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Home / Equine Research Bank / Equine Vet J / Recovery of horses from general anaesthesia: A systematic re...
Equine veterinary journal2021; 54(2); 219-261; doi: 10.1111/evj.13524

Recovery of horses from general anaesthesia: A systematic review (2000-2020) of the influence of anaesthetic protocol on recovery quality.

Abstract: The recovery phase after equine general anaesthesia (GA) is a time of considerable risk and therefore has been the subject of extensive research over the last 20 years. Various pharmacological interventions have been developed and studied with the objective of improving recovery quality and reducing anaesthetic-related mortality and morbidity. Nevertheless, some controversy remains regarding the influence of anaesthetic protocol choice on recovery quality from GA and its implications for recovery-related mortality and morbidity. A systematic review of the literature investigating the influence of anaesthetic protocol choice on recovery quality is currently lacking. Objective: To perform a detailed evaluation of the equine veterinary literature investigating the effect of anaesthetic protocol choice on equine recovery quality utilising the GRADE framework. Methods: A systematic evaluation of the equine veterinary literature was performed using the GRADE framework. Methods: A literature search was performed and studies were assessed for eligibility by both authors utilising PRISMA guidelines. Studies meeting inclusion criteria were evaluated by both authors, categorically summarised and the quality of evidence for each sub-topic was assessed using the GRADE framework. Results: A total of 124 studies were identified which directly assessed the impact of anaesthetic protocol choice on recovery quality after GA in horses. Evaluation of the available evidence indicated that certain partial intravenous anaesthesia (PIVA) agents, cessation of intravenous lidocaine 30 minutes prior to recovery and provision of adequate analgesia improves recovery quality. Conclusions: The validity of the results of some studies may have been compromised by missing data and small sample sizes. Conclusions: There is evidence to indicate that certain PIVA agents, cessation of intravenous lidocaine 30 minutes prior to recovery and provision of adequate analgesia improves recovery quality.
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Publication Date: 2021-11-12 PubMed ID: 34668220DOI: 10.1111/evj.13524Google Scholar: Lookup
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  • Journal Article
  • Systematic Review

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.

This research reviews multiple studies over the past 20 years that examine how different anaesthetic protocols affect a horse’s recovery from general anaesthesia. The researchers use established criteria to assess and summarize these studies and find evidence that certain interventions, such as using specific anaesthesia agents, stopping the use of lidocaine 30 minutes before a horse regains consciousness, and providing adequate pain relief, can improve the recovery process.

Objective and Approach

  • The research conducted a detailed review of studies focussing on equine anaesthesia recovery, spanning two decades from 2000 to 2020. This systematic review aimed to clarify how the choice of anaesthetic protocol could affect the recovery quality and potential mortality and morbidity risks associated with the recovery phase.
  • The researchers applied the GRADE framework, a standardised method for rating the quality of evidence in systematic reviews and assessing the strength of recommendations.
  • According to a set protocol, the researchers identified studies, screened them for relevance and assessed them for eligibility under the PRISMA guidelines, a set of best practices for conducting systematic reviews.

Findings

  • The researchers identified 124 studies that directly addressed the impact of different anaesthetic protocols on the quality of a horse’s recovery from general anaesthesia.
  • From the available evidence, the researchers concluded that certain partial intravenous anaesthesia (PIVA) agents enhance the recovery quality. The cessation of intravenous lidocaine – a typical anaesthetic used in veterinary medicine – approximately half an hour before recovery, and providing adequate pain relief, could also improve recovery from equine general anaesthesia.

Conclusions and Limitations

  • Despite highlighting that certain anaesthesia practices can improve the recovery process, the researchers also noted that some of the reviewed studies had certain limitations that could affect the reliability of the results. These limitations include missing data and smaller sample sizes.
  • Nevertheless, the consistency of findings across a number of studies supports the conclusion that the choice of certain PIVA agents, cessation of intravenous lidocaine before recovery and provision of adequate analgesia can enhance equine recovery quality from general anaesthesia.

Cite This Article

APA
Loomes K, Louro LF. (2021). Recovery of horses from general anaesthesia: A systematic review (2000-2020) of the influence of anaesthetic protocol on recovery quality. Equine Vet J, 54(2), 219-261. https://doi.org/10.1111/evj.13524

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 2
Pages: 219-261

Researcher Affiliations

Loomes, Kate
  • Rainbow Equine Hospital, Malton, UK.
Louro, Luís Filipe
  • School of Veterinary Science, University of Liverpool, Neston, UK.

MeSH Terms

  • Analgesia / veterinary
  • Anesthesia, General / veterinary
  • Anesthetics, Intravenous
  • Animals
  • Clinical Protocols
  • Horses
  • Lidocaine

References

This article includes 173 references
  1. Johnston GM, Eastment JK, Wood JLN, Taylor PM. The confidential enquiry into perioperative equine fatalities (CEPEF): mortality results of phases 1 and 2.. Vet Anaesth Analg 2002;29:159-70.
  2. Dugdale AH, Obhrai J, Cripps PJ. Twenty years later: a single-centre, repeat retrospective analysis of equine perioperative mortality and investigation of recovery quality.. Vet Anaesth Analg 2016;43:171-8.
  3. Laurenza C, Ansart L, Portier K. Risk factors of anesthesia-related mortality and morbidity in one equine hospital: a retrospective study on 1,161 cases undergoing elective or emergency surgeries.. Front Vet Sci 2020;6:514.
  4. Nicolaisen A-SK, Bendix Nygaard A, Christophersen MT, Jensen DB, Lindegaard C. Effect of head and tail rope-assisted recovery of horses after elective and emergency surgery under general anaesthesia.. Equine Vet Educ 2020; Epub ahead of print.
    doi: 10.1111/eve.13397google scholar: lookup
  5. Bidwell LA, Bramlage LR, Rood WA. Equine perioperative fatalities associated with general anaesthesia at a private practice - a retrospective case series.. Vet Anaesth Analg 2007;34:23-30.
  6. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.. BMJ 2021;372:2021.
    doi: 10.1136/bmj.n71google scholar: lookup
  7. Moberg J, Oxman AD, Rosenbaum S, Schünemann HJ, Guyatt G, Flottorp S. The GRADE Evidence to Decision (EtD) framework for health system and public health decisions.. Health Res Policy Syst 2018;16:45.
    doi: 10.1186/s12961-018-0320-2google scholar: lookup
  8. Carregaro AB, Ueda GI, Censoni JB, Bisetto SP, Alonso BB, Reginato GM. Effect of methadone combined with acepromazine or detomidine on sedation and dissociative anesthesia in healthy horses.. J Equine Vet Sci 2020;86:102908.
  9. Smith MC, Bass L, Damone J, Mama K, Rao S. Comparison of xylazine and detomidine in combination with midazolam/ketamine for field castration in Quarter Horses.. Equine Vet J 2020;52:516-21.
  10. Taylor PM, Bennett RC, Brearley JC, Luna SPL, Johnson CB. Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery.. Am J Vet Res 2001;62:359-63.
  11. Van Loon VJF, Van Den Brink TJ, Van Loon JPAM, Scheffer CJW, Bergman HJ. Influence of romifidine and detomidine on the induction of anesthesia and recovery from total intravenous anesthesia in horses.. Vlaams Diergeneeskd Tijdsch 2014;83:125-32.
  12. Bauquier SH, Kona-Boun J-J. Comparison of the effects of xylazine and romifidine administered perioperatively on the recovery of anesthetized horses.. Can Vet J 2011;52:987-93.
  13. Jaugstetter H, Jacobi R, Pellmann R. Comparison of romifidine and xylazine as premedicants before general anaesthesia in horses regarding the postsurgical recovery period.. Der Praktische Tierarzt 2002;83:786-91.
  14. Yamashita K, Muir WW, Tsubakishita S, Abrahamsen E, Lerch P, Hubbell JAE. Clinical comparison of xylazine and medetomidine for premedication of horses.. J Am Vet Med Assoc 2002;221:1144-9.
  15. Freeman SL, Bowen IM, Bettschart-Wolfensberger R, England GCW. Cardiopulmonary effects of romifidine and detomidine used as premedicants for ketamine/halothane anaesthesia in ponies.. Vet Record 2000;147:535-9.
  16. Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A. The 2011 Oxford CEBM levels of evidence (introductory document).. Oxford: Oxford Centre for Evidence-Based Medicine; 2011.
  17. Ruiz CC, Benedetti ICC, Guillebert I, Portier KG. Effect of pre- and postoperative phenylbutazone and morphine administration on the breathing response to skin incision, recovery quality, behavior, and cardiorespiratory variables in horses undergoing fetlock arthroscopy: a pilot study.. Front Vet Sci 2015;2:23.
  18. Sanz MG, Sellon DC, Cary JA, Hines MT, Farnsworth KD. Analgesic effects of butorphanol tartrate and phenylbutazone administered alone and in combination in young horses undergoing routine castration.. J Am Vet Med Assoc 2009;235:1194-203.
  19. Clark L, Clutton RE, Blissitt KJ, Chase-Topping ME. The effects of morphine on the recovery of horses from halothane anaesthesia.. Vet Anaesth Analg 2008;35:22-9.
  20. Chesnel MA, Clutton RE. A comparison of two morphine doses on the quality of recovery from general anaesthesia in horses.. Res Vet Sci 2013;95:1195-200.
  21. Love EJ, Geoffrey Lane J, Murison PJ. Morphine administration in horses anaesthetized for upper respiratory tract surgery.. Vet Anaesth Analg 2006;33:179-88.
  22. Mircica E, Clutton RE, Kyles KW, Blissitt KJ. Problems associated with perioperative morphine in horses: a retrospective case analysis.. Vet Anaesth Analg 2003;30:147-55.
  23. Steffey EP, Eisele JH, Baggot JD. Interactions of morphine and isoflurane in horses.. Am J Vet Res 2003;64:166-75.
  24. Corletto F, Raisis AA, Brearley JC. Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies.. Vet Anaesth Analg 2005;32:16-22.
  25. Taffarel MO, Luna SPL, Cardoso GS, de Oliveira FA, Alonso JM, Gozalo-Marcilla M. Preemptive analgesia, including morphine, does not affect recovery quality and times in either pain-free horses or horses undergoing orchiectomy.. J Equine Vet Sci 2017;48:82-5.
  26. Louro LF, Milner PI, Bardell D. Epidural administration of opioid analgesics improves quality of recovery in horses anaesthetised for treatment of hindlimb synovial sepsis.. Equine Vet J 2020;53(4):682-9.
  27. Natalini CC, Crosignani N, da Polidoro AS. Comparative evaluation of the effects of epidural morphine and 0.9% sodium chloride on cardiorespiratory function and anesthetic recovery in ponies.. Acta Sci Vet 2007;35:315-20.
  28. Taylor PM, Hoare HR, de Vries A, Love EJ, Coumbe KM, White KL. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery.. Equine Vet J 2016;48:442-50.
  29. Rigotti C, De Vries A, Taylor PM. Buprenorphine provides better anaesthetic conditions than butorphanol for field castration in ponies: results of a randomised clinical trial.. Vet Record 2014;175:623.
  30. Hopster K, Iversen C, Rohn K, Schiemann V, Ohnesorge B. Influence of the combination of butorphanol and detomidine within premedication on the preoperative sedations score, the intraoperative cardiovascular situation and the early recovery period in horses.. Pferdeheilkunde 2008;24:775-83.
  31. Harðardóttir H, Murison PJ, Blissitt K, Olason S, Clutton RE. A comparison of two ketamine doses for field anaesthesia in horses undergoing castration.. Equine Vet J 2019;51:458-63.
  32. Filzek U, Fischer U, Ferguson J. Intravenous anaesthesia in hoses: racemic ketamine versus S-(+)-ketamine.. Pferdeheilkunde Equine Med 2003;19:501-6.
  33. Casoni D, Spadavecchia C, Wampfler B, Thormann W, Levionnois OL. Clinical and pharmacokinetic evaluation of S-ketamine for intravenous general anaesthesia in horses undergoing field castration.. Acta Vet Scand 2015;57:21.
  34. Allison A, Robinson R, Jolliffe C, Taylor PM. Evaluation of the use of midazolam as a co-induction agent with ketamine for anaesthesia in sedated ponies undergoing field castration.. Equine Vet J 2018;50:321-6.
  35. 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.
  36. 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 Ass 2018;253:101-7.
  37. Posner LP, Kasten JI, Kata C. Propofol with ketamine following sedation with xylazine for routine induction of general anaesthesia in horses.. Vet Rec 2013;173:550.
  38. Wakuno A, Aoki M, Kushiro A, Mae N, Kodaira K, Maeda T. Comparison of alfaxalone, ketamine and thiopental for anaesthetic induction and recovery in Thoroughbred horses premedicated with medetomidine and midazolam.. Equine Vet J 2017;49:94-8.
  39. Gangl M, Grulke S, Caudron I, Serteyn D, Detilleux J. Comparison of thiopentone/guaifenesin, ketamine/guaifenesin and ketamine/midazolam for the induction of horses to be anaesthetised with isoflurane.. Vet Rec 2001;149:147-51.
  40. Keates HL, van Eps AW, Pearson MR. Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin.. Vet Anaesth Analg 2012;39:591-8.
  41. Goodwin WA, Keates HL, Pasloske K, Pearson M, Sauer B, Ranasinghe MG. The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse.. Vet Anaesth Analg 2011;38:431-8.
  42. Ferreira TH, Brosnan RJ, Shilo-Benjamini Y, Moore SB, Hollingsworth SR. Effects of ketamine, propofol, or thiopental administration on intraocular pressure and qualities of induction of and recovery from anesthesia in horses.. Am J Vet Res 2013;74:1070-7.
  43. Ishizuka T, Itami T, Tamura J, Saitoh Y, Saitoh M, Umar MA. Anesthetic and cardiorespiratory effects of propofol, medetomidine, lidocaine and butorphanol total intravenous anesthesia in horses.. J Vet Med Sci 2013;75:165-72.
  44. Boscan P, Steffey EP, Farver TB, Mama KR, Huang NJ, Harris SB. Comparison of high (5%) and low (1%) concentrations of micellar microemulsion propofol formulations with a standard (1%) lipid emulsion in horses.. Am J Vet Res 2006;67:1476-83.
  45. Frias AFG, Mársico F, Gómez de Segura IA, Nascimento PRL, Nascimento A, Soares JHN. Evaluation of different doses of propofol in xylazine pre-medicated horses.. Vet Anaesth Analg 2003;30:193-201.
  46. Oku K, Yamanaka T, Ashihara N, Kawasaki K, Mizuno Y, Fujinaga T. Clinical observations during induction and recovery of xylazine-midazolam- propofol anesthesia in horses.. J Vet Med Sci 2003;65:805-8.
  47. Wagner AE, Mama KR, Steffey EP, Brevard LF, Hellyer PW. Behavioral responses following eight anesthetic induction protocols in horses.. Vet Anaesth Analg 2002;29:207-11.
  48. Pratt S, Cunneen A, Perkins N, Farry T, Kidd L, McEwen M. Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.. Equine Vet J 2019;51:510-6.
  49. Romagnoli N, Rinnovati R, Lambertini C, Spadari A. Short-term general anesthesia with tiletamine/zolazepam in horses sedated with medetomidine for castration under field conditions.. J Equine Vet Sci 2018;67:50-4.
  50. Aarnes TK, Lerche P, Bednarski RM, Hubbell JAE. Total intravenous anesthesia using a midazolam-ketamine-xylazine infusion in horses: 46 cases (2011-2014).. Can Vet J 2018;59:500-4.
  51. Sage AM, Keating SC, Lascola KM, Schaeffer DJ, Clark-Price SC. Cardiopulmonary effects and recovery characteristics of horses anesthetized with xylazine-ketamine with midazolam or propofol.. Vet Anaesth Analg 2018;45:772-81.
  52. Twele L, Hopster K, Biernert-Zeit A, Rohn K, Kästner S. Comparison of intravenous anaesthesia protocols for castration.. Praktische Tierarzt 2017;98:686-98.
  53. Umar MA, Fukui S, Kawase K, Itami T, Yamashita K. Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidinepropofol (KMP-TIVA) in horses undergoing surgery.. J Vet Med Sci 2015;77:281-8.
  54. 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.
  55. Nóbrega Neto PI, Luna SPL, Queiroz-Williams P, Mama KR, Steffey EP, Carregaro AB. Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine.. BMC Vet Res 2013;9:199.
  56. Hubbell JAE, Aarnes TK, Lerche P, Bednarski RM. Evaluation of a midazolam-ketamine-xylazine infusion for total intravenous anesthesia in horses.. Am J Vet Res 2012;73:470-5.
  57. Klöppel H, Leece EA. Comparison of ketamine and alfaxalone for induction and maintenance of anaesthesia in ponies undergoing castration.. Vet Anaesth Analg 2011;38:37-43.
  58. Sinclair M, Valverde A. Short-term anaesthesia with xylazine, diazepam/ketamine for castration in horses under field conditions: use of intravenous lidocaine.. Equine Vet J 2009;41:149-52.
  59. Rossetti RB, Gaido Cortopassi SR, Intelizano T, De Lima MacHado TS, Ferreira Da Cruz RS. Comparison of ketamine and S(+)-ketamine, with romifidine and diazepam, for total intravenous anesthesia in horses.. Vet Anaesth Analg 2008;35:30-7.
  60. Yamashita K, Wijayathilaka TP, Kushiro T, Umar MA, Taguchi K, Muir WW. Anesthetic and cardiopulmonary effects of total intravenous anesthesia using a midazolam, ketamine and medetomidine drug combination in horses.. J Vet Med Sci 2007;69:7-13.
  61. Mama KR, Wagner AE, Steffey EP, Kollias-Baker C, Hellyer PW, Golden AE. Evaluation of xylazine and ketamine for total intravenous anesthesia in horses.. Am J Vet Res 2005;66:1002-7.
  62. Heeß D, Schatzmann U. Practical experiences and clinical parameters in a xylazine-ketamine-anaesthesia of horses.. Pferdeheilkunde 2003;19:28-32.
  63. Muir WW, Lerche P, Robertson JT, Hubbell JAE, Beard W, Miller T. Comparison of four drug combinations for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis.. J Am Vet Med Assoc 2000;217:869-73.
  64. Aoki M, Wakuno A, Kushiro A, Mae N, Kakizaki M, Nagata SI. Evaluation of total intravenous anesthesia with propofol-guaifenesin-medetomidine and alfaxalone-guaifenesin-medetomidine in Thoroughbred horses undergoing castration.. J Vet Med Sci 2017;79:2011-8.
  65. Oku K, Kakizaki M, Ono K, Ohta M. Clinical evaluation of total intravenous anesthesia using a combination of propofol and medetomidine following anesthesia induction with medetomidine, guaifenesin and propofol for castration in thoroughbred horses.. J Vet Med Sci 2011;73:1639-43.
  66. Rezende ML, Boscan P, Stanley SD, Mama KR, Steffey EP. Evaluation of cardiovascular, respiratory and biochemical effects, and anesthetic induction and recovery behavior in horses anesthetized with a 5% micellar microemulsion propofol formulation.. Vet Anaesth Analg 2010;37:440-50.
  67. Muir WW, Lerche P, Erichson D. Anaesthetic and cardiorespiratory effects of propofol at 10% for induction and 1% for maintenance of anaesthesia in horses.. Equine Vet J 2009;41:578-85.
  68. Bettschart-Wolfensberger R, Kalchofner K, Neges K, Kästner S, Fürst A. Total intravenous anaesthesia in horses using medetomidine and propofol.. Vet Anaesth Analg 2005;32:348-54.
  69. Ohta M, Oku K, Mukai K, Akiyama K, Mizuno Y. Propofol-ketamine anesthesia for internal fixation of fractures in racehorses.. J Vet Med Sci 2004;66:1433-6.
  70. Bettschart-Wolfensberger R, Bowen IM, Freeman SL, Weller R, Clarke KW. Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: Infusion rates and cardiopulmonary side effects.. Equine Vet J 2003;35:308-13.
  71. Bettschart-Wolfensberger R, Freeman SL, Jäggin-Schmucker N, Clarke KW. Infusion of a combination of propofol and medetomidine for long-term anesthesia in ponies.. Am J Vet Res 2001;62:500-7.
  72. Taylor PM, White KL, Fowden AL, Giussani DA, Bloomfield M, Sear JW. Propofol anaesthesia for surgery in late gestation pony mares.. Vet Anaesth Analg 2001;28:177-87.
  73. Goodwin WA, Keates HL, Pearson M, Pasloske K. Alfaxalone for total intravenous anaesthesia in horses.. Vet Anaesth Analg 2019;46:188-99.
  74. Deutsch J, Ekiri A, de Vries A. Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses.. Vet Anaesth Analg 2017;44:832-40.
  75. Ohmura H, Okano A, Mukai K, Fukuda K, Takahashi T. Cardiorespiratory and anesthetic effects of combined alfaxalone, butorphanol, and medetomidine in Thoroughbred horses.. J Equine Sci 2016;27:7-11.
  76. Goodwin WA, Keates HL, Pearson M, Pasloske K. Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration.. Equine Vet J 2013;45:315-9.
  77. Leece EA, Girard NM, Maddern K. Alfaxalone in cyclodextrin for induction and maintenance of anaesthesia in ponies undergoing field castration.. Vet Anaesth Analg 2009;36:480-4.
  78. Donaldson LL, Dunlop GS, Holland MS, Burton BA. The recovery of horses from inhalant anesthesia: a comparison of halothane and isoflurane.. Vet Surg 2000;29:92-101.
  79. Durongphongtorn S, McDonnell WN, Kerr CL, Teixeira Neto FJ, Mirakhur KK. Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery.. Am J Vet Res 2006;67:32-42.
  80. Johnston GM, Eastment JK, Taylor PM, Wood JLN. Is isoflurane safer than halothane in equine anaesthesia? Results from a prospective multicentre randomised controlled trial.. Equine Vet J 2004;36:64-71.
  81. Valente ACS, Brosnan RJ, Guedes AGP. Desflurane and sevoflurane elimination kinetics and recovery quality in horses.. Am J Vet Res 2015;76:201-7.
  82. Brosnan RJ, Steffey EP, Escobar A. Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses.. Vet Anaesth Analg 2012;39:335-44.
  83. Leece EA, Corletto F, Brearley JC. A comparison of recovery times and characteristics with sevoflurane and isoflurane anaesthesia in horses undergoing magnetic resonance imaging.. Vet Anaesth Analg 2008;35:383-91.
  84. Aida H, Steffey EP, Pascoe JR, Yarbrough TB, Takahashi T, Hiraga A. Use of sevoflurane for anesthetic management of horses during thoracotomy.. Am J Vet Res 2000;61:1430-7.
  85. Ohta M, Oku K, Yamanaka T, Mizuno Y. Anesthetic management with sevoflurane and oxygen for orthopedic surgeries in racehorses.. J Vet Med Sci 2000;62:1017-20.
  86. Alonso BB, La Rosa L, Carregaro AB, Gasthuys F, Schauvliege S. Recovery quality after romifidine versus detomidine infusion during isoflurane anesthesia in horses.. J Equine Vet Sci 2020;94:103243.
  87. Devisscher L, Schauvliege S, Dewulf J, Gasthuys F. Romifidine as a constant rate infusion in isoflurane anaesthetized horses: a clinical study.. Vet Anaesth Analg 2010;37:425-33.
  88. Schauvliege S, Marcilla MG, Verryken K, Duchateau L, Devisscher L, Gasthuys F. Effects of a constant rate infusion of detomidine on cardiovascular function, isoflurane requirements and recovery quality in horses.. Vet Anaesth Analg 2011;38:544-54.
  89. Mosing M, Iff I, Rezabek S. Combined anaesthesia with isoflurane and an infusion of a mixture of ketamine, midazolam and one of three a2-adrenoreceptor agonists for castration in horses.. Pferdeheilkunde Equine Med 2007;23:388-97.
  90. Kalchofner KS, Ringer SK, Boller J, Kästner SBR, Lischer C, Bettschart-Wolfensberger R. Clinical assessment of anesthesia with isoflurane and medetomidine in 300 equidae.. Pferdeheilkunde 2006;22:301-8.
  91. Bettschart-Wolfensberger R, Jäggin-Schmucker N, Lendl C, Bettschart RW, Clarke KW. Minimal alveolar concentration of desflurane in combination with an infusion of medetomidine for the anaesthesia of ponies.. Vet Rec 2001;148:264-7.
  92. Creighton CM, Lemke KA, Lamont LA, Horney BS, Doyle AJ. Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on the stress response, urine production, and anesthetic recovery characteristics in horses anesthetized with isoflurane.. J Am Vet Med Ass 2012;240:998-1002.
  93. Valverde A, Rickey E, Sinclair M, Rioja E, Pedernera J, Hathway A. Comparison of cardiovascular function and quality of recovery in isoflurane-anaesthetised horses administered a constant rate infusion of lidocaine or lidocaine and medetomidine during elective surgery.. Equine Vet J 2010;42:192-9.
  94. Ringer SK, Kalchofner K, Boller J, Fürst A, Bettschart-Wolfensberger R. A clinical comparison of two anaesthetic protocols using lidocaine or medetomidine in horses.. Vet Anaesth Analg 2007;34:257-68.
  95. Kempchen S, Kuhn M, Spadavecchia C, Levionnois OL. Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine.. Vet Anaesth Analg 2012;39:245-55.
  96. Tokushige H, Okano A, Arima D, Ito H, Kambayashi Y, Minamijima Y. Clinical effects of constant rate infusions of medetomidine-propofol combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.. Acta Vet Scand 2018;60(1).
    doi: 10.1186/s13028-018-0426-0google scholar: lookup
  97. Villalba M, Santiago I, Gómez de Segura IA. Effects of a constant rate infusion of medetomidine-propofol on isoflurane minimum alveolar concentrations in horses.. Vet J 2014;202:329-33.
  98. Tokushige H, Kushiro A, Okano A, Maeda T, Ito H, Wakuno A. Clinical evaluation of constant rate infusion of alfaxalone-medetomidine combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.. Acta Vet Scand 2018;60(1).
    doi: 10.1186/s13028-018-0406-4google scholar: lookup
  99. Mizobe F, Wakuno A, Okada J, Otsuka T, Ishikawa Y, Kurimoto S. Clinical usefulness of intravenous constant rate infusion of fentanyl and medetomidine under sevoflurane anesthesia in thoroughbred racehorses undergoing internal fixation surgery.. J Equine Sci 2017;28:143-7.
  100. Sacks M, Ringer SK, Bischofberger AS, Berchtold SM, Bettschart-Wolfensberger R. Clinical comparison of dexmedetomidine and medetomidine for isoflurane balanced anaesthesia in horses.. Vet Anaesth Analg 2017;44:1128-38.
  101. Bettembourg V, Dulgheriu D, Haga HA. Plasma concentrations at two dexmedetomidine constant rate infusions in isoflurane anaesthetized horses: a clinical study.. Vet Anaesth Analg 2019;46:627-35.
  102. Marcilla MG, Schauvliege S, Segaert S, Duchateau L, Gasthuys F. Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses.. Vet Anaesth Analg 2012;39:49-58.
  103. Simeonova GP, Dinev DN, Sleiman MU. Comparative study on sevoflurane anesthesia alone and combined with partial intravenous anesthesia using dexmedetomidine in healthy horses.. Pak Vet J 2017;37:155-9.
  104. Risberg ÅI, Ranheim B, Krontveit RI, Lervik A, Haga HA. The cardiovascular status of isoflurane-anaesthetized horses with and without dexmedetomidine constant rate infusion evaluated at equivalent depths of anaesthesia.. Vet Anaesth Analg 2016;43:412-23.
  105. Gozalo-Marcilla M, Steblaj B, Schauvliege S, Duchateau L, Gasthuys F. Comparison of the influence of two different constant-rate infusions (dexmedetomidine versus morphine) on anaesthetic requirements, cardiopulmonary function and recovery quality in isoflurane anaesthetized horses.. Res Vet Sci 2013;95:1186-94.
  106. Pöppel N, Hopster K, Geburek F, Kästner S. Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses - a controlled clinical trial.. Vet Anaesth Analg 2015;42:30-8.
  107. Villalba M, Santiago I, De Segura IAG. Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses.. Equine Vet J 2011;43:721-6.
  108. Lamuraglia R, Kirkby P, Funcia JP. Cardiopulmonary effects and recovery quality of remifentanil-isoflurane anesthesia in horses.. J Equine Vet Sci 2015;35:271-6.
  109. Benmansour P, Husulak ML, Bracamonte JL, Beazley SG, Withnall E, Duke-Novakovski T. Cardiopulmonary effects of an infusion of remifentanil or morphine in horses anesthetized with isoflurane and dexmedetomidine.. Vet Anaesth Analg 2014;41:346-56.
  110. Knych HKDM, Steffey EP, Mama KR, Stanley SD. Effects of high plasma fentanyl concentrations on minimum alveolar concentration of isoflurane in horses.. Am J Vet Res 2009;70:1193-200.
  111. Dias BP, De Araújo MA, Deschk M, Trein TA, Pinheiro NC, Venturolli Perri SH. Effects of a continuous rate infusion of butorphanol in isoflurane-anesthetized horses on cardiorespiratory parameters, recovery quality, gastrointestinal motility and serum cortisol concentrations.. Acta Cir Bras 2014;29:801-6.
  112. Bettschart-Wolfensberger R, Dicht S, Vullo C, Frotzler A, Kuemmerle JM, Ringer SK. A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics.. Vet Anaesth Analg 2011;38:186-94.
  113. Cruz Benedetti IC, Nottrott K, Fourel I, Le Bris M, Mongellas E, Portier K. Comparison of the effects of an intravenous lidocaine infusion combined with 1% isoflurane versus 2% isoflurane alone on selected cardiovascular variables and recovery characteristics during equine general anaesthesia.. Vet Anaesth Analg 2017;44:63-9.
  114. Nannarone S, Cenani A, Gialletti R, Pepe M. Clinical comparison of two regimens of lidocaine infusion in horses undergoing laparotomy for colic.. Vet Anaesth Analg 2015;42:150-6.
  115. Valverde A, Gunkel C, Doherty TJ, Giguère S, Pollak AS. Effect of a constant rate infusion of lidocaine on the quality of recovery from sevoflurane or isoflurane general anaesthesia in horses.. Equine Vet J 2005;37:559-64.
  116. Schuhbeck MM, Kuhn M, Spadavecchia C, Levionnois OL. Continuous intravenous lidocaine infusion during isoflurane anaesthesia in horses undergoing surgical procedures.. Pferdeheilkunde 2012;28:252-7.
  117. Menzies MPL, Ringer SK, Conrot A, Theurillat R, Kluge K, Kutter AP. Cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane and low-dose S-ketamine or medetomidine infusions.. Vet Anaesth Analg 2016;43:623-34.
  118. Larenza MP, Ringer SK, Kutter APN, Conrot A, Theurillat R, Kummer M. Evaluation of anesthesia recovery quality after low-dose racemic or S-ketamine infusions during anesthesia with isoflurane in horses.. Am J Vet Res 2009;70:710-8.
  119. Enderle AK, Levionnois OL, Kuhn M, Schatzmann U. Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia.. Vet Anaesth Analg 2008;35:297-305.
  120. Nannarone S, Spadavecchia C. Evaluation of the clinical efficacy of two partial intravenous anesthetic protocols, compared with isoflurane alone, to maintain general anesthesia in horses.. Am J Vet Res 2012;73:959-67.
  121. Yamashita K, Muir WW, Tsubakishita S, Abrahamsen E, Lerch P, Izumisawa Y. Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses.. J Am Vet Med Assoc 2002;221:1150-5.
  122. Spadavecchia C, Stucki F, Moens Y, Schatzmann U. Anaesthesia in horses using halothane and intravenous ketamine-guaiphenesin: a clinical study.. Vet Anaesth Analg 2002;29:20-8.
  123. Yamashita K, Satoh M, Umikawa A, Tsuda A, Yajima Y, Tsubakishita S. Combination of continuous intravenous infusion using a mixture of guaifenesin-ketamine-medetomidine and sevoflurane anesthesia in horses.. J Vet Med Sci 2000;62:229-35.
  124. Portier KG, Jaillardon L, Leece EA, Walsh CM. Castration of horses under total intravenous anaesthesia: analgesic effects of lidocaine.. Vet Anaesth Analg 2009;36:173-9.
  125. Morris TB, Lumsden JM, Dunlop CI, Locke V, Sommerauer S, Hurcombe SDA. Clinical assessment of an ipsilateral cervical spinal nerve block for prosthetic laryngoplasty in anesthetized horses.. Front Vet Sci 2020;7:284.
  126. Gaesser AM, Varner KM, Douglas HF, Barr CA, Hopster K, Levine DG. The effect of intra-articular mepivacaine administration prior to carpal arthroscopy on anesthesia management and recovery characteristics in horses.. Vet Surg 2020;49:1343-9.
  127. Crandall A, Hopster K, Grove A, Levine D. Intratesticular mepivacaine versus lidocaine in anaesthetised horses undergoing Henderson castration.. Equine Vet J 2020;52:805-10.
  128. Abass M, Picek S, Garzón JFG, Kühnle C, Zaghlou A, Bettschart-Wolfensberger R. Local mepivacaine before castration of horses under medetomidine isoflurane balanced anaesthesia is effective to reduce perioperative nociception and cytokine release.. Equine Vet J 2018;50:733-8.
  129. Kerr CL, McDonell WN, Young SS. A comparison of romifidine and xylazine when used with diazepam/ketamine for short duration anesthesia in the horse.. Can Vet J 1996;37:601-9.
  130. Bienert A, Bartmann CP, Von Oppen T, Poppe C, Schiemann V, Deegen E. Recovery phase of horses after inhalant anaesthesia with isofluorane (Isoflo®) and postanaesthetic sedation with romifidine (Sedivet®) or xylazine (Rompun®).. Dtsch Tierärztl Wochenschr 2003;110:244-8.
  131. Driessen B, Zarucco L, Kalir B, Bertolotti L. Contemporary use of acepromazine in the anaesthetic management of male horses and ponies: a retrospective study and opinion poll.. Equine Vet J 2011;43:88-98.
  132. Krein SR, Lindsey JC, Blaze CA, Wetmore LA. Evaluation of risk factors, including fluconazole administration, for prolonged anesthetic recovery times in horses undergoing general anesthesia for ocular surgery: 81 cases (2006-2013).. J Am Vet Med Assoc 2014;244:577-81.
  133. Marntell S, Nyman G. Effects of additional premedication on romifidine and ketamine anaesthesia in horses.. Acta Vet Scand 1996;37:315-25.
  134. Hector RC, Rezende ML, Mama KR, Hess AM. Recovery quality following a single post-anaesthetic dose of dexmedetomidine or romifidine in sevoflurane anaesthetised horses.. Equine Vet J 2020;52:685-91.
  135. Santos LCP, De Moraes AN, Saito ME. Effects of intraarticular ropivacaine and morphine on lipopolysaccharide- induced synovitis in horses.. Vet Anaesth Analg 2009;36:280-6.
  136. Pascoe PJ, Taylor PM. Effects of dopamine antagonists on alfentanil-induced locomotor activity in horses.. Vet Anaesth Analg 2003;30:165-71.
  137. Waterman AE, Robertson SA, Lane JG. Pharmacokinetics of intravenously administered ketamine in the horse.. Res Vet Sci 1987;42:162-6.
  138. Lankveld DPK, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE. Pharmacodynamic effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses.. J Vet Pharmacol Ther 2006;29:477-88.
  139. Muir WW, Skarda RT, Milne DW. Evaluation of xylazine and ketamine hydrochloride for anesthesia in horses.. Am J Vet Res 1977;38:195-201.
  140. Tokushige H, Araki M, Kusano K, Arima D, Ito H, Yamazaki Y. A retrospective comparison of induction with thiopental/guaifenesin and propofol/ketamine in Thoroughbred racehorses anesthetized with sevoflurane and medetomidine during arthroscopic surgery.. J Equine Sci 2019;30:25-31.
  141. 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.
  142. Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in premedicated horses.. Am J Vet Res 1996;57:512-6.
  143. Taylor PF. Thiopentone Anaesthesia in Horses.. Aust Vet J 1963;39:356-7.
  144. Abass BT, Weaver BMQ, Staddon GE, Waterman AW. Pharmacokinetics of thiopentone in the horse.. J Vet Pharmacol Ther 1994;17:331-8.
  145. Lindegaard C, Thomsen MH, Larsen S, Andersen PH. Analgesic efficacy of intra-articular morphine in experimentally induced radiocarpal synovitis in horses.. Vet Anaesth Analg 2010;37:171-85.
  146. Taylor PM, Luna SPL, Sear JW, Wheeler MJ. Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects.. Res Vet Sci 1995;59:17-23.
  147. Luna SPL, Taylor PM, Wheeler MJ. Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia.. J Vet Pharmacol Ther 1996;19:251-8.
  148. Tokushige H, Kushiro A, Okano A, Maeda T, Ito H, Wakuno A. Clinical evaluation of constant rate infusion of alfaxalone-medetomidine combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery.. Acta Vet Scand 2018;60:50.
  149. Yasui Y, Masaki E, Kato F. Sevoflurane directly excites locus coeruleus neurons of rats.. Anesthesiology 2007;107:992-1002.
  150. Esper T, Wehner M, Meinecke CD, Rrt H. Blood/gas partition coefficients for isoflurane, sevoflurane, and desflurane in a clinically relevant patient population.. Anest Analg 2015;120:45-50.
  151. Matthews NS, Hartsfield SM, Carroll GL, Martinez EA. Sevoflurane anaesthesia in clinical equine cases: maintenance and recovery.. Vet Anaesth Analg 1999;26:13-7.
  152. Carroll GL, Hooper RN, Rains CB, Martinez EA, Matthews NS, Hartsfield SM. Maintenance of anaesthesia with sevoflurane and oxygen in mechanically-ventilated horses subjected to exploratory laparotomy treated with intra- and post operative anaesthetic adjuncts.. Equine Vet J 1998;30:402-7.
  153. Matthews NS, Hartsfield SM, Mercer D, Beleau MH, MacKenthun A. Recovery from sevoflurane anesthesia in horses: Comparison to isoflurane and effect of postmedication with xylazine.. Vet Surg 1998;27:480-5.
  154. Grosenbaugh DA, Muir WW. Cardiorespiratory effects of sevoflurane, isoflurane, and halothane anesthesia in horses.. Am J Vet Res 1998;59:101-6.
  155. Gozalo-Marcilla M, Gasthuys F, Schauvliege S. Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia: Part 2: Opioids and alpha-2 adrenoceptor agonists.. Vet Anaesth Analg 2015;42:1-16.
  156. Gozalo-Marcilla M, Gasthuys F, Schauvliege S. Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia: Part 1: Lidocaine and ketamine.. Vet Anaesth Analg 2014;41:335-45.
  157. Yamashita K, Tsubakishita S, Futaoka S, Ueda I, Hamaguchi H, Seno T. Cardiovascular effects of medetomidine, detomidine and xylazine in horses.. J Vet Med Sci 2000;62:1025-32.
  158. Tokushige H, Ohta M, Okano A, Kuroda T, Kakizaki M, Ode H. Effects of medetomidine constant rate infusion on sevoflurane requirement, cardiopulmonary function, and recovery quality in thoroughbred racehorses undergoing arthroscopic surgery.. J Equine Vet Sci 2015;35:83-7.
  159. Doherty TJ, Frazier DL. Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies.. Equine Vet J 1998;30:300-3.
  160. Driessen B. Intravenous lidocaine infusion in balanced anaesthesia for abdominal surgery: update and clinical experiences.. Pferdeheilkunde 2005;21:133-41.
  161. Murrell JC, White KL, Johnson CB, Taylor PM, Doherty TJ, Waterman-Pearson AE. Investigation of the EEG effects of intravenous lidocaine during halothane anaesthesia in ponies.. Vet Anaesth Analg 2005;32:212-21.
  162. Feary DJ, Mama KR, Thomasy SM, Wagner AE, Enns RM. Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses.. Am J Vet Res 2006;67:317-22.
  163. Feary DJ, Mama KR, Wagner AE, Thomasy S. Influence of general anesthesia on pharmacokinetics of intravenous lidocaine infusion in horses.. Am J Vet Res 2005;66:574-80.
  164. Young SS, Taylor PM. Factors influencing the outcome of equine anaesthesia: a review of 1,314 cases.. Equine Vet J 1993;25:147-51.
  165. Andrade FS, Facó LL, Ida KK, Silva LC, Fantoni DT, Ambrósio AM. Effects of 12 and 17 cmH2O positive end-expiratory pressure applied after alveolar recruitment maneuver on pulmonary gas exchange and compliance in isoflurane-anesthetized horses.. Vet Anaesth Analg 2019;46:64-73.
  166. Hopster K, Rohn K, Ohnesorge B, Kästner SBR. Controlled mechanical ventilation with constant positive end-expiratory pressure and alveolar recruitment manoeuvres during anaesthesia in laterally or dorsally recumbent horses.. Vet Anaesth Analg 2017;44:121-6.
  167. Thompson KR, Bardell D. The effect of two different intra-operative end-tidal carbon dioxide tensions on apnoeic duration in the recovery period in horses.. Vet Anaesth Analg 2016;43:163-70.
  168. Hopster K, Kästner SB, Rohn K, Ohnesorge B. Intermittent positive pressure ventilation with constant positive end-expiratory pressure and alveolar recruitment manoeuvre during inhalation anaesthesia in horses undergoing surgery for colic, and its influence on the early recovery period.. Vet Anaesth Analg 2011;38:169-77.
  169. Ida KK, Fantoni DT, Ibiapina BT, Souto M-TTMR, Zoppa ALV, Silva LCLC. Effect of postoperative xylazine administration on cardiopulmonary function and recovery quality after isoflurane anesthesia in horses.. Vet Surg 2013;42:877-84.
  170. Levionnois OL, Zuehlke N, Kuhn M, Spadavecchia C. Impact of low inspired oxygen fraction on oxygenation in clinical horses under general anesthesia.. Pferdeheilkunde 2016;32:461-8.
  171. Schulte-Bahrenberg S, Hopster K, Kästner SB, Rohn K, Ohnesorge B. Influence on horse’s pulmonary function using a modified “Open-Lung-Concept”-Ventilation with different oxygen-concentration during general anaesthesia.. Pferdeheilkunde Equine Med 2011;27:311-5.
  172. Ida KK, Fantoni DT, Souto MT, Otsuki DA, Zoppa AL, Silva LC. Effect of pressure support ventilation during weaning on ventilation and oxygenation indices in healthy horses recovering from general anesthesia.. Vet Anaesth Analg 2013;40:339-50.
  173. Kalchofner KS, Picek S, Ringer SK, Jackson M, Hässig M, Bettschart-Wolfensberger R. A study of cardiovascular function under controlled and spontaneous ventilation in isoflurane-medetomidine anaesthetized horses.. Vet Anaesth Analg 2009;36:426-35.

Citations

This article has been cited 3 times.
  1. Boocock H, Flyps J, Escobar A, Redondo JI, Taylor PM, Gozalo-Marcilla M, Johnston GM, Bettschart-Wolfensberger R, Sullivan R. Donkey and Hybrid Anaesthetic Mortality in an Observational, Prospective, Multicentre Cohort Study. Animals (Basel) 2025 Jun 25;15(13).
    doi: 10.3390/ani15131880pubmed: 40646777google scholar: lookup
  2. Román Durá B, Dunham O, Grulke S, Salciccia A, Dupont J, Sandersen C. A Retrospective Study on Pre- and Intraoperative Predictors on the Recovery Quality of Horses After General Anesthesia. Vet Sci 2025 Mar 11;12(3).
    doi: 10.3390/vetsci12030262pubmed: 40266986google scholar: lookup
  3. Aitken MR, Floriano DA, Hopster K. Open Approach to the Transversus Abdominis Plane in Horses: A Cadaver Feasibility Study. Vet Sci 2024 Jan 22;11(1).
    doi: 10.3390/vetsci11010051pubmed: 38275933google scholar: lookup
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