Vol. 24, No. 5 May 2002 411 CE Article #5 (1.5 contact hours) Refereed Peer Review Comments? Questions? Email: compendium@medimedia.com Web: VetLearn.com Fax: 800-556-3288 KEY FACTS Achieving adequate sedation and muscle relaxation before administering an anesthetic induction agent is essential for a smooth transition from standing to recumbency. Unless respiratory support is provided, duration of intravenous anesthesia should be limited. Patient monitoring and support can minimize the incidence of anesthetic-related complications. Field Anesthetic Techniques for Use in Horses Animal Care Center of Sonoma County Sonoma, California Marcia L. Aubin, DVM, MS* Colorado State University Khursheed Mama, DVM, DACVA ABSTRACT: Smooth induction to and recovery from anesthesia are essential for the safety of the horse and all personnel involved. Adverse cardiorespiratory effects should be minimized during recumbency. Inducing and maintaining anesthetic recumbency in an ambulatory setting are best achieved using a combination of drugs. Although phenothiazine tranquilizers such as acepromazine may be used, sedation and muscle relaxation are usually achieved using α 2 -agonists either alone or in combination with benzodiazepine or guaifenesin. Dissociative agents are most often used for induction and short-term maintenance of anesthesia. Thiopental and propofol are also available, but adverse behavioral characteristics associated with their use make them less desirable. Inducing and maintaining recumbency in horses are important when performing short surgical or diagnostic procedures in the field, such as castration, laceration repair, enucleation, tendonectomy, or splint-bone excision. However, in horses, recumbency presents some unique concerns because of gravitational effects on ventilation, perfusion, and cardiac output. 1 Oxygen supplementation and the ability to provide ventilatory support are ideal, but intravenous (IV) anesthesia has been safely used for up to 60 minutes without these supportive measures, which are often unavailable in an ambulatory practice. 2 In a field setting, anesthetic induction and recovery must be smooth to avoid injuring attending personnel or the horse (Figure 1). An adequate plane of anesthesia and analgesia must also be achieved to facilitate surgical manipulations. Because no single anesthetic agent has proven to be ideal, a combination of agents that either work synergistically or balance undesirable effects is used. PREINDUCTION SEDATION Providing adequate sedation before administering anesthesia is critical to achieve smooth induction and may reduce the required dose of the induction agent. 2 The α 2 -agonists xylazine, detomidine (Table 1), and romifidine have * Dr. Aubin was affiliated with Colorado State University when this paper was written.
412 Equine Compendium May 2002 1A 1B 1C 1D Figure 1 Sedation (A) and induction of anesthesia (B, C, D, and E) are shown. The horse is assisted during the transition from standing to recumbency. A grassy surface provides good footing for anesthetic recovery. The images shown are not of the same horse. 1E largely replaced acepromazine for preanesthetic sedation because they have more reliable sedative, anxiolytic, and analgesic properties. 2,3 Acepromazine is an effective tranquilizer but does not provide analgesia and may cause significant hypotension. α 2 -Agonists are also more effective in combating the muscle hypertonicity and excitement associated with dissociative drugs often used to induce anesthesia. 3 The α 2 -agonists are differentiated by their affinity for α 2 - versus α 1 -adrenergic receptors. 4 6 Adrenoceptor pharmacology is complex and beyond the scope of this article; α 2 -adrenoceptor agonist actions generally have an inhibitory effect on the release of various neurotransmitters, including norepinephrine, serotonin, acetylcholine, and dopamine. 7 α 2 -Adrenoceptors have been identified in the central nervous system, gastrointestinal (GI) tract, uterus, kidney, vascular endothelium and smooth muscle, and platelets. 5 Inhibition of norepinephrine release produces sedation, analgesia, and muscle relaxation. 5,7 Less-desirable effects include hypotension, inhibition of sympathetic tone, and bradycardia. 5 Agonists with the greatest affinity also have the longest duration of action and are the most potent. 4 Detomidine and romifidine are more potent than xylazine, having a much lower effective dose and longer duration of action. Although all three drugs provide comparable sedation in horses, romifidine is associated with more prolonged effects than either detomidine or xylazine. 8 There is an apparent ceiling effect for sedation; increasing the dose of detomidine may improve analgesia but doing so fails to provide a concomitant increase in sedation, although the duration of effect is longer. 9 At equipotent doses, all α 2 -agonists have similar cardiopulmonary effects, including initial hypertension followed by prolonged hypoten-
Compendium May 2002 Field Anesthetic Techniques 413 Table 1. Injectable Drug Combinations to Sedate and Induce Anesthesia in Healthy Adult Horses Approximate Duration Drug Combination Dose (mg/kg) Route of Recumbency (min) Xylazine 1 or 2 IV or IM 15 20 Xylazine 0.6 1 or 1 2 IV or IM 15 30 Diazepam 0.02 0.1 IV Xylazine 0.3 0.5 or 1 2 IV or IM 20 30 Guaifenesin 25 100 IV Xylazine 1 IV 20 30 Butorphanol 0.02 0.04 IV Xylazine 1 IV 20 30 Morphine 0.03 0.06 IV Detomidine 0.02 IV 20 30 Detomidine 0.02 IV 30 40 Tiletamine/zolazepam 1 2 IV Xylazine 0.5 IV 15 20 Guaifenesin 50 100 IV Propofol 2 IV sion, initial bradycardia, dysrhythmia, decreased cardiac output, and mild respiratory depression. 8 Singh and colleagues 10 reported a decrease in GI motility for 3 to 6 hours after xylazine administration. It is plausible, although not documented, that the influence on motility may be greater with such drugs as detomidine because of a longer duration of action. The potential contribution of two drugs in predisposing a horse to develop colic has not been comprehensively addressed, but the usefulness of assessing GI motility in colicky horses receiving these drugs may be limited. Diuresis has been reported after administration of α 2 - adrenergic agonists and may result from osmotic diuresis caused by hyperglycemia or inhibition of antidiuretic hormone. 3,11 Exacerbation of dehydration or hypovolemia is therefore possible, especially with the use of longer-acting α 2 -agonists. 11,12 Xylazine, which has been widely used as a sedative and preinduction agent in horses, provides sedation within 5 minutes of IV administration. 13 16 This agent has been used as an IV premedicant before induction with thiobarbiturates, 2 dissociative agents, 13 16 and propofol. 17 Intramuscular administration of higher doses approximately 20 minutes before induction may be an alternative in fractious horses. 18 Detomidine has also been used with various induction agents but apparently has little advantage over xylazine for preanesthetic sedation. 13,14,19 Because of the increased relative potency and prolonged duration of effect for detomidine, residual sedation and ataxia may be observed. 13,14 Intravenous administration of detomidine 15 to 25 minutes before induction has been suggested because of a delayed onset of peak sedation. Romifidine is also more potent than xylazine and has been used in conjunction with dissociative agents. 20,21 Similar to detomidine, residual sedation can occur but with minimal ataxia. 21 When these agonist drugs do not provide adequate sedation or when the dose needs to be reduced, they may be combined with other drugs. Although they are infrequently used alone to provide tranquilization before anesthetic induction, phenothiazine tranquilizers (e.g., acepromazine) are occasionally combined with α 2 -agonists to enhance sedation. These tranquilizers also provide a potentially beneficial antiarrhythmic effect when used in combination with potent α 2 -agonists. Many opioids, including morphine and butorphanol, may also be used in conjunction with these agonists to augment the degree and duration of sedation and analgesia in horses. 2,22 Because opioids cause excitatory behaviors when administered alone, they are generally given with sedative or tranquilizing drugs. Other side effects include GI ileus and changes in respiratory function. Opioids are controlled substances, and accurate records must therefore be kept. ANESTHETIC AGENTS Induction In North America, the thiobarbiturates were once the mainstay of anesthetic induction but have been largely replaced by newer agents for field anesthesia primarily because of unpredictable inductions and prolonged ataxic recoveries. In horses, contemporary induction protocols include dissociative agents and, to a limited extent, propofol. Of the available dissociative agents, ketamine has become the most widely used. Dissociative anesthetics produce sedation and analgesia by interrupting ascending transmission from the unconscious to the conscious parts of the brain while producing a cataleptoid state. The onset of effect is rapid; and when used in conjunction with α 2 -agonists, induction
414 Equine Compendium May 2002 and recovery are generally smooth. 14 16 Duration of anesthesia is approximately 15 to 20 minutes. 16 The cardiovascular effects of the agonists are to some degree offset by ketamine. Muir and colleagues 16 demonstrated that mean arterial blood pressure in 26 horses was maintained despite xylazine-induced bradycardia and initial hypotension. An apneustic respiratory pattern characterized by a pause following inspiration is common. 23 Skeletal muscle movement and hypertonus occur to varying degrees. 23,24 Adequate sedation before induction is essential with the dissociatives to avoid using higher doses, which are more likely to result in excitatory effects, including rough inductions, inadequate anesthesia, and stormy recoveries. 16,20 Tiletamine/zolazepam (Telazol, Fort Dodge Animal Health, Fort Dodge, IA) a combination of a more potent, longer-acting dissociative agent (tiletamine) and the benzodiazepine zolazepam has been used in combination with xylazine and detomidine in horses. 13,24 26 Prolonged and rough recoveries have been reported with xylazine and tiletamine/zolazepam in ponies 24 and horses. 25,26 Smoother recoveries in horses may be achieved by adding butorphanol to xylazine or by using detomidine before tiletamine/zolazepam induction. 24,26 Duration of anesthesia (i.e., 30 to 40 minutes) is longer with a combination of detomidine and tiletamine/zolazepam than with combined xylazine ketamine. 24 Propofol is a popular induction agent in small animals because its rather unique pharmacokinetics provide both rapid and smooth induction and recovery. Its primary drawbacks are lack of shelf life after the vials have been opened and cost. Because of potential contamination, an open vial of propofol should be discarded within 24 hours. At current prices, an induction dose of propofol for a 500-kg horse costs approximately $50. In two separate studies 27,28 evaluating propofol alone and propofol combined with xylazine or detomidine, Mama and colleagues observed a wide range of anesthetic inductions. Matthews and colleagues 29 also noted initial excitement in some horses after detomidine premedication but found it was alleviated with slower (greater than 2 minutes) administration of propofol. The addition of guaifenesin to combined detomidine/propofol produced smooth induction and recovery and afforded less respiratory depression and a 25% decrease in the propofol dose. 30 Recovery quality reported for all horses in these studies was good to excellent. Given the risk of injury to the horse during anesthetic recovery, propofol may offer some advantage in high-risk patients. Appropriate respiratory support is highly recommended because decreases in respiratory rate, hypercapnia, and hypoxemia are common after induction with propofol. 27 29 Muscle Relaxants In an effort to improve skeletal muscle relaxation and facilitate smoother transition to recumbency during anesthetic induction, guaifenesin and diazepam are often added to the induction protocol. Guaifenesin is a central-acting skeletal muscle relaxant with mild sedative and negligible cardiopulmonary effects. 2 Predictable muscle relaxation and smoother transition from standing to recumbency are reported with guaifenesin use during induction with ketamine 15,31 33 or propofol. 30 Adding guaifenesin to the induction protocol also reduces the dose of induction agent needed and therefore helps minimize drug-related side effects. 2,30 When administering guaifenesin, an IV catheter is highly recommended to prevent extravasation (and resultant tissue damage) of the relatively large volume of drug needed to achieve the desired effect. Solutions with a concentration of less than 10% are suggested to avoid hemolysis. Diazepam, another central-acting muscle relaxant, may also be used as part of the anesthetic induction protocol. The agent is most often used with xylazine and/or ketamine because it provides good muscle relaxation comparable with that of guaifenesin with minimal cardiopulmonary depression and smaller injection volume. 32 However, diazepam is a controlled drug with the potential for abuse by humans. Therefore, maintaining accurate records is necessary. ANESTHETIC MAINTENANCE Options for maintaining longer anesthetic recumbency are available. Generally, these revolve around using longeracting drugs or repeating administration of short-acting drugs. For repeated drug administration, either a bolus or infusion technique may be used. Infusion technique should not be used until after considering the individual drug effects and duration of action. As previously mentioned, recumbency induced with combined xylazine ketamine lasts approximately 15 to 20 minutes, whereas a combination of detomidine and tiletamine/zolazepam provides recumbency for almost twice that duration. In either case, recumbency may be prolonged using additional drug. Most often, and in an effort to provide more control and less residual ataxia, shorter-acting drugs such as xylazine and ketamine are used. Although the dose varies among individuals and is often based on experience, approximately one third of both drugs may be administered if a horse is responding to stimulus and repeated as needed with the understanding that recovery time may increase and recovery quality may be compromised. Because recumbency is being prolonged, appropriate support and monitoring should be provided. Another option for prolonging recumbency is to use
Compendium May 2002 Field Anesthetic Techniques 415 a combination of guaifenesin (50 to 100 mg/kg), an α 2 - agonist (e.g., 1 mg/kg xylazine), and ketamine (1 to 2 mg/kg). 15,31 This is commonly referred to as triple drip and may be used to maintain anesthesia for procedures lasting up to 90 minutes, although 45 to 60 minutes is the recommended safe time limit. 2 Although this combination is effective, caution must be taken to prevent guaifenesin overdose, which is believed to occur at approximately 200 mg/kg. This precaution is especially important because early toxicity is manifested as increased muscle rigidity, which may be misdiagnosed as a lightly anesthetized patient. SUPPORT AND MONITORING Providing support and monitoring signs of anesthesia in nonhospital situations pose challenges, but their importance cannot be overemphasized, especially in high-risk patients or when recumbency will be prolonged. Attention to proper padding and positioning of patients, including pulling the lower forelimb forward, supporting the upper limbs, removing the halter or padding the halter buckle, and protecting the eyes, can facilitate a good outcome and should be practiced, regardless of the length of proposed recumbency. Basic monitoring of heart and respiratory rates is necessary. Although the heart rate decreases after α 2 -agonist administration, it generally returns to normal after a dissociative drug is administered. An irregular and apneustic respiratory pattern, characterized by an inspiratory pause, is common with α 2 -agonist dissociative drug combinations. As the anesthetic depth becomes lighter during drug-induced recumbency, respiration becomes more regular and forceful. When assessing anesthetic depth, this change in respiratory pattern may be more useful than monitoring eyelid reflexes, which are often maintained after a dissociative drug is administered. In adult horses, oxygen supplementation, which is desirable in all recumbent equine patients because hypoxemia is common, is accomplished by insufflating 10 to 15 L/min of oxygen nasally. Oxygen supplementation is strongly recommended in patients with respiratory compromise, in recumbency for longer than 20 to 30 minutes, or anesthetized at high altitude. The need for ventilatory support is less common when using α 2 -agonist dissociative drug combinations, but the ability to intubate and ventilate patients in the event of an unforeseen complication increases the likelihood of a positive outcome. Assessing both systolic blood pressure by Doppler and mean arterial pressure using an aneroid manometer can be useful in compromised patients. When using injectable anesthetic techniques, mean blood pressure generally ranges from approximately 80 to 160 mm Hg in horses. If lower pressures are recorded, the anesthetic plane should be reevaluated and IV fluids administered. RECOVERY Anesthetic recovery in the field creates risks of injury to the horse and attending personnel. A quiet, preferably dark environment with good footing is essential. When possible, recovery should be on either grass or sand because either medium provides comfortable footing and a natural environment (Figure 1). Covering the horse s eyes with a towel or cloth keeps the environment dark and may prevent the horse from prematurely attempting to stand. In general, horses induced with xylazine and ketamine experience smooth recoveries, characterized by a roll to sternal recumbency and a single attempt to stand. However, assistance at the head and tail may be provided if necessary. SUMMARY Intravenous anesthesia in the field can be accomplished using a variety of anesthetic agent combinations. No single anesthetic agent or combination of agents has been devoid of undesirable effects. An ideal protocol, with each anesthetic completely balancing the negative effects of the other, does not currently exist. Inducing recumbency in a 500-kg horse in less than ideal conditions is, therefore, a challenge. Individual variations in response to anesthetics add complexity. Recent advances in the development of anesthetic drugs and drug combinations afford veterinarians more options than before, but field anesthesia in horses remains challenging as the quest for an ideal anesthetic continues. REFERENCES 1. Gillespie JR, Tyler WS, Hall LW: Cardiopulmonary dysfunction in anesthetized, laterally recumbent horses. Am J Vet Res 30: 61 72, 1969. 2. Hubbell JA: Horses, in Thurmon J, Tranquilli W, Benson G (eds): Lumb and Jones Veterinary Anesthesia. Baltimore, Williams & Wilkins, 1996, pp 599 609. 3. England GCW, Clarke KW: Alpha-2 adrenoceptor agonists in the horse A review. Br Vet J 152:641 657,1996. 4. Dart CM: Advantages and disadvantages of using alpha-2 agonists in veterinary practice. J Vet Pharmacol Ther 21:107 111, 1998. 5. Paddleford RR, Harvey RC: Alpha-2 agonists and antagonists. Vet Clin North Am Small Anim Pract 29:737 745, 1999. 6. Schwartz DD, Clark TP: Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. J Vet Pharmacol Ther 21:107 111, 1998. 7. Lammintausta R: Introduction to adrenoceptor pharmacology. Acta Vet Scand 82:11 16, 1986. 8. 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 Pharmacol Ther 15:194 201,1992. 9. Jochle W: Field trial evaluation of detomidine as a sedative and
416 Equine Compendium May 2002 analgesic in horses with colic. Equine Vet J Suppl 7:117 120, 1989. 10. Singh S, McDonnell WN, Young SS, et al: Cardiopulmonary and gastrointestinal motility effects of xylazine/ketamineinduced anesthesia in horses previously treated with glycopyrrolate. Am J Vet Res 57:1762 1769, 1996. 11. Watson ZE, Steffey EP, Van Hoogmoed LM, Snyder JR: Urinary effects of xylazine and general anesthesia in horses. Proc Annu Meet Am Coll Vet Anesth:26, 2001. 12. Hernandez EN, Steffey EP, Camberos LO, et al: Effect of xylazine and detomidine on urine production in horses deprived of food and water. Proc Annu Meet Am Coll Vet Anesth:22, 2001. 13. Matthews NS, Hartsfield SM, Cornick JL, et al: A comparison of injectable anesthetic combinations in horses. Vet Surg 20(4):268 273, 1991. 14. Matthews NS, Miller SM, Slater MR, et al: A comparison of xylazine ketamine and detomidine ketamine anaesthesia in horses. J Vet Anaesth 20:68 72, 1993. 15. Young LE, Bartram D, Diamond M, et al: Clinical evaluation of an infusion of xylazine, guaifenesin and ketamine for maintenance of anesthesia in horses. Equine Vet J 25:115 119, 1993. 16. Muir WW, Skarda RT, Milne DW: Evaluation of xylazine and ketamine hydrochloride for anesthesia in horses. Am J Vet Res 38:195 201, 1977. 17. Mama K, Steffey E, Pascoe P: Evaluation of propofol for general anesthesia on premedicated horses. Am J Vet Res 57:512 516, 1996. 18. Trim C: Principles of chemical restraint, general anesthesia, and surgery, in Colahan P, Mayhew I, Merrit A, et al (eds): Equine Medicine and Surgery, vol I. St. Louis, Mosby, 1999, pp 256 263. 19. Clarke K, Taylor P: Detomidine: A new sedative for horses. Equine Vet J 18:366 370, 1986. 20. Marntell S, Nyman G: Prolonging dissociative anaesthesia in horses with a repeated bolus injection. J Vet Anaesth 23:64 69, 1996. 21. Young L: Clinical evaluation of romifidine/ketamine/halothane anesthesia in horses. J Vet Anaesth 19:89, 1992. 22. Joubert K, Briggs P, Gerber D, et al: The sedative and analgesic effects of detomidine butorphanol and detomidine alone in donkeys. J S Afr Vet Assoc 70:112 118, 1999. 23. Lin HC: Dissociative anesthetics, in Thurmon J, Tranquilli W, Benson G (eds): Lumb and Jones Veterinary Anesthesia. Baltimore, Williams & Wilkins, 1996, pp 599 609. 24. Lin H, Branson R, Thurmon J, et al: Ketamine, Telazol, xylazine and detomidine: A comparative anaesthetic drug combinations study in ponies. Acta Vet Scand 33:241 296, 1992. 25. Marsico F, Tendillo F, Segura G, et al: The tiletamine zolazepam detomidine combination in horses. Vet Surg 20:33, 1993. 26. Wan P, Trim C, Mueller P: Xylazine ketamine and detomidine tiletamine zolazepam anaesthesia in horses. Vet Surg 21:312 318, 1992. 27. Mama K, Steffey E, Pascoe P: Evaluation of propofol as a general anesthetic for horses. Vet Surg 24:188 194, 1995. 28. Mama KR, Pascoe PJ, Steffey EP, Kollias-Baker C: Comparison of two techniques for total intravenous anesthesia in horses. Am J Vet Res 59(10):1292 1297, 1998. 29. Matthews N, Hartsfield A, Hague B, et al: Detomidine propofol anesthesia for abdominal surgery in horses. Vet Surg 28: 196 201, 1996. 30. Aguiar J, Hussni C, Luna S, et al: Propofol compared with propofol/guaiphenesin after detomidine premedication for equine surgery. J Vet Anaesth 20:26 28, 1993. 31. Greene S, Thurmon J, Tranquilli W, et al: Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies. Am J Vet Res 47:2364 2367, 1986. 32. Brock N, Hildebrand S: A comparison of xylazine diazepam ketamine and xylazine guaifenesin ketamine in equine anesthesia. Vet Surg 19(6):468 474, 1990. 33. Taylor P, Kirby J, Shrimpton D, et al: Cardiovascular effects of surgical castration during anaessthesia maintained with halothane or infusion of detomidine, ketamine, and guaifenesin in ponies. Equine Vet J 30:304 309, 1998. ARTICLE #5 CE TEST The article you have read qualifies for 1.5 contact hours of Continuing Education Credit from the Auburn University College of Veterinary Medicine. Choose the best answer to each of the following questions; then mark your answers on the postage-paid envelope inserted in Compendium. 1. When using injectable anesthetics to maintain anesthesia in horses when limited support and monitoring is provided, the recommended safe duration should not exceed minutes. a. 60 b. 30 c. 90 d. 120 e. 75 2. Which of the following complications is associated with anesthetic drug-induced recumbency in horses? a. hypoxemia (low oxygen tension) b. hypercapnia (high carbon dioxide tension) c. injury to the horse or handler d. a and c e. all of the above 3. Which of the following drugs is not an α 2 -agonist? a. xylazine b. etomidate c. romifidine d. medetomidine e. detomidine 4. is commonly associated with IV administration of α 2 -agonists. a. Bradycardia b. Tachycardia c. Increased GI motility d. Decreased urine production e. Excitement
Compendium May 2002 Field Anesthetic Techniques 417 5. Which of the following α 2 -agonists has the shortest duration of action in horses? a. medetomidine b. romifidine c. xylazine d. detomidine e. clonidine 6. Thiobarbiturates are not commonly used for equine field anesthesia because they a. often cause fatal tachyarrhythmia. b. are associated with a rapid, shallow breathing pattern. c. cause muscle hypertonicity and seizurelike activity. d. are associated with unpredictable induction and recovery characteristics. e. are expensive. 7. Which of the following agents are frequently used to induce anesthesia in horses? a. Telazol and ketamine b. xylazine and ketamine c. tiletamine and ketamine d. zolazepam and tiletamine e. butorphanol and tiletamine 8. Xylazine is frequently used to minimize ketamine-associated a. hypertonicity. d. hypotension. b. tachycardia. e. apneustic breathing. c. pain. 9. When comparing diazepam and guaifenesin, diazepam has an advantage in that and a disadvantage in that. a. it is inexpensive; a large volume is needed to obtain an anesthetic effect b. it is a better muscle relaxant; it is very expensive to use in horses c. it is a good analgesic drug; it is a controlled substance d. it reduces the need for other drugs; it is a peripherally mediated muscle relaxant e. a small volume is needed to obtain an anesthetic effect; it is a controlled substance 10. Propofol use in horses has been associated with a. unpredictable anesthetic inductions. b. smooth, controlled anesthetic recovery. c. well-maintained oxygenation and ventilation. d. a and b e. all of the above