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Postanesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris)
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Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris) Shawna J. Hawkins MS, DVM , Grayson A. Doss DVM , Christoph Mans Dr. med. vet. PII: DOI: Reference:
S1557-5063(19)30185-5 https://doi.org/10.1053/j.jepm.2019.10.005 JEPM 50261
To appear in:
Journal of Exotic Pet Medicine
Please cite this article as: Shawna J. Hawkins MS, DVM , Grayson A. Doss DVM , Christoph Mans Dr. med. vet. , Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris), Journal of Exotic Pet Medicine (2019), doi: https://doi.org/10.1053/j.jepm.2019.10.005
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
1
Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris)
Shawna J. Hawkins, MS, DVM, Grayson A. Doss, DVM, Christoph Mans, Dr. med. vet.
From the Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI
*Corresponding author: [email protected]
2
Abstract
Background African pygmy hedgehogs (Atelerix albiventris) are popular companion animals that require chemical immobilization to facilitate examination. The objective of this study was to evaluate effects of isoflurane anesthetic duration on recovery time, food intake and body weight following anesthesia in African pygmy hedgehogs.
Methods Eight healthy, adult hedgehogs (4 male, 4 female) were used in this randomized, blinded, complete cross-over study. Two different isoflurane anesthetic durations of 15 minutes (ISO15) and 45 minutes (ISO45) were evaluated with a 2-week wash-out period between treatments. Physiologic parameters, reflexes and behaviors were monitored to assess anesthesia quality. Food intake (grams of food per kg of body weight) and body weight were measured both before and after anesthesia to assess post-sedation effects.
Results There was no statistically significant difference in body weight between or within treatments following the anesthetic events. A decrease in post-anesthetic food intake from baseline values was noted with both treatments (ISO15: -16% [-40% to 167%]); (ISO45: -13% [-38% to 43%]), but these fluctuations were not statistically significant between or within treatments. The total amount of food consumed per hedgehog over the 6 days following anesthesia was 99 ± 23 g/kg (ISO15) and 108 ± 28 g/kg (ISO45, P = 0.15).
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Conclusions and clinical relevance Differences in duration of isoflurane anesthesia of either 15 or 45 minutes does not have a clinically relevant effect on recovery time or post-anesthetic food intake in hedgehogs.
Keywords Anesthetic; bradycardia; Erinaceidae; Eulipotyphla; food intake; inhalant
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Background African pygmy hedgehogs (Atelerix albiventris) are popular companion animals that require chemical immobilization to facilitate examination due to their unique defense mechanism of rolling into a defensive ball, also known as ‘balling-up’, when startled. The presence of modified hollow hairs or spines along the dorsum dissuades potential predators from prehending the hedgehog.1 Isoflurane anesthesia, typically via chamber induction and maintained in 100% oxygen via facemask, is the most common method of immobilization in hedgehogs for physical examination, diagnostics, and procedures.2-4 Endotracheal intubation in the hedgehog is not routinely performed due to their small size and difficulty visualizing the trachea. A number of anecdotal injectable anesthetic protocols for African pygmy hedgehogs exist but recommended dosages vary widely, necessitating caution with their use.1-2,4-7 Injectable anesthetics in hedgehogs have been reported to be unreliable with rough, prolonged recovery periods, with inhalant anesthesia favored instead.3,8-9 A recent study evaluating alfaxalone-midazolam and ketamine-midazolam injectable sedation in African pygmy hedgehogs provided suitable alternatives to inhalant anesthesia for immobilization.10 Both protocols provided a deep level of sedation appropriate for basic procedures; however, ketamine-midazolam did result in a transient post-anesthetic decrease in food intake which lasted up to 3 days.10 Although isoflurane is commonly recommended for routine procedures in pet hedgehogs, little information exists regarding its safety. Inhalant anesthetics are known to induce dosedependent cardiovascular and respiratory depression in small mammals due to decreased blood pressure which can be life threatening.11 Post-anesthetic effects of isoflurane in small animal and exotic pet medicine include dose-dependent gastrointestinal effects such as nausea, vomiting, and ileus although ferrets have been shown to be insensitive to the gastrointestinal effects of
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isoflurane.12,13, 14 Effect of isoflurane on post- anesthetic food intake has been evaluated in chinchillas and ferrets with no significant effect on food intake observed.12, 15 Maintaining normal post anesthetic food intake is particularly important in small mammals due to their high metabolic rate, potential for rapid hypoglycemia in a fasting state, and high rates of obesity seen in captivity which can readily lead to hepatic lipidosis when appetite is compromised.2,11 The primary objective of this study was to evaluate the effect of duration of isoflurane anesthesia on recovery time, food intake, and body weight. Our hypotheses were that longer isoflurane anesthetic duration would result in a longer recovery time but have comparable postanesthetic effects on food intake and body weight and that isoflurane anesthesia would have less of a negative effect on food intake and body weight when compared with reported injectable sedation protocols in this species.
Methods Animals This study was approved by the (XX – blinded for review purposes). Eight captive bred African pygmy hedgehogs (4 male, 4 female), 9-12 months old, with a mean ± SD weight of 461 ± 124 g were used in this study. Animals were housed in a climate-controlled room with a 12:12h photoperiod and a room temperature of 27°C (80°F). Hedgehogs were kept individually in ventilated plastic enclosures measuring 84 x 51 x 36 cm (33 x 20 x 14 in). Each enclosure was lined with cardboard substrate, contained a hide box and exercise wheel, and shredded paper was provided for digging. Hedgehogs were offered fresh water ad libitum in a bowl and maintained on a commercial hedgehog diet. All hedgehogs were acclimated to the housing for several months prior to the study and were deemed healthy based upon baseline blood-work, serial
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physical examinations and long-term monitoring of food intake and body weight. Hedgehogs were fasted at least 80 minutes prior to anesthesia (median: 125 min, range: 80-220 min). Trials occurred in a separate climate-controlled room maintained within 3°C (5°F) of the housing room.
Anesthetic protocols and study design Hedgehogs were anesthetized with two separate durations of isoflurane anesthesia: 15 minutes (ISO15) and 45 minutes (ISO45) in a randomized, blinded, complete crossover study. The observer that evaluated recovery time was unable to be blinded to treatment. There was a minimum of a 2-week washout period between anesthetic events. The two durations of anesthesia were chosen to mimic clinically relevant scenarios with ISO15 representing a brief anesthetic event for baseline diagnostics such as physical examination and venipuncture and ISO45 representing an anesthetic duration needed for diagnostic imaging or simple procedures. Anesthetic induction was performed in a plastic chamber measuring 33 x 20 x 12.7 cm (13 x 8 x 5 in) with isoflurane (Isoflurane USP; Clipper Distribution Company, St. Joseph, MO, USA) at 4% in 100% oxygen (4 L/min) provided for a period of 5 minutes. The 5 minute induction time was included in the total anesthetic time for each treatment. The hedgehogs were then removed from the induction chamber and anesthesia was maintained with isoflurane (2-3%) and 100% oxygen (2 L/min) administered via facemask. After the intended duration of anesthesia was reached, the oxygen line was flushed for 2 seconds with 100% oxygen before providing flow-by oxygen (2 L/min) for recovery. Depth of anesthesia was monitored every 5 minutes using physiological parameters, reflexes and behaviors to maintain a light to moderate anesthetic plane characterized by loss of righting reflex and persistent maintenance of at least one of the following parameters/reflexes: jaw tone, palpebral reflex or pelvic limb withdrawal. The
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administered percentage of isoflurane varied between 2-3% in order to maintain hedgehogs at the desired depth of anesthesia.
Data collection All anesthetic monitoring was performed and recorded by a single investigator. Physiologic parameters including heart rate (HR), respiratory rate (RR), peripheral capillary oxygen saturation (SpO2%) and rectal temperature were recorded every 5 minutes after anesthetic induction. Heart rate and SpO2% were measured using a pulse oximetry probe placed on a metacarpal pad. Rectal temperature was obtained using a rodent rectal temperature probe inserted between 1-1.5 cm (Model 60001020, Barnant Company, Barrington, IL, USA). Respiratory rate was obtained by counting visible thoracic expansions. If the hedgehog was emitting defensive hissing vocalizations, the RR was routinely >100 brpm and was subsequently recorded as 100 brpm for data analysis purposes. Due to the defensive nature of the hedgehogs, RR was the only baseline parameter able to be recorded prior to onset of anesthesia. Thermal support was provided at all times during anesthesia through use of a recirculating water blanket. Palpebral, righting, and pelvic limb withdrawal reflexes as well as jaw tone were evaluated at 5-minute intervals after induction. Initially, balling-up and righting reflex were evaluated as two separate parameters; however, sedation scoring was consistently identical so righting reflex and balling-up response were considered interchangeable. Most reflexes and jaw tone were graded as normal, reduced or absent. Palpebral reflex was graded as present or absent. Hedgehogs with a normal righting reflex balled-up when handled to the point the observer could not restrain the hedgehog by scruffing the spiny dorsum or place a stethoscope on the ventral thorax. A reduced righting reflex was defined as the hedgehog rolling into an incomplete, loose
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ball when handled. An absent righting reflex occurred when the hedgehog did not attempt to roll into a ball when handled. The pelvic limb withdrawal reflex was assessed by applying pressure across the metatarsal bones with hemostatic forceps using steady, gentle force and observing for withdrawal of the pelvic limb away from the stimulus. The forceps were cushioned with plastic tubing to minimize trauma. Pelvic limb withdrawal was scored as normal if withdrawal happened immediately after applying pressure over the metatarsal bones, decreased if the withdrawal was delayed, or absent if no withdrawal occurred. Jaw tone was considered normal if the attempt to open the mouth was met with great resistance and an oral examination could not be performed. Jaw tone was graded as reduced if the mouth could be opened but the animal responded to manipulation of the tongue with jaw movement and would not allow the tongue to be pulled out of the mouth. Jaw tone was scored as absent if the mouth could be opened entirely with no resistance and the hedgehog did not respond to manipulation of the tongue with jaw movement. Physiologic parameters, reflexes and jaw tone were monitored until hedgehogs were recovered, which was defined as the return of a normal righting reflex, since this precluded evaluation of all other parameters. Body weight and food intake (g food per kg body weight) were measured every 24 hours in the morning during the same 1-hour period by a single recorder blinded to treatment. Hedgehogs were weighed in a plastic container using a gram scale (MyWeigh KD 7000, Phoenix, AZ, USA). Baseline values for body weight and food intake were calculated by averaging measurements obtained 48 and 24 hours prior to each trial and post-anesthetic data collection was then continued for 6 days.
Statistical analysis
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Randomization of the treatment sequence was performed using free online software (Research Randomizer version 4.0; Urbaniak GC, Plous S, Middletown, CN, USA.) and data analyzed using commercial software (SigmaPlot 13; Systat Software, San Jose, CA, USA). The data were tested for normality using the Shapiro-Wilk test and equal variance using the Brown Forsythe test. Simple data transformation or ranking was performed when necessary. Fixed effects of treatment and time on HR, RR, rectal temperature, and SpO2% was analyzed using one-way repeated measures ANOVA. Fixed effects of treatment and time on food intake and body weight were analyzed using two-way repeated measures ANOVA, and post-hoc analysis performed using the Holm-Sidak method. Comparisons between total food consumed between treatments were performed using a paired t-test. Statistical significance was defined as P < 0.05. Data are reported as mean ± SD unless indicated otherwise.
Results Time to loss of righting reflex was <5 minutes in all animals after start of induction. Recovery time was not statistically significantly different between treatments (median: 10 minutes; range: 5-10 minutes). Physiologic parameters, reflexes and jaw tone were recorded every 5 minutes for a total of 24 time points for ISO15 and a total of 72 time points for ISO45. For ISO15 treatment, palpebral was absent in 21/24 timepoints (88%) and jaw tone was absent in 18/24 timepoints (75%). For ISO45 treatment, palpebral was lost in 46/72 timepoints (64%) and jaw tone was absent in 60/72 timepoints (83%). In contrast, pelvic limb withdrawal was absent in only 24 (17%) ISO15 time points and 20/72 (28%) ISO45 time points.
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Heart rate was statistically significantly higher at 5 minutes post-anesthesia induction compared to other recorded time points for both treatments (ISO 15: 212 ± 11, ISO 45: 203 ± 10). Peak decrease in HR occurred at the 35 and 40-minute time points after induction of isoflurane for ISO45 with a mean decrease of 15 ± 16% and 18 ± 15%, respectively. Spontaneous ventilation was maintained in all hedgehogs at all time points for both treatments. Compared to baseline values there was no statistically significant difference in RR or rectal temperature regardless of duration of isoflurane anesthesia. Median temperatures at 5 minutes post induction was 34°C; range 33.4-35.5°C (93.3° F, range 92.2-95.9° F) and median temperatures after cessation of anesthesia were 33.9°C, range 33.1-34.7 °C (93°F, range 91.694.5° F) and 34°C, range 32.5-34.2°C (93.3°F, range 90.5-93.5°F) for ISO 15 and ISO 45, respectively. All hedgehogs maintained SpO2% measurements above 95% at all time-points for both treatments. A decrease in post-anesthetic food intake was noted with both ISO15 and ISO45 (Figure 1). The decreases in food intake were not statistically significantly different between or within treatments. The median percentage change in food intake was greatest over the 24 hours after anesthesia (Day 1) for both treatments (ISO15: -16%, range -40% to 169%; ISO45: -13%, range -56% to 43%). The total amount of food consumed over the 6 days following anesthesia was not statistically significantly different between treatments (P = 0.15) with ISO15 hedgehogs consuming 99 ± 23 g/kg and ISO45 hedgehogs consuming 108 ± 28 g/kg of food. There was no statistically significant difference in body weight between or within treatment following the anesthetic events. Body weight for ISO45 hedgehogs on day 6 (+2 ± 0.5%) post-anesthesia was statistically significantly (P = 0.007) higher than baseline. A nonstatistically significant (P = 0.133) increase in body weight was noted for ISO15 hedgehogs on
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Day 6 post-anesthesia (+1.1 ± 0.5%) when compared to baseline values. On day 6 post anesthesia, body weight had increased by 1.1 ± 0.5% for ISO15 and 2 ± 0.5% for ISO45 compared to baseline.
Discussion Isoflurane anesthesia via facemask had minimal effect on post-anesthetic food intake and body weight in African pygmy hedgehogs. There was no difference in recovery time in this study, regardless of isoflurane anesthetic duration. Hedgehogs anesthetized with isoflurane for 45 minutes in this study had shorter recoveries than hedgehogs sedated for the same period with alfaxalone-midazolam or ketaminemidazolam (mean: 15-20 min).10 The injectable protocols evaluated were only partially reversible which may have contributed to a longer recovery time compared to isoflurane anesthesia. Faster recovery times with inhalant anesthesia are well documented in exotic pet medicine where inhalant anesthesia is the preferred immobilization method for many species.16-18 Subjectively, recoveries from isoflurane anesthesia appear to be of better quality when compared to ketamine-midazolam immobilization in hedgehogs.10 The decrease in HR over time may reflect either an overall bradycardic effect of isoflurane anesthesia or an initial elevation of the HR from tachycardia induced by the stress of handling and induction. Bradycardia is a well-documented dose-dependent effect of isoflurane anesthesia in small mammals.11 The hedgehogs in this study could be considered mildly bradycardic or within normal range for anesthetized hedgehogs depending on which reference is used for comparison.19,20 The decreases in HR noted in this study, while statistically significant, was not considered to be clinically relevant.
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Maintenance of a similar depth of anesthesia in each hedgehog for the entire anesthetic length using a fixed administered isoflurane percentage was impossible, as anesthetic depth was highly dependent on the amount of manipulation of the anesthetized hedgehog. The minimal alveolar concentration (MAC) of isoflurane has not been established in hedgehogs; however, it would be expected to be similar to the MAC of other zoological companion animals with high metabolic rates such as the rat (1.3%), ferret (1.5%) or rabbit (2%).21,22,23 Evaluation of pelvic limb withdrawal reflex, righting reflex, and rectal temperature often resulted in a need to increase isoflurane percentage temporarily as hedgehogs began to show signs of arousal (limb twitching, attempting to ball-up) during measurement. This reactivity to physical stimuli is in contrast to immobilization with alfaxalone-midazolam. Subcutaneous alfaxalone-midazolam provided heavy sedation in hedgehogs with little to no reaction to the same stimuli performed in this study.10 Jaw tone was lost in the majority of hedgehogs in this study and, although not attempted, endotracheal intubation could likely be performed based on lack of response to tongue extension. Complete loss of jaw tone was observed in significantly more observation time points in this study compared to alfaxalone-midazolam and ketamine-midazolam injectable protocols which may indicate isoflurane anesthesia results in comparatively less muscle rigidity.10 Despite providing heat support, all hedgehogs were considered hypothermic at all time points compared to reported normal rectal temperatures for this species (normal: 35.5-37°C [95.7-98.6°F])19. Mean final temperature for each group was within 0.5°F of initial temperature indicating supplemental heat support contributed to maintenance of body temperature. Hypothermia is well documented in sedated or anesthetized small mammals where depressed thermoregulatory function is a common side-effect.11 Rectal temperatures observed in this study
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and for hedgehogs immobilized with two injectable protocols were similar.10 Based on these findings, thermal support should be started immediately for hedgehogs anesthetized with isoflurane, regardless of anesthetic duration. All hedgehogs were fasted a minimum of 80 minutes prior to anesthesia. Fasting recommendations in hedgehogs are inconsistent. Some reports recommend that hedgehogs be fasted for 4-6 hours for procedures lasting longer than 20 minutes while others recommend fasting is unwarranted due to the high metabolic rate and small glucose reserves of this species.12,7,24
None of the adverse gastrointestinal effects typically seen with an inappropriately short
fasting period (regurgitation, vomiting) were noted during this study suggesting that a prolonged fasting period prior to immobilization in this species may be unnecessary. Duration of isoflurane anesthesia did not have a statistically significant effect on postanesthetic food intake for the hedgehogs in this study. However, there was an initial decrease from baseline values during the first 48 hours following anesthesia which may become clinically relevant in debilitated individuals. This decrease in food intake was similar to that seen in hedgehogs immobilized with alfaxalone-midazolam but significantly less than the decrease seen following ketamine-midazolam immobilization.10 Isoflurane anesthesia did not result in a significant change in body weight in hedgehogs, which is similar to findings with alfaxalone-midazolam immobilization in this species.10 This is in contrast to a significant decrease in body weight seen following ketamine-midazolam immobilization in hedgehogs.10 Mean body weight for the ISO45 treatment was found to be statistically greater on day 6 following post-anesthesia, although this was not present in hedgehogs anesthetized for 15
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minutes. Although statistically significant, this discrepancy is likely not clinically relevant considering the increase in mean body weight was < 3% of baseline values. Limitations in this study include the inability to obtain baseline measurements for most monitoring parameters which was precluded by the normal defensive behavior of the hedgehogs. This behavior also prevented collection of further monitoring data after return of the righting reflex during recovery. Additionally, the inability to administer a fixed percentage of isoflurane administered to each animal may have affected the results of this study. Another limitation is the small sample size of the study, which may have resulted in type 2 statistical errors. However, given that the differences between treatments were small and there were no clinically relevant changes in any of the measured parameters, a large number of animals would have been necessary in order to have a sufficiently powered study and subsequently avoid type 2 errors.
Conclusions In conclusion, 15 or 45 minutes of isoflurane anesthesia via facemask does not result in a prolonged recovery time or have a clinically relevant impact on post-anesthetic food intake or body weight in African pygmy hedgehogs. Compared to studied injectable immobilization protocols in hedgehogs, isoflurane anesthesia resulted in less or similar effects on postimmobilization food intake and body weight. Speed and quality of isoflurane anesthesia recovery was considered superior when compared with published injectable sedation protocol
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References 1. Heatley JJ. Hedgehogs. In: Mitchell MA, Tully TN, editors. Manual of exotic pet practice. 1st ed. St. Louis: Saunders Elsevier; 2009, p. 433-455. 2. Ivey E, Carpenter JW. Hedgehogs. In: Quesenberry KE, Carpenter JW, editors. Ferrets, rabbits, and rodents clinical medicine and surgery. 3rd ed. St. Louis: Elsevier; 2012, p. 411428. 3. Mori M, O’Brien SE. Husbandry and medical management of African hedgehogs. Iowa State Univ Vet 1997;59(2)64-72. 4. Hoefer HL. Hedgehogs. Vet Clin N Am-Small 1994;24(1)113-120. 5. Földvári G, Jahfari S, Rigó K, Szekeres S, Majoros G, Tóth, Molnár V, Coipan EL, Sprong H. Candidatus Neoehrlichia mikurensis and Anaplasma phagocytophilum in urban hedgehogs. Emerg Infect Dis 2014;20(3)496-498. 6. Lightfoot TL. Therapeutics of African pygmy hedgehogs and prairie dogs. Vet Clin North Am Exot Anim Pract 2000;3:155-172. 7. Heard D. Insectivores. In: West G, Heard D, Caulkett N. editors. Zoo animal and wildlife immobilization and anesthesia. 2nd ed. Ames: Wiley Blackwell; 2014, p. 529-532. 8. Larsen RS, Carpenter JW. Husbandry and medical management of African hedgehogs. Vet Med-US 1999;877-888. 9. Pye GW. Marsupial, insectivore, and chiropteran anesthesia. Vet Clin North Am Exot Anim Pract 2001;4:211-237. 10. Hawkins SJ, Doss GA, Mans C. Evaluation of subcutaneous alfaxalone-midazolam and ketamine-midazolam sedation protocols in African pygmy hedgehogs (Atelerix albiventris). J Am Vet Med Assoc 2019; In Revision.
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11. Hawkins MG, Pascoe PG. Anesthesia, analgesia, and sedation of small mammals. In: Quesenberry KE, Carpenter JW, editors. Ferrets, rabbits, and rodents clinical medicine and surgery. 3rd ed. St. Louis: Elsevier; 2012, p. 429-451. 12. Horn CC, Meyers K, Pak D, Nagy A, Apfel CC, Wiliams BA. Post-anesthesia vomiting: impact of isoflurane and morphine on ferrets and musk shrews. Physiol Behav 2012;106(4):562-568. 13. Plumb DC. Plumb’s veterinary drug handbook. 8th ed. Ames: Wiley-Blackwell; 2015. 14. Torjman MC, Joseph JI, Munsick C, Morishita M, Grunwald Z. Effects of isoflurane on gastrointestinal motility after brief exposure in rats. Int J Pharm 2005;294:65-71. 15. Fox L, Snyder LBC, Mans C. Comparison of dexmedetomidine-ketamine with isoflurane for anesthesia of chinchillas (Chinchilla lanigera). J Am Assoc Lab Anim 2016;55(3):312-316. 16. Wolf TM. Ferrets. In: Mitchell MA, Tully TN, editors. Manual of exotic pet practice. 1st ed. St. Louis: Saunders Elsevier; 2009, p. 345-374. 17. Vennen KM, Mitchell MA. Rabbits. In: Mitchell MA, Tully TN, editors. Manual of exotic pet practice. 1st ed. St. Louis: Saunders Elsevier; 2009, p. 375-405. 18. Longley L. Anaesthesia of other small mammals. In: Longley L, Fiddes M, O’Brien M, editors. Anaesthesia of exotic pets. 1st ed. St. Louis: Saunders Elsevier 2008:96-102. 19. Helmer PJ, Carpenter JW. Hedgehogs. In: Carpenter JW, editor. Exotic animal formulary. 5th ed. St. Louis: Elsevier 2018;444-459. 20. Black PA, Marshall C, Seyfried AW, Bartin AM. Cardiac assessment of African hedgehogs (Atelerix albiventris). J Zoo Wildl Med 2011 Mar;42(1):49-53. 21. Drummond JC. MAC for halothane, enflurane, and isoflurane in the New Zealand white rabbit: And a test for the validity of MAC determinations. Anesthesiology 1985;62:316-338.
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22. Mural I, Housmans PR. Minimum alveolar concentration (MAC) of halothane, enflurane, and isoflurane in ferrets. Anesthesiology 1988;68:783-786. 23. Criado AB, Gómez de Seguar IA, Tendillo FJ, Marsico F. Reduction of isoflurane MAC with buprenorphine and morphine in rats. Lab Anim 2000;34:252-259. 24. D’Agostino J. Insectivores (Insectivora, Macroscelidea, Scandentia). In: Miller REM, Fowler ME, editors. Fowler’s zoo and wild animal medicine. 8th edition. St. Louis: Elsevier 2015; 275-281.
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Figure legends
Figure 1. Box and whisker plot of daily food intake (g of food per kg of body weight) in 8 African pygmy hedgehogs (Atelerix albiventris) immobilized with isoflurane administered via facemask for either 15 minutes (ISO15) or 45 minutes (ISO45). Baseline and Day 1 measurements correspond with food intake over either the 24-hour period prior to or after the anesthetic event, respectively.
Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris) Shawna J. Hawkins MS, DVM , Grayson A. Doss DVM , Christoph Mans Dr. med. vet. PII: DOI: Reference:
S1557-5063(19)30185-5 https://doi.org/10.1053/j.jepm.2019.10.005 JEPM 50261
To appear in:
Journal of Exotic Pet Medicine
Please cite this article as: Shawna J. Hawkins MS, DVM , Grayson A. Doss DVM , Christoph Mans Dr. med. vet. , Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris), Journal of Exotic Pet Medicine (2019), doi: https://doi.org/10.1053/j.jepm.2019.10.005
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
1
Post-anesthetic effects of two durations of isoflurane anesthesia in African pygmy hedgehogs (Atelerix albiventris)
Shawna J. Hawkins, MS, DVM, Grayson A. Doss, DVM, Christoph Mans, Dr. med. vet.
From the Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI
*Corresponding author: [email protected]
2
Abstract
Background African pygmy hedgehogs (Atelerix albiventris) are popular companion animals that require chemical immobilization to facilitate examination. The objective of this study was to evaluate effects of isoflurane anesthetic duration on recovery time, food intake and body weight following anesthesia in African pygmy hedgehogs.
Methods Eight healthy, adult hedgehogs (4 male, 4 female) were used in this randomized, blinded, complete cross-over study. Two different isoflurane anesthetic durations of 15 minutes (ISO15) and 45 minutes (ISO45) were evaluated with a 2-week wash-out period between treatments. Physiologic parameters, reflexes and behaviors were monitored to assess anesthesia quality. Food intake (grams of food per kg of body weight) and body weight were measured both before and after anesthesia to assess post-sedation effects.
Results There was no statistically significant difference in body weight between or within treatments following the anesthetic events. A decrease in post-anesthetic food intake from baseline values was noted with both treatments (ISO15: -16% [-40% to 167%]); (ISO45: -13% [-38% to 43%]), but these fluctuations were not statistically significant between or within treatments. The total amount of food consumed per hedgehog over the 6 days following anesthesia was 99 ± 23 g/kg (ISO15) and 108 ± 28 g/kg (ISO45, P = 0.15).
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Conclusions and clinical relevance Differences in duration of isoflurane anesthesia of either 15 or 45 minutes does not have a clinically relevant effect on recovery time or post-anesthetic food intake in hedgehogs.
Keywords Anesthetic; bradycardia; Erinaceidae; Eulipotyphla; food intake; inhalant
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Background African pygmy hedgehogs (Atelerix albiventris) are popular companion animals that require chemical immobilization to facilitate examination due to their unique defense mechanism of rolling into a defensive ball, also known as ‘balling-up’, when startled. The presence of modified hollow hairs or spines along the dorsum dissuades potential predators from prehending the hedgehog.1 Isoflurane anesthesia, typically via chamber induction and maintained in 100% oxygen via facemask, is the most common method of immobilization in hedgehogs for physical examination, diagnostics, and procedures.2-4 Endotracheal intubation in the hedgehog is not routinely performed due to their small size and difficulty visualizing the trachea. A number of anecdotal injectable anesthetic protocols for African pygmy hedgehogs exist but recommended dosages vary widely, necessitating caution with their use.1-2,4-7 Injectable anesthetics in hedgehogs have been reported to be unreliable with rough, prolonged recovery periods, with inhalant anesthesia favored instead.3,8-9 A recent study evaluating alfaxalone-midazolam and ketamine-midazolam injectable sedation in African pygmy hedgehogs provided suitable alternatives to inhalant anesthesia for immobilization.10 Both protocols provided a deep level of sedation appropriate for basic procedures; however, ketamine-midazolam did result in a transient post-anesthetic decrease in food intake which lasted up to 3 days.10 Although isoflurane is commonly recommended for routine procedures in pet hedgehogs, little information exists regarding its safety. Inhalant anesthetics are known to induce dosedependent cardiovascular and respiratory depression in small mammals due to decreased blood pressure which can be life threatening.11 Post-anesthetic effects of isoflurane in small animal and exotic pet medicine include dose-dependent gastrointestinal effects such as nausea, vomiting, and ileus although ferrets have been shown to be insensitive to the gastrointestinal effects of
5
isoflurane.12,13, 14 Effect of isoflurane on post- anesthetic food intake has been evaluated in chinchillas and ferrets with no significant effect on food intake observed.12, 15 Maintaining normal post anesthetic food intake is particularly important in small mammals due to their high metabolic rate, potential for rapid hypoglycemia in a fasting state, and high rates of obesity seen in captivity which can readily lead to hepatic lipidosis when appetite is compromised.2,11 The primary objective of this study was to evaluate the effect of duration of isoflurane anesthesia on recovery time, food intake, and body weight. Our hypotheses were that longer isoflurane anesthetic duration would result in a longer recovery time but have comparable postanesthetic effects on food intake and body weight and that isoflurane anesthesia would have less of a negative effect on food intake and body weight when compared with reported injectable sedation protocols in this species.
Methods Animals This study was approved by the (XX – blinded for review purposes). Eight captive bred African pygmy hedgehogs (4 male, 4 female), 9-12 months old, with a mean ± SD weight of 461 ± 124 g were used in this study. Animals were housed in a climate-controlled room with a 12:12h photoperiod and a room temperature of 27°C (80°F). Hedgehogs were kept individually in ventilated plastic enclosures measuring 84 x 51 x 36 cm (33 x 20 x 14 in). Each enclosure was lined with cardboard substrate, contained a hide box and exercise wheel, and shredded paper was provided for digging. Hedgehogs were offered fresh water ad libitum in a bowl and maintained on a commercial hedgehog diet. All hedgehogs were acclimated to the housing for several months prior to the study and were deemed healthy based upon baseline blood-work, serial
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physical examinations and long-term monitoring of food intake and body weight. Hedgehogs were fasted at least 80 minutes prior to anesthesia (median: 125 min, range: 80-220 min). Trials occurred in a separate climate-controlled room maintained within 3°C (5°F) of the housing room.
Anesthetic protocols and study design Hedgehogs were anesthetized with two separate durations of isoflurane anesthesia: 15 minutes (ISO15) and 45 minutes (ISO45) in a randomized, blinded, complete crossover study. The observer that evaluated recovery time was unable to be blinded to treatment. There was a minimum of a 2-week washout period between anesthetic events. The two durations of anesthesia were chosen to mimic clinically relevant scenarios with ISO15 representing a brief anesthetic event for baseline diagnostics such as physical examination and venipuncture and ISO45 representing an anesthetic duration needed for diagnostic imaging or simple procedures. Anesthetic induction was performed in a plastic chamber measuring 33 x 20 x 12.7 cm (13 x 8 x 5 in) with isoflurane (Isoflurane USP; Clipper Distribution Company, St. Joseph, MO, USA) at 4% in 100% oxygen (4 L/min) provided for a period of 5 minutes. The 5 minute induction time was included in the total anesthetic time for each treatment. The hedgehogs were then removed from the induction chamber and anesthesia was maintained with isoflurane (2-3%) and 100% oxygen (2 L/min) administered via facemask. After the intended duration of anesthesia was reached, the oxygen line was flushed for 2 seconds with 100% oxygen before providing flow-by oxygen (2 L/min) for recovery. Depth of anesthesia was monitored every 5 minutes using physiological parameters, reflexes and behaviors to maintain a light to moderate anesthetic plane characterized by loss of righting reflex and persistent maintenance of at least one of the following parameters/reflexes: jaw tone, palpebral reflex or pelvic limb withdrawal. The
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administered percentage of isoflurane varied between 2-3% in order to maintain hedgehogs at the desired depth of anesthesia.
Data collection All anesthetic monitoring was performed and recorded by a single investigator. Physiologic parameters including heart rate (HR), respiratory rate (RR), peripheral capillary oxygen saturation (SpO2%) and rectal temperature were recorded every 5 minutes after anesthetic induction. Heart rate and SpO2% were measured using a pulse oximetry probe placed on a metacarpal pad. Rectal temperature was obtained using a rodent rectal temperature probe inserted between 1-1.5 cm (Model 60001020, Barnant Company, Barrington, IL, USA). Respiratory rate was obtained by counting visible thoracic expansions. If the hedgehog was emitting defensive hissing vocalizations, the RR was routinely >100 brpm and was subsequently recorded as 100 brpm for data analysis purposes. Due to the defensive nature of the hedgehogs, RR was the only baseline parameter able to be recorded prior to onset of anesthesia. Thermal support was provided at all times during anesthesia through use of a recirculating water blanket. Palpebral, righting, and pelvic limb withdrawal reflexes as well as jaw tone were evaluated at 5-minute intervals after induction. Initially, balling-up and righting reflex were evaluated as two separate parameters; however, sedation scoring was consistently identical so righting reflex and balling-up response were considered interchangeable. Most reflexes and jaw tone were graded as normal, reduced or absent. Palpebral reflex was graded as present or absent. Hedgehogs with a normal righting reflex balled-up when handled to the point the observer could not restrain the hedgehog by scruffing the spiny dorsum or place a stethoscope on the ventral thorax. A reduced righting reflex was defined as the hedgehog rolling into an incomplete, loose
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ball when handled. An absent righting reflex occurred when the hedgehog did not attempt to roll into a ball when handled. The pelvic limb withdrawal reflex was assessed by applying pressure across the metatarsal bones with hemostatic forceps using steady, gentle force and observing for withdrawal of the pelvic limb away from the stimulus. The forceps were cushioned with plastic tubing to minimize trauma. Pelvic limb withdrawal was scored as normal if withdrawal happened immediately after applying pressure over the metatarsal bones, decreased if the withdrawal was delayed, or absent if no withdrawal occurred. Jaw tone was considered normal if the attempt to open the mouth was met with great resistance and an oral examination could not be performed. Jaw tone was graded as reduced if the mouth could be opened but the animal responded to manipulation of the tongue with jaw movement and would not allow the tongue to be pulled out of the mouth. Jaw tone was scored as absent if the mouth could be opened entirely with no resistance and the hedgehog did not respond to manipulation of the tongue with jaw movement. Physiologic parameters, reflexes and jaw tone were monitored until hedgehogs were recovered, which was defined as the return of a normal righting reflex, since this precluded evaluation of all other parameters. Body weight and food intake (g food per kg body weight) were measured every 24 hours in the morning during the same 1-hour period by a single recorder blinded to treatment. Hedgehogs were weighed in a plastic container using a gram scale (MyWeigh KD 7000, Phoenix, AZ, USA). Baseline values for body weight and food intake were calculated by averaging measurements obtained 48 and 24 hours prior to each trial and post-anesthetic data collection was then continued for 6 days.
Statistical analysis
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Randomization of the treatment sequence was performed using free online software (Research Randomizer version 4.0; Urbaniak GC, Plous S, Middletown, CN, USA.) and data analyzed using commercial software (SigmaPlot 13; Systat Software, San Jose, CA, USA). The data were tested for normality using the Shapiro-Wilk test and equal variance using the Brown Forsythe test. Simple data transformation or ranking was performed when necessary. Fixed effects of treatment and time on HR, RR, rectal temperature, and SpO2% was analyzed using one-way repeated measures ANOVA. Fixed effects of treatment and time on food intake and body weight were analyzed using two-way repeated measures ANOVA, and post-hoc analysis performed using the Holm-Sidak method. Comparisons between total food consumed between treatments were performed using a paired t-test. Statistical significance was defined as P < 0.05. Data are reported as mean ± SD unless indicated otherwise.
Results Time to loss of righting reflex was <5 minutes in all animals after start of induction. Recovery time was not statistically significantly different between treatments (median: 10 minutes; range: 5-10 minutes). Physiologic parameters, reflexes and jaw tone were recorded every 5 minutes for a total of 24 time points for ISO15 and a total of 72 time points for ISO45. For ISO15 treatment, palpebral was absent in 21/24 timepoints (88%) and jaw tone was absent in 18/24 timepoints (75%). For ISO45 treatment, palpebral was lost in 46/72 timepoints (64%) and jaw tone was absent in 60/72 timepoints (83%). In contrast, pelvic limb withdrawal was absent in only 24 (17%) ISO15 time points and 20/72 (28%) ISO45 time points.
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Heart rate was statistically significantly higher at 5 minutes post-anesthesia induction compared to other recorded time points for both treatments (ISO 15: 212 ± 11, ISO 45: 203 ± 10). Peak decrease in HR occurred at the 35 and 40-minute time points after induction of isoflurane for ISO45 with a mean decrease of 15 ± 16% and 18 ± 15%, respectively. Spontaneous ventilation was maintained in all hedgehogs at all time points for both treatments. Compared to baseline values there was no statistically significant difference in RR or rectal temperature regardless of duration of isoflurane anesthesia. Median temperatures at 5 minutes post induction was 34°C; range 33.4-35.5°C (93.3° F, range 92.2-95.9° F) and median temperatures after cessation of anesthesia were 33.9°C, range 33.1-34.7 °C (93°F, range 91.694.5° F) and 34°C, range 32.5-34.2°C (93.3°F, range 90.5-93.5°F) for ISO 15 and ISO 45, respectively. All hedgehogs maintained SpO2% measurements above 95% at all time-points for both treatments. A decrease in post-anesthetic food intake was noted with both ISO15 and ISO45 (Figure 1). The decreases in food intake were not statistically significantly different between or within treatments. The median percentage change in food intake was greatest over the 24 hours after anesthesia (Day 1) for both treatments (ISO15: -16%, range -40% to 169%; ISO45: -13%, range -56% to 43%). The total amount of food consumed over the 6 days following anesthesia was not statistically significantly different between treatments (P = 0.15) with ISO15 hedgehogs consuming 99 ± 23 g/kg and ISO45 hedgehogs consuming 108 ± 28 g/kg of food. There was no statistically significant difference in body weight between or within treatment following the anesthetic events. Body weight for ISO45 hedgehogs on day 6 (+2 ± 0.5%) post-anesthesia was statistically significantly (P = 0.007) higher than baseline. A nonstatistically significant (P = 0.133) increase in body weight was noted for ISO15 hedgehogs on
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Day 6 post-anesthesia (+1.1 ± 0.5%) when compared to baseline values. On day 6 post anesthesia, body weight had increased by 1.1 ± 0.5% for ISO15 and 2 ± 0.5% for ISO45 compared to baseline.
Discussion Isoflurane anesthesia via facemask had minimal effect on post-anesthetic food intake and body weight in African pygmy hedgehogs. There was no difference in recovery time in this study, regardless of isoflurane anesthetic duration. Hedgehogs anesthetized with isoflurane for 45 minutes in this study had shorter recoveries than hedgehogs sedated for the same period with alfaxalone-midazolam or ketaminemidazolam (mean: 15-20 min).10 The injectable protocols evaluated were only partially reversible which may have contributed to a longer recovery time compared to isoflurane anesthesia. Faster recovery times with inhalant anesthesia are well documented in exotic pet medicine where inhalant anesthesia is the preferred immobilization method for many species.16-18 Subjectively, recoveries from isoflurane anesthesia appear to be of better quality when compared to ketamine-midazolam immobilization in hedgehogs.10 The decrease in HR over time may reflect either an overall bradycardic effect of isoflurane anesthesia or an initial elevation of the HR from tachycardia induced by the stress of handling and induction. Bradycardia is a well-documented dose-dependent effect of isoflurane anesthesia in small mammals.11 The hedgehogs in this study could be considered mildly bradycardic or within normal range for anesthetized hedgehogs depending on which reference is used for comparison.19,20 The decreases in HR noted in this study, while statistically significant, was not considered to be clinically relevant.
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Maintenance of a similar depth of anesthesia in each hedgehog for the entire anesthetic length using a fixed administered isoflurane percentage was impossible, as anesthetic depth was highly dependent on the amount of manipulation of the anesthetized hedgehog. The minimal alveolar concentration (MAC) of isoflurane has not been established in hedgehogs; however, it would be expected to be similar to the MAC of other zoological companion animals with high metabolic rates such as the rat (1.3%), ferret (1.5%) or rabbit (2%).21,22,23 Evaluation of pelvic limb withdrawal reflex, righting reflex, and rectal temperature often resulted in a need to increase isoflurane percentage temporarily as hedgehogs began to show signs of arousal (limb twitching, attempting to ball-up) during measurement. This reactivity to physical stimuli is in contrast to immobilization with alfaxalone-midazolam. Subcutaneous alfaxalone-midazolam provided heavy sedation in hedgehogs with little to no reaction to the same stimuli performed in this study.10 Jaw tone was lost in the majority of hedgehogs in this study and, although not attempted, endotracheal intubation could likely be performed based on lack of response to tongue extension. Complete loss of jaw tone was observed in significantly more observation time points in this study compared to alfaxalone-midazolam and ketamine-midazolam injectable protocols which may indicate isoflurane anesthesia results in comparatively less muscle rigidity.10 Despite providing heat support, all hedgehogs were considered hypothermic at all time points compared to reported normal rectal temperatures for this species (normal: 35.5-37°C [95.7-98.6°F])19. Mean final temperature for each group was within 0.5°F of initial temperature indicating supplemental heat support contributed to maintenance of body temperature. Hypothermia is well documented in sedated or anesthetized small mammals where depressed thermoregulatory function is a common side-effect.11 Rectal temperatures observed in this study
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and for hedgehogs immobilized with two injectable protocols were similar.10 Based on these findings, thermal support should be started immediately for hedgehogs anesthetized with isoflurane, regardless of anesthetic duration. All hedgehogs were fasted a minimum of 80 minutes prior to anesthesia. Fasting recommendations in hedgehogs are inconsistent. Some reports recommend that hedgehogs be fasted for 4-6 hours for procedures lasting longer than 20 minutes while others recommend fasting is unwarranted due to the high metabolic rate and small glucose reserves of this species.12,7,24
None of the adverse gastrointestinal effects typically seen with an inappropriately short
fasting period (regurgitation, vomiting) were noted during this study suggesting that a prolonged fasting period prior to immobilization in this species may be unnecessary. Duration of isoflurane anesthesia did not have a statistically significant effect on postanesthetic food intake for the hedgehogs in this study. However, there was an initial decrease from baseline values during the first 48 hours following anesthesia which may become clinically relevant in debilitated individuals. This decrease in food intake was similar to that seen in hedgehogs immobilized with alfaxalone-midazolam but significantly less than the decrease seen following ketamine-midazolam immobilization.10 Isoflurane anesthesia did not result in a significant change in body weight in hedgehogs, which is similar to findings with alfaxalone-midazolam immobilization in this species.10 This is in contrast to a significant decrease in body weight seen following ketamine-midazolam immobilization in hedgehogs.10 Mean body weight for the ISO45 treatment was found to be statistically greater on day 6 following post-anesthesia, although this was not present in hedgehogs anesthetized for 15
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minutes. Although statistically significant, this discrepancy is likely not clinically relevant considering the increase in mean body weight was < 3% of baseline values. Limitations in this study include the inability to obtain baseline measurements for most monitoring parameters which was precluded by the normal defensive behavior of the hedgehogs. This behavior also prevented collection of further monitoring data after return of the righting reflex during recovery. Additionally, the inability to administer a fixed percentage of isoflurane administered to each animal may have affected the results of this study. Another limitation is the small sample size of the study, which may have resulted in type 2 statistical errors. However, given that the differences between treatments were small and there were no clinically relevant changes in any of the measured parameters, a large number of animals would have been necessary in order to have a sufficiently powered study and subsequently avoid type 2 errors.
Conclusions In conclusion, 15 or 45 minutes of isoflurane anesthesia via facemask does not result in a prolonged recovery time or have a clinically relevant impact on post-anesthetic food intake or body weight in African pygmy hedgehogs. Compared to studied injectable immobilization protocols in hedgehogs, isoflurane anesthesia resulted in less or similar effects on postimmobilization food intake and body weight. Speed and quality of isoflurane anesthesia recovery was considered superior when compared with published injectable sedation protocol
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22. Mural I, Housmans PR. Minimum alveolar concentration (MAC) of halothane, enflurane, and isoflurane in ferrets. Anesthesiology 1988;68:783-786. 23. Criado AB, Gómez de Seguar IA, Tendillo FJ, Marsico F. Reduction of isoflurane MAC with buprenorphine and morphine in rats. Lab Anim 2000;34:252-259. 24. D’Agostino J. Insectivores (Insectivora, Macroscelidea, Scandentia). In: Miller REM, Fowler ME, editors. Fowler’s zoo and wild animal medicine. 8th edition. St. Louis: Elsevier 2015; 275-281.
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Figure legends
Figure 1. Box and whisker plot of daily food intake (g of food per kg of body weight) in 8 African pygmy hedgehogs (Atelerix albiventris) immobilized with isoflurane administered via facemask for either 15 minutes (ISO15) or 45 minutes (ISO45). Baseline and Day 1 measurements correspond with food intake over either the 24-hour period prior to or after the anesthetic event, respectively.