FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Equine Vet J / The effects of flumazenil on ventilatory and recovery charac...
Equine veterinary journal2020; 53(6); 1257-1267; doi: 10.1111/evj.13391

The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia.

Abstract: Flumazenil antagonises the actions of benzodiazepines. There has been no prior research specifically investigating this anaesthetic reversal agent for horses. Objective: To determine the effects of flumazenil administration in horses on (a) ventilatory parameters after midazolam-ketamine induction and maintenance with isoflurane in oxygen and on (b) the characteristics of recovery from general anaesthesia. Methods: Blinded, randomised, crossover experiment. Methods: Six horses were randomly assigned to receive high-dose flumazenil (F , 20 µg/kg), low-dose flumazenil (F , 10 µg/kg) and saline (control). Cardioventilatory parameters were monitored. After 90 minutes of isoflurane anaesthesia, a bolus of F , F or saline was administered i.v. The horses were recovered using head and tail rope assistance. The times to first movement, to achievement of sternal recumbency, to the first attempt to stand and the total recovery time were determined. The recovery quality was evaluated using a 115-point recovery scoring system. The cardioventilatory parameters and recovery times were analysed using mixed-effects regression analyses. Intraclass correlation (ICC) analysis was used to evaluate the recovery scores. A Mann-Whitney U test assessed the relationship between recovery score and flumazenil administration. Results: A significant difference with flumazenil administration was found for SpO , mean arterial pressure, I:E ratio, minute volume of ventilation (MV) and peak inspiratory pressure. There was a significant difference with flumazenil administration for the time to sternal recumbency, the time to the first attempt to rise and the total recovery time. There was no significant difference in total recovery score with flumazenil administration. Conclusions: Plasma levels of midazolam and flumazenil were not obtained. Conclusions: Flumazenil has a dose-dependent effect on MV and recovery time, which may make it useful in cases for which a prolonged anaesthetic recovery is undesirable.
© 2020 EVJ Ltd.
Get Full Text
Publication Date: 2020-12-17 PubMed ID: 33220066DOI: 10.1111/evj.13391Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the effects of the drug flumazenil on horses during and following anaesthesia. The study tested how the drug impacted ventilation during anaesthesia and the recovery period and process post-anaesthesia.

Study Design and Methodology

  • This research conducted a blinded, randomised, and crossover experiment on six horses. The experiment was designed to replicate real-world conditions as closely as possible.
  • Three experiment groups were created by administering different doses of flumazenil: a high-dose group with 20 µg/kg of flumazenil, a low-dose group with 10 µg/kg, and a control group that received saline.
  • After induction with midazolam-ketamine combined with isoflurane in oxygen, the chosen dose of flumazenil or saline was administered intravenously to the horses.
  • The horses were observed through recovery with rope assistance and monitored for multiple parameters including cardioventilatory characteristics, total recovery time, and various milestones during the recovery process.
  • The quality of recovery was evaluated using a 115-point recovery score system to give a quantified measure of the recovery process.
  • Statistical analyses were conducted on the collected data, including mixed-effects regression analyses, intraclass correlation analysis, and a Mann-Whitney U test.

Results and Observations

  • Several cardioventilatory parameters were significantly affected by flumazenil, including the horse’s oxygen saturation, mean arterial pressure, ventilation volume per minute, and peak inspiratory pressure. These measures differed between the group given flumazenil and the control group.
  • Important indicators of the recovery process, such as the time required to reach a sternal lying position from anaesthesia, the time to the first attempt to rise, and the total recovery time, were significantly different with flumazenil administration.
  • However, no significant difference was observed in the total recovery score with the administration of flumazenil. This indicator remained consistent across all groups.

Conclusions and Potential Applications

  • No measurements for the plasma level of midazolam or flumazenil were taken during this study, which may be considered for future research.
  • The study found a dose-dependent effect of flumazenil on the minute ventilation volume and recovery time in horses after anaesthesia. These findings suggest flumazenil could be beneficial in cases where a prolonged recovery from anaesthetic is undesirable.
  • This research provides valuable insights into the use of flumazenil in the field of veterinary anaesthesia, particularly for horses.

Cite This Article

APA
Douglas H, Hopster K, Cerullo M, Hopster-Iversen C, Stefanovski D, Driessen B. (2020). The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia. Equine Vet J, 53(6), 1257-1267. https://doi.org/10.1111/evj.13391

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 6
Pages: 1257-1267

Researcher Affiliations

Douglas, Hope
  • Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Hopster, Klaus
  • Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Cerullo, Michelle
  • Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Hopster-Iversen, Charlotte
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, Denmark.
Stefanovski, Darko
  • Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Driessen, Bernd
  • Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.

MeSH Terms

  • Anesthesia / veterinary
  • Anesthesia Recovery Period
  • Animals
  • Flumazenil / pharmacology
  • Horses
  • Isoflurane
  • Ketamine / pharmacology
  • Midazolam / pharmacology

Grant Funding

  • University of Pennsylvania Firestone Trust and Tamworth/Raker/Tulleners Research Fund

References

This article includes 42 references
  1. de Vries A, Thomson S, Taylor PM. Comparison of midazolam and diazepam as co-induction agents with ketamine for anaesthesia in sedated ponies undergoing field castration.. Vet Anaesth Analg 2015;42:512-7.
  2. Queiroz Neto A, Zamur G. Comparison of the sedative and antinociceptive effects of midazolam and diazepam in horses.. ARS Vet 2002;18:210-7.
  3. Shini S. A review of diazepam and its use in the horse.. J Equine Vet Sci 2000;20:443-9.
  4. Hubbell JAE, Kelly EM, Aarnes TK, Bednarski RM, Lerche P, Liu Z. Pharmacokinetics of midazolam after intravenous administration to horses.. Equine Vet J 2013;45:721-5.
  5. Muir WW, Sams RA, Huffman RH, Noonan JS. Pharmacodynamic and pharmacokinetic properties of diazepam in horses.. Am J Vet Res 1982;43:1756-62.
  6. Jarrett MA, Bailey KM, Messenger KM, Prange T, Gaines B, Posner LP. Recovery of horses from general anesthesia after induction with propofol and ketamine versus midazolam and ketamine.. J Am Vet Med Assoc 2018;253:101-7.
  7. Hoffman EJ, Warren EW. Flumazenil: a benzodiazepine antagonist.. Clin Pharm 1993;12:641-56.
  8. Vuyk J, Sitsen E, Reekers M. Intravenous anesthetics.. In: Miller RD, editor. Miller's anesthesia, 8th edn. Philadelphia, PA: Elsevier Inc.,; 2015; p. 821-863.
  9. Meyer RE, Fish RE. Pharmacology of injectable anesthetics, sedatives, and tranquilizers.. In: Fish RE, Brown MJ, Danneman PJ, Karas AZ, editors. Anesthesia and analgesia in laboratory animals, 2nd edn. London: Elsevier Inc., 2008; p. 27-82.
  10. Rankin D. Sedatives and tranquilizers.. In: Grimm KA, Lamont L, Tranquilli WJ, et al., editors. Veterinary anaesthesia and analgesia, 5th edn. Ames, IA: Wiley, 2015; p. 196-206.
  11. Artru AA. Flumazenil reversal of midazolam in dogs: dose-related changes in cerebral blood flow, metabolism, EEG, and CSF pressure.. J Neurosurg Anesthesiol 1989;1:46-55.
  12. Ilkiw JE, Farver TB, Suter C, Mcneal D, Steffey EP. The effect of intravenous administration of variable-dose flumazenil after fixed-dose ketamine and midazolam in healthy cats.. J Vet Pharmacol Ther 2002;25:181-8.
  13. Lee JY, Kim MC. Anesthesia of growing pigs with tiletamine-zolazepam and reversal with flumazenil.. J Vet Med Sci 2012;74:335-9.
  14. Heniff MS, Moore GP, Trout A, Cordell WH, Nelson DR. Comparison of routes of flumazenil administration to reverse midazolam-induced respiratory depression in a canine model.. Acad Emerg Med 1997;4:1115-8.
  15. Gross JB, Weller RS, Conard P. Flumazenil antagonism of midazolam-induced ventilatory depression.. Anesthesiology 1991;75:179-85.
  16. Ritter J, Hoshizaki G. Flumazenil antagonizes midazolam-induced respiratory rate depression.. Anesthesia Analg 1990;70:S324.
  17. Mora CT, Torjman M, White PF. Sedative and ventilatory effects of midazolam infusion: effect of flumazenil reversal.. Can J Anaesth 1995;42:677-84.
  18. Restall J, Johnston IG, Robinson DN. Flumazenil in ketamine and midazolam anaesthesia.. Anaesthesia 1990;45:938-40.
  19. Weinbroum AA, Geller E. Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia.. Can J Anesth 2001;48:963-72.
  20. Safavynia SA, Keating G, Speigel I, Fidler JA, Kreuzer M, Rye DB. Effects of γ-aminobutyric acid type A receptor modulation by flumazenil on emergence from general anesthesia.. Anesthesiology 2016;125:147-58.
  21. Shannon M, Albers G, Burkhart K, Liebelt E, Kelly M, McCubbin MM. Safety and efficacy of flumazenil in the reversal of benzodiazepine- induced conscious sedation.. J Pediatr 1997;131:582-6.
  22. Plumb D. Flumazenil.. In: Plumb’s veterinary drug handbook, 6th edn. Ames, IA: Blackwell Publishing Ltd, 2008; p. 396.
  23. Hopster K, Müller C, Hopster-Iversen C, Stahl J, Rohn K, Kästner S. Effects of dexmedetomidine and xylazine on cardiovascular function during total intravenous anaesthesia with midazolam and ketamine and recovery quality and duration in horses.. Vet Anaesth Analg 2014;41:25-35.
  24. Clark-Price SC, Posner LP, Gleed RD. Recovery of horses from general anesthesia in a darkened or illuminated recovery stall.. Vet Anaesth Analg 2008;35:473-9.
  25. Vettorato E, Chase-Topping ME, Clutton RE. A comparison of four systems for scoring recovery quality after general anaesthesia in horses.. Equine Vet J 2010;42:400-6.
  26. Platt JP, Simon BT, Coleman M, Martinez EA, Lepiz MA, Watts AE. The effects of multiple anaesthetic episodes on equine recovery quality.. Equine Vet J 2018;50:111-6.
  27. Nyman G, Hedenstierna G. Ventilation-perfusion relationships in the anaesthetised horse.. Equine Vet J 1989;21:274-81.
  28. Nakamura S, Ohno R, Satoshi M, Hitosugi N, Suzuki M, Nagasaka H. Flumazenil antagonizes respiratory depression caused by diazepam and induces expiratory excitation of hypoglossal nerve.. Masui 2002;51:1107-10.
  29. Roze H, Germain A, Perrier V, Dewitte A, Joannes-Boyau O, Fleureau C. Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome.. Br J Anaesth 2015;114:269-75.
  30. Gillis RA, Namath IJ, Easington C, Abrahams TP, Guidotti A, Quest JA. Drug interaction with gamma-aminobutyric acid/benzodiazepine receptors at the ventral surface of the medulla results in pronounced changes in cardiorespiratory activity.. J Pharmacol Exp Ther 1989;248:863-70.
  31. Flogel CM, Ward DS, Ritter JW, Wada DR. The effects of large-dose flumazenil on midazolam-induced ventilatory depression.. Anesth Analg 1993;77:1207-14.
  32. Forster A, Morel D, Bachmann M, Gemperle M. Respiratory depressant effects of different doses of midazolam and lack of reversal with naloxone: a double-blind randomized study.. Anesth Analg 1983;62:920-4.
  33. Petrenko AB, Baba H. A rising tide lifts all boats: increased ventilation may be involved in accelerated recovery from isoflurane anesthesia after flumazenil administration.. Anesthesiology 2017;126:351-2.
  34. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations.. Respir Med 2013;107:789-99.
  35. Geller E, Weinbrum A, Schiff B, Speiser Z, Nevo Y, Halpern P. The effects of flumazenil on the process of recovery from halothane anaesthesia.. Eur J Anaesthesiol Suppl 1988;2:151-3.
  36. Karakosta A, Andreotti B, Chapsa C, Pouliou A, Anastasiou E. Flumazenil expedites recovery from sevoflurane remifentanil anaesthesia when administered to healthy unpremedicated patients.. Eur J Anaesthesiol 2010;27:955-9.
  37. Dias Cicarelli D, Rojas-Álvarez NE, Fuller P, Lacava Pagnocca M, Frerichs E, Martins Benseñor FE. Effect of flumazenil on recovery from general anesthesia with isoflurane: a randomized controlled trial.. Colomb J Anesthesiol 2016;44:8-12.
  38. Palner M, Beinat C, Banister S, Zanderigo F, Park JH, Shen B. Effects of common anesthetic agents on [18F] flumazenil binding to the GABA A receptor.. EJNMMI Res 2016;6:80.
  39. Roald OK, Forsman M, Steen PA. Partial reversal of the cerebral effects of isoflurane in the dog by flumazenil.. Acta Anaesthesiol Scand 1988;32:209-12.
  40. Dahaba AA, Bornemann H, Rehak PH, Wang G, Wu XM, Metzler H. Effect of flumazenil on bispectral index monitoring in unpremedicated patients.. Anesthesiology 2009;110:1036-40.
  41. Kim YJ, Lee H, Kim CH, Lee GY, Baik HJ, Han JI. Effect of flumazenil on recovery from anesthesia and the bispectral index after sevoflurane/fentanyl general anesthesia in unpremedicated patients.. Korean J Anesthesiol 2012;62:19.
  42. Clark-Price S, Lascola K, Carter J, da Cunha A, Donaldson L, Doherty T. Assessment of agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scoring the recovery of horses from anesthesia by use of subjective grading scales and development of a system for evaluation of the recovery of horses from anesthesia by use of accelerometry.. Am J Vet Res 2017;78:668-76.

Citations

This article has been cited 1 times.
  1. Gozalo-Marcilla M, Ringer SK. Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature. Animals (Basel) 2021 Jun 14;11(6).
    doi: 10.3390/ani11061777pubmed: 34198637google scholar: lookup
Subscribe to our newsletter
Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.