Introduction
Medetomidine, an α2-adrenergic agonist, is widely used in cats due to its well-established sedative and analgesic effects.1 However, it produces dose-dependent side effects, such as reduced heart rate (HR), decreased cardiac output, increased total vascular resistance, and transient blood pressure fluctuations, with an initial dose-dependent rise in blood pressure that gradually normalizes over time.2,3 Intranasal (IN) administration of anesthetics offers an effective route by enabling absorption through the nasal mucosa or direct transport to the brain via the olfactory nerve.4 Medetomidine’s low molecular weight and lipophilicity further enhance its suitability for IN delivery by promoting efficient absorption.5
Thoracic radiography is commonly used for the clinical evaluation of heart disease in cats.6 Previous studies have reported cardiac enlargement on radiographs following IM dexmedetomidine administration in cats,7 and increased vertebral heart size (VHS) in dogs.8 However, a comprehensive literature search (Web of Science, Scopus, and Google Scholar; November 2024) revealed no studies investigating the effects of medetomidine delivered via IN and IM routes on cardiac size in cats. Therefore, this study aimed to evaluate and compare the effects of IN and IM administration of medetomidine on cardiac size in cats. Additionally, the study sought to assess the impact of IN and IM medetomidine administration on sedation variables.
Methods
Burdur Mehmet Akif Ersoy University Local Board of Ethics Committee for Animal Experiments approved the experimental protocol (Decision No. 2024/1259). This study was conducted at a Burdur Mehmet Akif Ersoy University Animal Hospital between June and August 2024. Before sedation, owners were informed about the sedation protocol and the planned procedures, and written informed consent was obtained.
Animals
This study included a total of 14 male tabby cats aged 1 to 3 years with an American Society of Anesthesiologists status of 1 to 2. The included cats were brought to the hospital for oral examination, ear examination, or dental radiography. A 22-gauge intravenous catheter was placed in the cephalic vein of each cat’s forelimb before starting the sedation protocol. Blood samples were collected to evaluate hematology (H60; EDAN Instruments Inc), biochemistry (respons 910; DiaSys Diagnostic Systems GmbH), and blood gas parameters (i15Vet; EDAN Instruments Inc). American Society of Anesthesiologists status was determined based on a combination of physical examination findings, medical history, and blood work results before inclusion in the study. Exclusion criteria included animals that did not meet the inclusion criteria; those that could not undergo radiography during the presedation phase; those whose presedative VHS, cardiothoracic ratio (CTR), atrial size, or ventricular size fell outside the reference range; or those with abnormal cardiothoracic auscultation findings, such as murmurs, arrhythmias, or crackles.
Groups
Cats were randomly (www.randomization.org) assigned to 2 groups; IN medetomidine (1 mg/mL [Domitor; Zoetis]) or IM medetomidine at 0.08 mg/kg.9 For IM administration, agents were drawn into a 22-gauge syringe and injected into the right quadriceps femoris muscle while the cat was in a lateral position. For IN administration, cats were positioned in sternal recumbency, with the head elevated to a 30° angle. A mucosal atomization device (MAD300; Teleflex Medical Srl) was used for IN administration; half the dose was administered into one nostril and the remaining half into the other.10
Sedation variables
The following parameters were monitored: HR using a stethoscope, respiratory rate by counting abdominal movements over 1 minute, rectal temperature (RT) via rectal probe inserted 4 cm into the rectum, systolic blood pressure (SBP) and diastolic blood pressure with a cuff placed proximally to the tarsal joint, and peripheral arterial oxygen saturation (Spo2) via a probe placed on the ear. If the Spo2 dropped below 90%, supplemental oxygen was provided at a flow rate of 2 L/min. Oxygen was delivered directly in front of the animal’s nares via tubing connected to an oxygen flowmeter. All data were recorded every 5 minutes using a veterinary monitor (iM8 VET; EDAN). Onset of sedation (moment when cat’s eye ceased to actively follow movement of objects), onset of lateral recumbency (moment after test drug administration when cat began to be laterally recumbent), arousal time (first time after lateral recumbency when repeated spontaneous body movements reappeared), righting time (first time when cat managed to lift its head up without assistance), sternal recumbency (first time when cat managed to recover sternal recumbency), and walking time (time when cat was seen taking its first step either spontaneously or after agitation) were recorded.11 Occurrence of vomiting was also documented.
Radiography
Radiographic images were taken at baseline (Tb) and immediately after administration (T0) and following at 5 (T5), 15 (T15), 30 (T30), 45 (T45), and 60 (T60) minutes after sedation, in 4 views (right lateral, left lateral, ventrodorsal [VD], and dorsoventral [DV]) at peak inspiration. Lateral radiographs were obtained with settings of 65 kV, 320 mA, and 20 milliseconds, while VD radiographs were obtained with 68 kV, 250 mA, and 28 milliseconds.12 The focus-film distance was set at 100 cm. For lateral radiographs, the head and neck were extended with the forelimbs cranially positioned and the hind limbs caudally positioned. Collimation was centered at the caudal scapular border and midline between the sternum and thoracic spine. For VD radiographs, cats were positioned sternally with the head and neck extended, forelimbs cranially positioned, and hind limbs caudally positioned. The x-rays were aligned to include the thoracic inlet and diaphragm, centered at the caudal scapula. For DV radiographs, animals were positioned supine, with forelimbs pulled forward and hind limbs in a neutral position. Abdomen and pelvis were leveled, and collimation centered at the midsternum to include the diaphragm. A left or right marker was positioned in the defined field, as applicable.12
Vertebral heart score
The R-VHS, L-VHS, VD-VHS, and DV-VHS radiographs were assessed with the method described by Litster and Buchanan.13 This method measured the long and short axes in lateral, VD, and DV radiographs (CR-IR 392; Fujifilm). The long axis (LA) extended from the ventral tracheal bifurcation (carina) to the heart apex, and the short axis (SA) was measured horizontally from the widest point of the heart at the junction of the caudal vena cava and the caudal heart border to the cranial border, perpendicular to the LA. Starting from the cranial boundary of T4, the combined length of these 2 axes was assessed as the VHS.13
The T4-R-VHS and T4-L-VHS radiographs were evaluated according to the previous method11; they covered the LA from the cranioventral border of the carina to the apex on lateral radiographs and the SA at the widest point of the heart at the vena cava level perpendicular to the LA. Both axes were divided by the length from the cranial edge of the fourth to the fifth thoracic vertebrae (T4 to T5) to yield the vertebral heart score. The VHS was calculated as follows:
VHS = (LA / T4) + (SA / T4)14
Cardiothoracic ratio
The VD-CTR, DV-CTR, VD T6-10, DV-T6-10, and R T5-7 radiographs were assessed with the following measurement method: for the DV and VD positions, a line was drawn across the widest part of the heart, and a parallel line was drawn between the pleural surfaces at the eighth rib level. The ratio of these 2 measurements was then calculated.15 Additionally, the LA from the tracheal bifurcation to the apex and the distance from the cranial border of the sixth rib to the caudal border of the tenth rib were measured for a similar ratio calculation.16 In the lateral position, the maximum distance between the cranial and caudal heart borders (SA) and the lateral distance between the cranial edge of the fifth rib and caudal edge of the seventh rib were measured, and their ratio was calculated.6,16
Statistical analyses
The sample size was calculated using G*power, version 3.1.9.6 (Heinrich-Heine 9 University), based on the assumption of achieving 95% statistical power to detect a 0.6–mm Hg difference in VHS cardiac size-to-thorax ratio with an estimated SD of 0.04 and a significant level of 5%. According to these parameters, a minimum of 7 cats/group were required for the study. This sample size calculation was performed with data from a previous study that compared the effects of dexmedetomidine on cardiac size in dogs.8 All statistical analyses were performed with SPSS, version 27.0 (SPSS Inc; IBM Corp). Data normality was evaluated via the Shapiro-Wilk test. Comparisons between groups for physiological variables at each time point were conducted with independent-samples t tests or Mann-Whitney U tests where appropriate. Changes in variables over time were analyzed by means of repeated-measures analysis of variance or the Kruskal-Wallis test, followed by a Tukey or Mann-Whitney U test where appropriate. Onset of clinical sedation, onset of lateral recumbency, arousal time, righting time, sternal recumbency, and walking time were analyzed with independent-samples t tests or Mann-Whitney U tests. The occurrence of vomiting was compared between groups using the Fisher exact test. Data are presented as mean ± SD or median (range), with P < .05 considered statistically significant.
Results
Vomiting was observed in 5 cats and sneezing in 1 cat following IN drug administration. After IM administration, vomiting occurred in 3 cats, and 1 case of mydriasis was noted at the sixth minute following drug administration. The occurrence of vomiting was not significantly different between groups (P = .592). No abnormalities were encountered during recovery in either group. Both administration routes were well tolerated by the cats, and all animals completed the study without complications.
No significant differences were observed between the 2 administration routes at any time point for R-VHS, L-VHS, VD-VHS, DV-VHS, T4-R-VHS, T4-L-VHS, R T5-7, DV T6-10, and DV-CTR. Additionally, these parameters did not significantly change over time. At T30, VD T6-10 values were significantly higher in the IM group (1.18 ± 0.12) compared to the IN group (1.04 ± 0.06; P = .0245). No significant differences were observed between the 2 administration routes at any time point for VD-CTR. For the IM group, compared to the baseline (0.54 ± 0.06), VD-CTR values were significantly higher at T5 (0.62 ± 0.064), T15 (0.64 ± 0.079), T30 (0.63 ± 0.059), T45 (0.63 ± 0.03), and T60 (0.63 ± 0.05). For the IN group, VD-CTR values were significantly higher at T5 (0.58 ± 0.035), T15 (0.60 ± 0.05), T30 (0.61 ± 0.06), T45 (0.60 ± 0.036), and T60 (0.58 ± 0.035) compared to the Tb (Supplementary Material S1).
Heart rate, respiratory rate, RT, SBP, and diastolic blood pressure values did not differ significantly between the 2 groups at any time point. Heart rate was lower in both groups at all time points compared to baseline, except for the IN group at T0. Respiratory rate and RT were lower in both groups at multiple time points compared to baseline. The Spo2 was significantly lower in the IM group (90 [range, 85 to 93]) than in the IN group (95 [range, 92 to 100]; P = .006). The Spo2 was lower in the IM group at T25 and in the IN group at T30 compared to baseline. The SBP and diastolic blood pressure values did not significantly differ from baseline at any time point (Supplementary Material S2). The onset of clinical sedation was significantly faster in the IM group (3.85 ± 1.21 minutes) compared to the IN group (9.85 ± 4.98 minutes; P = .009). Similarly, the onset of lateral recumbency occurred earlier in the IM group (7.28 ± 1.79 minutes) than in the IN group (12.42 ± 4.79 minutes; P = .021). No significant differences were observed between the groups for arousal time (P = .327), righting time (P = .654), sternal recumbency (P = .488), or walking time (P = .727; Table 1).
Effects of intranasal (IN) or IM administration of 0.08 mg/kg of medetomidine in cats on sedation variables.
| Variables | Group | P value | |
|---|---|---|---|
| IM | IN | ||
| Onset of clinical sedation | 3.85 ± 1.21 | 9.85 ± 4.98 | .009 |
| Onset of lateral recumbency | 7.28 ± 1.79 | 12.42 ± 4.79 | .021 |
| Arousal time | 38.28 ± 14.93 | 30.57 ± 13.26 | .327 |
| Righting time | 55.42 ± 15.73 | 52.14 ± 10.46 | .654 |
| Sternal recumbency | 62.28 ± 15.40 | 57.14 ± 11.15 | .488 |
| Walking time | 70.28 ± 15.03 | 67.28 ± 16.35 | .727 |
Data are presented as mean ± SD. P values indicate the differences between treatments.
Discussion
In this study, no significant differences were found between the 2 administration routes at any time point for all measurements, except for the VD-CTR values, which were significantly higher at multiple time points in both groups compared to baseline. A previous study7 reported that IM administration of 40 µg/kg of dexmedetomidine in cats significantly increased R-VHS, VD-CTR, and DV-CTR values. Similarly, IV dexmedetomidine administration in dogs resulted in increased cardiac dimensions.8 In the current study, while some VHS values exceeded the normal reference range, no statistical differences were observed. The significant enlargement in VD-CTR, despite no changes in R-VHS and DV-CTR, may be explained by the heart appearing elongated on VD radiographs. This elongation may occur because medetomidine induces changes in cardiac preload and afterload, leading to alterations in the overall cardiac silhouette. Specifically, medetomidine’s vasoconstrictive effects and its impact on HR and myocardial contractility could contribute to increased venous return and transient cardiac dilation. These changes are more apparent on VD radiographs, where the cranial right aspect of the cardiac silhouette can appear more rounded and dilated. Additionally, VHS measurements use a consistent intercostal distance, while CTR measurements are influenced by variations in rib spacing.17 This methodological difference may also contribute to the apparent discrepancy between VHS and VD-CTR changes, further emphasizing the importance of radiographic positioning and measurement technique when interpreting these findings.
A previous study18 found that administering 20 μg/kg of dexmedetomidine to cats resulted in more frequent vomiting with IN delivery compared to IM. In our study, no differences in the incidence of vomiting were observed between groups. This discrepancy may be related to the method of IN administration, as instilling the drug via drop technique might lead to swallowing, which could increase the likelihood of vomiting.18 In dogs, 40 µg/kg of medetomidine induced a faster onset of sedation via IM administration compared to IN delivery.19 Similarly, our study found that sedation onset occurred earlier in the IM group than in the IN group. In contrast, another study20 reported no difference in sedation onset between IN and IM administration of 5 µg/kg of dexmedetomidine. These discrepancies may stem from differences in administration techniques, such as delivering the drug into 1 nostril versus both nostrils. Splitting a small drug volume between 2 nostrils may limit its absorption by the olfactory epithelium, reducing efficacy.
In our study, no significant differences in HR were observed between groups, though HR decreased significantly from baseline. Similarly, previous studies3,21 reported HR reductions after medetomidine or dexmedetomidine administration, regardless of the route. For example, 20 µg/kg of dexmedetomidine resulted in lower HR in the IM group compared to the IN group,22 while 5 µg/kg of dexmedetomidine caused a comparable decrease in both groups.20 In contrast, 40 µg/kg of medetomidine produced no significant HR differences between IN and IM routes.19 Variations in drug potency, dosage, administration routes, or species may explain these discrepancies. In the current study, some cats experienced hypoxemia despite receiving supplemental oxygen. This was likely due to the positioning or handling of the cats during radiography, which may have affected the optimal delivery of oxygen, potentially contributing to the lower Spo2 values observed in some cats. Additionally, improper positioning of the Spo2 probe on the ear during recordings may have led to inaccurate readings.
In this study, sedation scores were not recorded, which limits the assessment of precise sedation levels and the duration of effective sedation. This omission prevents a more comprehensive understanding of sedation progression and its relationship to the administered treatment. Additionally, the absence of mean arterial pressure recordings limits the evaluation of blood pressure regulation, and changes in SAP and DAP compared to baseline were not analyzed in detail. Furthermore, the accuracy of the monitor used to record SAP and DAP has not been fully validated in sedated or awake cats. The absence of echocardiography is another limitation, as it could have provided a more accurate and detailed evaluation of cardiac size and enlargement, offering better insights into potential cardiovascular effects and confirming findings observed through radiography.
Both administration routes resulted in significant increases in VD-CTR values compared to baseline, with no significant differences between the 2 groups for this parameter. The cats tolerated both IN and IM medetomidine administration well, and no significant differences were observed in most clinical parameters, suggesting that both methods were equally effective and safe in inducing sedation. While the IM route led to a faster onset of sedation and lateral recumbency, there were no significant differences in recovery times or overall clinical outcomes between the groups.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
The authors sincerely thank the Burdur Mehmet Akif Ersoy University Animal Hospital for their valuable support during the study.
Disclosures
Dr. Yanmaz is a member of the JAVMA Scientific Review Board, but was not involved in the editorial evaluation of or decision to accept this article for publication.
No AI-assisted technologies were used in the generation of this manuscript.
Funding
This study was supported by Burdur Mehmet Akif Ersoy University Scientific Research Projects Commission (Project No. 1002-YL-24).
ORCID
L. E. Yanmaz https://orcid.org/0000-0001-5890-8271
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