Use of alfaxalone in bearded dragons (Pogona vitticeps): optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography
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Use of alfaxalone in bearded dragons (Pogona vitticeps): optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography Joanna K. Webb, DVM, MS1; Krista A. Keller, DVM, DACZM1,2*; Sathya K. Chinnadurai, DVM, MS, DACZM, DACVAA, DACAW3; Saki Kadotani, DVM, MS, DACVIM1; Matthew C. Allender, DVM, PhD, DACZM1,2; Ryan Fries, DVM, DACVIM1 1Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 2Wildlife Epidemiology Lab, University of Illinois, Urbana, IL 3Chicago Zoological Society, Brookfield Zoo, Brookfield, IL *Corresponding author: Dr. Keller (kak@illinois.edu) doi.org/10.2460/javma.22.08.0371 OBJECTIVE Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for proce- dures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has been performed in squamate species using alfaxalone without preservatives at various doses and routes of administration, but it is unknown whether preservatives affect quality of sedation or cardiac function. ANIMALS 10 bearded dragons. PROCEDURES This complete crossover study evaluated the pharmacodynamic effects of alfaxalone with preservatives adminis- tered to bearded dragons via intracoelomic (ICo; n = 10), SC (10), IM (9), and IV (9) injection at 15 mg/kg. RESULTS Deep sedation was achieved in 9 of 10 ICo, 8 of 10 SC, 8 of 9 IM, and 9 of 9 IV administrations. Heart rate significantly decreased from baseline for ICo (P = .008; median heart rate, 46), IM (P = .018; 54), and IV (P = .033; 54) routes, but maintained within clinically acceptable limits. Respiratory rate significantly decreased from baseline for ICo (P = .011; median respiratory rate, 30), SC (P = .024; 12), IM (P = .028; 12), and IV (P = .043; 12) routes. Spontaneous ventilation was retained during all events. Time to first effects was significantly sooner with IV (0 min) administration compared with ICo (P = .02; 5 min) and IM (P = .008; 5 min). Time to loss and recovery of withdrawal, righting reflex, deep pain, and purposeful movement were not significantly different between routes of administration. End-systolic volume was the only echocardiographic parameter significantly affected by IV sedation. CLINICAL RELEVANCE Sedation quality was most consistent via IV administration at 15 mg/kg, and minimal changes in cardiac function were observed. A lfaxalone, an injectable GABAA-agonist anesthet- ic steroid molecule, is currently available in a vial usable for 28 days after first use.1 Previous research (Intellagama lesueurii).2–5 Among bearded dragons alone, doses ranging from 9 to 15 mg/kg, IV or SC, have been evaluated.2–5 However, none of the stud- utilizing alfaxalone in reptilian species has been con- ies have compared route of administration or inves- ducted with the prior formulation (alfaxalone with- tigated an ideal dose for achieving deep sedation. out preservatives). Alfaxalone without preservatives Bearded dragons are evaluated and sedated in has been investigated in the literature in several lizard zoological companion practice for diagnostic sample species, including inland bearded dragons (Pogona collection, minimally invasive procedures, and sur- vitticeps), coastal bearded dragons (Pogona barba- gery. Considering the current literature has most ta), green iguanas (Iguana iguana), leopard geckos commonly reported alfaxalone as a modality of se- (Eublepharis macularius), eastern bluetongue skinks dation or anesthesia, clinicians may reach for this (Tiliqua skincoides), blotched bluetongue skinks drug as a first-line option. In bearded dragons with (Tiliqua nigrolutea), and Gippsland water dragons clinical signs of heart disease such as atherosclerosis 126 JAVMA | JANUARY 2023 | VOL 261 | NO. 1 Unauthenticated | Downloaded 09/29/23 09:22 PM UTC
with secondary hypertension, pericardial effusion, All bearded dragons were fasted 12 hours prior and aneurysmal dilation of the internal carotid artery to sedation, and all sedation events took place in the or aorta, computed tomography and echocardiogra- room in which they are routinely housed. phy are recommended diagnostics.5,6 These patients may require sedation to decrease the stress of man- Pilot study ual restraint or facilitate the placement of an intraos- Four bearded dragons were randomly selected seous catheter for contrast administration. Although using slips of paper blindly selected from a cup. In- standardization of 2-D echocardiography has been tramuscular administration was chosen for the pilot published in awake, manually restrained bearded study to ensure absorption by muscle capillary beds dragons,7 no literature exists on the effect of alfaxa- and ease of administration in practice. Two were lone on cardiac function. administered alfaxalone (Alfaxan Multidose IDX [10 This study was designed to evaluate the efficacy mg/kg], IM [0.29 to 0.31 mL]), and 2 were adminis- of multiple routes of administration and echocardio- tered 20 mg/kg, IM (0.66 to 0.82 mL), into a single graphic changes of a novel formulation of alfaxalone bicep due to concerns for hepatic portal or renal (Alfaxan Multidose IDX) in the bearded dragon. The portal metabolism and excretion if administered in authors hypothesized that (1) the shortest time to the pelvic limbs.8 The 10 mg/kg of alfaxalone admin- effect would occur with IV administration; (2) no istered IM did not produce a loss of righting reflex, difference would be seen in time to initial effect be- and a 20-mg/kg dose resulted in 1 animal becoming tween intracoelomic (ICo), SC, or IM administration; apneic; hence, a 15-mg/kg dose was chosen for the (3) there would be no significant difference between main study. baseline and maximal sedation heart rate; and (4) al- faxalone would lead to reduced cardiac contractility. Part 1 Over the course of 3 months, 4 sedation episodes were performed in a complete crossover design on Materials and Methods all 10 bearded dragons, including the 4 animals that Ten P vitticeps (6 males and 4 females; weight took part in the pilot study 2 months prior. Random- range, 254 to 415 g) maintained as a teaching and izing the order of sedation events and route of ad- research colony were enrolled in this study based on ministration for each bearded dragon was performed a power analysis (0.8) performed prior to the experi- by blindly drawing slips of paper individually labeled ment. Bearded dragons were at least 3 years old at ICo, SC, IM, and IV from a cup without replacement. the time of this study. All procedures were performed Sedation events were separated by at least 1 week, in accordance with an approved IACUC (#19004). and no other anesthetic or sedation medications For the entirety of the study, each bearded were administered during this time. dragon was housed individually in a 91.45 X 71.12 X Prior to injection, a baseline respiratory rate was 45.72-cm enclosure located in the same room main- collected visually after removing the animal from its tained between 24 and 25.5 °C. Daily diet offered enclosure and placing it on a table. Then heart rate included dark leafy greens with shredded vegetables was measured using a Doppler placed in the left axil- supplemented with calcium carbonate powder and lary region while under manual restraint. Heart rate twice-weekly offerings of gut-loaded king worms and respiratory rate are hereafter referred to as vital (Zophobas morio). Individual heat lamps and UVA/ parameters. Baseline presence or absence of reflexes UVB-emitting bulbs were situated above each habi- and responses (limb withdrawal, jaw tone, head tone, tat, and 12 hours of darkness was provided daily with righting, deep pain, purposeful movement; hereafter a basking temperature of 35 to 37 °C. All bearded referred to as milestones) were recorded (Table 1). dragon housing and husbandry was in accordance The bearded dragon was then administered alfaxa- with IACUC protocol #18056. Bearded dragons nei- lone (Alfaxan Multidose IDX) at a dose extrapolated ther participated in other studies nor received medi- from pilot data (15 mg/kg; 0.38 to 0.62 mL) using cal therapy within 4 weeks of participation in part 1 a 25-g hypodermic needle under manual restraint. or 2 of this research. Injection sites were the ventral coccygeal vein (IV), Table 1—Evaluation of sedative milestones in bearded dragons (Pogona vitticeps) sedated with alfaxalone. Milestone Test Recording Head tone Lifting the head from beneath the mandible, observe it falling Absent, mild, or present Jaw tone Manual opening and closing of mandible and maxilla Absent or present Withdrawal reflex Manual extension of limbs without application of pain; Absent or present monitoring for resistance to extension and retraction of limb Deep pain response Pinching of distal aspects of alternating pelvic limb digits Absent or present with hemostats for a maximum of 15 s Righting reflex Placing animal in dorsal recumbency and monitoring Absent or present for ability to completely return to sternal recumbency Purposeful movement Ability of animal to walk or track movement within its surroundings Absent or present using its head, assessed prior to stimulation from other milestone measurements JAVMA | JANUARY 2023 | VOL 261 | NO. 1 127 Unauthenticated | Downloaded 09/29/23 09:22 PM UTC
right and left biceps muscle (split-dose IM), dorsal to in elapsed and time to loss of anesthetic milestones the left scapula-humeral joint (SC), and caudoventral between the different routes of administration were coelom (ICo). After injection, the bearded dragon assessed using a Kruskal-Wallis test (P < .05), and was placed into its enclosure, and the first vital and post hoc analyses were performed with a Dunn test. milestone measurements were taken at 5 minutes of All echocardiographic variables were measured elapsed time. Time to first effects was recorded as 3 times from archived video clips obtained pre- and immediate (0 minutes) or evaluated every 5 minutes postalfaxalone administration for each animal and thereafter. Milestones (marked as absent or present) averaged. The averaged echocardiographic parame- and vital parameters were collected every 5 minutes ters for pre- and postalfaxalone administration were until return to purposeful movement. Assessment of evaluated for normality using the Shapiro-Wilk test purposeful movement was performed at each time (P < .05). Based on these results, a paired t test was point prior to the stimulatory effects measuring performed (P < .05). milestones and vital parameters. Deep pain assess- ment was discontinued after return of the righting reflex. The ideal dose and route of administration Results were defined as those which provided a consistent deep sedation with loss of righting reflex, mainte- Pilot nance of spontaneous respiration, and a clinically Two males and 2 females (288 to 410 g) partici- acceptable heart rate even if significantly different pated in the pilot study. One bearded dragon that from baseline. received 20 mg/kg lost spontaneous ventilation at 5 minutes after injection; the bearded dragon was Part 2 intubated with an 18-g catheter and provided inter- Nine bearded dragons participated in part 2, at mittent positive-pressure ventilation at 1 breath/min 4 months after their last alfaxalone sedation event using room air. Spontaneous ventilation returned 1 in part 1 of the study. Prior to sedation, the beard- hour after injection. The other bearded dragon that ed dragons were manually restrained in left lateral received 20 mg/kg maintained shallow spontane- recumbency, and a baseline echocardiogram was ous respiration. Both bearded dragons that received performed using the left axillary window for all vari- the 10-mg/kg dose maintained their righting reflex ables, in addition to the right axillary window to eval- and ability to spontaneously respire, whereas both uate pulmonary artery flow, as previously described bearded dragons that received 20-mg/kg doses lost in this species.7 Determined measurements included their righting reflex. Response to deep pain was lost diastolic ventricular length (cm), end-diastolic vol- at 10 minutes in both 20-mg/kg animals but neither ume (mL), systolic ventricular length (cm), end-sys- animal dosed with 10 mg/kg. Overall, alfaxalone tolic volume (ESV; mL), ejection fraction (%), stroke with preservatives administered at 10 mg/kg, IM, in volume (mL), heart rate (beats per minute), cardiac bearded dragons was deemed insufficient for deep output (mL/min), and pulmonary artery flow (m/s). sedation, and 20 mg/kg put animals at risk for loss Using the optimal dose and route of administration of spontaneous ventilation. Therefore, a dose of 15 determined in part 1, each bearded dragon was ad- mg/kg was decided for part 1 of the project. Due ministered alfaxalone (Alfaxan Multidose IDX; 15 to concerns for volume of injection into 1 muscle, mg/kg, IV). An echocardiogram was repeated 2 to the decision was made to split the dose between the 5 minutes after injection at the time of maximum se- right and left bicep for part one. dation, and the same variables were collected. After the postsedation echocardiogram was completed, Part 1 the bearded dragon was returned to its enclosure All 10 bearded dragons participated in the first 2 and visually monitored for continued spontaneous sedation events. One bearded dragon was euthanized ventilation and return to purposeful movement. halfway through the study period due to marked ca- Data were evaluated with standard statisti- chexia and detection of a coelomic mass. This beard- cal software (Prism8 and Prism9, GraphPad; Excel, ed dragon received alfaxalone via SC and ICo routes Microsoft Corp; R, R Studio). All data were evaluated of administration prior to death, and its data are in- for normality using the Shapiro-Wilk test (P < .05), cluded for those routes but led to imbalanced design and median with 10th and 90th percentiles were cal- for other routes. Upon necropsy the dragon was diag- culated. Heart rate and respiratory rate at baseline nosed with a cholelith, deemed unrelated to the cur- were compared with the vital parameters at point of rent study as this diagnosis has been associated with maximum sedation using a Wilcoxon rank sum test dietary origins.9 The dragon was clinically healthy (P < .05). A bearded dragon’s data was excluded during the 2 sedation episodes in which it participat- from baseline and postalfaxalone statistical analysis ed. Nine ICo, 8 SC, 8 IM, and 9 IV sedation events were if it never lost purposeful movement. Median times to included in the statistical analysis; those not included first effect, loss of withdrawal, elapsed lack of with- either did not become sedate (n = 1 ICo, 2 SC, and drawal, loss of righting reflex, elapsed lack of right- 1 IM) or were euthanized prior to completion of data ing reflex, loss of jaw tone, elapsed lack of jaw tone, collection (1 IM and 1 IV). All bearded dragons admin- loss of head tone, elapsed loss of head tone, loss of istered IV alfaxalone lost their righting reflex; however, deep pain, elapsed lack of deep pain, and return of several bearded dragons administered alfaxalone via purposeful movement were calculated. Differences other routes of administration retained their righting 128 JAVMA | JANUARY 2023 | VOL 261 | NO. 1 Unauthenticated | Downloaded 09/29/23 09:22 PM UTC
reflex (n = 1 ICo, 4 SC, and 1 IM). All bearded dragons time of deep pain lost range, 5 to 10 minutes), 5 IM for all routes of administration retained spontaneous (elapsed time of deep pain lost range, 10 to 55 min- ventilation. Heart rate did not significantly decrease utes), and 6 IV (elapsed time of deep pain lost range, from baseline for ICo (P = .2578), SC (P = .1094), IM 10 to 50 minutes) sedation events (Table 2). There (P > .9999), or IV (P = .8008). Respiratory rate did not were no differences in elapsed lack of righting reflex significantly decrease from baseline at time of maxi- (P = .3915), elapsed lack of jaw tone (P = .6033), mum sedation when alfaxalone was administered ICo time to loss of deep pain (P = .5375), or return of (P = .2344) and IM (P = .0625). However, when al- purposeful movement (P = .9766) between routes faxalone was administered SC (P = .0469) and IV of administration. There was a significant difference (P = .0078), respiratory rate did significantly decrease for time to loss of jaw tone between the 4 routes (P from baseline. Descriptive statistics for heart rate and = .0147), but this was not supported on post hoc respiratory rate at baseline and time of maximum se- analysis. The range for return to purposeful move- dation are summarized (Table 2). ment was 30 to 95 minutes (ICo), 40 to 200 minutes Time to first effects (P = .0005), loss of righting (SC), 40 to 135 minutes (IM), and 35 to 140 minutes reflex (P = .0178), and elapsed time of deep pain (IV). Descriptive statistics for milestones are summa- lost (P = .0336) were significantly different among rized. When observing for the return of purposeful the 4 routes. The elapsed time for deep pain loss movement, some bearded dragons would not move was significantly longer for IV (P = .0138) and IM voluntarily, but when stimulated during collection of (P = .0088) compared with SC. Righting reflex was milestones (Table 1) and vital parameters, many of lost significantly faster when alfaxalone was admin- them would move, which was not counted toward istered IM than ICo (P = .0384). Time to first effects purposeful movement unless this activity was per- was significantly faster when administered IV com- formed by the lizard prior to stimulation. Head tone pared with ICo (P = .0093), SC (P = .0011), and IM (P and withdrawal reflex were not reliably lost or re- = .0102). Deep pain was lost in 3 ICo (elapsed time of gained; therefore, these milestones were not includ- deep pain lost range, 5 to 20 minutes), 2 SC (elapsed ed in statistical analysis. Many bearded dragons had Table 2—Descriptive statistics (median and 10th- to 90th-percentile CIs) of vital parameters and milestones from 9 bearded dragons (Pogona vitticeps) sedated with alfaxalone (15 mg/kg) via intracoelomic, SC, IM, and IV routes of administration. Intracoelomic (n = 9) SC (n = 8) IM (n = 8) IV (n = 9) Variable Median (CI) n Median (CI) n Median (CI) n Median (CI) n Vital parameters Baseline HR (beats/min) 66 (53–104) 9 69 (48–88) 8 78 (64–106) 8 80 (58–160) 9 Alfaxalone HR (beats/min) 60 (48–90) 9 55 (45–60) 8 81 (66–100) 8 70 (54–96) 9 Baseline RR (breaths/min) 30 (17–40) 9 22 (12–26) 8 24 (12–38) 8 18 (9–27) 9 Alfaxalone RR (breaths/min) 12 (10–20) 9 10 (6–18)* 8 12 (12–24) 8 6 (0–20)* 9 Milestones Time to first effect (min) 5 (4–7) 9 5 (4–13) 8 5 8 0 (0–1)* 9 Time to righting reflex loss (min) 10 (5–22) 9 13 (5–24) 4 5* 7 5 (5–8) 9 Elapsed time of lost righting 40 (22–61) 9 28 (10–84) 4 70 (25–101) 7 50 (22–85) 9 reflex (min) Time to jaw tone loss (min) 5 (5–15) 9 10 (5–25) 7 5 8 5 8 Elapsed time of lost jaw tone (min) 55 (19–111) 9 55 (29–138) 7 88 (50–135) 8 80 (12–88) 8 Time to deep pain loss (min) 5 (5–13) 3 5 2 5 (5–8) 5 5 6 Elapsed time of lost deep pain (min) 5 (5–17) 3 8 (6–10) 2 30 (14–51)* 5 30 (18–43)* 6 Time to purposeful movement (min) 75 (50–95) 9 75 (47–137) 8 70 (44–132) 8 80 (39–120) 9 Because every bearded dragon did not meet each milestone, n is reported. *A significant difference exists between pre- and postalfaxalone measurements of vital parameters or in milestones between the 4 routes of administration. HR = Heart rate. RR = Respiratory rate. Table 3—Bearded dragon (Pogona vitticeps; n = 9) echocardiographic measurements obtained 2 to 5 minutes after sedation with 15 mg/kg of alfaxalone IV. Prealfaxalone Postalfaxalone Variable Mean Range Mean Range Ventricular length diastole (cm) 1.3 0.9–1.6 1.2 1.0–1.5 End-diastolic volume (mL) 2.1 1.5–3.0 2.2 1.5–3.5 Ventricular length systole (cm) 0.93 0.7–1.2 1.0 0.8–1.3 End-systolic volume (mL)* 1.1 0.68–1.6 1.4 0.79–2.4 Ejection fraction (%) 46 31–64 38 21–59 Stroke volume (mL) 0.97 0.54–1.6 0.82 0.26–1.5 Heart rate (beats/min) 93 48–136 99 66–116 Cardiac output (mL/min) 89 41–190 83 19–164 Pulmonary artery flow velocity (m/s) 0.58 0.36–0.76 0.54 0.39–0.7 *A significant difference exists between pre- and postalfaxalone measurements. JAVMA | JANUARY 2023 | VOL 261 | NO. 1 129 Unauthenticated | Downloaded 09/29/23 09:22 PM UTC
an absent righting reflex but would spontaneously rates may be influenced by other hormonal factors. twitch without being otherwise stimulated, which Crocodilian heart rates will increase secondary to may be secondary to a lighter depth of sedation at epinephrine administration, and epinephrine and that point in time. norepinephrine increased secondary to handling juvenile alligators (Alligator mississippiensis).11,12 Part 2 Heart rate did not significantly decrease from base- All variables were normally distributed. End-sys- line in bearded dragons administered alfaxalone at tolic volume increased up to 2.1 mL in all bearded 9 mg/kg, IV, or 15 mg/kg, SC.2,5 In contrast, heart dragons after alfaxalone administration at time to rate significantly decreased from baseline in green maximum effect. The remainder of the variables did iguanas (Iguana iguana) receiving medium- (20 not exhibit differences (diastolic ventricular length, mg/kg) and high-dose (30 mg/kg) alfaxalone, IM, end-diastolic volume, systolic ventricular length, and leopard geckos receiving a low dose (5 mg/kg) ejection fraction, stroke volume, heart rate, cardiac of alfaxalone, IV.3,13,14 output, and pulmonary artery flow; Table 3). Respiratory effect was expected to decrease from baseline secondary to sedation in this study as Discussion similarly observed in prior alfaxalone studies in mul- tiple Australian lizards.2,3,5 Although the respiratory The results of this study supported our hypoth- rate significantly decreased in 2 routes of adminis- esis that a novel alfaxalone formulation administered tration, all bearded dragons in all routes of admin- IV at 15 mg/kg provided the shortest time to maxi- istration in the main study maintained spontaneous mum effect. Intravenous administration predictably ventilation and did not require intubation or manual induces a deep plane of sedation, including loss of ventilation. Similar to the apnea observed in our pi- deep pain, for 35 to 140 minutes characterized by lot study, green iguanas (n = 3/6) anesthetized with a loss of jaw tone, purposeful movement, and right- 30 mg/kg of alfaxalone, IM, became apneic and re- ing reflex. Subclinical respiratory depression occurs, quired intermittent positive-pressure ventilation.13 and limited changes in contractility were observed As a GABAA-agonist, there are inherently no an- on echocardiography. Other routes of administration algesic effects of alfaxalone. However, dragons lost were less predictable in inducing deep sedation. deep pain for 5 to 55 minutes, which suggests that Differences in the pharmacodynamic effects of these animals reached a plane of anesthesia. More 15 mg/kg of alfaxalone SC exist. Research describ- bearded dragons lost deep pain when anesthetized ing a group of bearded dragons sedated with 15 mg/ with IV alfaxalone than the other 3 routes of adminis- kg of alfaxalone, SC, prior to administration of lido- tration. At twice the dose of our study, green iguanas caine at the sacrococcygeal junction was published (6/6) sedated with alfaxalone (30 mg/kg, IM) as a sole during our data collection.2 However, in the control agent were able to undergo laparotomy,13 suggest- group of the lidocaine study, where only alfaxalone ing that a higher IV dose in bearded dragons could was administered, 8 of 8 became sedate, whereas result in a longer, more consistent surgical anesthe- only 8 of 10 became sedate in our study.2 The am- sia. The inconsistency observed in the length of time bient temperature of the room during the lidocaine the bearded dragons in our study lost deep pain indi- research was up to 2 °C higher than the environment cates that alfaxalone as a sole agent is not sufficient of this study and may have played a role in the me- to provide surgical anesthesia when used at a dose tabolism of the alfaxalone. of 15 mg/kg. Clinicians using alfaxalone at the dose If IV administration of alfaxalone is not clinically described here should consider adding additional sys- feasible, the current study suggests IM as the second temic or local analgesia to ensure a bearded dragon is choice based upon 8 of 9 bearded dragons reach- anesthetized for painful surgical procedures.2,15 ing a predictable level of deep sedation. However, Through echocardiographic analysis of bearded considering the volume of a 15-mg/kg injection, cli- dragon hearts before and after alfaxalone admin- nicians should consider splitting an IM injection be- istration at 15 mg/kg, IV, the investigators have tween 2 sites if IV access is not available. While there shown that cardiac function itself is overtly pre- are no published IM volume limits in lizards, a volume served with only a 30% increase in ESV likely sec- limit of 1.2 mL/kg has been verified in guinea pigs.10 ondary to decreased contractility. A published The number of bearded dragons that reached a deep ESV reference interval in healthy bearded dragons plane of sedation with IM or SC was approximately does not exist, as the previous echocardiographic equal, and their time return to purposeful movement evaluation data measured systolic ventricular area was not significantly different. Therefore, if volume as their equivalent measure of contractility.7 The of injection continues to be a clinical concern, SC ad- change in contractility in bearded dragons sedated ministration may be an acceptable alternative. with alfaxalone contrasts with an equivalent study As hypothesized, there was no significant dif- in prairie rattlesnakes. Prairie rattlesnakes sedat- ference in heart rate from baseline to time of ed with alfaxalone had no significant difference in maximal effect via any route of administration. As echocardiographic measurements compared with bearded dragons were sedated and maintained in presedation measurements.16 Clinicians should be their preferred optimal temperature zone through- aware that administration of alfaxalone is unlikely out the study, it was expected that heart rate would to alter echocardiographic results in cases where not significantly differ.6 However, reptilian heart diagnostic echocardiography is warranted. Given 130 JAVMA | JANUARY 2023 | VOL 261 | NO. 1 Unauthenticated | Downloaded 09/29/23 09:22 PM UTC
the contractility alterations noted, clinicians should bearded dragons (Pogona vitticeps). Vet Anaesth Analg. be cautious in the use of the dose investigated here 2019;46(1):126–134. doi:10.1016/j.vaa.2018.09.001 3. Perrin KL, Bertelsen MF. Intravenous alfaxalone and in bearded dragons with known or suspected car- propofol anesthesia in the bearded dragon (Pogona vit- diac dysfunction. To further characterize whether ticeps). J Herpetol Med Surg. 2017;27(3-4):123–126. cardiovascular function is affected secondary to doi:10.5818/16-01-071.1 decreased contractility, future studies including im- 4. Ratliff C, Parkinson LAB, Mans C. Effects of the frac- plantable intraarterial telemetry devices to study tion of inspired oxygen on alfaxalone-sedated inland healthy bearded dragons and bearded dragons se- bearded dragons (Pogona vitticeps). Am J Vet Res. 2019;80:(2)129–134. doi:10.2460/ajvr.80.2.129 dated with alfaxalone should be performed. 5. Scheelings TF, Baker RT, Hammersley G, Hollis K, Elton Combining the results of this study with previ- I, Holz P. A preliminary investigation into the chemical ous alfaxalone research in bearded dragons does not restraint with alfaxalone of selected Australian squa- lend a clear conclusion as to why increasing the dose mate species. J Herpetol Med Surg. 2011;21(2-3):63–67. of alfaxalone does not result in consistently deeper doi:10.5818/1529-9651-21.2.63 sedation. Nonlinear pharmacokinetics were record- 6. Raiti P. Husbandry, diseases, and veterinary care of the bearded dragon (Pogona vitticeps). J Herpetological Med ed in domestic cats (Felis catus) anesthetized with Surg. 2012;22(3-4):117–131. doi:10.5818/1529-9651- alfaxalone without preservatives, which means that 22.3.117 drug effect, distribution, and clearance are not dose 7. Silverman S, Guzman DSM, Stern J, Gustavsen KA, Griffiths dependent.17 If bearded dragons are assumed to also LG. Standardization of the two-dimensional trancoelomic follow nonlinear pharmacokinetics with alfaxalone, echocardiographic examination in the central bearded it would explain why the dose and route of admin- dragon (Pogona vitticeps). J Vet Cardiol. 2016;18:168– 178. doi:10.1016/j.jvc.2015.10.011 istration of alfaxalone result in such varying effects 8. Holz PH. Anatomy and physiology of the reptile renal sys- between and within species. Along the same lines, tem. Vet Clin North Am Exot Anim Pract. 2020;23(1):103– after inconsistencies were observed in the length 114. doi:10.1016/j.cvex.2019.08.005 of elapsed time for loss of deep pain, performing a 9. Gimmel A, Kempf H, Öfner S, Müller D, Liesegang A. Cho- second study looking at alfaxalone (15 mg/kg, IV) lelithiasis in adult bearded dragons: retrospective study with an opioid analgesic would allow the authors to of nine adult bearded dragons (Pogona vitticeps) with cholelithiasis between 2013 and 2015 in southern Germa- further determine whether this dose is appropriate ny. J Anim Physiol Anim Nutr (Berl). 2017;101:122–126. for minor invasive procedures such as toe or tail am- doi:10.1111/jpn.12616 putation, abscess debridement, laceration repair, or 10. Bencivenga MA, Bowling PA, Fiallos JO, et al. Investiga- biopsy. Further hemodynamic effects of alfaxalone tion of various intramuscular volumes delivered to the and how they relate to the changes in heart rate and semimembranous muscle of Cavia porcellus. J Am As- blood flow (cardiac shunting) may be characterized soc Lab Anim Sci. 2020;59(3):310–321. doi:10.30802/ AALAS-JAALAS-19-000101 with the use of implantable telemetry and direct 11. Benn AL, McLelland DJ, Whittaker AL. A review of welfare blood pressure monitoring. assessment methods in reptiles, and preliminary applica- With hundreds of lizard species existing and tion of the Welfare Quality protocol to the pygmy blue- many of them cared for in zoological institutions or tongue skink, Tiliqua adelaidensis, using animal-based as part of private collections, it is difficult to have measures. Animals (Basel). 2019;9(1):27. doi:10.3390/ data available on all species for each anesthetic. The ani9010027 12. Gatson BJ, Goe A, Granone TD, Wellehan JFX. Intramus- data collected in bearded dragons regarding the op- cular epinephrine results in reduced anesthetic recovery timal dose and route of administration of alfaxalone time in American alligators (Alligator mississippien- with preservatives can act as a model for other aga- sis) undergoing isoflurane anesthesia. J Zoo Wildl Med. mid lizards to facilitate examination and nonpainful 2017;48(1):55–61. doi:10.1638/2015-0293.1 procedures. 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