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Traditional and non-traditional uses of anesthetic drugs—an update
Vet Clin Equine 18 (2002) 169–179
Traditional and non-traditional uses of anesthetic drugs—an update Khursheed R. Mama, DVM Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA
Introduction Sedative or tranquilizing drugs are frequently used to restrain standing horses to facilitate performance of necessary diagnostic or therapeutic procedures. When this form of restraint is inadequate, short-term recumbency may be induced using injectable anesthetic drugs. The ideal anesthetic drug or drug combination should provide a smooth, coordinated transition to and from recumbency and a predictable duration of recumbency. The drugs should consistently provide analgesia and muscle relaxation, but no cardiopulmonary depression. Despite the availability of many new drugs, these ideal characteristics can still only be approximated, leaving the veterinary practitioner with many, sometimes confusing, choices. A brief review of selected characteristics of commonly used drugs and an introduction to newer drugs and techniques for induction and maintenance of short term anesthesia is presented. Information pertaining to the role of injectable drugs in other aspects equine anesthesia is also included. Additional and in-depth information on commonly used injectable techniques for short term restraint may be obtained elsewhere [1–4]. For specific information pertaining to the analgesic properties of the drugs the reader is referred to other chapters within this issue. Injectable drugs for sedation and induction of short-term anesthesia Sedative or tranquilizing drugs Adequate sedation prior to the induction of anesthesia is the key to achieving a smooth transition to lateral recumbency. Phenothiazine tranquilizers (e.g., acepromazine) have largely been replaced by alpha-2 agonist drugs Portions of this text have been excerpted or modified, with permission, from chapters previously written by this author for Current Veterinary Therapy (Equine) and International Veterinary Information Systems. E-mail address: [email protected] (K. Mama). 0749-0739/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 7 3 9 ( 0 1 ) 0 0 0 0 8 - 6
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(e.g., xylazine, detomidine), both for standing chemical restraint and for sedation prior to induction of anesthesia. Desirable (sedation, analgesia and muscle relaxation) and undesirable (bradycardia, bradydysrhythmias and hypotension) alpha-2 adrenoceptor agonist actions are largely mediated by the inhibition of the central and peripheral release of excitatory neurotransmitters such as norepinephrine [5]. Drug affinity for the alpha-2 receptor determines the duration of drug effect [5–8]. Xylazine has the lowest receptor affinity, highest dose requirement and shortest duration of action of the clinically available alpha-2 agonists. Detomidine and romifidine (a newer alpha-2 agent that is not yet available in the United States) are more potent than xylazine, having a much lower effective dose and longer duration of action. Medetomidine, which is licensed in the United States for use in dogs, has also been used to provide sedation prior to general anesthesia in horses [9,10]. Due to the potential for significant ataxia, its usefulness for chemical restraint in a standing horse may be limited. Drug combinations are also used for standing or pre-anesthetic sedation. Phenothiazine tranquilizers are sometimes combined with alpha-2 agonists to enhance sedation and provide a potentially beneficial anti-arrhythmic effect. Either drug class may also be combined with opioid drugs (e.g., morphine, butorphanol) in the hope of providing more reliable restraint. These opioid drugs are not generally used alone, as they have the potential to cause excitatory behaviors (e.g., pacing) in horses. Record keeping is also an essential component of their use. Induction drugs For many years ultra short-acting barbiturates were the agents of choice to induce short-term recumbency in tranquilized horses. While thiamylal is no longer commercially available, at least in the United States, thiopental is still used for anesthetic induction in sedated horses, prior to maintenance with inhalation anesthetics. The unpredictable quality of anesthetic induction and recovery with thiopental, and the need for special drug storage and handling procedures do, however, tend to limit its routine use in non hospital-based practices. Today, dissociative drugs such as ketamine have largely replaced thiobarbiturates in these non-hospital (‘‘field’’) circumstances. This change has improved the quality and consistency of both anesthetic induction and recovery. However, because ketamine-associated recumbency is associated with skeletal muscle movement and hypertonus, concurrent administration of behavior-modifying drugs (such as those mentioned in the preceding section) is important. In the United States, xylazine and ketamine are most commonly used together to induce anesthesia in horses [11–13]. Anesthetic drug-induced recumbency lasts about 15 to 20 minutes, but incremental repeated administration of both drugs may be used to safely extend the duration of anesthesia for approximately one hour.
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Telazol, a combination of the longer-acting, more potent dissociative agent tiletamine, and the benzodiazepine zolazepam, may be used instead of ketamine [12]. While induction quality and muscle relaxation during drug-induced recumbency are often better with Telazol use, prolonged ataxia may be seen during anesthetic recovery. This can be improved on by appropriate use of adjunct drugs. While varying slightly with specific drugs, heart rate and blood pressure during recumbency with alpha-2/dissociative drug combinations tend to be well maintained [13–18]. At a surgical plane, respiration is generally characterized by an apneustic breathing pattern that becomes more regular as the patient becomes lightly anesthetized. Ocular reflexes are well maintained during anesthesia induced with dissociative agents, and should not be relied upon as a sole indicator of anesthetic depth. Propofol, a newer anesthetic agent characterized as having a rapid onset and short duration of action, has been evaluated for use in ponies, foals, and adult horses. As with thiopental, it is associated with unpredictable anesthetic induction that may be modified with the use of sedative and muscle relaxant drugs. Currently, cost and storage issues are primary limiting factors to its routine use. Among its advantages over the aforementioned induction drugs are the generally excellent quality of recovery from anesthesia. This quality seems to be consistent whether propofol is used as a single bolus or for maintenance of anesthesia. Details of selected studies follow: Foals were anesthetized for surgical castration with either ketamine (2 mg/ kg) or propofol (2 mg/kg) after premedication with xylazine (1.1 mg/kg) and butorphanol (0.01 mg/kg) [19]. Castration was performed successfully with both drug protocols. Foals receiving propofol had higher heart rates and lower blood pressures during recumbency than foals induced with ketamine, and they recovered faster than foals receiving ketamine (mean time to standing: 12.3 minutes versus 19.7 minutes). In adult horses, recorded behavioral and cardiopulmonary characteristics associated with propofol were more variable. Anesthetic induction quality was unpredictable, and ranged from good to poor in unsedated horses [20]. Surprisingly, results of many studies suggest that these induction characteristics are not significantly improved following premedication with various alpha-2 agents; xylazine (0.5 and 1.0 mg/kg), detomidine (0.015 and 0.030 mg/kg), or medetomidine (7 lg/kg) [10,21]. However, addition of guaifenesin to the anesthetic-induction protocol does improve the induction characteristics [22,23]. Recovery quality was reported to be good to excellent in all studies. Heart rate, which decreased from unsedated values after xylazine and detomidine administration, remained lower than pre-drug values during propofolinduced recumbency. At deep planes of anesthesia, respiratory depression occurred, as shown by a decrease in respiratory rate, an increase in PaCO2, and a decrease in PaO2. The PaO2 decrease was significant during recumbency induced by both xylazine/propofol and detomidine/propofol [21].
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In an effort to improve upon induction characteristics seen with propofol, and to minimize the cost associated with its use in horses, various combinations of propofol and thiopental or ketamine were evaluated in premedicated horses [24]. While only a limited number of horses received each drug combination, results support the authors’ hypothesis that induction characteristics of propofol could be modified with concurrent use of another induction agent. Muscle relaxing drugs Centrally acting muscle relaxants (e.g., guaifenesin, diazepam) are used to prolong anesthetic recumbency and improve skeletal muscle relaxation during injectable anesthesia. While the site of action within the central nervous system is different for the two drugs, the end result is similar; equivalent muscle relaxation is observed at doses of diazepam (0.1 mg/kg) and guaifenesin (100 mg/kg) [14]. Neither drug offers any analgesia. Record keeping is necessary with diazepam use, as it is a scheduled drug. The reader should be aware that the selection of benzodiazepines will vary based on cost and availability. For example, zolazepam is only available as the benzodiazepine component of Telazol. Midazolam, a water-soluble benzodiazepine, is sometimes used in place of diazepam during anesthetic induction inhorses. Midazolam is available in the United States, whereas climazolam, flunitrazepam, and other benzodiazepine drugs are currently only available for clinical use outside of the United States. Injectable techniques for maintenance of anesthesia As suggested previously, anesthesia can be maintained with injectable drugs simply by repeated administration of drugs used for anesthetic induction. While this technique may be successfully used for procedures lasting 20 to 30 minutes and requiring one or two ‘‘top up’’ administrations, a more practical solution is desirable to maintain recumbency for longer periods. This has led to studies evaluating many combinations of sedative, muscle relaxant, and anesthetic drugs given by infusion. Some clinically useful combinations are mentioned below. Dissociative based combinations While xylazine and ketamine are commonly used for induction and short-term anesthetic maintenance in horses, comprehensive study of the behavioral and cardiopulmonary responses associated with varied dose combinations of these drugs for anesthetic maintenance has only recently been described [16,25]. Quality of anesthesia and speed of recovery from anesthesia varied with drug and dose. Quality of recovery was good to excellent in all horses. Relative (to FIO2) hypoxemia, low heart rate and cardiac output were commonly recorded, despite maintenance of normal blood pressure. A more widely accepted technique for maintenance of anesthesia for procedures
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(e.g., laceration repair, castration) lasting up to one hour is the combination of xylazine, guaifenesin, and ketamine. The technique was first described in the mid 1970s and has been used extensively since then [15,18,26]. More recently, climazolam (0.4 mg/kg/h) has been used with ketamine (6 mg/kg/h) to maintain anesthesia (for two hours) in ponies premedicated with xylazine and acepromazine [27]. Although recovery quality was not as good as that reported with other techniques, the authors felt cardiopulmonary function was better maintained. Many other combinations of alpha-2 agonist, dissociatives and/or muscle relaxants have been used for maintenance of anesthesia. Varying doses of detomidine plus guaifenesin and ketamine have been evaluated for induction and maintenance of anesthesia in ponies and to a limited degree in horses [28–30]. While the concurrent administration of other drugs (e.g., acepromazine, flunixin) with potential behavioral, cardiovascular, or analgesic effects may influence interpretation of the results from these studies, authors report that blood pressure and cardiac index were well maintained. When compared to halothane anesthesia for castration, authors report surgical conditions and recovery from anesthesia were comparable for the two protocols. In another study, an intravenous bolus of both romifidine (40 lg/kg) and ketamine (1.1 mg/kg), administered approximately 18 to 20 minutes after the induction dose of ketamine, was used to maintain anesthesia [31]. Lateral recumbency was maintained for an average of 43 minutes, but response to noxious stimulation (pinprick) was observed 35 minutes after the initial ketamine dose. Compared to pre-sedation values, heart rate and arterial oxygen tensions were decreased and mean arterial pressure was increased during anesthetic induced recumbency. A combination of romifidine (82.5 lg/kg/hr), ketamine (6.6 mg/kg/hr) and guaifenesin (100 mg/kg/hr for 30 minutes, then 50 mg/kg/hr) has also been used to maintain anesthesia [17]. Except for changes in pulmonary artery pressures authors reported no significant differences in recorded cardiopulmonary variables between this technique and halothane anesthesia. Propofol based combinations Many studies have evaluated the usefulness of propofol for maintenance of anesthesia. Due to its unique pharmacokinetic profile, it is ideally suited for prolonged administration, which translates to a short clinical duration of action and rapid recovery. For example, an infusion of propofol (0.26– 0.47 mg/kg/min) was used to maintain anesthesia in foals to facilitate performance of non-invasive diagnostic procedures [32]. Quality of anesthetic maintenance and recovery was satisfactory, with foals taking an average of 27 minutes to stand following discontinuation of the infusion. Heart rate and mean blood pressure ranged from 84–92 beats per minute and 98–123 mm Hg, respectively. In foals breathing room air the PaCO2 ranged from 45–60 mm Hg and the PaO2 ranged from 65–103 mm Hg.
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Although adequate for non-invasive procedures as described in the previous example, the sole use of propofol frequently does not provide a surgical plane of anesthesia at a dose devoid of side effects. Hence, it is frequently used in combination with other sedative, analgesic, or anesthetic drugs. In adult horses, anesthetic maintenance with xylazine and both low (0.15 mg/kg/min) and high (0.25 mg/kg/min) dose propofol infusion has been described [23]. The proportion of horses responding to a noxious stimulus (electrical) decreased as the propofol dose was increased. Further, at the high dose, marked respiratory depression was observed. Cardiac index and heart rate, however, were similar to those previously described for halothane anesthetized horses. This is likely the result of the indirect sympathomimetic effect of an increased arterial carbon dioxide tension at the deeper anesthetic plane. Cardiopulmonary effects of medetomidine and propofol infusion have been evaluated in ponies [10]. During a four-hour infusion period, authors report wide variations in recorded cardiopulmonary measurements. In large part, however, cardiovascular parameters (including heart rate, mean arterial blood pressure, and cardiac output) were comparable to that observed with other alpha-2/propofol combinations. Marked hypoxemia during the maintenance period was notable, despite oxygen administration. Although some differences were noted between horses receiving atipamezole (reversal agent for medetomidine) and those receiving a placebo, overall recovery quality was rated good to excellent in all ponies. The use of propofol and ketamine together for maintenance of short-term anesthesia has been described [33,34]. Authors report very good operating conditions and quiet recoveries from anesthesia following an average maintenance dose of ketamine (0.04 mg/kg/min) and propofol (0.12 mg/kg/min) [33]. While these techniques do have useful clinical applications, the reader is cautioned that prolonged use may result in cumulative drug effects and prolonged or poor quality anesthetic recovery. Reversal of some agents is possible, but this must be done only with consideration first given to residual effects of remaining drugs and the needs (e.g., analgesic requirement) of the patient. Due to the frequency of hypoxemia and bradycardia with many of these techniques, monitoring and support of respiratory and cardiovascular function during anesthetic-induced recumbency is strongly recommended, as is attention to appropriate patient positioning. Other applications for injectable anesthetic drugs Injectable drugs as part of a balanced anesthetic technique In an effort to reduce the administered inhaled-anesthetic dose, and therefore dose-dependent cardiopulmonary depression, balanced anesthetic techniques have been advocated. A balanced anesthetic technique targets all of the components of general anesthesia (amnesia, analgesia, muscle relaxation, and unconsciousness) with the use of low doses of drugs with these
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specific properties. By decreasing the dose of any individual drug, negative aspects of the individual drugs and the drug combination on cardiopulmonary function should be reduced. The use of balanced anesthesia is common in human beings and small animal patients, but limited in horses. This has been due both to a lack of drugs able to target the specific components of anesthesia, and a lack of information regarding the technique. Recent investigative work focusing on available drugs provides a starting point to facilitate increased clinical use of balanced anesthesia in horses. Many studies have documented the efficacy of alpha-2 adrenergic drugs for sedation and analgesia in horses. It is therefore a reasonable assumption that these drugs would reduce the dose of concurrently administered anesthetic drugs. Two studies demonstrating the inhalation anesthetic sparing effect of the alpha-2 agonists are highlighted. The isoflurane dose requirement was reduced 25–34%, 40 to 60 minutes following administration of clinically relevant doses of xylazine (0.5 mg/kg and 1.0 mg/kg, IV) [35]. Similarly the halothane dose requirement was reduced to approximately 55% of control values as detomidine dose (and plasma concentration) increased [36]. It is important to recognize that whereas in these studies the drugs were administered to horses during inhalation anesthesia, an anesthetic-sparing effect will also be seen after premedication with alpha-2 agonists, because these effects last for a substantial period of time following administration. Clinically this effect is most notable in horses receiving high doses of alpha-2 agonist drugs for pain or transport before presenting for general anesthesia. Although this technique does have the potential for improving analgesia and reducing inhalation-anesthetic dose, in-depth study of cardiopulmonary effects needs to be done before recommending its routine use. Inhalation anesthetics have also been combined with injectable anesthetic agents and muscle relaxants to achieve balanced anesthesia. For example, Muir et al. describe a study evaluating the use of ketamine during halothane anesthesia [37]. As ketamine plasma concentration increased, halothane dose requirement decreased and cardiovascular function was improved. However, authors also described poor and prolonged recoveries from anesthesia and suggest further clinically based evaluation of this technique. The use of a combination of guaifenesin and ketamine in combination with halothane has also been described [38]. This clinical study of horses presented for diagnostic evaluation and emergency surgery reported stable anesthetic conditions and predominantly good recoveries from anesthesia. Recently, lidocaine, a familiar local anesthetic agent, has received significant attention for use during the anesthetic period. In large part, this has been driven by the discovery of a novel use for lidocaine, namely as a pro-motility agent [39,40]. While the mechanism of action is not clearly understood and outcome assessments of true benefit need to be completed, equine clinicians believe that lidocaine minimizes ileus in horses presenting with colic. It is thought that early administration may enhance this benefit, and hence there is a desire to use lidocaine during the anesthetic period.
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While a full evaluation of the beneficial or adverse effects of combining lidocaine with inhalation anesthetics has not been completed, increasing plasma concentrations of lidocaine have been shown to reduce halothane minimum alveolar concentration (MAC) in ponies by 20 to 70% [41]. Injectable drugs as modifiers of recovery following inhalation anesthesia In the 1980s, Rose et al. reported that recovery following isoflurane anesthesia in the adult horse was unpredictable and less than ideal [42]. Because of continued observations of unpredictable recovery from inhalation anesthesia, and the potential for great risk to both the horse and handler in this period, there have been ongoing efforts to modulate equine recovery behavior. As recovery following short- and intermediate-duration injectable anesthesia is generally and predictably good, there is an interest in modulating recovery from inhaled agents by using injectable drugs. A commonly used clinical manifestation of this interest is evidenced by the frequent administration of a sedative or tranquilizing drug early in the anesthetic recovery period. Due to limited study of the benefit of this technique, drug and dose selection is frequently based on personal preference and prior experience. While it appears that use of the short-acting drug xylazine predominates, acepromazine is also occasionally used. Low doses of opioid drugs, such as butorphanol and morphine, are favored by some clinicians when presented with a painful horsee. Regardless of the drug selected, the technique of post-inhalation drug administration has become more common with the increased use of inhaled anesthetics with low blood-gas solubility. The potential benefit to the quality of recovery is supported by results of limited investigative efforts [43,44]. Information regarding potential adverse consequences such as hypoxemia or hypotension is not available. There are two ongoing studies designed to evaluate the use of injectable anesthetic drugs as modifiers of equine recovery behavior following standardized administration of inhalation anesthetics. Preliminary data from a prior study in four horses suggest that the use of injectable anesthetic drugs, such as propofol, in the early recovery period, improves recovery quality from isoflurane anesthesia, and allows patients to stand with fewer attempts [45]. Results of ongoing studies will further highlight benefits and complications of using injectable drugs in horses recovering from different inhalation anesthetics. Summary Many new or modified injectable anesthetic techniques are available for use in horses. This increased availability allows the clinician to select the technique most appropriate for the patient and clinical circumstance. The use of sedative and anesthetic drugs in managing a variety of anesthesia-related and unrelated aspects of patient care is also increasing. As we begin to use these techniques in the clinical management of our patients, it is important
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to remember that, while there are more options, no single anesthetic agent or combination of agents is devoid of undesirable effects. Knowledge of the pertinent advantages and disadvantages of the drugs when used individually and in combination and appropriate patient monitoring are essential to ensure a positive outcome. References [1] Benson GJ, Thurmon JC. Intravenous Anesthesia. Vet Clin North Am Equine Pract 1990;6:513–28. [2] Geiser DR. Chemical restraint and analgesia in the horse. Vet Clin North Am Equine Pract 1990;6:495–512. [3] Hubbell JA. Horses. In: Thurmon J, Tranquilli W, Benson G, editors. Lumb and Jones’ veterinary anesthesia, 3rd edition. Baltimore: Williams and Wilkins, 1996;599–609. [4] Mama KR. Anesthetic management of the horse: intravenous anesthesia. In: Steffey EP, editor. Recent advances in anesthetic management of large domestic animals. International Veterinary Information Services, 2000. Available at: http://www.ivis.org/advances/Steffey_ Anesthesia/mama_horse. [5] Lammintausta R. Introduction to adrenoceptor pharmacology. Acta Vet Scand 1986;82: 11–6. [6] England GCW, Clarke KW. Alpha2 adrenoreceptor agonists in the horse—a review. Br Vet J 1996;152:641–57. [7] England GCW, Clarke KW, Goosens L. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse. J Vet Pharm Therap 1992;15:194–201. [8] Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. J Vet Pharm Therap 1998;21:107–11. [9] Bettschart-Wolfsenberger R, Freeman S, Bettschart RW, Forst A, Clarke KW. Assessment of medetomidine/propofol total intravenous anaesthesia (TIVA) for clinical anaesthesia in equidae. In: Proceedings of the Association of Veterinary Anaesthetists Spring Meeting; 2000. [10] Bettschart-Wolfensberger R, Bowen MI, Freeman SL, et al. Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies. Am J Vet Res 2001;62:1428–35. [11] Mathews NS, Miller SM, Slater MR, et al. A comparison of xylazine-ketamine and detomidine-ketamine anaesthesia in horses. J Vet Anaesth 1993;20:68–72. [12] Matthews NS, Hartsfield SM, Cornick JL, et al. A comparison of injectable anesthetic combinations in horses. Vet Surg 1991;204:268–73. [13] Muir WW, Skarda RT, Milne DW. Evaluation of xylazine and ketamine hydrochloride for anesthesia in horses. Am J Vet Res 1977;38:195–201. [14] Brock N, Hildebrand SV. A comparison of xylazine-diazepam-ketamine and xylazineguaifenesin-ketamine in equine anesthesia. Vet Surg 1990;19:468–74. [15] Greene SA, Thurmon JC, Tranquilli WJ, et al. Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies. Am J Vet Res 1986;47: 2364–7. [16] Mama KR, Wagner AE, Steffey EP, et al. Evaluation of xylazine and ketamine for maintenance of anesthesia in horses. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Dallas (TX); 1999. p. 18. [17] McMurphy RM, Young LE, Marlin DJ, et al. Comparison of the cardiopulmonary effects of total intravenous anesthesia with romifidine, guaiphenesin, and ketamine vs halothane in horses. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Orlando (FL); 1998. p. 13.
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[18] Muir WW, Skarda RT, Sheehan W. Evaluation of xylazine, guaifenesin, and ketamine hydrochloride for restraint in horses. Am J Vet Res 1978;38:1274–8. [19] Donaldson LL, Dunlop GS, Cooper WL. A comparison of propofol with ketamine after xylazine and butorphanol as field anesthesia for young foals. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Orlando (FL); 1998. p. 11. [20] Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol as a general anesthetic for horses. Vet Surg 1995;24:188–94. [21] Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in premedicated horses. Am J Vet Res 1996;57:512–6. [22] Aguiar AJA, Hussni CA, Luna SPL, et al. Propofol compared with propofol/guaiphenesin after detomidine premedication for equine surgery. J vet Anaesth 1993;20:26–8. [23] Mama KR, Pascoe PJ, Steffey EP, et al. Comparison of two techniques for total intravenous anesthesia in horses. Am J Vet Res 1998;59:1292–8. [24] Mama KR, Wagner AE, Steffey EP, et al. Behavioral responses following eight anesthetic induction protocols in horses. In: Proceedings 7th World Congress of Veterinary Anaesthesia. Berne, Switzerland; 2000. p. 56. [25] Mama KR, Wagner AE, Steffey EP, et al. Behavioral response associated with xylazine and ketamine anesthesia in horses. In: Proceedings of the Association of Veterinary Anaesthetists Autumn Meeting. Madrid, Spain; 1999. p. 24. [26] Young LE, Bartram DH, Diamond MJ, et al. Clinical evaluation of an infusion of xylazine, guaifenesin and ketamine for maintenance of anaesthesia in horses. Equine Vet J 1993;25:115–9. [27] Bettschart-Wolfsenberger R, Taylor PM, Sear JW, et al. Physiologic effects of anesthesia induced and maintained by intravenous administration of climazolam-ketamine combination in ponies premedicated with acepromazine and xylazine. Am J Vet Res 1996;57:1472–7. [28] Taylor PM, Luna SPL, Brearley JC, et al. Physiological effects of total intravenous surgical anaesthesia using detomidine-guaiphenesin-ketamine in horses. J Vet Anaesth 1992; 19:24–31. [29] Taylor PM, Luna SP. Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects. Res Vet Sci 1995;59:17–22. [30] Taylor PM, Kirby JJ, Shrimpton J, et al. Cardiovascular effects of surgical castration during anaesthesia maintained with halothane or infusion of detomidine, ketamine and guaifenesin in ponies. Equine Vet J 1998;30:304–9. [31] Marntell S, Nyman G. Prolonging dissociative anaesthesia in horses with a repeated bolus injection. J vet Anaesth 1996;23:64–9. [32] Matthews NS, Chaffin MK, Hartsfield SM. Propofol immobilization of neonatal foals. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Washington, DC; 1993. p. 12. [33] Flaherty D, Reid J, Welsh E, et al. A pharmacodynamic study of propofol or propofol and ketamine infusions in ponies undergoing surgery. Res Vet Sci 1997;62:179–84. [34] Nolan AM, Reid J, Welsh E, et al. Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study. Res Vet Sci 1996;60: 262–6. [35] Steffey EP, Pascoe PJ, Woliner MJ, et al. Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses. Am J Vet Res 2000;61:1225–31. [36] Dunlop CI, Daunt DA, Chapman PL, et al. The anesthetic potency of 3 steady-state plasma levels of detomidine in halothane anesthetized horses. In: Proceedings of the 4th International Congress Veterinary Anaesthesia. Utrecht, Netherlands; 1991. p. 7. [37] Muir WW, Sams R. Effects of ketamine infusion on halothane minimal alveolar concentration. Am J Vet Res 1992;53:1802–6. [38] Spadavecchia C, Stucki F, Schatzmann U. Ketamine-guaiphenesin infusion to maintain general anaesthesia in horses receiving halothane in subanaesthetic dose: a clinical study, in
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Proceedings. Association of Veterinary Anaesthetists Autumn meeting. Madrid, Spain; 1999. p. 23. Groudine SB, Fisher HAG, Kaufman RP, et al. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg 1998;86:235–9. Malone ED, Turner TA, Wilson JH. Intravenous lidocaine for treatment of equine ileus. In: Proceedings of the Sixth Equine Colic Research Symposium. Athens (GA); 1998. p. 42. Doherty TJ, Frazier DL. Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies. Equine Vet J 1998;30:300–3. Rose JA, Rose EA. Clinical experience with isoflurane anesthesia in foals and adult horses. Proceedings American Association of Equine Practitioners; 1988. p. 555–61. Carroll GL, Hooper RN, Rains CB, et al. 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. Matthews NS, Hartsfield SM, Carroll GL, et al. Sevoflurane anaesthesia in clinical equine cases: maintenance and recovery. J Vet Anaesth 1999;26:13–7. Mama KR, Steffey EP, Pascoe PJ. A preliminary study comparing anesthetic recovery in horses following isoflurane of isoflurane propofol. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Atlanta (GA); 1995. p. 13.
Traditional and non-traditional uses of anesthetic drugs—an update Khursheed R. Mama, DVM Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA
Introduction Sedative or tranquilizing drugs are frequently used to restrain standing horses to facilitate performance of necessary diagnostic or therapeutic procedures. When this form of restraint is inadequate, short-term recumbency may be induced using injectable anesthetic drugs. The ideal anesthetic drug or drug combination should provide a smooth, coordinated transition to and from recumbency and a predictable duration of recumbency. The drugs should consistently provide analgesia and muscle relaxation, but no cardiopulmonary depression. Despite the availability of many new drugs, these ideal characteristics can still only be approximated, leaving the veterinary practitioner with many, sometimes confusing, choices. A brief review of selected characteristics of commonly used drugs and an introduction to newer drugs and techniques for induction and maintenance of short term anesthesia is presented. Information pertaining to the role of injectable drugs in other aspects equine anesthesia is also included. Additional and in-depth information on commonly used injectable techniques for short term restraint may be obtained elsewhere [1–4]. For specific information pertaining to the analgesic properties of the drugs the reader is referred to other chapters within this issue. Injectable drugs for sedation and induction of short-term anesthesia Sedative or tranquilizing drugs Adequate sedation prior to the induction of anesthesia is the key to achieving a smooth transition to lateral recumbency. Phenothiazine tranquilizers (e.g., acepromazine) have largely been replaced by alpha-2 agonist drugs Portions of this text have been excerpted or modified, with permission, from chapters previously written by this author for Current Veterinary Therapy (Equine) and International Veterinary Information Systems. E-mail address: [email protected] (K. Mama). 0749-0739/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 7 3 9 ( 0 1 ) 0 0 0 0 8 - 6
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(e.g., xylazine, detomidine), both for standing chemical restraint and for sedation prior to induction of anesthesia. Desirable (sedation, analgesia and muscle relaxation) and undesirable (bradycardia, bradydysrhythmias and hypotension) alpha-2 adrenoceptor agonist actions are largely mediated by the inhibition of the central and peripheral release of excitatory neurotransmitters such as norepinephrine [5]. Drug affinity for the alpha-2 receptor determines the duration of drug effect [5–8]. Xylazine has the lowest receptor affinity, highest dose requirement and shortest duration of action of the clinically available alpha-2 agonists. Detomidine and romifidine (a newer alpha-2 agent that is not yet available in the United States) are more potent than xylazine, having a much lower effective dose and longer duration of action. Medetomidine, which is licensed in the United States for use in dogs, has also been used to provide sedation prior to general anesthesia in horses [9,10]. Due to the potential for significant ataxia, its usefulness for chemical restraint in a standing horse may be limited. Drug combinations are also used for standing or pre-anesthetic sedation. Phenothiazine tranquilizers are sometimes combined with alpha-2 agonists to enhance sedation and provide a potentially beneficial anti-arrhythmic effect. Either drug class may also be combined with opioid drugs (e.g., morphine, butorphanol) in the hope of providing more reliable restraint. These opioid drugs are not generally used alone, as they have the potential to cause excitatory behaviors (e.g., pacing) in horses. Record keeping is also an essential component of their use. Induction drugs For many years ultra short-acting barbiturates were the agents of choice to induce short-term recumbency in tranquilized horses. While thiamylal is no longer commercially available, at least in the United States, thiopental is still used for anesthetic induction in sedated horses, prior to maintenance with inhalation anesthetics. The unpredictable quality of anesthetic induction and recovery with thiopental, and the need for special drug storage and handling procedures do, however, tend to limit its routine use in non hospital-based practices. Today, dissociative drugs such as ketamine have largely replaced thiobarbiturates in these non-hospital (‘‘field’’) circumstances. This change has improved the quality and consistency of both anesthetic induction and recovery. However, because ketamine-associated recumbency is associated with skeletal muscle movement and hypertonus, concurrent administration of behavior-modifying drugs (such as those mentioned in the preceding section) is important. In the United States, xylazine and ketamine are most commonly used together to induce anesthesia in horses [11–13]. Anesthetic drug-induced recumbency lasts about 15 to 20 minutes, but incremental repeated administration of both drugs may be used to safely extend the duration of anesthesia for approximately one hour.
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Telazol, a combination of the longer-acting, more potent dissociative agent tiletamine, and the benzodiazepine zolazepam, may be used instead of ketamine [12]. While induction quality and muscle relaxation during drug-induced recumbency are often better with Telazol use, prolonged ataxia may be seen during anesthetic recovery. This can be improved on by appropriate use of adjunct drugs. While varying slightly with specific drugs, heart rate and blood pressure during recumbency with alpha-2/dissociative drug combinations tend to be well maintained [13–18]. At a surgical plane, respiration is generally characterized by an apneustic breathing pattern that becomes more regular as the patient becomes lightly anesthetized. Ocular reflexes are well maintained during anesthesia induced with dissociative agents, and should not be relied upon as a sole indicator of anesthetic depth. Propofol, a newer anesthetic agent characterized as having a rapid onset and short duration of action, has been evaluated for use in ponies, foals, and adult horses. As with thiopental, it is associated with unpredictable anesthetic induction that may be modified with the use of sedative and muscle relaxant drugs. Currently, cost and storage issues are primary limiting factors to its routine use. Among its advantages over the aforementioned induction drugs are the generally excellent quality of recovery from anesthesia. This quality seems to be consistent whether propofol is used as a single bolus or for maintenance of anesthesia. Details of selected studies follow: Foals were anesthetized for surgical castration with either ketamine (2 mg/ kg) or propofol (2 mg/kg) after premedication with xylazine (1.1 mg/kg) and butorphanol (0.01 mg/kg) [19]. Castration was performed successfully with both drug protocols. Foals receiving propofol had higher heart rates and lower blood pressures during recumbency than foals induced with ketamine, and they recovered faster than foals receiving ketamine (mean time to standing: 12.3 minutes versus 19.7 minutes). In adult horses, recorded behavioral and cardiopulmonary characteristics associated with propofol were more variable. Anesthetic induction quality was unpredictable, and ranged from good to poor in unsedated horses [20]. Surprisingly, results of many studies suggest that these induction characteristics are not significantly improved following premedication with various alpha-2 agents; xylazine (0.5 and 1.0 mg/kg), detomidine (0.015 and 0.030 mg/kg), or medetomidine (7 lg/kg) [10,21]. However, addition of guaifenesin to the anesthetic-induction protocol does improve the induction characteristics [22,23]. Recovery quality was reported to be good to excellent in all studies. Heart rate, which decreased from unsedated values after xylazine and detomidine administration, remained lower than pre-drug values during propofolinduced recumbency. At deep planes of anesthesia, respiratory depression occurred, as shown by a decrease in respiratory rate, an increase in PaCO2, and a decrease in PaO2. The PaO2 decrease was significant during recumbency induced by both xylazine/propofol and detomidine/propofol [21].
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In an effort to improve upon induction characteristics seen with propofol, and to minimize the cost associated with its use in horses, various combinations of propofol and thiopental or ketamine were evaluated in premedicated horses [24]. While only a limited number of horses received each drug combination, results support the authors’ hypothesis that induction characteristics of propofol could be modified with concurrent use of another induction agent. Muscle relaxing drugs Centrally acting muscle relaxants (e.g., guaifenesin, diazepam) are used to prolong anesthetic recumbency and improve skeletal muscle relaxation during injectable anesthesia. While the site of action within the central nervous system is different for the two drugs, the end result is similar; equivalent muscle relaxation is observed at doses of diazepam (0.1 mg/kg) and guaifenesin (100 mg/kg) [14]. Neither drug offers any analgesia. Record keeping is necessary with diazepam use, as it is a scheduled drug. The reader should be aware that the selection of benzodiazepines will vary based on cost and availability. For example, zolazepam is only available as the benzodiazepine component of Telazol. Midazolam, a water-soluble benzodiazepine, is sometimes used in place of diazepam during anesthetic induction inhorses. Midazolam is available in the United States, whereas climazolam, flunitrazepam, and other benzodiazepine drugs are currently only available for clinical use outside of the United States. Injectable techniques for maintenance of anesthesia As suggested previously, anesthesia can be maintained with injectable drugs simply by repeated administration of drugs used for anesthetic induction. While this technique may be successfully used for procedures lasting 20 to 30 minutes and requiring one or two ‘‘top up’’ administrations, a more practical solution is desirable to maintain recumbency for longer periods. This has led to studies evaluating many combinations of sedative, muscle relaxant, and anesthetic drugs given by infusion. Some clinically useful combinations are mentioned below. Dissociative based combinations While xylazine and ketamine are commonly used for induction and short-term anesthetic maintenance in horses, comprehensive study of the behavioral and cardiopulmonary responses associated with varied dose combinations of these drugs for anesthetic maintenance has only recently been described [16,25]. Quality of anesthesia and speed of recovery from anesthesia varied with drug and dose. Quality of recovery was good to excellent in all horses. Relative (to FIO2) hypoxemia, low heart rate and cardiac output were commonly recorded, despite maintenance of normal blood pressure. A more widely accepted technique for maintenance of anesthesia for procedures
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(e.g., laceration repair, castration) lasting up to one hour is the combination of xylazine, guaifenesin, and ketamine. The technique was first described in the mid 1970s and has been used extensively since then [15,18,26]. More recently, climazolam (0.4 mg/kg/h) has been used with ketamine (6 mg/kg/h) to maintain anesthesia (for two hours) in ponies premedicated with xylazine and acepromazine [27]. Although recovery quality was not as good as that reported with other techniques, the authors felt cardiopulmonary function was better maintained. Many other combinations of alpha-2 agonist, dissociatives and/or muscle relaxants have been used for maintenance of anesthesia. Varying doses of detomidine plus guaifenesin and ketamine have been evaluated for induction and maintenance of anesthesia in ponies and to a limited degree in horses [28–30]. While the concurrent administration of other drugs (e.g., acepromazine, flunixin) with potential behavioral, cardiovascular, or analgesic effects may influence interpretation of the results from these studies, authors report that blood pressure and cardiac index were well maintained. When compared to halothane anesthesia for castration, authors report surgical conditions and recovery from anesthesia were comparable for the two protocols. In another study, an intravenous bolus of both romifidine (40 lg/kg) and ketamine (1.1 mg/kg), administered approximately 18 to 20 minutes after the induction dose of ketamine, was used to maintain anesthesia [31]. Lateral recumbency was maintained for an average of 43 minutes, but response to noxious stimulation (pinprick) was observed 35 minutes after the initial ketamine dose. Compared to pre-sedation values, heart rate and arterial oxygen tensions were decreased and mean arterial pressure was increased during anesthetic induced recumbency. A combination of romifidine (82.5 lg/kg/hr), ketamine (6.6 mg/kg/hr) and guaifenesin (100 mg/kg/hr for 30 minutes, then 50 mg/kg/hr) has also been used to maintain anesthesia [17]. Except for changes in pulmonary artery pressures authors reported no significant differences in recorded cardiopulmonary variables between this technique and halothane anesthesia. Propofol based combinations Many studies have evaluated the usefulness of propofol for maintenance of anesthesia. Due to its unique pharmacokinetic profile, it is ideally suited for prolonged administration, which translates to a short clinical duration of action and rapid recovery. For example, an infusion of propofol (0.26– 0.47 mg/kg/min) was used to maintain anesthesia in foals to facilitate performance of non-invasive diagnostic procedures [32]. Quality of anesthetic maintenance and recovery was satisfactory, with foals taking an average of 27 minutes to stand following discontinuation of the infusion. Heart rate and mean blood pressure ranged from 84–92 beats per minute and 98–123 mm Hg, respectively. In foals breathing room air the PaCO2 ranged from 45–60 mm Hg and the PaO2 ranged from 65–103 mm Hg.
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Although adequate for non-invasive procedures as described in the previous example, the sole use of propofol frequently does not provide a surgical plane of anesthesia at a dose devoid of side effects. Hence, it is frequently used in combination with other sedative, analgesic, or anesthetic drugs. In adult horses, anesthetic maintenance with xylazine and both low (0.15 mg/kg/min) and high (0.25 mg/kg/min) dose propofol infusion has been described [23]. The proportion of horses responding to a noxious stimulus (electrical) decreased as the propofol dose was increased. Further, at the high dose, marked respiratory depression was observed. Cardiac index and heart rate, however, were similar to those previously described for halothane anesthetized horses. This is likely the result of the indirect sympathomimetic effect of an increased arterial carbon dioxide tension at the deeper anesthetic plane. Cardiopulmonary effects of medetomidine and propofol infusion have been evaluated in ponies [10]. During a four-hour infusion period, authors report wide variations in recorded cardiopulmonary measurements. In large part, however, cardiovascular parameters (including heart rate, mean arterial blood pressure, and cardiac output) were comparable to that observed with other alpha-2/propofol combinations. Marked hypoxemia during the maintenance period was notable, despite oxygen administration. Although some differences were noted between horses receiving atipamezole (reversal agent for medetomidine) and those receiving a placebo, overall recovery quality was rated good to excellent in all ponies. The use of propofol and ketamine together for maintenance of short-term anesthesia has been described [33,34]. Authors report very good operating conditions and quiet recoveries from anesthesia following an average maintenance dose of ketamine (0.04 mg/kg/min) and propofol (0.12 mg/kg/min) [33]. While these techniques do have useful clinical applications, the reader is cautioned that prolonged use may result in cumulative drug effects and prolonged or poor quality anesthetic recovery. Reversal of some agents is possible, but this must be done only with consideration first given to residual effects of remaining drugs and the needs (e.g., analgesic requirement) of the patient. Due to the frequency of hypoxemia and bradycardia with many of these techniques, monitoring and support of respiratory and cardiovascular function during anesthetic-induced recumbency is strongly recommended, as is attention to appropriate patient positioning. Other applications for injectable anesthetic drugs Injectable drugs as part of a balanced anesthetic technique In an effort to reduce the administered inhaled-anesthetic dose, and therefore dose-dependent cardiopulmonary depression, balanced anesthetic techniques have been advocated. A balanced anesthetic technique targets all of the components of general anesthesia (amnesia, analgesia, muscle relaxation, and unconsciousness) with the use of low doses of drugs with these
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specific properties. By decreasing the dose of any individual drug, negative aspects of the individual drugs and the drug combination on cardiopulmonary function should be reduced. The use of balanced anesthesia is common in human beings and small animal patients, but limited in horses. This has been due both to a lack of drugs able to target the specific components of anesthesia, and a lack of information regarding the technique. Recent investigative work focusing on available drugs provides a starting point to facilitate increased clinical use of balanced anesthesia in horses. Many studies have documented the efficacy of alpha-2 adrenergic drugs for sedation and analgesia in horses. It is therefore a reasonable assumption that these drugs would reduce the dose of concurrently administered anesthetic drugs. Two studies demonstrating the inhalation anesthetic sparing effect of the alpha-2 agonists are highlighted. The isoflurane dose requirement was reduced 25–34%, 40 to 60 minutes following administration of clinically relevant doses of xylazine (0.5 mg/kg and 1.0 mg/kg, IV) [35]. Similarly the halothane dose requirement was reduced to approximately 55% of control values as detomidine dose (and plasma concentration) increased [36]. It is important to recognize that whereas in these studies the drugs were administered to horses during inhalation anesthesia, an anesthetic-sparing effect will also be seen after premedication with alpha-2 agonists, because these effects last for a substantial period of time following administration. Clinically this effect is most notable in horses receiving high doses of alpha-2 agonist drugs for pain or transport before presenting for general anesthesia. Although this technique does have the potential for improving analgesia and reducing inhalation-anesthetic dose, in-depth study of cardiopulmonary effects needs to be done before recommending its routine use. Inhalation anesthetics have also been combined with injectable anesthetic agents and muscle relaxants to achieve balanced anesthesia. For example, Muir et al. describe a study evaluating the use of ketamine during halothane anesthesia [37]. As ketamine plasma concentration increased, halothane dose requirement decreased and cardiovascular function was improved. However, authors also described poor and prolonged recoveries from anesthesia and suggest further clinically based evaluation of this technique. The use of a combination of guaifenesin and ketamine in combination with halothane has also been described [38]. This clinical study of horses presented for diagnostic evaluation and emergency surgery reported stable anesthetic conditions and predominantly good recoveries from anesthesia. Recently, lidocaine, a familiar local anesthetic agent, has received significant attention for use during the anesthetic period. In large part, this has been driven by the discovery of a novel use for lidocaine, namely as a pro-motility agent [39,40]. While the mechanism of action is not clearly understood and outcome assessments of true benefit need to be completed, equine clinicians believe that lidocaine minimizes ileus in horses presenting with colic. It is thought that early administration may enhance this benefit, and hence there is a desire to use lidocaine during the anesthetic period.
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While a full evaluation of the beneficial or adverse effects of combining lidocaine with inhalation anesthetics has not been completed, increasing plasma concentrations of lidocaine have been shown to reduce halothane minimum alveolar concentration (MAC) in ponies by 20 to 70% [41]. Injectable drugs as modifiers of recovery following inhalation anesthesia In the 1980s, Rose et al. reported that recovery following isoflurane anesthesia in the adult horse was unpredictable and less than ideal [42]. Because of continued observations of unpredictable recovery from inhalation anesthesia, and the potential for great risk to both the horse and handler in this period, there have been ongoing efforts to modulate equine recovery behavior. As recovery following short- and intermediate-duration injectable anesthesia is generally and predictably good, there is an interest in modulating recovery from inhaled agents by using injectable drugs. A commonly used clinical manifestation of this interest is evidenced by the frequent administration of a sedative or tranquilizing drug early in the anesthetic recovery period. Due to limited study of the benefit of this technique, drug and dose selection is frequently based on personal preference and prior experience. While it appears that use of the short-acting drug xylazine predominates, acepromazine is also occasionally used. Low doses of opioid drugs, such as butorphanol and morphine, are favored by some clinicians when presented with a painful horsee. Regardless of the drug selected, the technique of post-inhalation drug administration has become more common with the increased use of inhaled anesthetics with low blood-gas solubility. The potential benefit to the quality of recovery is supported by results of limited investigative efforts [43,44]. Information regarding potential adverse consequences such as hypoxemia or hypotension is not available. There are two ongoing studies designed to evaluate the use of injectable anesthetic drugs as modifiers of equine recovery behavior following standardized administration of inhalation anesthetics. Preliminary data from a prior study in four horses suggest that the use of injectable anesthetic drugs, such as propofol, in the early recovery period, improves recovery quality from isoflurane anesthesia, and allows patients to stand with fewer attempts [45]. Results of ongoing studies will further highlight benefits and complications of using injectable drugs in horses recovering from different inhalation anesthetics. Summary Many new or modified injectable anesthetic techniques are available for use in horses. This increased availability allows the clinician to select the technique most appropriate for the patient and clinical circumstance. The use of sedative and anesthetic drugs in managing a variety of anesthesia-related and unrelated aspects of patient care is also increasing. As we begin to use these techniques in the clinical management of our patients, it is important
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to remember that, while there are more options, no single anesthetic agent or combination of agents is devoid of undesirable effects. Knowledge of the pertinent advantages and disadvantages of the drugs when used individually and in combination and appropriate patient monitoring are essential to ensure a positive outcome. References [1] Benson GJ, Thurmon JC. Intravenous Anesthesia. Vet Clin North Am Equine Pract 1990;6:513–28. [2] Geiser DR. Chemical restraint and analgesia in the horse. Vet Clin North Am Equine Pract 1990;6:495–512. [3] Hubbell JA. Horses. In: Thurmon J, Tranquilli W, Benson G, editors. Lumb and Jones’ veterinary anesthesia, 3rd edition. Baltimore: Williams and Wilkins, 1996;599–609. [4] Mama KR. Anesthetic management of the horse: intravenous anesthesia. In: Steffey EP, editor. Recent advances in anesthetic management of large domestic animals. International Veterinary Information Services, 2000. Available at: http://www.ivis.org/advances/Steffey_ Anesthesia/mama_horse. [5] Lammintausta R. Introduction to adrenoceptor pharmacology. Acta Vet Scand 1986;82: 11–6. [6] England GCW, Clarke KW. Alpha2 adrenoreceptor agonists in the horse—a review. Br Vet J 1996;152:641–57. [7] England GCW, Clarke KW, Goosens L. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse. J Vet Pharm Therap 1992;15:194–201. [8] Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. J Vet Pharm Therap 1998;21:107–11. [9] Bettschart-Wolfsenberger R, Freeman S, Bettschart RW, Forst A, Clarke KW. Assessment of medetomidine/propofol total intravenous anaesthesia (TIVA) for clinical anaesthesia in equidae. In: Proceedings of the Association of Veterinary Anaesthetists Spring Meeting; 2000. [10] Bettschart-Wolfensberger R, Bowen MI, Freeman SL, et al. Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies. Am J Vet Res 2001;62:1428–35. [11] Mathews NS, Miller SM, Slater MR, et al. A comparison of xylazine-ketamine and detomidine-ketamine anaesthesia in horses. J Vet Anaesth 1993;20:68–72. [12] Matthews NS, Hartsfield SM, Cornick JL, et al. A comparison of injectable anesthetic combinations in horses. Vet Surg 1991;204:268–73. [13] Muir WW, Skarda RT, Milne DW. Evaluation of xylazine and ketamine hydrochloride for anesthesia in horses. Am J Vet Res 1977;38:195–201. [14] Brock N, Hildebrand SV. A comparison of xylazine-diazepam-ketamine and xylazineguaifenesin-ketamine in equine anesthesia. Vet Surg 1990;19:468–74. [15] Greene SA, Thurmon JC, Tranquilli WJ, et al. Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies. Am J Vet Res 1986;47: 2364–7. [16] Mama KR, Wagner AE, Steffey EP, et al. Evaluation of xylazine and ketamine for maintenance of anesthesia in horses. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Dallas (TX); 1999. p. 18. [17] McMurphy RM, Young LE, Marlin DJ, et al. Comparison of the cardiopulmonary effects of total intravenous anesthesia with romifidine, guaiphenesin, and ketamine vs halothane in horses. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Orlando (FL); 1998. p. 13.
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[18] Muir WW, Skarda RT, Sheehan W. Evaluation of xylazine, guaifenesin, and ketamine hydrochloride for restraint in horses. Am J Vet Res 1978;38:1274–8. [19] Donaldson LL, Dunlop GS, Cooper WL. A comparison of propofol with ketamine after xylazine and butorphanol as field anesthesia for young foals. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Orlando (FL); 1998. p. 11. [20] Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol as a general anesthetic for horses. Vet Surg 1995;24:188–94. [21] Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in premedicated horses. Am J Vet Res 1996;57:512–6. [22] Aguiar AJA, Hussni CA, Luna SPL, et al. Propofol compared with propofol/guaiphenesin after detomidine premedication for equine surgery. J vet Anaesth 1993;20:26–8. [23] Mama KR, Pascoe PJ, Steffey EP, et al. Comparison of two techniques for total intravenous anesthesia in horses. Am J Vet Res 1998;59:1292–8. [24] Mama KR, Wagner AE, Steffey EP, et al. Behavioral responses following eight anesthetic induction protocols in horses. In: Proceedings 7th World Congress of Veterinary Anaesthesia. Berne, Switzerland; 2000. p. 56. [25] Mama KR, Wagner AE, Steffey EP, et al. Behavioral response associated with xylazine and ketamine anesthesia in horses. In: Proceedings of the Association of Veterinary Anaesthetists Autumn Meeting. Madrid, Spain; 1999. p. 24. [26] Young LE, Bartram DH, Diamond MJ, et al. Clinical evaluation of an infusion of xylazine, guaifenesin and ketamine for maintenance of anaesthesia in horses. Equine Vet J 1993;25:115–9. [27] Bettschart-Wolfsenberger R, Taylor PM, Sear JW, et al. Physiologic effects of anesthesia induced and maintained by intravenous administration of climazolam-ketamine combination in ponies premedicated with acepromazine and xylazine. Am J Vet Res 1996;57:1472–7. [28] Taylor PM, Luna SPL, Brearley JC, et al. Physiological effects of total intravenous surgical anaesthesia using detomidine-guaiphenesin-ketamine in horses. J Vet Anaesth 1992; 19:24–31. [29] Taylor PM, Luna SP. Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects. Res Vet Sci 1995;59:17–22. [30] Taylor PM, Kirby JJ, Shrimpton J, et al. Cardiovascular effects of surgical castration during anaesthesia maintained with halothane or infusion of detomidine, ketamine and guaifenesin in ponies. Equine Vet J 1998;30:304–9. [31] Marntell S, Nyman G. Prolonging dissociative anaesthesia in horses with a repeated bolus injection. J vet Anaesth 1996;23:64–9. [32] Matthews NS, Chaffin MK, Hartsfield SM. Propofol immobilization of neonatal foals. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Washington, DC; 1993. p. 12. [33] Flaherty D, Reid J, Welsh E, et al. A pharmacodynamic study of propofol or propofol and ketamine infusions in ponies undergoing surgery. Res Vet Sci 1997;62:179–84. [34] Nolan AM, Reid J, Welsh E, et al. Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study. Res Vet Sci 1996;60: 262–6. [35] Steffey EP, Pascoe PJ, Woliner MJ, et al. Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses. Am J Vet Res 2000;61:1225–31. [36] Dunlop CI, Daunt DA, Chapman PL, et al. The anesthetic potency of 3 steady-state plasma levels of detomidine in halothane anesthetized horses. In: Proceedings of the 4th International Congress Veterinary Anaesthesia. Utrecht, Netherlands; 1991. p. 7. [37] Muir WW, Sams R. Effects of ketamine infusion on halothane minimal alveolar concentration. Am J Vet Res 1992;53:1802–6. [38] Spadavecchia C, Stucki F, Schatzmann U. Ketamine-guaiphenesin infusion to maintain general anaesthesia in horses receiving halothane in subanaesthetic dose: a clinical study, in
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Proceedings. Association of Veterinary Anaesthetists Autumn meeting. Madrid, Spain; 1999. p. 23. Groudine SB, Fisher HAG, Kaufman RP, et al. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg 1998;86:235–9. Malone ED, Turner TA, Wilson JH. Intravenous lidocaine for treatment of equine ileus. In: Proceedings of the Sixth Equine Colic Research Symposium. Athens (GA); 1998. p. 42. Doherty TJ, Frazier DL. Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies. Equine Vet J 1998;30:300–3. Rose JA, Rose EA. Clinical experience with isoflurane anesthesia in foals and adult horses. Proceedings American Association of Equine Practitioners; 1988. p. 555–61. Carroll GL, Hooper RN, Rains CB, et al. 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. Matthews NS, Hartsfield SM, Carroll GL, et al. Sevoflurane anaesthesia in clinical equine cases: maintenance and recovery. J Vet Anaesth 1999;26:13–7. Mama KR, Steffey EP, Pascoe PJ. A preliminary study comparing anesthetic recovery in horses following isoflurane of isoflurane propofol. Proceedings Annual Meeting American College Veterinary Anesthesiologists. Atlanta (GA); 1995. p. 13.