Use of computed tomography to determine a species-specific formula for body surface area in bearded dragons (Pogona vitticeps)

Caitlin M. Hepps Keeney From the Department of Clinical Sciences and Molecular, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Nathan C. Nelson From the Department of Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Tara M. Harrison From the Department of Clinical Sciences and Molecular, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

OBJECTIVE

To use CT-derived measurements to calculate a shape constant (K constant) and create a formula to calculate body surface area (BSA) on the basis of body weight in bearded dragons (Pogona vitticeps).

ANIMALS

12 adult client-owned bearded dragons that underwent CT between December 4, 2019, and April 2, 2020.

PROCEDURES

Each bearded dragon in this prospective cohort study underwent physical examination, body weight measurement, and CT. A 3-D surface model was then reconstructed from CT data with available software and used for BSA calculations. Animals were considered collectively and grouped by sex and age. Nonlinear regression analysis of BSA versus body weight was performed, and a species-specific formula was derived for calculating BSA in bearded dragons.

RESULTS

Mean age, body weight, and CT-derived BSA were 2.1 years, 356 g, and 580 cm2. The calculated K constant was 11.6 (R2 = 0.994; SE = 0.275) for the 12 bearded dragons, and the CT-derived BSA formula was as follows: BSA in cm2 = 11.6 × (body weight in g)2/3. The K constant differed substantially for bearded dragons grouped by age (12.1 for younger [between 1 and ≤ 2 years of age; n = 8] vs 10.9 for older [> 2 years of age; 4] animals) but did not differ on the basis of sex.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that because the K constant for bearded dragons in the present study was larger than the preexisting K constant of 10 used for reptiles or the various K constants established for some companion mammals, doses of chemotherapeutic drugs needed to treat affected bearded dragons may be higher than previously thought.

Abstract

OBJECTIVE

To use CT-derived measurements to calculate a shape constant (K constant) and create a formula to calculate body surface area (BSA) on the basis of body weight in bearded dragons (Pogona vitticeps).

ANIMALS

12 adult client-owned bearded dragons that underwent CT between December 4, 2019, and April 2, 2020.

PROCEDURES

Each bearded dragon in this prospective cohort study underwent physical examination, body weight measurement, and CT. A 3-D surface model was then reconstructed from CT data with available software and used for BSA calculations. Animals were considered collectively and grouped by sex and age. Nonlinear regression analysis of BSA versus body weight was performed, and a species-specific formula was derived for calculating BSA in bearded dragons.

RESULTS

Mean age, body weight, and CT-derived BSA were 2.1 years, 356 g, and 580 cm2. The calculated K constant was 11.6 (R2 = 0.994; SE = 0.275) for the 12 bearded dragons, and the CT-derived BSA formula was as follows: BSA in cm2 = 11.6 × (body weight in g)2/3. The K constant differed substantially for bearded dragons grouped by age (12.1 for younger [between 1 and ≤ 2 years of age; n = 8] vs 10.9 for older [> 2 years of age; 4] animals) but did not differ on the basis of sex.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that because the K constant for bearded dragons in the present study was larger than the preexisting K constant of 10 used for reptiles or the various K constants established for some companion mammals, doses of chemotherapeutic drugs needed to treat affected bearded dragons may be higher than previously thought.

Introduction

Bearded dragons (Pogona vitticeps) are popular pets. Although reports1,2,3,4,5,6,7,8 of neoplasia in bearded dragons are limited, findings from a 2004 retrospective survey9 indicate that the overall prevalence of neoplasia in reptiles may be as high as 6.2% (81/1,297). Chemotherapy in reptiles has many challenges, and there is a paucity of information to help guide such treatments.1,8,10,11,12 Among the challenges is the lack of information describing appropriate dosing of chemotherapeutic agents in reptiles.

Conventionally, many chemotherapy drugs are administered on the basis of BSA rather than body weight.13,14,15,16,17 The formula typically used to calculate BSA is as follows: BSA = K X (body weight in g)2/3, where K is a shape constant that is species specific. Values of K have been determined for multiple species through several methods.15,18,19,20,21,22,23,24,25 Historically, BSA has been determined by use of the traditional tape method14 or by making physical measurements on skinned specimens20,22 or molds of cadavers.24 Recently, CT has been used successfully as a noninvasive, highly accurate modality for determining BSA in ferrets18 and rabbits.19 This method has also been used to determine BSA in human neonates26 and adults.27

The BSA in bearded dragons is currently estimated with the use of either constants derived for dogs and cats or allometric scaling recommendations for reptiles based on empirical clinical experience.3,27 To our knowledge, no K constant for BSA has been calculated for any species of reptile, and we are unaware of any supportive evidence that traditional formulas for BSA provide accurate estimates in reptiles. The objective of the study reported here was to use CT-derived measurements to calculate a K constant and create a formula to calculate BSA on the basis of body weight for bearded dragons (Pogona vitticeps). By establishing a K constant for bearded dragons, we aim to improve the accuracy of chemotherapeutic dosing in this species. However, further research is indicated to determine the efficacy, toxicity, and pharmacokinetics of chemotherapeutic drugs in bearded dragons.

Materials and Methods

Animals

Healthy adult client-owned bearded dragons were recruited for the study through the use of email to owners. The recruitment period was from November 23, 2019, to January 11, 2020. For inclusion, bearded dragons had to have been healthy with no body-deforming injuries or malformations and had to have been displaying clinically normal behavior in their environment. Informed written consent was obtained from the owners of all the bearded dragons enrolled. The study protocol was reviewed and approved by the North Carolina State University Institutional Animal Care and Use Committee (No. 19-709) and the Clinical Core Studies Committee.

Examinations

Each bearded dragon underwent a physical examination performed by a licensed veterinarian (CMHK) for evaluation of health status and to identify any external abnormalities that deformed the body contour. Body weight measurement was recorded for each animal.

For CT, the bearded dragons were awake, and no sedative or anesthetic drugs were administered. This was made possible by the animals' calm and sedentary temperaments. Each animal was positioned in ventral recumbency on an approximately 3-cm-deep piece of foam in a plastic box. The foam supported the animal and achieved separation from the surface of the plastic box, facilitating later 3-D segmentation. Transverse images with a 0.6-mm slice thickness were acquired at 130 kVp and 25 mA and obtained from the tip of the rostrum to the tip of the tail with a 64-slice helical CT scanner.a

3-D CT reconstruction

The CT images were reconstructed and downloaded in a bone window reconstruction algorithm (window width, 2,000 HU; window level, 400 HU) and analyzed with dedicated CT image analysis software.b An automated 3-D surface model was created for each bearded dragon by use of a minimum threshold value of –500 HU with no upper limit so that densities outside the animal were excluded. Air imaged in each animal (eg, in the lungs and gastrointestinal tract) was manually removed with a tracing tool as previously described.18,27 The 3-D model generated through reconstruction for each bearded dragon was visually assessed to ensure it was continuous and complete (CMHK). The CT image analysis software automatically calculated BSA for each subject. This process was performed once for each animal, and the BSA value for each animal was then used for further analysis.

Statistical analysis

Body surface area was plotted against body weight, and a K constant was calculated with the use of nonlinear regression. The R2 and SE of the regression were calculated to determine the goodness of fit. Results were plotted for all animals and animals grouped by sex and age (younger [1 to ≤ 2 years old] vs older [> 2 years old]). A K constant was calculated for each bearded dragon. A 2-tailed t test was performed to determine whether the K constant values differed significantly for males versus females and for younger versus older animals. Values of P < 0.05 were considered significant. All statistical analyses were performed with available software.c

Results

Animals

Twelve adult bearded dragons (5 females and 7 males) were included in the study. The mean age was 2.1 years (range, 1 to 4 years; median, 2 years), with 8 animals that were from 1 to ≤ 2 years of age (younger group) and 4 animals that were > 2 years age (older group; Table 1). The mean body weight was 356 g (range, 159 to 657 g; median, 355 g). All animals were client owned and reportedly healthy and behaving normally at home. Additionally, all animals were confirmed healthy on the basis of findings from physical examination, and none had external abnormalities that deformed their body contour.

Table 1

Summary results for 12 healthy client-owned bearded dragons stratified by sex and age (1 to ≤ 2 years old [younger] vs > 2 years old [older]) that underwent CT between December 4, 2019, and April 2, 2020, so that 3-D CT reconstructed surface models could be created and used to determine each animal's BSA.

Variable All bearded dragons Females (n = 5) Males (n = 7) Younger (n = 8) Older (n = 4)
Mean Median (range) Mean Median (range) Mean Median (range) Mean Median (range) Mean Median (range)
Age (y) 2.1 2 (1–4) 2 1 (1–4) 2.1 2 (1–3) 1.5 1.5 (1–2) 3.3 3 (3–4)
Body weight (g) 356 355 (159–657) 317 260 (159–657) 383 393 (177–272) 314 308 (159–449) 438 415 (265–392)
CT-derived BSA (cm2) 580 614 (371–784) 526 503 (371–784) 619 624 (566–650) 559 591 (280–371) 23 620 (469–784)

All CTs were performed without complication between December 4, 2019, and April 2, 2020. Adequate separation from the CT table was achieved such that the reconstruction software was able to isolate the subject without the need for manual outlining or reconstruction for 11 of the 12 bearded dragons. For the remaining animal, the reconstructed model required minimal manual editing to achieve separation at the connection point for the body outline and underlying support. The rest of the reconstruction and calculations for this animal were then performed in the same fashion as for the other 11 bearded dragons. The resulting reconstructions had subjectively uniform visual detail (Figure 1). The mean CT-derived BSA was 580 cm2 (range, 371 to 784 cm2; median, 614 cm2; Table 1).

Figure 1
Figure 1

Representative 3-D CT reconstructed surface models used to calculate BSA for 3 of 12 healthy adult client-owned bearded dragons between December 4, 2019, and April 2, 2020.

Citation: American Journal of Veterinary Research 82, 8; 10.2460/ajvr.82.8.629

Results were compiled for BSA plotted against body weight for each bearded dragon and for animals grouped by sex and age (Figure 2). Results for K constants were compiled (Table 2). When results for all 12 bearded dragons were considered, the K constant derived was 11.6 (SE = 0.27; R2 = 0.994). For K constants derived for bearded dragons grouped on the basis of sex and age, results of a 2-tailed t test revealed no significant (P = 0.911) difference in K constants for males (11.7) versus females (11.3); however, the K constant was significantly (P = 0.015) higher for animals in the younger group (12.1) versus the older group (10.9).

Figure 2
Figure 2

Comparisons of nonlinear regression analysis of CT-derived BSA versus body weight measurements for the bearded dragons described in Figure 1 when grouped together (A) and when grouped by sex (all 5 females [B] vs all 7 males [C]) and age (all 8 younger animals [between 1 and ≤ 2 years of age; D] vs all 4 older animals [> 2 years of age; E]). For each grouping, the derived shape constant (K) is shown for the species-specific formula: BSA in cm2 = K X (body weight in g)2/3.

Citation: American Journal of Veterinary Research 82, 8; 10.2460/ajvr.82.8.629

Table 2

Results of nonlinear regression analysis of the CT-derived BSA versus body weight for the 12 bearded dragons described in Table 1 to determine the shape constant (K) for creating a species-specific formula for calculating BSA on the basis of body weight in bearded dragons: BSA in cm2 = K X (body weight in g)2/3.

Groups of bearded dragons K constant SE R2 P value*
All 11.6 0.275 0.994 1.72E-13
Females 11.3 0.516 0.992 2.56E-05
Males 11.7 0.328 0.995 3.27E-08
Younger 12.1 0.305 0.996 1.69E-09
Older 10.9 0.257 0.998 2.93E-05

Reported as the exponential notation (E) for powers of 10 (eg, 1.72E-13 means 1.70 × 10−13).

Discussion

The use of 3-D CT reconstruction to derive BSA is relatively new. The technique has rarely been reported18,19 in veterinary medicine, and to our knowledge, the present report was the first to describe the use of the technique in reptiles. The technique was minimally invasive, required no anesthesia of the bearded dragons, and produced detailed and accurate 3-D CT surface models without the need for manual editing of the body contour, except for the model for 1 animal that required minimal editing to eliminate represented contact with the CT table.

On the basis of our results, the CT-derived BSA formula for bearded dragons is as follows: BSA in cm2 = 11.6 × (body weight in g)2/3. The nonlinear regression model had excellent goodness of fit (SE = 0.275; R2 = 0.994; P < 0.01). The derived K constant, 11.6, was larger than the constants used in dogs and cats (10.1 and 10.0, respectively)13 and those derived with CT reconstruction techniques in ferrets (9.94)18 and rabbits (9.9).19 Previously, the K constant for reptiles was estimated as K = 10 on the basis of metabolic energy requirements.28 Thus, the K constant derived in the present study could have clinical impacts because the higher value suggested that doses of chemotherapeutic agents may need to be higher than previously thought. Further research is indicated to determine whether the K constant we derived is applicable across reptilian species or specific to bearded dragons.

The K constant derived for males did not differ substantially from that for females, and this finding was consistent with the fact that bearded dragons are not sexually dimorphic in their size.29 There was a significant difference between the K constant derived for younger versus older animals, and the clinical impact of this finding warrants further investigation. Reptile growth rates can be influenced by many extrinsic factors, including food intake, habitat, and habitat temperature.30 Their growth also can continue past sexual maturity and throughout the entirety of their lifespan.30

A limitation of the present study was that we did not evaluate bearded dragons of ages across the species' life span, which is approximately 10 years.7 There were also few animals in each group. Further research is indicated with the use of larger sample sizes and wider age ranges to determine whether an age-based difference exists for bearded dragons across their life span. Measuring the BSA of individuals at multiple time points throughout their lives could also be useful in answering this question. Another concern was whether the scales covering bearded dragons could artificially increase their BSA. However, a recent study31 that used gel-based stereo-profilometry to examine scaling patterns of lizards shows that scale size increases isometrically with body size and that scale shape does not change with ontogeny.31 Given the small size of bearded dragons and the fact that their scales are relatively small and minimally alter their body contour, their scales were considered to have had little clinical influence on BSA.

Questions exist regarding the utility of BSA for chemotherapeutic drug dosing in human and veterinary medicine.13,27,32 This type of dosing is reliant on the assumption that processes such as glomerular filtration rate and metabolic rate are proportional to BSA. Given the fact that reptile species have lower metabolic rates, compared with mammals, the question regarding the utility of BSA is important and is worthy of further research. In addition, studies evaluating pharmacokinetics and pharmacodynamics of chemotherapeutic agents in bearded dragons are indicated so that the most appropriate recommendations on dosing these agents can be obtained. In dogs, the dosing of chemotherapeutic drugs is based on BSA, and that basis has been questioned owing to the great variability in body size across breeds. For instance, the use of BSA has been reported13 to lead to a greater risk of overdosing chemotherapeutic drugs in smaller breeds, and the use of dosing by body weight (eg, milligrams of drug per kilogram of body weight) may be more appropriate for smaller breeds to avoid toxicoses.13 However, in standard oncologic practice, chemotherapeutic doses for dogs that weigh < 15 kg are calculated on the basis of body weight rather than BSA for only the most toxic chemotherapeutic agents, such as doxorubicin.13 Therefore, we appreciate that BSA continues to be useful for accurate chemotherapeutic dosing, even in smaller species such as bearded dragons; however, we also recommend caution when veterinarians need to prescribe highly toxic chemotherapeutic agents and suggest that the calculation of dosage on the basis of body weight rather than BSA be considered on a case-by-case basis.

The present study provided a minimally invasive method for determining the BSA and a species-specific formula for bearded dragons. This information could be used to calculate doses of chemotherapeutic agents or other medications that have low therapeutic indices for use in bearded dragons. Further research is indicated to determine pharmacokinetic data in this species, the effects of age on BSA in reptiles, and BSA formulas in other reptilian species.

Acknowledgments

The study was funded by the North Carolina State University Turtle Rescue Team.

The authors declare that there were no conflicts of interest.

Footnotes

a.

SOMATOM Perspective, Siemens Healthcare, Malvern, Pa.

b.

Mimics Innovation Suite, Materialise NV, Leuven, Belgium.

c.

R: A language and environment for statistical computing, version 3.6.1, R Foundation for Statistical Computing, Vienna, Austria. Available at: www.R-project.org. Accessed Apr 8 and Oct 18, 2020.

Abbreviations

BSA

Body surface area

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