Effects of isoflurane with and without dexmedetomidine or remifentanil on heart rate variability before and after nociceptive stimulation at different multiples of minimum alveolar concentration in dogs

Anne M. Voigt Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, D–30559 Hannover, Germany.

Search for other papers by Anne M. Voigt in
Current site
Google Scholar
PubMed
Close
 DVM, Dr med vet
,
Carina Bergfeld Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, D–30559 Hannover, Germany.

Search for other papers by Carina Bergfeld in
Current site
Google Scholar
PubMed
Close
 DVM, Dr med vet
,
Martin Beyerbach Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Bünteweg 2, D–30559 Hannover, Germany.

Search for other papers by Martin Beyerbach in
Current site
Google Scholar
PubMed
Close
 Dipl-Ing agr, Dr rer hort
, and
Sabine B. R. Kästner Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, D–30559 Hannover, Germany.
Center for Systems Neuroscience Hannover, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, D–30559 Hannover, Germany.

Search for other papers by Sabine B. R. Kästner in
Current site
Google Scholar
PubMed
Close
 DVM, Prof Dr med vet

Abstract

Objective—To evaluate the influence of 3 anesthetic protocols and multiples of minimum alveolar concentration (MAC) on heart rate variability (HRV) with and without nociceptive stimulation in dogs.

Animals—6 healthy adult Beagles.

Procedures—Each dog was anesthetized 3 times: with isoflurane alone, with isoflurane and a constant rate infusion of dexmedetomidine (IsoD; 3 μg/kg/h, IV), and with isoflurane and a constant rate infusion of remifentanil (IsoR; 18 μg/kg/h, IV). Individual MAC was determined via supramaximal electrical stimulation. Sinus rhythm–derived intervals between 2 adjacent R-R intervals were exported from ECG recordings. Selected HRV time and frequency domain variables were obtained (at 2-minute intervals) and analyzed offline with signed rank tests before and after stimulation at 0.75, 1.0, and 1. 5 MAC for each anesthetic session.

Results—The isoflurane session had the overall lowest prestimulation SDNN (SD of all R-R intervals) values. Prestimulation SDNN values decreased significantly with increasing MAC in all sessions. For the IsoD session, SDNN (milliseconds) or high-frequency power (milliseconds2) was inversely correlated with MAC (Spearman rank correlation coefficient for both variables, −0.77). In the isoflurane and IsoR sessions, heart rate increased significantly after stimulation. In the IsoD session, poststimulation SDNN was increased significantly, compared with prestimulation values, at 0.75 and 1.0 MAC.

Conclusions and Clinical Relevance—On the basis of SDNN and high-frequency power values, anesthetic levels between 0.75 and 1.5 MAC within the same anesthetic protocol could be differentiated, but with a large overlap among protocols. Usefulness of standard HRV variables for assessment of anesthetic depth and nociception in dogs is questionable.

Abstract

Objective—To evaluate the influence of 3 anesthetic protocols and multiples of minimum alveolar concentration (MAC) on heart rate variability (HRV) with and without nociceptive stimulation in dogs.

Animals—6 healthy adult Beagles.

Procedures—Each dog was anesthetized 3 times: with isoflurane alone, with isoflurane and a constant rate infusion of dexmedetomidine (IsoD; 3 μg/kg/h, IV), and with isoflurane and a constant rate infusion of remifentanil (IsoR; 18 μg/kg/h, IV). Individual MAC was determined via supramaximal electrical stimulation. Sinus rhythm–derived intervals between 2 adjacent R-R intervals were exported from ECG recordings. Selected HRV time and frequency domain variables were obtained (at 2-minute intervals) and analyzed offline with signed rank tests before and after stimulation at 0.75, 1.0, and 1. 5 MAC for each anesthetic session.

Results—The isoflurane session had the overall lowest prestimulation SDNN (SD of all R-R intervals) values. Prestimulation SDNN values decreased significantly with increasing MAC in all sessions. For the IsoD session, SDNN (milliseconds) or high-frequency power (milliseconds2) was inversely correlated with MAC (Spearman rank correlation coefficient for both variables, −0.77). In the isoflurane and IsoR sessions, heart rate increased significantly after stimulation. In the IsoD session, poststimulation SDNN was increased significantly, compared with prestimulation values, at 0.75 and 1.0 MAC.

Conclusions and Clinical Relevance—On the basis of SDNN and high-frequency power values, anesthetic levels between 0.75 and 1.5 MAC within the same anesthetic protocol could be differentiated, but with a large overlap among protocols. Usefulness of standard HRV variables for assessment of anesthetic depth and nociception in dogs is questionable.

Contributor Notes

Dr. Voigt's present address is Kleintierklinik Hannover, Hildesheimer Str. 386, 30161 Hannover, Germany.

This manuscript represents a portion of a dissertation submitted by Dr. Voigt to the University of Veterinary Medicine Hannover, Germany, as partial fulfillment of the requirements for a Dr med vet degree.

Dr. Voigt was supported by a scholarship from Cusanuswerk.

Presented in abstract form at the Association of Veterinary Anaesthetists Autumn Meeting, Santorini, Greece, September 2010.

Address correspondence to Dr. Voigt (anne_voigt@gmx.de).
  • 1. Haskins SC. Monitoring anesthetized patients. In: Tranquilli WJ, Thurmon JC, Grimm KA, eds. Lumb & Jones' veterinary anesthesia and analgesia. 4th ed. Ames, Iowa: Blackwell Publishing, 2007;533558.

    • Search Google Scholar
    • Export Citation
  • 2. Pumprla J, Howorka K, Groves D, et al. Functional assessment of heart rate variability: physiological basis and practical applications. Int J Cardiol 2002; 84:114.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Huang HH, Lee YH, Chan HL, et al. Using a short-term parameter of heart rate variability to distinguish awake from isoflurane anesthetic states. Med Biol Eng Comput 2008; 46:977984.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 1996; 93:10431065.

    • Search Google Scholar
    • Export Citation
  • 5. Rasmussen CE, Falk T, Zois NE, et al. Heart rate, heart rate variability, and arrhythmias in dogs with myxomatous mitral valve disease. J Vet Intern Med 2012; 26:7684.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 1986; 59:178193.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Motte S, Mathieu M, Brimioulle S, et al. Respiratory-related heart rate variability in progressive experimental heart failure. Am J Physiol Heart Circ Physiol 2005; 289:H1729H1735.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Doxey S, Boswood A. Differences between breeds of dog in a measure of heart rate variability. Vet Rec 2004; 154:713717.

  • 9. Rietmann TR, Stauffacher M, Bernasconi P, et al. The association between heart rate, heart rate variability, endocrine and behavioural pain measures in horses suffering from laminitis. J Vet Med A Physiol Pathol Clin Med 2004; 51:218225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Kato M, Komatsu T, Kimura T, et al. Spectral analysis of heart rate variability during isoflurane anesthesia. Anesthesiology 1992; 77:669674.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Kanaya N, Hirata N, Kurosawa S, et al. Differential effects of propofol and sevoflurane on heart rate variability. Anesthesiology 2003; 98:3440.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Luginbühl M, Ypparila-Wolters H, Rüfenacht M, et al. Heart rate variability does not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia. Br J Anaesth 2007; 98:728736.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Nishiyama T. Recent advance in patient monitoring. Korean J Anesthesiol 2010; 59:144159.

  • 14. Pascoe PJ, Raekallio M, Kuusela E, et al. Changes in the minimum alveolar concentration of isoflurane and some cardiopulmonary measurements during three continuous infusion rates of dexmedetomidine in dogs. Vet Anaesth Analg 2006; 33:97103.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Valverde A, Morey TE, Hernández J, et al. Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits. Am J Vet Res 2003; 64:957962.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Quasha AL, Eger EI II, Tinker JH. Determination and applications of MAC. Anesthesiology 1980; 53:315334.

  • 17. Campagnol D, Teixeira Neto FJ, Giordano T, et al. Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs. Am J Vet Res 2007; 68:13081318.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Sonner JM. Issues in the design and interpretation of minimum alveolar anesthetic concentration (MAC) studies. Anesth Analg 2002; 95:609614.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Matsunaga T, Harada T, Mitsui T, et al. Spectral analysis of circadian rhythms in heart rate variability of dogs. Am J Vet Res 2001; 62:3742.

  • 20. Kuusela E, Raekallio M, Anttila M, et al. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. J Vet Pharmacol Ther 2000; 23:1520.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Link RE, Desai K, Hein L, et al. Cardiovascular regulation in mice lacking alpha-2 adrenergic receptor subtypes b and c. Science 1996; 273:803805.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Bol CJ, Vogelaar JP, Mandema JW. Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats. J Pharmacol Exp Ther 1999; 291:153160.

    • Search Google Scholar
    • Export Citation
  • 23. Schwinn DA, McIntyre RW, Reves JG. Isoflurane-induced vasodilation: role of the alpha-adrenergic nervous system. Anesth Analg 1990;71:451459.

    • Search Google Scholar
    • Export Citation
  • 24. Eger EI II. The pharmacology of isoflurane. Br J Anaesth 1984; 56 (suppl 1):71S99S.

  • 25. Seagard JL, Hopp FA, Bosnjak ZJ, et al. Sympathetic efferent nerve activity in conscious and isoflurane-anesthetized dogs. Anesthesiology 1984; 61:266270.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Skovsted P, Sapthavichaikul S. The effects of isoflurane on arterial pressure, pulse rate, autonomic nervous activity, and barostatic reflexes. Can Anaesth Soc J 1977; 24:304314.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. James MK, Vuong A, Grizzle MK, et al. Hemodynamic effects of GI 87084B, an ultra-short acting mu-opioid analgesic, in anesthetized dogs. J Pharmacol Exp Ther 1992; 263:8491.

    • Search Google Scholar
    • Export Citation
  • 28. Toweill DL, Kovarik WD, Carr R, et al. Linear and nonlinear analysis of heart rate variability during propofol anesthesia for short-duration procedures in children. Pediatr Crit Care Med 2003; 4:308314.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1965; 26:756763.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Lang E, Kapila A, Shlugman D, et al. Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 1996; 85:721728.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Savola MK, Woodley SJ, Maze M, et al. Isoflurane and an alpha 2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord. Anesthesiology 1991; 75:489498.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Correa-Sales C, Rabin BC, Maze M, et al. A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology 1992; 76:948952.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Carpenter RL, Eger EI II, Johnson BH, et al. The extent of metabolism of inhaled anesthetics in humans. Anesthesiology 1986; 65:201205.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Kapila A, Glass PS, Jacobs JR, et al. Measured context-sensitive half-times of remifentanil and alfentanil. Anesthesiology 1995; 83:968975.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Hoke JF, Cunningham F, James MK, et al. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther 1997; 281:226232.

    • Search Google Scholar
    • Export Citation
  • 36. Olsen LH, Mow T, Koch J, et al. Heart rate variability in young, clinically healthy Dachshunds: influence of sex, mitral valve prolapsed status, sampling period and time of day. J Vet Cardiol 1999; 1:716.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Seely AJ, Macklem PT. Complex systems and the technology of variability analysis. Crit Care 2004; 8:R367R384.

  • 38. Montano N, Porta A, Cogliati C, et al. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. Neurosci Biobehav Rev 2009; 33:7180.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39. Huang HH, Chan HL, Lin PL, et al. Time-frequency spectral analysis of heart rate variability during induction of general anaesthesia. Br J Anaesth 1997; 79:754758.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Boardman A, Schlindwein FS, Rocha AP, et al. A study on the optimum order of autoregressive models for heart rate variability. Physiol Meas 2002; 23:325336.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41. Akselrod S, Gordon D, Ubel FA, et al. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981; 213:220222.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement