasma concentration of dexmedetomidine in humans. Anesthesiology. 2020;939(2):382-94
22. Hsu Y-W, Cortinez LI, Robertson KM, et al. Dexmedetomidine pharmacodynamics; part I. Crossover comparison of the respiratory effects of dexmedetomidine and remifentanyl in healthy volunteers. Anesthesiology 2004;(5):1066-76
23. Hall JC, Uhrich TD, Barney JA, et al. Sedative, amnestic and analgesic properties of small-dose dexmedetomidine infusions. Anesth. Analg. 2000;90(3):699:705
24. Shehabi Y, Ruettimann U, Adamson H, et al. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004;30(12);2188-96
25. Venn RM, Grounds RM. Comparison between Dexmedetomidine and propofol for sedation in the intensive care unit, patient and clinician perceptions. Br. J. Anaesth. 2001;87(5):684-90
26. Triltsch AE, Welte M. von Homeger P, et al. Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double-blinded, placebo-controlled phase II study. Crit. Care Med. 2002;30(5):1007-14
27. Venn RM, Newman PJ, Grounds RM. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. 2003;29(2):201-7
28. Nelson LE, Lu J, Guo T, et al. The a2-adrenoreceptor agonist dexmedetomidine conveges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003;98(2):428-36
29. Huupponen E, Maksimow A, Lapinlampi P, et al. Electroencephalogram Spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol. Scand.2008;52(2):289-94
30. Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanyl, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol. Clin. 2011;29(4):587-605
31. Bloor BC, Ward DS, Belleville JP, et al. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesilogy. 1992;77(6):1134-42
32. Kallio A, Scheinin M, Koulu M, et al. Effects of dexmedetomidne, a selective a2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther.1989;46(10:33-42
33. Talke P, Richardson CA, Scheinin M, et al. Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth. Analg. 1997;85(5):1136-42
34. MacMillan LB, Hein L, Smith M, et al. Central hypotensive effects of the alpha2 adrenergic receptor subtype. Science. 1996;273:801-3
35. Ebert T, Hall JE, Barney JA, et al. The effects of increasing plasma concentrations of dexmedetomdine in humans. Anesthesiology. 2000;93:382-94
36. Sulaiman S, Karthekeyan RB, Vakamudi M, et al. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Ann Card Anaesth. 2012;15:39-43
37. Kunisawa T, Ueno M, Kurosawa A, et al. Dexmedetomidine can stabilize hemodynamics and spare anesthetics before cardiopulmonary bypass. J Anesth. 2001;25:818-22
38. Yildiz M, Tavlan A, Tuncer S, et al. Effect of dexmedetomidine on hemodynamic responses to laryngoscopy and intubation: perioperative haemodynamics and anaesthetic requirements. Drugs R D. 2006;7:43-52
39. Tsaousi G, Lamperti M, Bilota F. Role of Dexmedetomidine for Sedation in Neurocritical Care Patients: A Qualitative Systematic Review and Meta-analysis of Current Evidence. Clin Neuropharm 2016;39:144-151
40. Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW (2005) Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 9:R375-R381
41. Shehabi Y, Ruettimann U, Adamson H, Innes R, Ickeringill m. Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med. 2004;30:2188-96.doi:10.1007/s00134-004-2417-z
42. Marek A. Mirski et al. Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: The Acute Neurological ICU Sedation Trial (ANIST) (doi:10.1007/s00134-010-1874-9).
43. Reade MC, Eastwood GM, Bellomo R et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315:1460-1468
44. Srivastrava VK, Agrawal S, Kumar S, et al. Comparison of dexmedetomidine, propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients. J. Clin Diagn Res. 2014;8:GC04-GC07
45. Erdman MJ, Doepker BA, Gerlach AT. et al. A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. Crit Care Med. 2014;42:1696-1702
46. Zhao LH, Shi ZH, Chen GQ, et al. Use of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy; a randomized controlled trial. J. Neurosurg Anesthesiol. 2017;29:132-139
47. Edgcombe H, Carter K, Yarrow S 92008). Anesthesia in the prone position. Br J anaesth 100:165-183
48. Willner D, Spennativ V, Stohl S, Tosti G, Aloisio S, Bilotta F (2016) Spine surgery and blood loss: systematic review of clinical evidence. Anesth Analg 123:1307-1315
49. Sharma S, Balireddy RK, Vorenkamp KE, Durieux ME. Beyond opioid patient-controlled analgesia: a systematic review of of analgesia after major spine surgery. Reg Anesth Pain Med 2012;37:79-98
50. Sekimoto K, Nishikawa K, Ishizeki J, Kubo K, Sato S, Goto F. 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 2006;18:106-111
51. Mathiesen O, Dahl B, Thomsen BA, Kitter B, Sonne N, Dahl JB, Kehlet H. A comprehensive multimodal pain treatment reduses opioid consumption after multilevel spine surgery. Eur Spine J 2013;22;2089-2096
52. Deinsberger W, Christophis P, Jodicke A, Iteesen M, Boker DK, Somatosensory evoked potential monitoring during positioning of the patient for posterior fossa surgery in the semisitting position. Neurosurgery 1998;43:36-40
53. Ofiram E, Lonstein JE, Skinner S, Perra JH. The disappearing evoked potentials; a special problem of positioning patients with skeletal dysplasia. Spine 2006;31;E464-70
54. Lorenzini NA, Poterack KA. Somatosensory evoked potentials are not a sensitive indicator of potential positioning injury in the prone patient. Journal of Clinical Monitoring and Computing 1996;12:171-6
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