Effect of four sedative and anesthetic protocols on quantitative thyroid scintigraphy in euthyroid cats

Irene A. Schaafsma Division of Diagnostic Imaging, Department of Clinical, Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 10, NL-3508 TD, Utrecht, The Netherlands.

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Yvonne W. E. A. Pollak Division of Diagnostic Imaging, Department of Clinical, Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 10, NL-3508 TD, Utrecht, The Netherlands.

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Paul Y. Barthez Division of Diagnostic Imaging, Department of Clinical, Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 10, NL-3508 TD, Utrecht, The Netherlands.

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Abstract

Objectives—To determine the effect of sedation and anesthesia on thyroid and salivary gland uptake of technetium Tc 99m pertechnetate (99mTcO4) in euthyroid cats.

Animals—6 euthyroid cats.

Procedures—Thyroid scintigraphy was performed by use of a high-resolution low-energy parallel-hole collimator after IV injection of 117 to 133 MBq (3.16 to 3.59 mCi) of 99mTcO4. The procedure was performed 4 times on each cat during different sedative and anesthetic protocols in a rotating schedule as follows: propofol, ketamine-midazolam-atropine, ketaminemidazolam, and medetomidine. Regions of interest were drawn around thyroid and salivary glands and counts corrected for background and decay. Percentage of 99mTcO4 uptake in salivary and thyroid glands and thyroid-to-salivary gland 99mTcO4 uptake ratio were calculated at 20 and 40 minutes. Relative effects of anesthesia and sedation on salivary and thyroid gland 99mTcO4 uptake were compared.

Results—Significant differences among sedativeanesthetic protocols were found for thyroid gland 99mTcO4 uptake, salivary gland 99mTcO4 uptake, and thyroid-to-salivary gland 99mTcO4 uptake ratio. Thyroid gland 99mTcO4 uptake for the ketamine-midazolam protocol at 20 and 40 minutes after 99mTcO4 administration was significantly higher than for the propofol protocol. A significant difference in salivary gland99m TcO4 uptake was found between ketamine-midazolam and ketamine-midazolam-atropine protocols at 40 minutes. The thyroid-to-salivary gland 99mTcO4uptake ratio for the ketamine-midazolam protocol was significantly higher at 40 minutes than for propofol or ketamine-midazolam-atropine protocols.

Conclusions and Clinical Relevance—Sedation and anesthesia have a significant effect on thyroid and salivary gland 99mTcO4 uptake in euthyroid cats that may interfere with thyroid scintigraphic image interpretation.

Abstract

Objectives—To determine the effect of sedation and anesthesia on thyroid and salivary gland uptake of technetium Tc 99m pertechnetate (99mTcO4) in euthyroid cats.

Animals—6 euthyroid cats.

Procedures—Thyroid scintigraphy was performed by use of a high-resolution low-energy parallel-hole collimator after IV injection of 117 to 133 MBq (3.16 to 3.59 mCi) of 99mTcO4. The procedure was performed 4 times on each cat during different sedative and anesthetic protocols in a rotating schedule as follows: propofol, ketamine-midazolam-atropine, ketaminemidazolam, and medetomidine. Regions of interest were drawn around thyroid and salivary glands and counts corrected for background and decay. Percentage of 99mTcO4 uptake in salivary and thyroid glands and thyroid-to-salivary gland 99mTcO4 uptake ratio were calculated at 20 and 40 minutes. Relative effects of anesthesia and sedation on salivary and thyroid gland 99mTcO4 uptake were compared.

Results—Significant differences among sedativeanesthetic protocols were found for thyroid gland 99mTcO4 uptake, salivary gland 99mTcO4 uptake, and thyroid-to-salivary gland 99mTcO4 uptake ratio. Thyroid gland 99mTcO4 uptake for the ketamine-midazolam protocol at 20 and 40 minutes after 99mTcO4 administration was significantly higher than for the propofol protocol. A significant difference in salivary gland99m TcO4 uptake was found between ketamine-midazolam and ketamine-midazolam-atropine protocols at 40 minutes. The thyroid-to-salivary gland 99mTcO4uptake ratio for the ketamine-midazolam protocol was significantly higher at 40 minutes than for propofol or ketamine-midazolam-atropine protocols.

Conclusions and Clinical Relevance—Sedation and anesthesia have a significant effect on thyroid and salivary gland 99mTcO4 uptake in euthyroid cats that may interfere with thyroid scintigraphic image interpretation.

Thyroid scintigraphy is used routinely in veterinary medicine for the clinical workup of cats suspected of having hyperthyroidism.1 Thyroid scintigraphy is indicated to confirm the diagnosis of hyperthyroidism, determine unilateral or bilateral thyroid involvement, and identify ectopic thyroid tissue.1–3 Routinely, 99mTcO4 is used because of its similarities with iodine.3,4 It has been reported that 99mTcO4 accumulates in the thyroid gland, choroid plexus, salivary and sweat glands, and gastric mucosa after IV injection.2 Hyperplasia or tumors of the thyroid gland will result in an increased uptake of 99mTcO4 that is proportional to the metabolic hyperactivity.3–5 The ratio of thyroid-to-salivary gland uptake of 99mTcO4 has been used routinely as the main criterion to diagnose hyperthyroidism in cats.1–4,6 An increase in this ratio is considered diagnostic for hyperthyroidism.2,3 Thyroid scintigraphy is commonly performed without the use of any chemical restraint. Sedation or anesthesia, however, may be required for noncooperative cats or with the use of a pinhole collimator.7 Drugs used commonly for sedation may interfere with thyroid or salivary gland metabolism and change 99mTcO4 uptake.

The purpose of the study reported here was to determine the influence of 4 sedative and anesthetic protocols on the accumulation of 99mTcO4 in the salivary and thyroid glands in euthyroid cats. It was hypothesized that the method of sedation or anesthesia that increases salivation the most would cause a decrease in intensity of the salivary glands on scintigraphy and thus an increase in the thyroid-to-salivary gland 99mTcO4 uptake ratio because of excretion of pertechnetate.

Materials and Methods

Animals—Six adult European shorthair cats were used for this study, including 3 neutered females and 3 neutered males. Male cats were all 7 years old, and female cats ranged from 12 to 14 years old. Cats were housed in 2 groups. Results of physical examination, CBC, serum biochemical analysis, and plasma concentration of free thyroxine were within reference range limits. The animal ethical committee of Utrecht University approved the protocol.

Scintigraphy—A dynamic study of the thyroid gland was performed by use of a gamma cameraa equipped with a lowenergy high-resolution parallel-hole collimator and connected to a computer with dedicated software.b The technetium Tc 99m photopeak was centered at 140 KeV with a window of 20%. Cats were positioned in sternal recumbency, stabilized with sandbags on the top of the collimator, and injected IV with a dose of 117 to 133 MBq (3.16 to 3.59 mCi) of pertechnetate. The dynamic study was performed in 2 phases during a period of 45 minutes by use of a 256 X 256 matrix with a 1.78 zoom factor. The first phase included 12 images every 10 seconds and the second phase 43 images every 60 seconds. A 1-minute image of the syringe used for the injection of the radiopharmaceutical was acquired before and after the injection. Exact activity injected was calculated by subtracting decaycorrected counts before and after IV injection of 99mTcO4.

Image analysis—A composite image, generated by adding all images of the dynamic series, was used for drawing ROIs (Figure 1). All ROIs were drawn manually by the same person (YWEAP), copied to each individual image of the dynamic series, and manually adjusted for movement. Separate ROIs were drawn over the zygomatic glands, and both lobes of the thyroid gland were included in a single ROI. A background ROI was drawn at the tip of the right or left shoulder, avoiding any vascular structures. The number of pixels for each ROI and the total number of counts for each individual image were recorded. Counts were corrected for decay and background. The ROIs of both salivary glands were merged for further data analysis.

Figure 1—
Figure 1—

Composite scintigraphic image of the head and shoulders of a cat. Notice the ROI around the salivary glands, the ROI around both lobes of the thyroid gland, and a background ROI.

Citation: American Journal of Veterinary Research 67, 8; 10.2460/ajvr.67.8.1362

The percentage of 99mTcO4 uptake by the thyroid and salivary gland was determined by dividing the background and decay-corrected counts by the injected dose. The thyroid-to-salivary gland 99mTcO4 uptake ratios were determined by dividing the mean count density of the thyroid by the mean count density of both salivary glands as follows3:

article image

Time versus activity curves were generated for thyroid gland 99mTcO4 uptake, salivary gland 99mTcO4 uptake, and thyroid-to-salivary gland 99mTcO4 uptake ratio for the 4 sedative-anesthetic protocols.

Sedation and anesthesia—Cats were assigned to 1 of 4 sedative or anesthetic protocols. Each cat received all 4 sedative-anesthetic regimens with a minimum interval of 1 week by use of a rotating schedule that was randomly assigned. The 4 sedative-anesthetic protocols were as follows: medetomidine (0.08 to 0.1 mg/kg, IM), ketamine (10 mg/kg, IM) in combination with midazolam (1.0 mg/kg, IM), propofol (maximum of 30 mg/kg, h, IV), and ketamine (10 mg/kg, IM) with midazolam (1.0 mg/kg, IM) in combination with atropine (0.02 mg/kg, IM). Additional dosages for the ketamine-midazolam and ketamine-midazolam-atropine combinations were 1 mg of ketamine/kg (IV) in combination with 0.1 mg of midazolam/kg (IV) as clinically indicated. For each cat, additional administrations of ketamine and midazolam were necessary on average 2 times for the ketamine-midazolam combination and the ketamine-midazolam-atropine combination. Cats were not intubated, and a tube placed in front of the nose supplied oxygen. Monitoring included an ECG, measurement of rectal temperature, and visual inspection of breathing. During the experiment, cats were covered with a blanket that was perfused with warm air. After completion of the study, medetomidine was antagonized by atipamezole administration (75 μg/kg, IM), while the cats sedated with ketamine combinations were sedated with medetomidine to ensure a calm recovery. All cats recovered underneath a heat lamp to prevent hypothermia.

Statistical analysis—Percentage of 99mTcO4 uptake in thyroid and salivary glands and the thyroid-to-salivary gland 99mTcO4 uptake ratio for the different sedative and anesthetic protocols were compared by use of a repeated-measures ANOVA and post hoc multiple comparison procedures with Bonferroni adjustment by use of a software program.c Comparisons were performed at 20 and 40 minutes after IV injection of 99mTcO4. Values of P ≤ 0.05 were considered significant.

Results

Percentage of thyroid gland 99mTcO4 uptake during the 45-minute observation period increased progressively for all sedative-anesthetic protocols (Figure 2). Data for each sedative-anesthetic protocol were normally distributed. Thyroid gland 99mTcO4 uptake for all cats ranged from 0.40% to 1.12% at 20 minutes and from 0.48% to 1.24% at 40 minutes after IV injection of99mTcO4(Table 1). Significant differences in percentage of thyroid gland 99mTcO4 uptake were found among sedative-anesthetic protocols at 20 (P = 0.022) and 40 (P = 0.003) minutes. A significant difference was found in percentage of thyroid gland 99mTcO4 uptake between the ketamine-midazolam protocol and propofol protocol at 20 minutes (P = 0.022) and 40 minutes (P = 0.038).

Table 1—

Mean ± SD, median, and range of the percentage of thyroid gland uptake of 99mTcO4 in 6 euthyroid cats during 4 sedative-anesthetic protocols.

TimeValueSedative-anesthetic protocols
PropofolMedetomidineKetamine-midazolamKetamine-midazolam-atropine
20 minMean0.51 ± 0.160.57 ± 0.120.85 ± 0.20*0.69 ± 0.13
Median0.450.570.910.69
Range0.42–0.830.40–0.710.59–1.120.52–0.84
40 minMean0.60 ± 0.190.70 ± 0.150.97 ± 0.23*0.82 ± 0.19
Median0.550.681.030.79
Range0.48–0.970.53–0.900.73–1.240.64–1.07

Significantly (P < 0.05) higher than other sedative-anesthetic protocols.

Figure 2—
Figure 2—

Mean time versus activity curves of thyroid gland99m TcO4 uptake during 4 sedative-anesthetic protocols (propofol [X], medetomidine [open square], ketamine-midazolam [open triangle], and ketamine-midazolam-atropine [open diamond]) in euthyroid cats.

Citation: American Journal of Veterinary Research 67, 8; 10.2460/ajvr.67.8.1362

Figure 3—
Figure 3—

Mean time versus activity curves of salivary gland99mTcO4 uptake during 4 sedative-anesthetic protocols (propofol [X]; medetomidine [open square]; ketamine-midazolam [open triangle]; and ketamine-midazolam-atropine [open diamond]) in euthyroid cats.

Citation: American Journal of Veterinary Research 67, 8; 10.2460/ajvr.67.8.1362

Figure 4—
Figure 4—

Thyroid scintigraphic image obtained at 40 minutes after injection of 99mTcO4 in a euthyroid cat following ketaminemidazolam (A) and ketamine-midazolam-atropine (B) administration. Notice the difference in salivary gland 99mTcO4 uptake.

Citation: American Journal of Veterinary Research 67, 8; 10.2460/ajvr.67.8.1362

Figure 5—
Figure 5—

Plot of thyroid-to-salivary gland 99mTcO4 uptake ratio versus time during the 45-minute dynamic acquisition in euthyroid cats that underwent 4 sedative-anesthetic protocols (propofol [X], medetomidine [open square], ketamine-midazolam [open triangle], and ketamine-midazolam-atropine [open diamond])

Citation: American Journal of Veterinary Research 67, 8; 10.2460/ajvr.67.8.1362

Percentage of salivary gland 99mTcO4 uptake during the 45-minute observation period increased progressively for all sedative-anesthetic protocols (Figure 3). Percentage of 99mTcO4 uptake for all cats ranged from 0.17% to 0.77% at 20 minutes and from 0.18% to 1.04% at 40 minutes after IV injection of 99mTcO4(Table 2). Significant differences in percentage of salivary gland 99mTcO4 uptake were found among sedative-anesthetic protocols at 20 (P = 0.019) and 40 minutes (P = 0.006). A significant (P = 0.040) difference in percentage of salivary gland 99mTcO4 uptake was found between the ketamine-midazolam protocol and ketaminemidazolam-atropine protocol at 40 minutes after injection (Figure 4); differences at 20 minutes were not significant. The decline in the salivary gland 99mTcO4 uptake during the ketamine-midazolam protocol from 30 to 45 minutes was not significant.

Table 2—

Mean ± SD, median, and range of the percentage of salivary gland uptake of 99mTcO4 in 6 euthyroid cats during 4 sedative-anesthetic protocols.

TimeValueSedative-anesthetic protocols
PropofolMedetomidineKetamine-midazolamKetamine-midazolam-atropine
20 minMean0.32 ± 0.090.22 ± 0.100.33 ± 0.110.45 ± 0.17
Median0.320.200.330.41
Range0.18–0.430.17–0.390.20–0.460.31–0.77
40 minMean0.38 ± 0.100.29 ± 0.100.32 ± 0.120.59 ± 0.24*
Median0.400.270.290.51
Range0.23–0.490.18–0.450.22–0.530.41–1.04

See Table 1 for key.

Thyroid-to-salivary gland 99mTcO4 uptake ratios decreased during the first 10 minutes of observation and were fairly stable between 10 and 40 minutes (Figure 5). Thyroid-to-salivary gland 99mTcO4 uptake ratios of all cats ranged from 0.47 to 1.53 at 20 minutes and from 0.45 to 1.28 at 40 minutes after IV injection of 99mTcO4 (Table 3). Significant differences in thyroid-to-salivary gland 99mTcO4 uptake ratios were found among sedativeanesthetic protocols at 20 (P = 0.034) and 40 minutes (P = 0.001). The thyroid-to-salivary gland 99mTcO4 uptake ratio at 20 minutes did not differ among the 4 sedativeanesthetic protocols. At 40 minutes, however, significant differences were found between the ketamine-midazolam protocol (1.06 ± 0.22) and propofol protocol (0.67 ± 0.10; P = 0.025) and between the ketamine-midazolam protocol (1.06 ± 0.22) and ketamine-midazolamatropine protocol (0.63 ± 0.19; P = 0.004).

Table 3—

Mean ± SD, median, and range of the thyroid-to-salivary gland 99mTcO4 uptake ratio in 6 euthyroid cats during 4 sedative-anesthetic protocols.

TimeValueSedative-anesthetic protocols
PropofolMedetomidineKetamine-midazolamKetamine-midazolam-atropine  
20 minMean0.69 ± 0.091.04 ± 0.330.88 ± 0.210.67 ± 0.15
Median0.660.980.850.70
Range0.60–0.850.62–1.530.62–1.250.47–0.86
40 minMean0.67 ± 0.100.95 ± 0.211.06 ± 0.22*0.63 ± 0.19
Median0.640.901.080.65
Range0.52–0.830.73–1.230.76–1.280.45–0.85

See Table 1 for key.

Discussion

Results of our study indicate that the influence of anesthesia or sedation on salivary and thyroid gland uptake of 99mTcO4 in euthyroid cats may interfere with scintigraphic image interpretation. A change in thyroid-to-salivary gland 99mTcO4 uptake ratio induced by sedation or anesthesia may lead to a false diagnosis of hyperthyroidism, if the effect of sedative-anesthetic drugs is not taken into account. This is especially true for the ketamine-midazolam combination. It is therefore recommended to take sedative-anesthetic drugs into account when interpreting quantitative thyroid scintigraphy in cats and, if cats have to be sedated, anesthetized, or both for the procedure, to use reference range values established with the same sedative-anesthetic protocol to eliminate any potential bias.

The thyroid-to-salivary gland 99mTcO4 uptake ratio at 20 minutes after the injection of 99mTcO4 in euthyroid cats is reported to range between 0.82 and 1.2.2,3,5,8 In all of these studies, cats were anesthetized or sedated with various drugs. In 1 study,8 9 of 12 cats were sedated with 200 μg of medetomidine. In 2 other studies, ketamine was used in all5 and in 7 of 10 cats.2 In 1 study,3 cats were anesthetized with a combination of unknown injectable and inhalant anesthetics. In our study, a control, unsedated group could not be included, as initially planned, because cats were not cooperative enough for the procedure, even for a single 1-minute image at 20 and 40 minutes after IV injection of 99mTcO4. The effect of sedation or anesthesia on thyroid and salivary gland 99mTcO4 uptake could not be compared with the unsedated state, but significant differences between sedative-anesthetic protocols in our study indicate that sedation or anesthesia influences thyroid and salivary gland uptake of 99mTcO4.

The zygomatic salivary gland of cats is easily made to secrete reflexively even in deep anesthesia. This reflex can be abolished by atropine administration.9 Salivary gland 99mTcO4 uptake increased when atropine was added to the ketamine-midazolam protocol. The use of atropine has been advised2,10 to prevent salivation, which could mask the visibility of ectopic thyroid tissue, and to counteract the bradycardia induced by medetomidine. Atropine may induce an increase in salivary gland 99mTcO4 uptake when used in combination with medetomidine and cause an artifactual decrease in the thyroid-to-salivary gland 99mTcO4 uptake ratio because the thyroid gland 99mTcO4 uptake during medetomdine sedation is already low.

Thyroid gland 99mTcO4 uptake was significantly higher with ketamine-midazolam and ketamine-midazolam-atropine protocols, compared with medetomidine and propofol protocols. Cardiovascular effects of medetomidine and propofol could explain this finding. Medetomidine induces peripheral vascular constriction and bradycardia,11 and propofol induces cardiovascular suppression.12 Deliverance of the 99mTcO4 to the thyroid gland may be delayed as a result of these cardiovascular effects.

We chose to concentrate our analysis on data collected at 20 and 40 minutes after IV injection of 99mTcO4. Most investigators acquire thyroid scintigraphic images in cats at 20 minutes after injection of the radiopharmaceutical.3,5,13 In our clinic, however, images are acquired at 40 minutes after injection of the radiopharmaceutical because thyroid gland 99mTcO4 uptake at that time is high.14

The number of cats used in our study was limited to 6 for ethical and financial reasons. However, the small number of cats may have influenced detection of significant differences. When a significant effect was found at 40 minutes, it can be speculated that the same significant effect may have already been present at 20 minutes, but not detected because of the small number of cats in our study.

Our study was designed to investigate the effect of sedation and anesthesia on thyroid scintigraphy. Therefore, the worst-case scenario, in which the cat has to be anesthetized for the entire procedure, including the injection of the radiopharmaceutical, was simulated. Some cats may not accept the manual restraint needed for image acquisition, but will tolerate the IV injection without the use of sedation or anesthesia. The effect of short-lasting sedation or anesthesia at the time of image acquisition was not investigated in our study, but is likely to be less than reported herein.

ABBREVIATIONS

99mTcO4

Technetium Tc 99m pertechnetate

ROI

Region of interest

a.

Integrated ORBITER gamma camera, Siemens Medical Systems, Hoffman Estates, Ill.

b.

Siemens ICON computer system, Siemens Medical Systems, Hoffman Estates, Ill.

c.

Microsoft Excel, Microsoft Corp, Redmond, Wash.

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