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

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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

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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

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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.

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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

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the contractility alterations noted, clinicians should                     bearded dragons (Pogona vitticeps). Vet Anaesth Analg.
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                                                                     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.
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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. Based on this study, the recommended                     13.   Bertelsen MF, Buchanan R, Jensen HM, et al. Assessing
dose for deep sedation in bearded dragons is 15 mg/                        the influence of mechanical ventilation on blood gases
                                                                           and blood pressure in rattlesnakes. Vet Anaesth Analg.
kg. IV, and clinicians should expect respiratory de-
                                                                           2015;42(4):386–393. doi:10.1111/vaa.12221
pression. Only ESV is expected to increase during                    14.   Morici M, Di Giuseppe M, Spadola F, Oliveri M, Knotkova
the sedation period, and the echocardiography val-                         Z, Knotek Z. Intravenous alfaxalone anesthesia in leop-
ues reported here can be used as a guide for clinical-                     ard geckos (Eublepharis macularius). J Exot Pet Med.
ly normal bearded dragons. Providing heat support                          2018;27(3):11–14. doi:10.1053/j.jepm.2017.08.008
to maintain the bearded dragon in its preferred opti-                15.   Sladky KK, Kinney ME, Johnson SM. Analgesic efficacy
                                                                           of butorphanol and morphine in bearded dragons and
mal temperature zone will help the clinician observe
                                                                           corn snakes. J Am Vet Med Assoc. 2008;233(2):267–273.
similar pharmacodynamic effects to those cataloged                         doi:10.2460/javma.233.2.267
in this study.                                                       16.   Webb JK, Keller KA, Chinnadurai SK, Kadotani S,
                                                                           Allender MC, Fries R. Optimizing the pharmacodynam-
                                                                           ics and evaluating cardiogenic effects of the injectable
Acknowledgments                                                            anesthetic alfaxalone in prairie rattlesnakes (Crota-
                                                                           lus viridis). J Zoo Wildl Med. 2021;52(4):1105–1112.
     The authors declare that there were no conflicts of interest.
                                                                           doi:10.1638/2021-0056
                                                                     17.   Whittem T, Pasloske KS, Heit MC, Ranasinghe MG. The
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