The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study
The genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine.
A total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4 μg.mL-1 was infused at a dose of 2 μg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]).
A total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p > 0.217), bispectral index at mRSS 4 (p > 0.620), and time to obtain mRSS 4 (p > 0.349).
This study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.
1 J.P. Belleville, D.S. Ward, B.C. Bloor, et al. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate Anesthesiology., 77 (1992), pp. 1125-1133
2 J.E. Hall, T.D. Uhrich, J.A. Barney, et al. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions Anesth Analg., 90 (2000), pp. 699-705
3 M.A.S. Weerink, M. Struys, L.N. Hannivoort, et al. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine Clin Pharmacokinet., 56 (2017), pp. 893-913
4 S. Yagar, S. Yavas, B. Karahalil The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery Mol Biol Rep., 38 (2011), pp. 3383-3389
5 A. Sigurdsson, P. Held, K. Swedberg Short- and long-term neurohormonal activation following acute myocardial infarction Am Heart J., 126 (1993), pp. 1068-1076
6 D. Kurnik, M. Muszkat, C. Li, et al. Genetic variations in the α(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine Circ Cardiovasc Genet., 4 (2011), pp. 179-187
7 T.J. Ebert, J.E. Hall, J.A. Barney, et al. The effects of increasing plasma concentrations of dexmedetomidine in humans Anesthesiology., 93 (2000), pp. 382-394
8 S.M. Jakob, E. Ruokonen, R.M. Grounds, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials JAMA., 307 (2012), pp. 1151-1160
9 D.L. Herr, S.T. Sum-Ping, M. England ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens J Cardiothorac Vasc Anesth., 17 (2003), pp. 576-584
10 H. Turunen, S.M. Jakob, E. Ruokonen, et al. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation Crit Care., 19 (2015), p. 67
11 PL Smithburger, RB Smith, SL Kane-Gill, et al. Identification of patient predictors for dexmedetomidine effectiveness for ICU sedation Am J Crit Care, 23 (2014), p. 160
12 B.R. Tellor, H.M. Arnold, S.T. Micek, et al. Occurrence and predictors of dexmedetomidine infusion intolerance and failure Hosp Pract., 40 (2012), pp. 186-192
13 R.R. Riker, Y. Shehabi, P.M. Bokesch, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial JAMA., 301 (2009), pp. 489-499
14 UA Meyer Pharmacogenetics and adverse drug reactions Lancet., 356 (2000), pp. 1667-1671
15 L. Park, J.T. Nigg, I.D. Waldman, et al. Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD Mol Psychiatry., 10 (2005), pp. 572-580
16 J.C. Hunter, D.J. Fontana, L.R. Hedley, et al. Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice Br J Pharmacol., 122 (1997), pp. 1339-1344
17 JW Johansen Update on bispectral index monitoring Best Pract Res Clin Anaesthesiol., 20 (2006), pp. 81-99
18 L.E. Nelson, J. Lu, T. Guo, et al. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects Anesthesiology., 98 (2003), pp. 428-436
19 E. Huupponen, A. Maksimow, P. Lapinlampi, et al. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep Acta Anaesthesiol Scand., 52 (2008), pp. 289-294
20 M. Gill, S.M. Green, B. Krauss A study of the bispectral index monitor during procedural sedation and analgesia in the emergency department Ann Emerg Med., 41 (2003), pp. 234-241
21 Y. Kasuya, R. Govinda, S. Rauch, et al. The correlation between bispectral index and observational sedation scale in volunteers sedated with dexmedetomidine and propofol Anesth Analg., 109 (2009), pp. 1811-1815
22 C.S. Weaver, W.H. Hauter, C.E. Duncan, et al. An assessment of the association of bispectral index with 2 clinical sedation scales for monitoring depth of procedural sedation Am J Emerg Med., 25 (2007), pp. 918-924