Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both.
Abstract: Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected.
Publication Date: 2021-07-13 PubMed ID: 34359209PubMed Central: PMC8300393DOI: 10.3390/ani11072081Google 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.
- Journal Article
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 paper studies the cardiorespiratory, sedative, and antinociceptive effects of continuous infusion combinations of medetomidine with morphine, ketamine, or both on standing horses. The study concludes that all these drug combinations are safe, suitable protocols for horse sedation during standing surgeries, and do not significantly alter cardiorespiratory variables or improve sedation and antinociception.
Objective and Design of the Study
- The primary goal of the research was to compare the impacts of medetomidine, a sedative, combined with morphine or ketamine or both in a constant rate infusion (CRI) on the cardiorespiratory effects, sedation quality, antinociception (pain relief), and ataxia (loss of body movement control) in standing horses. It aimed to find a combination that could enhance pain relief during stand-up surgeries in horses without significantly affecting their cardiorespiratory system.
- The research employed a prospective, blind, randomized crossover, experimental design on six healthy adult horses. It involved administering four treatments—medetomidine alone, medetomidine with ketamine, medetomidine with morphine, and a combination of medetomidine, morphine and ketamine—to the horses, with a washout period of at least two weeks in between.
Procedure and Measurements
- The dosages for all treatment groups were the same and the drug infusions lasted for 120 minutes. The researchers then measured the cardiorespiratory variables, sedation degree, and antinociceptive effects during the procedure.
- The dosage for medetomidine was 5 µg/kg bwt followed by 5 µg/kg bwt/h, for ketamine it was 0.4 mg/kg/h, and for morphine it was 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h.
Findings
- All of the drug combinations resulted in similar sedation and antinociceptive effects, and none caused clinically relevant changes in the cardiorespiratory variables.
- The medetomidine CRI, in combination with morphine, ketamine, or both, are suitable and safe protocols for standing sedation in horses.
- However, adding morphine and/or ketamine to the medetomidine CRI did not have any negative effects nor did it improve the sedation and antinociceptive effects.
Cite This Article
APA
Troya-Portillo L, López-Sanromán J, Villalba-Orero M, Santiago-Llorente I.
(2021).
Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both.
Animals (Basel), 11(7).
https://doi.org/10.3390/ani11072081 Publication
Researcher Affiliations
- Departamento de Medicina y Cirugía Animal, Universidad Complutense de Madrid, 28040 Madrid, Spain.
- Departamento de Medicina y Cirugía Animal, Universidad Complutense de Madrid, 28040 Madrid, Spain.
- Hospital Clínico Veterinario Complutense, Universidad Complutense de Madrid, 28040 Madrid, Spain.
- Departamento de Medicina y Cirugía Animal, Universidad Complutense de Madrid, 28040 Madrid, Spain.
- Hospital Clínico Veterinario Complutense, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Grant Funding
- N/A / Fundación General de la Universidad Complutense de Madrid
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 69 references
- Brodbelt DC, Blissitt KJ, Hammond RA, Neath PJ, Young LE, Pfeiffer DU, Wood JLN. The risk of death: The Confidential Enquiry into Perioperative Small Animal Fatalities.. Vet. Anaesth. Analg. 2008;35:365–373.
- Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of Anesthesia-related Mortality in the United States, 1999–2005.. Anesthesiology 2009;110:759–765.
- Johnston GM. Findings from the CEPEF epidemiological studies into equine perioperative complications.. Equine Vet. Educ. 2005;15:64–68.
- 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.
- Senior MK. Morbidity, mortality, and risk of general anesthesia in horses.. Vet. Clin. N. Am. Equine Pract. 2013;29:1–18.
- Johnston GM, Eastment JK, Wood JL, Taylor PM. The confidential equiry into perioperative equine fatalities (CEPEF): Mortality results of Phases 1 and 2.. Vet. Anaesth. Analg. 2000;29:159–170.
- Doherty T, Valverde A. Manual of Equine Anesthesia and Analgesia.. Blackwell Publishing Ltd; Oxford, UK: 2006.
- Michou J, Leece E. Sedation and analgesia in the standing horse 1. Drugs used for sedation and systemic analgesia.. In Pract. 2012;34:524–531.
- Muir WW, Hubbell JAE. Equine Anesthesia.. Elsevier; Amsterdam, The Netherlands: 2009.
- Bettschart-Wolfensberger R, Clarke KW, Vainio O, Aliabadi FS, Demuth D. Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.. Res. Vet. Sci. 1999;67:41–46.
- Bueno AC, Cornick-Seahorn J, Seahorn TL, Hosgood G, Moore RM. Cardiopulmonary and sedative effects of intravenous administration of low doses of medetomidine and xylazine to adult horses.. Am. J. Vet. Res. 1999;60:1371–1376.
- Yamashita K, Tsubakishita S, Futaoka S, Ueda I, Hamaguchi H, Seno T, Katoh S, Izumisawa Y, Kotani T, William WM. Cardiovascular Effects of Medetomidine, Detomidine and Xylazine in Horses.. J. Vet. Med. Sci. 2000;62:1025–1032.
- Muir WW, Skarda RT, Sheehan WC. Hemodynamic and respiratory effects of xylazine-morphine sulfate in horses.. Am. J. Vet. Res. 1979;40:1417–1420.
- Kalpravidh M, Lumb WV, Wright M, Heath RB. Effects of butorphanol, flunixin, levorphanol, morphine, and xylazine in ponies.. Am. J. Vet. Res. 1984;45:217–223.
- Boscan P, Van Hoogmoed LM, Farver TB, Snyder JR. Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses.. Am. J. Vet. Res. 2006;67:992–997.
- Muir WW, Skarda RT, Sheehan WC. Cardiopulmonary effects of narcotic agonists and a partial agonist in horses.. Am. J. Vet. Res. 1978;39:1632–1635.
- Roberts MC, Argenzio A. Effects of amitraz, several opiate derivatives and anticholinergic agents on intestinal transit in ponies.. Equine Vet. J. 1986;18:256–260.
- Clark L, Clutton RE, Blissitt KJ, Chase-Topping ME. Effects of peri-operative morphine administration during halothane anaesthesia in horses.. Vet. Anaesth. Analg. 2005;32:10–15.
- Solano AM, Valverde A, Desrochers A, Nykamp S, Boure LP. Behavioural and cardiorespiratory effects of a constant rate infusion of medetomidine and morphine for sedation during standing laparoscopy in horses.. Equine Vet. J. 2009;41:153–159.
- Benredouane K, Ringer SK, Fourel I, Lepage OM, Portier KG, Bettschart-Wolfensberger R. Short communications: Comparison of xylazine-butorphanol and xylazine-morphine-ketamine infusions in horses undergoing a standing surgery.. Vet. Rec. 2011;169:364.
- Lankveld DPK, Bull S, Van Dijk P, Fink-Gremmels J, Hellebrekers LJ. Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line.. Vet. Res. 2005;36:257–262.
- Lankveld DPK, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE, Dijk PVAN, Hellebrekers LJ, Rudy J, Dijk V. Pharmacodynamic effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses.. J. Vet. Pharmacol. Ther. 2006;29:477–488.
- Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: A review.. Anesth. Analg. 2003;97:1108–1116.
- Müller TM, Hopster K, Bienert-Zeit A, Rohn K, Kästner SBR. Effect of butorphanol, midazolam or ketamine on romifidine based sedation in horses during standing cheek tooth removal.. BMC Vet. Res. 2017;13:381.
- Blissitt KJ, Young LE, Jones RS, Darke PGG, Utting J. Measurement of cardiac output in standing horses by Doppler echocardiography and thermodilution.. Equine Vet. J. 1997;29:18–25.
- Ringer SK, Portier KG, Fourel I, Bettschart-Wolfensberger R. Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses.. Vet. Anaesth. Analg. 2012;39:12–20.
- Ringer SK, Portier KG, Fourel I, Bettschart-Wolfensberger R. Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses.. Vet. Anaesth. Analg. 2012;39:1–11.
- Chambers JP, Livingston A, Waterman AE. A device for testing nociceptive thresholds in horses.. J. Assoc. Vet. Anaesth. Gt. Britain Irel. 1990;17:42–44.
- Chambers JP, Waterman AE, Livingston A. Further development of equipment to measure nociceptive thresholds in large animals.. Vet. Anaesth. Analg. 1994;21:66–72.
- Haussler KK, Erb HN. Mechanical nociceptive thresholds in the axial skeleton of horses.. Equine Vet. J. 2006;38:70–75.
- Haussler KK. Pressure Algometry for the Detection of Mechanical Nociceptive Thresholds in Horses.. Animals 2020;10:2195.
- Merritt AM, Burrow JA, Hartless CS. Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility.. Am. J. Vet. Res. 1998;59:619–623.
- Freeman SL, England GC. Effect of romifidine on gastrointestinal motility, assessed by transrectal ultrasonography.. Equine Vet. J. 2001;33:570–576.
- Daunt DA, Steffey EP. Alpha-2 adrenergic agonists as analgesics in horses.. Vet. Clin. North Am. Equine Pract. 2002;18:39–46.
- Sinclair MD. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice.. Can. Vet. J. 2003;44:885–897.
- Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio O. Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.. Equine Vet. J. 2019;51:646–652.
- Rousseau-Blass F, Pigé C, Pang DS. Agreement between invasive and oscillometric arterial blood pressure measurements using the LifeWindow multiparameter monitor and two cuff sizes in anesthetized adult horses.. Vet. Anaesth. Analg. 2020;47:315–322.
- Parry BW, Gay CC, McCarthy MA. Influence of head height on arterial blood pressure in standing horses.. Am. J. Vet. Res. 1980;41:1626–1631.
- Mcconachie E, Barton MH, Rapoport G, Giguère S. Doppler and volumetric echocardiographic methods for cardiac output measurement in standing adult horses.. J. Vet. Intern. Med. 2013;27:324–330.
- Zhang Y, Wang Y, Shi J, Hua Z, Xu J. Cardiac output measurements via echocardiography versus thermodilution: A systematic review and meta-analysis.. PLoS ONE 2019;14:e0222105.
- Figueiredo JP, Muir WW, Sams R. Cardiorespiratory, gastrointestinal, and analgesic effects of morphine sulfate in conscious healthy horses.. Am. J. Vet. Res. 2012;73:799–808.
- Gozalo-Marcilla M, Luna SP, Crosignani N, Filho JNP, Possebon FS, Pelligand L, Taylor PM. Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses.. Vet. Anaesth. Analg. 2017;44:1116–1127.
- Marly C, Bettschart-Wolfensberger R, Nussbaumer P, Moine S, Ringer SK. Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses.. Vet. Anaesth. Analg. 2014;41:491–497.
- Gozalo-Marcilla M, Oliveira AR, Fonseca MW, Possebon FS, Pelligand L, Taylor PM, Luna SPL. Sedative and antinociceptive effects of different detomidine constant rate infusions, with or without methadone in standing horses.. Equine Vet. J. 2019;51:530–536.
- Schauvliege S, Cuypers C, Michielsen A, Gasthuys F, Gozalo-Marcilla M. How to score sedation and adjust the administration rate of sedatives in horses: A literature review and introduction of the Ghent Sedation Algorithm.. Vet. Anaesth. Analg. 2019;46:4–13.
- De Oliveira AR, Gozalo-Marcilla M, Ringer SK, Schauvliege S, Fonseca MW, Trindade PHE, Puoli Filho JNP, Luna SPL. Development, Validation, and Reliability of a Sedation Scale in Horses (EquiSed). Front. Vet. Sci. 2021;8.
- Lizarraga I, Beths T. A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses.. Vet. Anaesth. Analg. 2012;39:533–538.
- Lizarraga I, Janovyak E. Comparison of the mechanical hypoalgesic effects of five α2-adrenoceptor agonists in donkeys.. Vet. Rec. 2013;173:294.
- Lizarraga I, Castillo-Alcala F, Robinson LS. Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys.. Vet. Anaesth. Analg. 2017;44:509–517.
- Sanchez LC, Elfenbein JR, Robertson SA. Effect of acepromazine, butorphanol, or N-butylscopolammonium bromide on visceral and somatic nociception and duodenal motility in conscious horses.. Am. J. Vet. Res. 2008;69:579–585.
- Carregaro AB, Luna SPL, Mataqueiro MI, Queiroz-Neto A de. Effects of buprenorphine on nociception and spontaneous locomotor activity in horses.. Am. J. Vet. Res. 2007;68:246–250.
- Spadavecchia C, Arendt-Nielsen L, Spadavecchia L, Mosing M, Auer U, Van Den Hoven R. Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses.. Vet. Anaesth. Analg. 2007;34:48–58.
- Dönselmann Im Sande P, Hopster K, Kästner S. Effects of morphine, butorphanol and levomethadone in different doses on thermal nociceptive thresholds in horses.. Tierarztl. Prax. Ausg. G Grosstiere Nutztiere. 2017;45:98–106.
- McGowan KT, Elfenbein JR, Robertson SA, Sanchez LC. Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.. Equine Vet. J. 2013;45:503–506.
- Schatzmann U, Armbruster S, Stucki F, Busato A, Kohler I. Analgesic Effect of Butorphanol and Levomethadone in Detomidine Sedated Horses.. J. Vet. Med. Ser. A. 2001;48:337–342.
- Bennett RC, Steffey EP. Use of opioids for pain and anesthetic management in horses.. Vet. Clin. North Am. Equine Pract. 2002;18:47–60.
- Echelmeyer J, Taylor PM, Hopster K, Rohn K, Delarocque J, Kästner SBR. Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration.. Vet. J. 2019;249:82–88.
- Crabtree NE, Mochal-King CA, Sloan PB, Eddy AL, Wills RW, Meredith AN, Fontenot RL. Synovial butorphanol concentrations and mechanical nociceptive thresholds after intravenous regional limb perfusion in standing sedated horses.. Vet. Surg. 2019;48:1473–1482.
- 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;43:721–726.
- Clutton RE. Opioid Analgesia in Horses.. Vet. Clin. N. Am. Equine Pract. 2010;26:493–514.
- Knobloch M, Portier CJ, Levionnois OL, Theurillat R, Thormann W. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion.. Toxicol. Appl. Pharmacol. 2006;216:373–386.
- López-Sanromán FJ, Cruz JM, Santos M, Mazzini RA, Tabanera A, Tendillo FJ. Evaluation of the local analgesic effect of ketamine in the palmar digital nerve block at the base of the proximal sesamoid (abaxial sesamoid block) in horses.. Am. J. Vet. Res. 2003;64:475–478.
- Svensson P, Baad-Hansen L, Pigg M, List T, Eliav E, Ettlin D, Michelotti A, Tsukiyama Y, Matsuka Y, Jääskeläinen SK. Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions—A taskforce report.. J. Oral Rehabil. 2011;38:366–394.
- Lopes C, Luna SPL, Rosa AC, Quarterone C, Crosignani N, Taylor PM, Pantoja JC, Puoli JNP. Antinociceptive effects of methadone combined with detomidine or acepromazine in horses.. Equine Vet. J. 2016;48:613–618.
- Luna SPL, Lopes C, Rosa AC, Oliveira FA, Crosignani N, Taylor PM, Pantoja JC. Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses.. Equine Vet. J. 2015;47:609–614.
- Clarke KW, Paton BS. Combined use of detomidine with opiates in the horse.. Equine Vet. J. 1988;20:331–334.
- Ringer SK, Portier K, Torgerson PR, Castagno R, Bettschart-Wolfensberger R. The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation, ataxia and response to stimuli in horses.. Vet. Anaesth. Analg. 2013;40:157–165.
- Love EJ, Murrell J, Whay HR. Thermal and mechanical nociceptive threshold testing in horses: A review.. Vet. Anaesth. Analg. 2011;38:3–14.
- Nielsen CS, Staud R, Price DD. Individual differences in pain sensitivity: Measurement, causation, and consequences.. J. Pain. 2009;10:231–237.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists