The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The Effect of a Target Controlled Infusion of Low-Concentration Ketamine on the Heart Rate Variability of Normal Volunteers

정상인 자원자에서 목표농도조절주입법으로 투여한 저농도의 케타민이 심장박동수변이도에 미치는 영향

  • Jung, Jai Yun (Department of Anesthesiology and Pain Medicine, Sanbon Hospital, College of Medicine, Wonkwang University) ;
  • Lee, Jun Ho (Department of Anesthesiology and Pain Medicine, Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Lee, Jeong Seok (Department of Anesthesiology and Pain Medicine, Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Kim, Yong Ik (Department of Anesthesiology and Pain Medicine, Bucheon Hospital, Soonchunhyang University College of Medicine)
  • 정재윤 (원광대학교 의과대학 산본병원 마취통증의학교실) ;
  • 이준호 (순천향대학교 의과대학 부천병원 마취통증의학교실) ;
  • 이정석 (순천향대학교 의과대학 부천병원 마취통증의학교실) ;
  • 김용익 (순천향대학교 의과대학 부천병원 마취통증의학교실)
  • Received : 2009.01.04
  • Accepted : 2009.02.04
  • Published : 2009.04.01
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Abstract

Background: Ketamine has an indirect sympathetic stimulation effect. We investigated heart rate variability (HRV) as a marker of cardiac autonomic function after a target controlled infusion (TCI) of ketamine with a plasma concentration of 30 or 60 ng/ml. Methods: In 20 adult volunteers, the mean of the R wave to the adjacent R wave interval (RRI), the range of RRI, the root mean square successive difference of intervals (RMSSD), the total power, the low frequency (LF, 0.04-0.15 Hz) power, the high frequency (HF, 0.15-0.4 Hz) power, the normal unit HF (nuHF), the normal unit LF (nuLF), the LF/HF ratio and the SD1 and the SD2 in the Poincare plot were measured before and after a TCI of ketamine. We observed for any psychedelic symptoms or sedation. Results: There were no differences in the mean and range of the RRI, RMSSD, total power, LF power, HF power, nuHF, nuLF, LF/HF ratio, SD1 and SD2 between before and after ketamine administration. The OAA/S score was higher and there were more psychedelic symptoms with a 60 ng/ml plasma concentration than with a 30 ng/ml plasma concentration. Conclusions: This study did not show any effect of a low plasma concentration of ketamine on the autonomic nervous system.

Keywords

Acknowledgement

Supported by : 원광대학교

References

  1. Baughman VL: Brain protection during neurosurgery. Anesthesiol Clin North America 2002; 20: 315-27 https://doi.org/10.1016/S0889-8537(01)00004-9
  2. Soliman MG, Brindle GF, Kuster G: Response to hypercapnia under ketamine anaesthesia. Can Anaesth Soc J 1975; 22: 486-94 https://doi.org/10.1007/BF03004864
  3. Bevan RK, Rose MA, Duggan KA: Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors. Clin Exp Pharmacol Physiol 1997; 24: 923-6 https://doi.org/10.1111/j.1440-1681.1997.tb02720.x
  4. Barash PG, Cullen BF, Stoelting RK: Clinical anesthesia. 5th ed. Lippincott Williams & Wilkins. 2006, p 345
  5. Harris J, Joules C, Stanley C, Thomas P, Clarke RW:Glutamate and tachykinin receptors in central sensitization of withdrawal reflexes in the decerebrated rabbit. Exp Physiol 2004; 89: 187-98 https://doi.org/10.1113/expphysiol.2003.002646
  6. Ishikawa T, Nakanishi O, Funatsu N, Kameyama H: Nerve growth factor inducer, 4-methyl catechol, potentiates central sensitization associated with acceleration of spinal glutamate release after mustard oil paw injection in rats. Cell Mol Neurobiol 1999; 19: 587-96 https://doi.org/10.1023/A:1006928317312
  7. Neugebauer V, Chen PS, Willis WD: Role of metabotropic glutamate receptor subtype mGluR1 in brief nociception and central sensitization of primate STT cells. J Neurophysiol 1999; 82: 272-82 https://doi.org/10.1152/jn.1999.82.1.272
  8. Warncke T, Stubhaug A, J$\phi$rum E: Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo. Pain 1997; 72: 99-106 https://doi.org/10.1016/S0304-3959(97)00006-7
  9. Chizh BA: Low dose ketamine: a therapeutic and research tool to explore N-methyl-D-aspartate (NMDA) receptormediated plasticity in pain pathways. J Psychopharmacol 2007; 21: 259-71 https://doi.org/10.1177/0269881105062484
  10. Schmid RL, Sandler AN, Katz J: Use and efficacy of lowdose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999; 82: 111-25 https://doi.org/10.1016/S0304-3959(99)00044-5
  11. Webster LR, Walker MJ: Safety and efficacy of prolonged outpatient ketamine infusions for neuropathic pain. Am J Ther 2006; 13: 300-5 https://doi.org/10.1097/00045391-200607000-00004
  12. Benrath J, Scharbert G, Gustorff B, Adams HA, Kress HG: Long-term intrathecal S(＋)-ketamine in a patient with cancer-related neuropathic pain. Br J Anaesth 2005; 95: 247-9 https://doi.org/10.1093/bja/aei158
  13. Vranken JH, van der Vegt MH, Kal JE, Kruis MR: Treatment of neuropathic cancer pain with continuous intrathecal administration of S-ketamine. Acta Anaesthesiol Scand 2004; 48: 249-52 https://doi.org/10.1111/j.0001-5172.2004.00284.x
  14. Kvarnstr$\ddot{o}$m A, Karlsten R, Quiding H, Emanuelsson BM, Gordh T: The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand 2003; 47: 868-77 https://doi.org/10.1034/j.1399-6576.2003.00187.x
  15. Lee TS, Hou X: Vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Chest 1995; 107: 1152-5 https://doi.org/10.1378/chest.107.4.1152
  16. White PF, Way WL, Trevor AJ: Ketamine-its pharmacology and therapeutic uses. Anesthesiology 1982; 56: 119-36 https://doi.org/10.1097/00000542-198202000-00007
  17. Komatsu T, Singh PK, Kimura T, Nishiwaki K, Bando K, Shimada Y: Differential effects of ketamine and midazolam on heart rate variability. Can J Anaesth 1995; 42: 1003-9 https://doi.org/10.1007/BF03011073
  18. JR, Domino KE, et al: Ketamine kinetics in unmedicated and diazepam-premedicated subjects. Clin Pharmacol Ther 1984; 36: 645-53 https://doi.org/10.1038/clpt.1984.235
  19. Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, et al: Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244-51
  20. Bowdle TA, Radant AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne PP: Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology 1998; 88: 82-8 https://doi.org/10.1097/00000542-199801000-00015
  21. Anis NA, Berry SC, Burton NR, Lodge D: The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methylaspartate. Br J Pharmacol 1983; 79: 565-75 https://doi.org/10.1111/j.1476-5381.1983.tb11031.x
  22. Lodge D, Anis NA, Burton NR: Effects of optical isomers of ketamine on excitation of cat and rat spinal neurones by amino acids and acetylcholine. Neurosci Lett 1982; 29:281-6 https://doi.org/10.1016/0304-3940(82)90330-5
  23. Zukin SR, Fitz-Syage ML, Nichtenhauser R, Zukin RS: Specific binding of [3H]phencyclidine in rat central nervous tissue: further characterization and technical considerations. Brain Res 1983; 258: 277-84 https://doi.org/10.1016/0006-8993(83)91151-4
  24. MacDonald JF, Bartlett MC, Mody I, Pahapill P, Reynolds JN, Salter MW, et al: Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones. J Physiol 1991; 432: 483-508 https://doi.org/10.1113/jphysiol.1991.sp018396
  25. MacDonald JF, Miljkovic Z, Pennefather P: Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J Neurophysiol 1987; 58: 251-66 https://doi.org/10.1152/jn.1987.58.2.251
  26. Durieux ME: Inhibition by ketamine of muscarinic acetylcholine receptor function. Anesth Analg 1995; 81: 57-62 https://doi.org/10.1097/00000539-199507000-00012
  27. Sarton E, Teppema LJ, Olievier C, Nieuwenhuijs D, Matthes HW, Kieffer BL, et al: The involvement of the mu-opioid receptor in ketamine-induced respiratory depression and antinociception. Anesth Analg 2001; 93: 1495-500 https://doi.org/10.1097/00000539-200112000-00031
  28. Goodchild CS: Nonopioid spinal analgesics: animal experimentation and implications for clinical developments. Pain Rev 1997; 4: 33-58
  29. Spotoft H, Korshin JD, Sorensen MB, Skovsted P: The cardiovascular effects of ketamine used for induction of anaesthesia in patients with valvular heart disease. Can Anaesth Soc J 1979; 26: 463-7 https://doi.org/10.1007/BF03006157
  30. Byrne AJ, Tomlinson DR, Healy TE: Ketamine and sympathetic mechanisms in cardiac and smooth muscle. Acta Anaesthesiol Scand 1982; 26: 479-84 https://doi.org/10.1111/j.1399-6576.1982.tb01803.x
  31. Lundy P, Colhoun EH, Gowdey CW: Pressor responses of ketamine and circulating biogenic amines. Nat New Biol 1973; 241: 80-2
  32. Rajendra Acharya U, Paul Joseph K, Kannathal N, Lim CM, Suri JS: Heart rate variability: a review. Med Biol Eng Comput 2006; 44: 1031-51 https://doi.org/10.1007/s11517-006-0119-0
  33. Guyton AC, Hall JE: Textbook of medical physiology. 11th ed. Philadelphia, Elsevier Inc. 2006, p 755
  34. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, et al: Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199-214 https://doi.org/10.1001/archpsyc.1994.03950030035004
  35. Tucker AP, Kim YI, Nadeson R, Goodchild CS: Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain [ISRCTN83088383]. BMC Anesthesiol 2005; 5: 2 https://doi.org/10.1186/1471-2253-5-2
  36. Wasner G, Schattschneider J, Baron R: Skin temperature side differences--a diagnostic tool for CRPS? Pain 2002; 98:19-26 https://doi.org/10.1016/S0304-3959(01)00470-5