Behavioral responses following eight anesthetic induction protocols in horses

Veterinary Anaesthesia and Analgesia, 2002, 29, 207^211 RESEARCH PAPER Behavioral responses following eight anesthetic induction protocols in horses Ann E Wagner DVM, MS, Diplomate ACVP, ACVA, Khursheed R Mama DVM, Diplomate ACVA, Eugene P Ste eyy VMD, PhD, Diplomate ACVA, ECVA, Lucien FBrevardz BS, Peter W Hellyer DVM, MS, Diplomate ACVA Department of Clinical Sciences, and zveterinary Teaching Hospital, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA ydepartment of Surgical and Radiological Sciences (Ste ey), School of Veterinary Medicine, Universityof California, Davis, CA, USA Correspondence: Dr Ann E Wagner, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA. E-mail: aewagner@lamar.colostate.edu Abstract Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 2.4 years (mean SD) of age, and weighing 505 31 kg. Methods After xylazine pre-medication, each of eight horses was anesthetized on four occasions using one of eight di erent anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg 1 ; THIO 6 mg kg 1 þ PRO 0.5 mg kg 1 ; THIO 4 mg kg 1 þ PRO 1 mg kg 1 ; THIO 2 mg kg 1 þ PRO1.5 mg kg 1 ;KET2mgkg 1 ; KET 1.5 mg kg 1 þ PRO 0.5 mg kg 1 ; KET 1mg kg 1 þ PRO 1 mg kg 1 ; KET 0.5 mg kg 1 þ PRO 1.5 mg kg 1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, rst movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration di ered signi cantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO-8 (mean SD, 0.5 0.3 minutes) and longest in horses receiving KET-2 (1.4 0.2 minutes). The best scores for induction quality were associated with KET-1.5 þ PRO-0.5, and the worst scores for induction quality were associated with KET-2, although the di erence was not signi cant.time to rst movement varied signi cantly among drug protocols (p ¼ 0.0133), being shortest in horses receiving KET-2 (12.7 3.6 minutes) and longest in horses receiving THIO-8 (29.9 1.5 minutes). Horses receiving THIO-8 made the greatest number of attempts to attain sternal posture (6.5 4.7) and to stand (1.6 0.8). Horses in the THIO-8 treatment also received the poorest recovery scores (3.3 1.0 and 3.0 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modi es behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine. Keywords anesthesia, equine, recovery from anesthesia, ketamine, propofol, thiopental. Introduction Ketamine (KET) and thiopental (THIO) are commonly used to induce general anesthesia in horses 207

(Hubbell 1996). Propofol (PRO), a newer and more expensive injectable anesthetic, appears to have no advantage over KET or THIO as an induction agent for horses, but has been associated with high quality recoveries (Mama et al.1995). Because recovery from anesthesia in horses is a critical phase which is di cult to control (Hubbell 1996), any drug or combination of drugs which has the potential to improve recovery characteristics warrants further investigation. In an e ort to maximize quality of recovery, maintain quality of induction, and minimize expense associated with use of PRO, this pilot study was undertaken to determine if combining PRO with either KETor THIO would modify behavioral characteristics associated with use of the individual drugs. The hypothesis for this study was that combining PRO with either KET or THIO would improve the quality of induction and recovery characteristics associated with the individual drugs alone. Materials and methods The study protocol was approved by Colorado State University s Animal Care and Use Committee. The subjects were eight mares, 5.5 2.4 years (mean SD) of age, and weighing 505 31 kg. Each mare was anesthetized four times, with a minimum of 72 hours between anesthetic episodes. Food, but not water, was withheld for 12 hours prior to each study. At the beginning of each study, the mares were weighed, and temperature, heart rate, and respiratory rate were obtained. After aseptic preparation of the skin and subcutaneous in ltrationwith 2% lidocaine (2% Lidocaine HCl, Abbott Laboratories, North Chicago, IL, USA), 1 or 2 IV catheters (either 1 or 2 14-SWG catheters) (Abbocath-T, Abbott Laboratories Inc., North Chicago, IL, USA), or 1 14-SWG and1 18-SWG catheter (Insyte, Becton Dickinson, Sandy, UT, USA), depending on the volume of drugs to be administered) were placed in a single jugular vein for administration of anesthetic drugs. The mares were walked to a padded recovery stall where they were sedated with xylazine (TranquiVed,VEDCO Inc., St.Joseph,MO,USA),1mgkg 1 IV. Then ropes were attached to the halter and tail and passed through rings mounted at a height of approximately 6 ft (1.82 m) on opposite walls of the recovery stall. The horses stood near, but not in contact with, the back wall of the stall. Five minutes after xylazine administration, the induction drugs were administered by IV bolus injection. No manual assistance was provided to the horses during induction, other than the support of the halter and tail ropes, which were held taut to promote a safe transitionto lateral recumbency, and removed immediately after induction. Induction drug combinations were assigned using a computer-generated incomplete block design, such that each combination was used four times, and no combination was repeated in any individual horse. The doses for each drug or combination of drugs were based on the premise that equivalent induction doses for each drug were: thiopental (Veterinary Pentothal, Rhone Merieux Inc., Athens, GA, USA), 8 mg kg 1 ; ketamine (Ketaset, Fort Dodge Laboratories, Fort Dodge, IA, USA), 2 mg kg 1 ; and propofol (PropoFlo, Abbott Laboratories, North Chicago, IL, USA), 2mgkg 1 (Muir 1991; Mama et al. 1998). The drugs and combinations studied were (dosages in mg kg 1 ): thiopental 8 (THIO-8); thiopental 6 þ propofol 0.5 (THIO-6 þ PRO-0.5); thiopental 4 þ propofol 1 (THIO-4 þ PRO-1); thiopental 2 þ propofol 1.5 (THIO-2 þ PRO-1.5); ketamine 2 (KET-2); ketamine 1.5 þ propofol 0.5 (KET-1.5 þ PRO-0.5); ketamine 1 þ propofol 1 (KET-1 þ PRO-1); and ketamine 0.5 þ propofol 1.5 (KET-0.5 þ PRO-1.5). Data for administration of PRO alone have been previously published (Mama et al.1995; 1998). Quality of sedation was subjectively scored by two observers (AEW, LFB) on a scale of1^5:1, poor;2, marginal; 3, fair; 4, good; and 5, excellent. Induction drugs were not mixed together, but were administered from individual syringes; when two drugs were used, they were given simultaneously via separate IV catheters. After administration of anesthetic induction drugs, the following times were recorded: time from administration of induction drugs to lateral recumbency; rst movement; attainment of sternal recumbency; and standing. The number of attempts required by each horse to attain sternal recumbencyand then standing position, respectively were counted. In addition, the quality of induction to lateral recumbency, recovery to sternal recumbency, and recovery to standing were subjectively assessed by the same two observers using the numeric scale (1^5) described previously (Mama et al.1996). The observers were blinded to the combination of induction drugs used in each study, and could not see the syringes or catheters used for induction, because the observers were positioned on the opposite side of the horse from where the induction drugs were administered. As soon as each horse became recumbent, a 20- SWG catheter (Insyte, Becton Dickinson, Sandy, UT, 208 Veterinary Anaesthesia and Analgesia, 2002, 29, 207^211

USA) was placed in the transverse facial artery and connected to a calibrated strain gauge transducer (Monitoring Set with Transducer, Cobe, Lakewood, CO, USA) for measurement of arterial blood pressure and collection of arterial blood samples. At 5-minute intervals during recumbency, heart rate (HR), respiratory rate (RR), and mean arterial blood pressure (MAP) were recorded (Escort II, MDE, Arleta, CA, USA), and a sample of arterial blood was collected for analysis of ph, PCO 2 and PO 2. Blood gas samples were maintained anerobically on ice and analyzed within 30 minutes (ABL 505, Radiometer Medical A/S, Copenhagen, Denmark). Behavioral data, including elapsed times, number of attempts to various positions, and quality scores were analyzed by anova (Proc GLM in SAS Version 8), with p < 0.05.Where signi cant di erences were found, multiple comparisons were performed using Tukey s HSD. Cardiorespiratory data were tabulated but not statistically analyzed. Results There were no signi cant di erences between treatments in pre-anesthetic temperature, heart rate, or respiratory rate, nor in sedation scores. Mean sedation score for all horses was 4.3, indicating good-toexcellent sedation quality. Administration of induction drugs was completed within 30-seconds in all cases. Times are tabulated in Table 1, while quality of induction and recovery and number of attempts to achieve sternal recumbency and standing are tabulated in Table 2. Time taken from start of induction drug administration to achieve lateral recumbencydi ered signi cantly(p < 0.0001) among the various drug combinations, being shortest in horses receiving THIO-8 or THIO-6 þ PRO-0.5 (mean SD,0.5 0.3 and 0.5 0.1 minutes, respectively) and longest in horses receiving KET-2 (1.4 0.2 minutes). The best scores for induction quality were associated with KET-1.5 þ PRO-0.5, and the worst scores for induction quality were associated with KET-2, althoughthe di erences were not signi cant. Time to rst movement and to attainment of sternal recumbency varied signi cantly among drug protocols (p ¼ 0.0133 and.0164, respectively), being shortest in horses receiving KET-2 (12.7 3.6 and 21.7 9.3 minutes, respectively) and longest in horses receiving THIO-8 (29.9 1.5 and 47.1 12.9 minutes, respectively). Horses receiving THIO-8 made signi cantly (p ¼ 0.0264) more attempts to attain sternal posture (6.5 4.7) than did horses receiving any other treatment except THIO-6 þ PRO-0.5. Horses in the THIO-8 treatment also received the poorest initial recovery scores (3.3 1.0 for attaining sternal recumbency) but these scores were only signi cant when compared with THIO-2 þ PRO-1.5 and KET-1.5 þ PRO-0.5 (5.0 0 and 4.8 0.4, respectively). The scores for the quality of standing ranged from 3.0 0.7 with the THIO-8 treatment to 5.0 0 with KET-0.5 þ PRO-1.5 but the di erences between treatments were not signi cant. Because the focus of this study was the behavioral observations, and because the short duration of recumbency in many experiments precluded consistent data collection beyond 10 minutes, cardiorespiratory and blood gas data were not analyzed statistically. However, values remained within Table 1 Times (minutes, mean SD) from administration of anesthetic induction drugs to attainment of lateral recumbency, rst spontaneous movement, sternal recumbency, and standing position Time to lateral Time to first movement Time to sternal Time to standing THIO-8 0.5 0.3 c 29.9 1.5 a 47.1 12.9 a 53.1 11.1 a THIO-6 þ PRO-0.5 0.5 0.1 c 24.4 8.4 ab 38.8 6.6 ab 44.2 11.0 ab THIO-4 þ PRO-1 0.6 0.2 c 17.4 4.7 bc 36.5 7.2 abc 45.6 7.0 ab THIO-2 þ PRO-1.5 0.7 0.3 bc 20.1 2.9 abc 35.6 4.0 abc 43.0 10.1 abc KET-2 1.4 0.2 a 12.7 3.6 c 21.7 9.3 c 24.9 8.0 e KET-1.5 þ PRO-0.5 1.1 0.3 ab 18.7 5.6 bc 31.8 7.2 abc 39.1 5.8 bcd KET-1 þ PRO-1 1.1 0.1 ab 15.9 3.8 bc 26.8 6.9 bc 32.8 13.1 cd KET-0.5 þ PRO-1.5 0.9 0.2 bc 19.2 6.2 abc 25.7 4.3 bc 29.1 6.8 d p-value <0.0001 0.0133 0.0164 <0.0001 Within each column values that do not share at least one superscript letter are significantly different from each other. Veterinary Anaesthesia and Analgesia, 2002, 29, 207^211 209

Table 2 Scores (mean SD) for quality of induction to lateral recumbencyand attainment of sternal and standing positions; and number of attempts required to achieve sternal and standing positions Induction quality # Attempts to sternal Quality of sternal # Attempts to standing Quality of standing THIO-8 3.6 0.5 6.5 4.7 a 3.3 1.0 a 1.6 0.8 3.0 0.7 THIO-6 þ PRO-0.5 4.4 0.8 3.0 2.4 ab 4.3 0.8 ab 1.5 0.4 4.0 1.0 THIO-4 þ PRO-1 4.1 0.6 1.5 0.6 b 4.5 0.5 ab 1.0 0 4.5 0.5 THIO-2 þ PRO-1.5 3.9 0.9 1.5 0.5 b 5.0 0 b 1.0 0 4.8 0.4 KET-2 2.9 1.3 1.0 0 b 4.5 0.5 ab 1.0 0 4.4 0.6 KET-1.5 þ PRO-0.5 4.8 0.3 1.3 0.4 b 4.8 0.4 b 1.0 0 4.5 0.5 KET-1 þ PRO-1 4.1 0.5 1.1 0.2 b 4.6 0.4 ab 1.0 0 4.4 0.6 KET-0.5 þ PRO-1.5 4.0 1.1 1.0 0 b 4.6 0.4 ab 1.0 0 5.0 0 p-value NS 0.0264 0.0355 NS NS Within each column values that do not share at least one superscript letter are significantly different from each other. ranges considered clinically acceptable for horses subjected to short-term drug-induced recumbency at the local elevation of approximately 1500 m. For various treatments, mean values for HR were 27^38 beats minute 1 ; for RR, 10^20 breaths minute 1 ;for MAP, 85^125 mm Hg; for ph, 7.41^7.45; for arterial PCO 2, 38^45 mm Hg; and for arterial PO 2, 51^ 66 mm Hg. Typical ambient barometric pressure at Fort Collins, Colorado, is approximately 640 mm Hg; typical values (mean SE) for PaCO 2 and PaO 2 in standing, nonsedated horses are 41.8 2.5 and 75.8 6.8 mm Hg, respectively (Mama, unpublished data). Discussion Results of this study indicate that qualityof induction of anesthesia, which was generally fair to excellent, was not signi cantly altered by the addition of varying fractions of PRO to either KET or THIO. Despite the lack of statistically signi cant di erences in this small number of horses, it is interesting to note that KET alone, commonly used for eld anesthesia of horses, was associated with inductions that were consistently rated poorest in quality (mean score, 2.9 versus scores of 3.6^4.8 for other inductions). In a previously published study of six thoroughbred horses pre-medicated with the same dosage of xylazine, induction with PRO 2 mg kg 1 resulted in a mean induction quality score of 3.5, which suggests that KET as a sole induction agent may be qualitatively even less satisfactory than PRO used alone (Mama et al. 1996). From a clinical perspective, it appears that combining either KETor PRO with other induction drugs mayo er an opportunity to enhance quality of induction. Although induction to lateral recumbency was faster when THIO or both THIO and PRO were used, this time di erence may not be clinically important. All of the induction techniques studied produced lateral recumbency within about 1.5 minutes, which is a clinically acceptable time frame for most circumstances. Duration of anesthesia, as indicated by time from induction to rst spontaneous movement, to sternal recumbency, and to standing, was generally longest when THIO alone, or combinations incorporating a high proportion of THIO were used. However, as no noxious stimuli were applied during this study, the duration during which surgery could have been performed is not known. Recovery from short-term IVanesthesia in horses is generally smoother when KET, rather than THIO, is used (Muir1991). In the study reported here, horses which received THIO alone required signi cantly more attempts to attain sternal recumbency than did horses which received almost any other induction. Not surprisingly, scores for quality of recovery to sternal recumbency were also poorest for horses which received THIO alone. Conversely, the best scores for quality of recovery to sternal recumbency were associated with use of THIO-2 þ PRO-1.5, and KET-1.5 þ PRO-0.5 and these scores were signi cantly better than THIO-8. Propofol is popular in human anesthesia because of rapid awakening with less hangover than is associated with barbiturates (Stoelting 1987). To date, PRO has not been as widely used in horses as in small animals, partly because of 210 Veterinary Anaesthesia and Analgesia, 2002, 29, 207^211

its expense, and partly because PRO administration to horses does not necessarily produce smooth inductions (Mama et al. 1995, 1996). However, the current study suggests that PRO may have a place in equine anesthesia, in that substituting PRO for a portion of the induction dose of THIO might promote a smoother, more co-ordinated recovery, and combining PRO with KETo ers the possibility of improving both induction and recovery. Although no signi cant di erences among treatments were detected for number of attempts required to stand, or for quality of recovery to standing, horses which received THIO alone or THIO-6 þ PRO-0.5 tended to require more attempts to stand and to have poorer scores for quality of recovery to standing. Although each treatment was used in only four horses, the study utilized a computer generated randomized incomplete block design that should minimize e ects of any individual horse. While the idiosyncrasies of an individual animal could potentially in uence overall results, the narrow standard deviations for recovery parameters suggest this was not the case. While limited in size and scope. the study reported here suggests that behavioral characteristics associated with KET or THIO induction and recovery in horses can be improved upon by combining either drug with PRO. Cardiorespiratory variables were maintained in a clinically acceptable range, no matter which induction drug or combination was used. Acknowledgements This project was supported by funding from the College Research Council, College of Veterinary Medicine and Biomedical Sciences, Colorado State University. The authors wish to thank Sue Duval for statistical consultation. References Hubbell JAE (1996) Anesthesia and immobilization of speci c species ^ horses. In: Lumb and Jones Veterinary Anesthesia (3rd edn). Thurmon JC, Tranquilli WJ, Benson GJ (eds).williams & Wilkins, Baltimore, USA, pp. 606^608. Mama KR, Pascoe PJ, Ste ey EP et al. (1998) Comparison of two techniques for total intravenous anesthesia in horses. Am J Vet Res 59,1292^1298. Mama KR, Ste ey EP, Pascoe PJ (1995) Evaluation of propofol as a general anesthetic for horses.vet Surg 24,188^194. Mama KR, Ste ey EP, Pascoe PJ (1996) Evaluationof propofol for general anesthesia in pre-medicated horses. Am J Vet Res 57, 512^516. Muir WW (1991) Intravenous anesthetics and anesthetic techniques in horses. In: EquineAnesthesia ^ Monitoring and Emergency Therapy. Muir WW, Hubbell JAE (eds). MosbyYearBook,St.Louis,USA,pp.281^309. Stoelting RK (1987) Pharmacology and Physiology in Anesthetic Practice. JB Lippincott Co., Philadelphia, USA, p.143. Received13 November 2001; accepted1may 2002. Veterinary Anaesthesia and Analgesia, 2002, 29, 207^211 211