Effect of gabapentin on ambulatory,direct,systemic arterial blood pressure in apparently healthy cats in the at-home and in-clinic environments

Abstract

Objectives

Situational increases in blood pressure (BP) frequently confound the accurate diagnosis of pathological systemic hypertension in cats. The objective of this study was to investigate the effect of gabapentin on direct, ambulatory systolic arterial BP (SBP) in cats in at-home and in-clinic environments.

Methods

Six adult purpose-bred cats with surgically implanted femoral artery telemetric BP-sensing catheters were administered 100 mg of gabapentin or a placebo orally in two randomized, masked, crossover study phases. In the first, direct BP was measured continuously in undisturbed cats for 24 h before (at-home baseline) and 4 h after administration of study drug. The mean SBP after administration of the drug was compared between treatments. In the second study period, cats were administered gabapentin or placebo 90 mins before transport to a clinic, where direct BP was measured continuously during a simulated veterinary visit that included an indirect BP measurement session. Changes in mean direct SBP relative to the 24-h at-home pre-treatment period were calculated for each of one waiting room and two examination-room periods, and compared between treatments. Concurrent in-clinic direct and indirect SBP measurements were compared within-cat. Data were compared using linear mixed models.

Results

Direct SBP data from one cat were excluded due to implant failure. There were no differences in at-home or in-clinic SBP between treatment groups, with large inter-individual variability. Cats in both treatment groups experienced in-clinic increases in direct SBP relative to at-home baseline (range 11–50 and 10–52 mmHg in placebo- and gabapentin-treated cats, respectively). Across all visits, direct SBP was 15.6 mmHg higher than indirect SBP (P <0.001). No effects of treatment on difference between direct and indirect SBP were identified.

Conclusions and relevance

Significant effects of gabapentin on direct SBP were not identified, though a type II error is possible. Situational increases cannot be excluded in gabapentin-treated cats with high SBP.

Introduction

Despite their designation as the most popular pet in the USA, the number of annual veterinary visits for cats has decreased significantly in recent years. ¹ Among the most frequently cited impediments to regular veterinary care is owners’ concern for excessive visit-associated stress to their pet.^2–4 Nevertheless, failure to seek routine care represents an important missed opportunity for disease prevention, detection and treatment.

In cats, veterinary visit-associated stress can cause situational hypertension, an increase in systemic arterial blood pressure (BP) that is caused by the measurement process itself in an animal that is otherwise normotensive. ⁵ This phenomenon is well known in cats and commonly confounds the accurate diagnosis of pathologic systemic arterial hypertension, especially prevalent in older cats with chronic kidney disease, hyperthyroidism or both.^5–8

One approach to minimizing visit-associated stress involves pre-emptive administration of oral anxiolytics. The results of previous studies in healthy cats suggest that administration of a single oral dose of gabapentin before a veterinary visit increases compliance with examination and decreases stress-related behaviors.^9,10 Gabapentin is widely available and inexpensive, has good oral bioavailability and is associated with measurable sedative effects that peak approximately 2–3 h after a single oral dose.^9,11 As such, it represents an attractive option for reducing cat stress during veterinary visits, and might prevent situational increases in BP, thereby improving clinician confidence in the diagnosis of pathologic hypertension.

To date, gabapentin’s effects on systemic BP in cats have not been well characterized. In one study of apparently healthy cats, systolic (SBP) and mean BP measured by oscillometry during an office visit were no different between cats pre-treated with gabapentin and those pre-treated with a placebo. ⁹ A more recent randomized, masked study compared hemodynamic and echocardiographic variables in gabapentin- vs placebo-treated young cats and found no significant difference in Doppler-derived SBP between groups. ¹² However, no studies are available using direct measurement of BP, which is particularly important in this species to overcome the known inaccuracy and imprecision of indirect BP measurement methods.

The accurate evaluation of BP and the effects of pharmacologic agents on BP in awake cats presents a unique challenge, owing to both the confounding effects of physical restraint and environmental stressors, and the known unreliability of indirect BP measurement methods. The use of telemetric arterial implants overcomes these challenges by allowing accurate BP determination without the need for sedation, anesthesia or even direct handling during measurement.

The main objective of this study was to evaluate the effect of a single oral dose of gabapentin on directly measured systemic arterial BP in apparently healthy cats in an undisturbed ‘home’ environment and during a simulated veterinary visit. We hypothesized that there would be no difference in ambulatory, direct SBP up to 4 h post-dose in gabapentin- vs placebo-treated cats. We also hypothesized that treatment with gabapentin 90 mins before a veterinary visit would mitigate situational increases in BP; that is, directly measured SBP would be similar between in-hospital and at-home environments in gabapentin-, but not placebo-treated, cats. Finally, we also sought to evaluate whether pre-treatment with gabapentin might improve the ability of indirect Doppler sphygmomanometry to approximate concurrently measured direct SBP measurements in the hospital setting. We hypothesized that there would be a smaller difference between concurrent indirect and direct SBP measurements in gabapentin- vs placebo-treated cats.

Materials and methods

Animals

Six adult purpose-bred domestic shorthair cats were used for this prospective, randomized, placebo-controlled, masked, crossover experimental study. Approximately 14 months before inclusion in the present study, cats were inoculated with Brugia malayi as part of an unrelated project but failed to become persistently microfilaremic. Activities of that study were approved by the University of Georgia Institutional Animal Care and Use Committee (IACUC; protocol number A2019 04-010). One cat developed chronic, mild, bilateral, distal hindlimb edema that did not interfere with its daily activities and had been present and stable for several months before the start of the present study. Otherwise, before inclusion, cats were found to have normal physical examination findings, serum biochemistry profile, complete blood count and urinalysis. All cats were vaccinated against common viral diseases and had negative test results for feline leukemia virus antigen and antibodies against feline immunodeficiency virus. Cats had free access to water and commercially available adult cat kibble and were group-housed, except as needed to facilitate fasting requirements and during BP measurement periods. An ambient temperature between 20°C and 22°C was maintained, and cats were exposed to a 12-h light–dark cycle. All parts of the present study were approved by the University of Georgia IACUC (protocol number A2021 02-002-Y2-A5) and followed American Association for Laboratory Animal Science (AALAS) guidelines for the humane care and use of laboratory animals.

General study design

The general design of the present study is outlined in Figure 1. Cats were allowed a minimum of 30 days to acclimate to the vivarium before the start of the study. During this acclimation period and for the remainder of the study, a single individual designated as the ‘owner’ cared for and interacted with the cats on all weekdays, to encourage and simulate a robust cat–owner relationship. After the acclimation period, a BP-sensing radiotelemetry device (Model HD-S10; Data Sciences International) was surgically implanted into a femoral artery of each cat, after which a 3-week recovery period was allowed. The technique used for radiotelemetry device placement has been described elsewhere in detail. ¹³

Figure 1

(a) General design of the present study, which consisted of (b) an at-home evaluation and (c) a simulated veterinary visit (phase 2). BP = blood pressure; HR = heart rate; SBP = systolic blood pressure; VTH = Veterinary Teaching Hospital

The first phase of the study evaluated the effect of a single oral dose of gabapentin on directly measured ambulatory systemic arterial BP. Cats were administered 100 mg of gabapentin or placebo as a single oral dose in a randomized crossover study with a 1-week washout period. For 24 h before and 4 h after each oral treatment, direct arterial BP, heart rate (HR) and activity counts, all telemetry-derived, were continuously measured and recorded in undisturbed cats in the home environment.

After a 2-week washout period, the second study phase was begun, which evaluated the effects of gabapentin on BP in cats undergoing a simulated veterinary visit. Cats were administered 100 mg of gabapentin or placebo as a single oral dose, approximately 90 mins before transportation. This phase was carried out in randomized crossover fashion with a 2-week washout period between treatments.

For each simulated veterinary visit, 90 mins after administration of gabapentin or placebo, cats were removed from their cage by the ‘owner’, placed in a portable animal carrier after having their arterial radiotelemetry devices turned on and transported on foot to a vehicle. Carriers were placed in the vehicle and driven for approximately 20 mins along a predetermined route that ended at the Veterinary Teaching Hospital. The carriers were then transported into the waiting area of the teaching hospital, where they were placed atop two radiotelemetry receivers that were used to continuously measure and record the cats’ direct arterial BP and HR for 5 mins (waiting-room period).

After the 5-mins waiting-room period, cats were brought into an examination room outfitted with radiotelemetry receivers and released from their carriers. A 10-mins examination room acclimation period was allowed, during which only the ‘owner’ was present. After that time, three additional individuals entered the room for indirect Doppler blood pressure measurement. One individual performed Doppler sphygmomanometry, another recorded SBP values and the exact time at which each reading was taken, and the last individual continuously monitored the quality of simultaneously obtained direct BP tracings, from which direct arterial BP and HR were measured and recorded continuously during the entire time spent in the examination room.

All simulated veterinary visits were conducted during normal operating hours. Hospital areas used for waiting, acclimation and indirect BP measurement sessions were identical across all visits. Personnel remained constant between the two simulated veterinary visits for each cat. A single person was responsible for indirect BP measurement and cat compliance assessment at all simulated visits.

Study drug administration and investigator masking

Cats were administered gabapentin (gabapentin capsules 100 mg; Ascend Laboratories) as a single oral dose of 100 mg/cat. Placebo was administered as a capsule containing 100 mg lactose (composed of D-lactose monohydrate powder, JT Baker). All treatments were administered by an individual familiar with the cats who did not participate in any activities related to BP recording. On each treatment day, food was withheld for 12 h before administration of the study drug and was offered approximately 4 h after dosing. The dose of gabapentin chosen for this study was based on that used commonly in clinical practice.^9,14 Other than the individual administering the study drugs, all participants, including the study investigators, were masked to the study assignments for the duration of the study.

Blood pressure measurements

A radiotelemetry system (Data Sciences International) was used to measure and record direct BP, HR and activity counts for all time periods in which direct BP was evaluated. Briefly, direct BP data, transmitted as a radio signal by the femoral artery implant, were detected by one or more radiotelemetry receivers (Model RMC-1; Data Sciences International) and routed to a dedicated computer-based acquisition system (Ponemah V 5.2; Data Sciences International), which saved them in two formats. First, real-time BP data were displayed as a graphed tracing, with time (seconds) and pressure (mmHg) on the x- and y-axes, respectively. Second, BP parameters (including SBP and mean arterial pressure [MAP]), continuously derived HR and activity counts were recorded for later analysis in a spreadsheet. Blood pressure parameters and HR were recorded as single values obtained by averaging data over predetermined periods and intervals, as described below. The BP and HR measurements were expressed in mmHg and pulsations/min, respectively, and data were visually inspected for quality before analysis. Activity was assessed via the detection of movement by the recording platform (ie, receiver) and reported as the average cat movement in counts per 2-s sampling period. Atmospheric pressure was measured by a reference monitor (Ambient Pressure Reference Model E2S-1; Data Sciences International), which was used to provide a dynamic digital signal against which BP measurements were corrected.

For the first phase of the study, during which direct BP and activity were recorded in the home environment, cats were individually housed in kennels outfitted with radiotelemetry receivers. These receivers were placed at least 72 h before the start of the BP measurement period to facilitate the cats’ acclimation to the equipment. During recording periods, traffic into the vivarium was limited to three instances, once between 7:30 am and 10:00 am for general husbandry, once between 4:00 pm and 8:00 pm for withdrawal of food, and once at approximately 9:00 am for administration of the study medication. During these at-home recording periods (two per cat), BP, HR and activity were measured and averaged for 10 s every 22 s for 24 h before and 4 h after administration of the study drug. For each cat, the average of all SBP values recorded during the two 24-h time periods preceding administration of the study drug (ie, the average of all values obtained before administration of either study drug) was taken as the cat’s at-home baseline direct SBP, against which SBP values obtained in the second phase of the study were compared.

For the second phase of the study, in which direct blood pressure was recorded during simulated veterinary visits, proximity of the cats to radiotelemetry receivers was ensured by confining the cat to a carrier (during the waiting-room period) or through gentle restraint performed by the ‘owner’ (during the examination-room acclimation period) or individuals performing sphygmomanometry (during the indirect BP measurement session). Real-time visual examination of the direct BP tracing was used to ensure adequate quality of recorded data. Direct BP and HR data were measured continuously and averaged in 2-s intervals, which were saved in a spreadsheet that included a timestamp for each averaged value. For each visit, averages of all direct SBP and HR values recorded during the 5-mins waiting-room period were calculated and taken as the waiting-room SBP and waiting-room HR, respectively. In addition, for each visit, averages of all SBP and HR values recorded during the last 2 mins of the examination room acclimation period (ie, over minutes 8–10) were calculated and taken as the acclimation-period SBP and acclimation-period HR, respectively. Finally, for each visit, the averages of all direct SBP, MAP and HR values recorded over the indirect BP measurement session were taken as the average BP measurement session direct SBP, average BP measurement session direct MAP and average BP measurement session HR, respectively.

Indirect SBP was measured at all visits using a Doppler ultrasonic device (Model 811-B; Parks Medical Electronics), following the guidelines set forth by the American College of Veterinary Internal Medicine. ⁵ A single trained individual, masked to treatment and values for concurrently measured direct SBP, obtained indirect BP measurements at all visits. Traffic into and within the examination room was not allowed during the measurement period. Cats were gently restrained in sternal recumbency and an inflatable BP measurement cuff (NeoCheck; Zefon International), with a width approximately 30–40% of the cuff site, was applied to the tail. Cats were allowed 30–60 s to acclimate to the cuff and settle into the position of their choosing,^5,15 after which the cuff was connected to a sphygmomanometer (Series DS66 Trigger Aneroids; Welch Allyn). A Doppler ultrasound probe with coupling gel was placed over the coccygeal artery, distal to the cuff. The cuff was inflated to a pressure approximately 20–30 mmHg greater than the pressure at which the Doppler signal became inaudible, and slowly deflated. Indirect SBP was taken as the pressure at which the Doppler signal was first heard again. The first BP measurement was discarded and the process was repeated until six consecutive consistent measurements were obtained. If a downward trend was observed, measurements were continued until a plateau was reached. For each SBP measurement, the exact time, to the nearest second, at which the measurement was obtained was recorded; this time was later used to identify the corresponding simultaneous direct SBP measurement by examination of spreadsheet timestamps. The average BP measurement session indirect SBP was calculated as the average of all six recorded indirect SBP measurements.

Subjective assessments

At each simulated veterinary visit, the ‘owner’ assigned a single stress score for the transportation and waiting room periods using a previously published 7-point scoring system (Table 1).^9,16 In addition, the individual performing indirect BP measurement assigned a single compliance score for the indirect BP measurement session, using a 4-point scoring system (Table 1). ⁹

Table 1

Scoring systems used to assess cat stress during transportation and veterinary visit and compliance during indirect blood pressure measurement in the present study

Value	Description
Cat stress score during transport
1	Fully relaxed
2	Weakly relaxed
3	Weakly tense
4	Very tense
5	Fearful or stiff
6	Very fearful
7	Terrorized
Cat compliance score
0	No resistance to handling
1	Minimally resistant to handling
2	Struggling and difficult to handle
3	Extreme struggling +/- urination or defecation

Statistical analysis

All analyses were performed using commercial statistical software (Stata version 17.0; StataCorp). Distributions of values for continuous variables were examined for normality by visual assessment of histograms and normal quantile plot, and the Shapiro–Wilk test. Descriptive statistics for normally distributed data are presented as mean ± standard deviation (SD) and for non-normally distributed data are presented as median (range).

Direct SBP measured during the 4 h immediately after treatment in the first phase of the study was plotted against time to visually evaluate patterns of response. Based on these patterns, average SBP, HR and activity were calculated for each of eight consecutive 30-min intervals after administration of the study drug. In addition, for each of the three average direct SBP values obtained in the second phase of the study (ie, average waiting-room SBP, average acclimation-period SBP, average direct SBP during indirect BP measurement), difference (∆) compared with the at-home baseline direct SBP value was calculated as ∆ direct SBP = direct SBP – baseline at-home direct SBP. The values above were analyzed using linear mixed models with fixed effects for study week (ie, week 1 vs week 2), study drug treatment, time period and the two-way interaction between drug treatment and time period. Cat was included as a random effect to account for repeated measurements within the same subject. Models used restricted maximum likelihood estimation and denominator degrees of freedom for F-tests were calculated using the Kenward-Roger method. Residuals were modeled using an autoregressive-1 (AR-1) correlation structure.

The average BP-measurement-session direct SBP and average BP-measurement-session direct MAP (ie, the average of direct BP values obtained over the entire indirect BP measurement session) were compared with the average BP-measurement-session indirect SBP (ie, the average of the six indirect SBP measurements). In addition, concurrent direct BP and indirect BP measurements were evaluated by comparing each individual indirect SBP measurement with simultaneously obtained 2-s average direct SBP and MAP values. Comparisons between measurement methods were performed using a linear mixed model with fixed effects for study week, drug treatment, measurement method, time period (ie, individual measurements during indirect BP-measurement session), two-way interactions between drug treatment and measurement method and between drug treatment and time period, and the three-way interaction between drug treatment, time period and measurement method. Cat was included as a random effect.

Cat stress and compliance scores were compared between drug treatments using the Wilcoxon signed-rank test. For all analyses, pairwise comparisons were performed using the Bonferroni procedure to limit the overall type I error probability to 5%, and values of P ⩽0.05 were considered statistically significant.

Results

All cats were castrated males aged 2–3 years with a mean weight of 5.98 ± 1.02 kg. Surgical implantation of telemetric BP catheters was successful in all cats, with no observed procedure-related complications, although device failure was noted shortly after implantation in one case. Direct BP, HR and activity data for this cat were excluded from analyses, while data obtained by other methods (eg, stress and compliance scores) were included. For all cats, the mean dose of gabapentin administered was 17.05 ± 2.97 mg/kg (range 13.8–22.6). No cat suffered adverse effects related to gabapentin or placebo administration during the study.

Study phase 1: at-home evaluation

In a mixed-model analysis of direct SBP in the home environment, there was no significant effect of time after treatment (P = 0.13), no significant effect of drug (P = 0.094) and no significant interaction between the effects of time and drug (P = 0.73) (Figure 2). The estimated marginal mean difference in SBP measurements (placebo – gabapentin) over the 4 h after treatment was 3.8 mmHg (95% confidence interval [CI] -0.7–8.3; P = 0.094). Individual cats varied markedly in terms of their response (Figure 3).

Figure 2

Estimated marginal mean (95% confidence interval) systolic blood pressure (BP) by treatment and time after administration in a crossover study of five cats treated with gabapentin (100 mg/cat) or placebo in their home environment (study phase 1). Values for each time point represent the mean of all values obtained during the corresponding 30-min BP measurement period. BPs were measured for the same five cats under both treatment conditions, with a 1-week washout period between treatments

Figure 3

Line plots of mean systolic blood pressure over time, separated by cat and by drug for phase 1. See Figure 2 for the complete legend

With respect to HR, there was a significant effect of time after treatment (P <0.001), with the marginal mean HR being higher during the first 30 mins after treatment than during any of the subsequent time periods (Figure 4). In addition, there was a significant effect of drug (P = 0.004), with the mean HR over the 4 h after treatment being 12 bpm lower (95% CI 4.7–20) when cats were treated with gabapentin compared with placebo. There was no significant interaction between the effects of time and drug (P = 0.19).

Figure 4

Estimated marginal mean (95% confidence interval) heart rate (HR) by treatment and time after administration in a crossover study of five cats treated with gabapentin or placebo in their home environment (phase 1). Each time point represents the mean of a 30-min period of continuous monitoring. HRs were measured for the same five cats under both treatment conditions, with a 1-week washout period between treatments

Regarding activity and movement, there was no significant effect of time after treatment (P = 0.069), no significant effect of drug (P = 0.17) and no significant interaction between the effects of time and drug (P = 0.32) (Figure 5). The estimated marginal mean difference in activity measurements (placebo – gabapentin) over the 4 h after treatment was 0.03 counts/2-s interval (95% CI -0.01–0.07; P = 0.17).

Figure 5

Estimated marginal mean (95% confidence interval) activity (movement counts/2-s interval) by treatment and time after administration in a crossover study of five cats treated with gabapentin or placebo in their home environment (phase 1). Each time point represents the mean of a 30-min period of continuous monitoring. Activity was assessed for the same five cats under both treatment conditions, with a 1-week washout period between treatments

Study phase 2: simulated veterinary visits

Only one cat was notably subdued during a simulated visit and had mild ataxia after the administration of gabapentin. The dose (22 mg/kg) administered to this cat was the highest given to any cat on a per-weight basis. Regarding the effect of gabapentin on subjective assessments of cat stress during transportation and veterinary visits, the median stress scores for all six cats after administration of gabapentin or placebo were 1 (range 1–2) and 3 (range 1–5), respectively (P = 0.13). For all six cats, the median compliance scores during indirect BP measurement sessions after administration of gabapentin or placebo were 2 (range 1–3) and 1 (range 0–2.5), respectively (P = 0.31).

In a mixed-model analysis of direct SBP in the clinic environment, there was no significant effect of time period (ie, waiting-room period vs end-of-acclimation period vs indirect BP measurement session; P = 0.61), no significant effect of drug (P = 0.86) and no significant interaction between the effects of time period and drug (P = 0.45) (Figure 6). The estimated marginal mean difference in direct SBP measurements averaged over the three time periods (placebo – gabapentin) was 1.5 mmHg (95% CI -22.6–25.6; P = 0.86).

Figure 6

Estimated marginal mean (95% confidence interval) systolic blood pressure (SBP) at each time period during a simulated veterinary visit by treatment and time after administration in a crossover study of five cats treated with gabapentin or placebo. Along the x-axis, ‘waiting room’ corresponds to the 5-min waiting time in the Veterinary Teaching Hospital lobby, ‘end of acclimation period’ corresponds to the last 2 mins of the 10-min acclimation period in the examination room and ‘during indirect BP’ corresponds to the period during which cats were handled for Doppler SBP. Blood pressures were measured for the same five cats under both treatment conditions, with a 2-week washout period between treatments

Regardless of treatment, all cats experienced in-clinic increases in direct SBP, relative to at-home baseline SBP, in all three simulated visit measurement time periods (ie, average waiting-room SBP, average acclimation-period SBP and average BP-measurement-session direct SBP; range, 11–50 and 10–52 mmHg in placebo- and gabapentin-treated cats, respectively). Therefore, average ∆ direct SBP (ie, direct SBP – baseline at-home direct SBP) was positive for both treatment groups for all of these time periods (Figure 7). When comparing ∆ direct SBP measurements, there was no significant effect of time period (P = 0.63), no significant effect of drug (P = 0.82) and no significant interaction between time period and drug (P = 0.43). The estimated marginal mean difference in ∆ direct SBP measurements averaged over the three measurement time periods (placebo – gabapentin) was 1.7 mmHg (95% CI -18.1–21.4; P = 0.82).

Figure 7

Estimated marginal mean (95% confidence interval) direct systolic blood pressure (SBP) – at-home 24-h average SBP by drug and time for a crossover study of five cats treated with gabapentin or placebo before a simulated veterinary visit. See Figure 6 for the complete legend

When individual indirect BP measurements were compared with concurrent direct BP measurements, there were significant differences between measurements taken with different methods, with marginal mean direct SBP being 15.6 mmHg (95% CI 7.5–23.7) higher than marginal mean indirect SBP (P <0.001), and marginal mean indirect SBP being 17.1 mmHg (95% CI 6.2–28.0) higher than the marginal mean direct MAP (P = 0.002) (Figure 8). While the difference between direct and indirect SBP appeared to be larger after treatment with gabapentin compared with placebo, there was no statistically significant interaction between the effects of drug and measurement method (P = 0.32).

Figure 8

Marginal mean (95% confidence interval) direct systolic blood pressure (Dir SBP) and direct mean arterial pressure (Dir MAP) measured via telemetric blood pressure-sensing catheters, and concurrent indirect systolic blood pressure (Ind BP) measured using Doppler sphygmomanometry in five cats undergoing a simulated veterinary visit treated with gabapentin (100 mg/cat PO) or placebo in a crossover study design. Time points 1–6 represent the time at each individual Doppler BP measurement

In an analysis of HR in the clinic environment, there was a significant effect of time period (P = 0.002) (Figure 9), with the marginal mean acclimation-period HR being greater than waiting-room HR. The mean average BP measurement session HR was intermediate to, and did not significantly differ from, those of either of the other two time periods. There was no significant effect of drug (P = 0.073), and no significant interaction between the effects of time period and drug (P = 0.47). The estimated marginal mean difference in HR averaged over the three time periods (placebo – gabapentin) was 30.4 bpm (95% CI -4.8–65.6; P = 0.073).

Figure 9

Estimated marginal mean heart rate in a crossover study of five cats treated with gabapentin or placebo before a simulated veterinary visit. Along the x-axis, ‘waiting room’ corresponds to the 5-min waiting time in the Veterinary Teaching Hospital lobby, ‘end of acclimation period’ corresponds to the last 2 mins of the 10-min acclimation period in the examination room and ‘during indirect BP’ corresponds to the period during which cats were handled for Doppler systolic blood pressure

Discussion

The results of the present study suggest that a single oral dose of gabapentin administered to apparently healthy cats might not have effects – direct or indirect – on BP. These data support our hypothesis that compared with placebo, there would be no difference in ambulatory, direct SBP up to 4 h after dose in undisturbed gabapentin-treated cats. However, they do not support our hypotheses that treatment with gabapentin 90 mins before a veterinary visit would mitigate situational increases in BP, or that compared with placebo, differences between directly obtained and indirectly obtained SBP would be less in gabapentin-treated cats. Importantly, our findings are limited by a small sample size and wide inter-individual variability.

The gabapentin dose (100 mg/cat) evaluated in the present study reflects common clinical practice, but also resulted in a range of per-weight doses (13.8–22.6 mg/kg). The cat administered the highest dose on a per-weight basis was also the only cat to experience mild ataxia and behavior-altering sedative effects, which were noted during the simulated veterinary visit. In undisturbed cats in the home environment, compared with placebo, gabapentin administration was associated with numerically lower activity counts; however, the difference between treatment groups was not statistically significant. Follow-up studies could include an assessment of higher doses of gabapentin on BP or situational increases in BP in cats.

No serious adverse effects of gabapentin administration were observed in the present study. This is in keeping with the findings of previous studies, in which reported side effects (eg, sedation) have been mild, temporary (ie, persisting fewer than 8 h after administration) and well tolerated.^9,11,17

Cats are prone to situational (also referred to as ‘white-coat’) hypertension, a physiologic response to stressful situations that is associated with increases in BP,^5,18 and which complicates the diagnosis of pathologic systemic arterial hypertension. ¹⁹ An inexpensive, readily available and well-tolerated intervention or drug that successfully prevents situational increases in BP without exerting a direct effect on BP (thereby masking pathological hypertension) would be welcome, as such a treatment would allow for greater confidence in measurements taken in-clinic. Although we were unable to demonstrate that healthy cats treated with 100 mg of gabapentin are less likely to experience situational increases in BP during a simulated veterinary visit, this study did not evaluate cats with pathologic systemic arterial hypertension. Therefore, whether gabapentin might mask pathological hypertension remains to be examined. Data from the first phase of the present study (ie, at-home evaluation) failed to identify a significant direct effect of gabapentin on BP in cats; however, as noted above, this study’s small sample size and high data variability increase the likelihood of a type II error. Ultimately, the results of the present study suggest that situational increases in BP cannot be excluded with confidence in cats with abnormally high SBP measurements that have received gabapentin before their veterinary appointment.

Almost all previous studies focused on the evaluation of indirect BP measurement methods in cats have used anesthetized animals instrumented with direct arterial catheters, with a relative lack of data from conscious, unsedated cats.^20–26 Prior studies of anesthetized cats have inconsistently shown that Doppler-derived BP might correlate better with direct MAP than direct SBP.^20,25 To investigate the ability of the Doppler to approximate directly measured BP, comparisons were made between simultaneously obtained indirect measurements and direct SBP and MAP recordings. Unfortunately, indirect BP measurements differed significantly from both direct SBP and MAP measurements, and pre-treatment with gabapentin was not associated with a reduction in bias.

In the present study, treatment with gabapentin was not associated with significantly lower scores for cat stress and compliance, though numeric differences were observed. A prior report documented a significant improvement in owners’ perceptions of their cats’ stress when gabapentin was administered before a veterinary visit. ⁹ It is likely that the assessment of cat stress in the present study was limited by the smaller sample size, the subjectivity of the assessment and the fact that the assessor was a veterinary technician rather than a true cat owner.

This study has some limitations, many related to the small sample size, which reduces the power of the study and increases the likelihood of a type II error for all comparisons. In addition, cats were young, healthy and purpose-bred, with responses that might not accurately reflect those of older, hypertensive or client-owned cats. Repeating this study in a sample of cats with known systemic arterial hypertension or comorbidities that could lead to pathologic hypertension would help determine the effects of gabapentin on BP in hypertensive individuals. Finally, a standard dose of gabapentin was administered to cats of a range of body weights; increasing the dose administered or dosing on a per-weight basis might yield different results.

Conclusions

This small study was unable to detect an effect of 100 mg of gabapentin, administered orally 90 mins before simulated veterinary appointments, on BP or situational increases in BP. Given the likelihood of a type II error, future studies evaluating larger numbers of cats are warranted. For cats receiving gabapentin before a veterinary visit in which abnormally high SBP is documented, situational increases should still be considered.