KNOWLEDGE SUMMARY
Keywords: BEHAVIOUR; CATS; FELINE FACIAL PHEROMONE; FELINE FRIENDLY; FELINE; FELIWAY; HANDLING; STRESS
Effectiveness of F3 feline facial pheromone analogue for acute stress reduction within clinical veterinary practice
Ebony Crump, BSc DVM 1*
1 Murdoch University, 90 South St, Murdoch WA 6150, Australia
* Corresponding author email: ebony_crump@hotmail.com
Vol 8, Issue 4 (2023)
Submitted 17 Jan 2023; published: 06 Dec 2023; next review: 03 Aug 2025
DOI: https://doi.org/10.18849/ve.v8i4.669
PICO question
In cats within a clinical veterinary context, does the application of the F3 feline facial pheromone (Feliway™), when compared to placebo, reduce signs of acute stress?
Clinical bottom line
Category of research
Treatment.
Number and type of study designs reviewed
Five papers were critically reviewed. There were three prospective, double-blinded, randomised controlled trials, one prospective, single-blinded, randomised controlled trial and one prospective, single-blinded, non-randomised controlled trial.
Strength of evidence
Moderate.
Outcomes reported
Four studies found improvement in select indicators of acute stress following F3 feline facial pheromone analogue (FFPA) exposure. One study showed FFPA reduced patient stress during routine physical examination, and improved caregiver impression of patient relaxation and ease of handling. One study revealed FFPA decreased vocalisations but had no effect upon systolic blood pressure during physical examination. One study determined that FFPA calmed but did not reduce struggling during venous catheterisation. One study demonstrated reduced time to sedation and propofol induction dose for routine surgical procedures when a transport protocol incorporating FFPA was applied. Finally, one study found no significant effect of FFPA upon behavioural and physiologic measures of acute stress during physical examination. No studies reported outward negative effects associated with FFPA exposure.
Conclusion
It can be concluded that FFPA may reduce signs of acute stress within a clinical veterinary context. Additionally, exposure to FFPA is unlikely to cause patient harm. To optimise patient welfare, FFPA is not recommended as a sole agent for stress mitigation and should instead be incorporated holistically with patient friendly handling, clinic design, and pharmacotherapy where indicated.
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Clinical scenario
Animals of the same species may emit and detect chemical cues capable of influencing reproductive and social behaviour, known as pheromones (Frank et al., 2010; and Vitale-Shreve & Udell, 2017). Five pheromones (F1 to F5) have been isolated from sebaceous cheek gland secretions of the domestic cat (Felis catus) (Mills, 2005; Pageat & Gaultier, 2003; and Vitale-Shreve & Udell, 2017). The F3 fraction of feline facial pheromone is deposited when the cheek is rubbed against objects within the environment, in a process known as ‘bunting’ (Da Silva et al., 2017; DePorter, 2016; and Pageat & Gaultier, 2003). It is associated with spatial orientation and perception of territory (Da Silva et al., 2017; and Pageat & Gaultier, 2003). As a species, cats are recognised as solitary hunters that evade and avoid threats to survive (Ellis et al., 2013; Griffith et al., 2000; and Rodan et al., 2011). Consequently, they prefer familiar environments which facilitate a sense of control (Ellis et al., 2013; and Riemer et al., 2021). As such, application of synthetic F3 feline facial pheromone analogue (FFPA) may be associated with stress reduction in cats when they are placed in unfamiliar environments by signaling that they are within safe territory (Da Silva et al., 2017; and Griffith et al., 2000).
In cats, veterinary visits are associated with acute stress due to changes in routine, loud or unfamiliar noises, unfamiliar environment, presence of strangers (humans, cats, or other animals), and physical manipulation (Amat et al., 2016; Shu & Gu, 2021; and Stella & Croney, 2019). Stress has a negative impact upon patient welfare and the immune system (Amat et al., 2016; Marti et al., 2016; and Tateo et al., 2021). Additionally, in a clinical setting the physiologic effects of stress can impede safe animal handling and confound the outcome of physical examinations and diagnostic tests (Griffith et al., 2000; and Urrutia et al., 2019). Consequently, the reduction and mitigation of stress has become a priority in clinical veterinary practice (Herron & Shreyer, 2014; Riemer et al., 2021; and Rodan et al., 2011). Besides improving the patient experience, it has been recognised that implementing low-stress methods promotes caregiver satisfaction and clinic loyalty, and reduces rates of staff injury (Anseeuw et al., 2006; Herron & Shreyer, 2014; Marti et al., 2016; and Tateo et al., 2021). The application of FFPA has been recommended as a measure to decrease stress in cats without associated adverse effects (Anseeuw et al., 2006; Da Silva et al., 2017; Griffith et al., 2000; and Shu & Gu, 2021). Consequently, this review aims to investigate such claims in association with acute stress lasting 1 hour or less within a clinical veterinary context (Dickerson & Kemeny, 2004).
The evidence
All studies specifically investigated the effect of the F3 fraction of feline facial pheromone, hereafter referred to as FFPA. Two prospective, double-blinded, randomised controlled trials compared the effect of FFPA to placebo (Conti et al., 2017), and placebo and no treatment (Pereira et al., 2016), upon physiologic and/or behavioral parameters during clinical examination. One also investigated the effect of environment, comparing the home and a clinical context (Conti et al., 2017). A third prospective, double-blinded, randomised controlled trial compared the effects of FFPA combined with acepromazine, placebo combined with acepromazine, FFPA alone, and placebo alone, upon behavioral parameters during intravenous catheterisation (Kronen et al., 2006). One prospective, single-blinded, randomised controlled trial compared the effects of FFPA application and bypassing the waiting room upon blood pressure, physiologic, and behavioral outcomes to no treatment (Van Vertloo et al., 2021). Finally, one prospective, single-blinded, non-randomised controlled trial incorporated FFPA into a low-stress transport protocol applied before routine anaesthesia, to determine its effect upon pre-anaesthetic and behavioral parameters when compared to no treatment (Argüelles et al., 2021).
Summary of the evidence
Argüelles et al. (2021)
Population: |
Recruitment:
Criteria for eligibility and inclusion:
Criteria for exclusion and rejection:
Enrolled study population:
|
---|---|
Sample size: |
67 cats. |
Intervention details: |
Group allocation: Non-randomised. Treatment: Caregivers followed the transport protocol correctly.
Control: Transport protocol followed but FFPA not applied, or no aspects of the protocol followed.
Blinding: Single-blinded.
Low-stress transport protocol:
Treatment application:
|
Study design: |
Prospective, single-blinded, non-randomised, controlled trial. |
Outcome studied: |
Character of the animal (subjective):
Handling before sedation (subjective):
Quality of sedation (subjective):
Cardiac rate and respiratory rate (objective): Sedation time (objective): Cortisol levels (objective): Induction dose (objective): |
Main findings |
|
Limitations: |
|
Conti et al. (2017)
(also including a Letter to the Editor from Beck [2017])
Population: |
Recruitment: Method of recruitment was not defined. Criteria for eligibility and inclusion:
Enrolled study population:
|
---|---|
Sample size: |
30 cats. |
Intervention details: |
Group allocation: Randomised (method not defined).
Blinding: Double-blinded.
Consultation locations:
Veterinary hospital: A standard clinic office was selected for evaluation, approximately 9 m2 in size.
Interventions:
Total environments evaluated:
Consultation procedure:
|
Study design: |
Prospective, double-blinded, randomised, controlled, crossover trial. |
Outcome studied: |
Stress related behaviour (subjective): Respiratory rate (objective): Heart rate (objective): Systolic blood pressure (objective): Electrocardiography (objective):
|
Main findings |
|
Limitations: |
|
Kronen et al. (2006)
Population: |
Recruitment:
Criteria for eligibility and inclusion:
Criteria for exclusion and rejection:
Enrolled study population:
|
---|---|
Sample size: |
77 cats. |
Intervention details: |
Group allocation: Randomised (block randomisation by lottery)
Blinding: Double-blinded.
Interventions:
Treatment groups:
Test procedure:
|
Study design: |
Prospective, double-blinded, randomised, controlled trial. |
Outcome studied: |
Stress related behaviour (subjective):
Degree of sedation (subjective):
Impression of calmness (subjective):
Response to catheterisation (subjective):
|
Main findings |
|
Limitations: |
|
Pereira et al. (2016)
Population: |
Recruitment:
Criteria for eligibility and inclusion:
Criteria for exclusion and rejection:
Enrolled study population:
|
---|---|
Sample size: |
87 cats. |
Intervention details: |
Group allocation: Treatment: F3 feline facial pheromone analogue (FFPA) (Feliway Classic™) applied.
Placebo: Placebo solution applied.
Control: No solution applied.
Blinding: Double-blinded.
Consultation locations: Interventions:
Test procedure:
Consultation procedure:
|
Study design: |
Prospective, double-blinded, randomised, controlled trial. |
Outcome studied: |
Stress level without interaction (subjective): Ease of handling (subjective):
Owner opinion (subjective):
|
Main findings |
|
Limitations: |
Lack of significant results in relation to ease of handling may have been due to the following limitations:
|
Van Vertloo et al. (2021)
Population: |
Recruitment:
Criteria for eligibility and inclusion:
Criteria for exclusion and rejection:
Enrolled study population:
|
---|---|
Sample size: |
39 cats. |
Intervention details: |
Group allocation: Randomised (simple randomisation by random number generator)
Blinding: Single-blinded.
Waiting locations:
Interventions:
Consultation procedure:
|
Study design: |
Prospective, single-blinded, randomised, controlled clinical trial. |
Outcome studied: |
Vocalisations during acclimation (objective): Systolic blood pressure (objective):
Time to complete blood pressure (objective): Heart rate (objective): Respiratory rate (objective): |
Main findings |
|
Limitations: |
|
Appraisal, application and reflection
During stressful situations, environmental demands exceed the natural regulatory capacity of an organism, eliciting adaptive physiologic and behavioural responses to restore homeostasis (Amat et al., 2016; Lefman & Prittie, 2019; and Stella & Croney, 2019). In cats, physiologic components of this response may include hypertension, tachycardia, tachypnoea, mydriasis, hyperthermia; and biochemical changes such as hyperglycaemia, stress leukogram, and elevated plasma cortisol (Lefman & Prittie, 2019; Quimby et al., 2011; and Tateo et al., 2021). Behavioural changes vary between individuals and may include changes in normal behaviours such as eating, grooming, playing, exploration, urination, defaecation, vocalisation, and affiliation; as well as hiding, vigilance, compulsive, and aggressive behaviours (Amat et al., 2016; Shu & Gu, 2021; and Tateo et al., 2021).
In all five papers, the primary outcome investigated was the response of participants to acutely stressful events within clinical veterinary practice, which was quantified through both objective and subjective parameters (Argüelles et al., 2021; Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021). Objective measurements included cardiac rate, respiratory rate, systolic blood pressure, electrocardiographic parameters, vocalisations, time to sedation, time to complete blood pressure measurements, cortisol levels, and induction dose of injectable anaesthetic (Argüelles et al., 2021; Conti et al., 2017; and Van Vertloo et al., 2021). One study used only objective measurements (Van Vertloo et al., 2021). Subjective assessments included behavioural descriptions applied to numerical rating scales (Argüelles et al., 2021; Conti et al., 2017; Kronen et al., 2006; and Pereira et al., 2016). Two studies used only subjective measurements in their study design (Kronen et al., 2006; and Pereira et al., 2016).
Good subjective stress assessment tools should select for species-specific behavioural measures that are consistent across repeated testing (Urrutia et al., 2019). Stress scales are commonly developed for this purpose and can be used to identify stress and assess its severity (Lefman & Prittie, 2019). Scales to assess feline behaviour have been developed, however the primary focus within the literature has been the shelter environment, and therefore chronic stress (Kessler & Turner, 1997; and Hirsch et al., 2021). Additionally, the scales that do exist, such as the Cat Stress Score, are challenging to validate (Hirsch et al., 2021; and Urrutia et al., 2019). Consequently, all studies evaluated used unvalidated behavioural scales to assess acute stress. Limitations associated with unvalidated behavioural scales include insufficient detail, which limits the refinement of a scale, and inability to capture the complexity of feline stress responses (de Rivera et al., 2017; Pereira et al., 2016). For example, certain stressed cats may freeze and thus be interpreted as easy to handle, while others may be more active, which can be interpreted as less fearful (Carlstead et al., 1993; Kronen et al., 2006; and Pereira et al., 2016). Additionally, the effect of some factors, such as vocalisation, have produced conflicting results within the literature (de Rivera et al., 2017; Urrutia et al., 2019; and Van Vertloo et al., 2021). A laboratory based model utilising open-field testing and the human interaction test has been developed for assessing acute fear and anxiety in cats (de Rivera et al., 2017). This could be employed in a laboratory based study upon the influence of FFPA on acute stress. Ultimately, a validated acute stress scale for use within a clinical veterinary context would be of use.
The findings of each study must be interpreted in context with the inherent difficulties associated with accurate stress measurement and assessment. Additionally, individual responses to the same stressor vary, and interpretation is further complicated by the numerous confounding factors that may influence how, and to what degree, stress is expressed through behaviour, including health status, temperament, and age (Lefman & Prittie, 2019).
Normal animal behaviour may be altered by the presence of pain, illness, and disease (Mills et al., 2020; Lefman & Prittie, 2019; Riemer et al., 2021; and Waran et al., 2007). All studies screened participants on the basis of health and excluded animals previously diagnosed with disease or taking medications (Argüelles et al., 2021; Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021). However, Pereira et al. (2016) only utilised physical examination without palpation during this process, and thus may not have eliminated pain as a confounding factor.
In cats, temperament has been implicated as a factor that may influence the behavioural expression of stress (Amat et al., 2016; Foster & Ijichi, 2017; and Stella & Croney, 2019). Temperament is defined as the behavioural differences between individuals that are stable across time and contexts (Amat et al., 2016; Travnik et al., 2020; and Travnik & Sant’Anna, 2021). Coping styles are a facet of temperament related to the physiologic and behavioural stress response of an animal, which are consistent over time (Koolhaas et al., 1999). Two coping styles, known as proactive and reactive, have been described in the domestic cat (Stella & Croney, 2019; and Travnik et al., 2020). The proactive coping style is physiologically associated with high sympathetic nervous system activation and low hypothalamic-pituitary-adrenal (HPA) axis activation (Stella & Croney, 2019). Behavioural responses involve offensive aggression and territorial control (Koolhaas et al., 1999; Stella & Croney, 2019; and Travnik et al., 2020). Conversely, the reactive coping style is physiologically characterised by high parasympathetic nervous system activation and higher HPA-axis activation (Stella & Croney, 2019). Behaviourally this strategy involves withdrawal, immobility, and low levels of aggression (Koolhaas et al., 1999; Stella & Croney, 2019; and Travnik et al., 2020).
Two of the examined studies, Kronen et al. (2006) and Van Vertloo et al. (2021), excluded participants on the basis of aggressive behaviour. It is possible therefore that participants with proactive coping styles, which behaviourally align with offensive aggression, were preferentially excluded. This may have skewed findings associated with subjective behavioural assessment, particularly in relation to activity levels. The confounding effect of temperament between selected participants is likely to have been negated by the study design employed by both Conti et al. (2017) and Van Vertloo et al. (2021) as all study participants received all treatments in a randomised fashion. The Feline Temperament Score offers a validated, non-invasive means of objectively quantifying feline temperament for inclusion in statistical analysis (Foster & Ijichi, 2017; and Siegford et al, 2003). In future study designs where all participants do not receive all treatments, the Feline Temperament Score may be an appropriate means of mitigating temperament as a confounding factor.
As animals grow and mature, their behaviour changes and consequently, behavioural expressions of stress in cats are likely to evolve over time (Foster & Ijichi, 2017; Tateo et al., 2021; and Urrutia et al., 2019). Pereira et al. (2016) and Van Vertloo et al. (2021) actively excluded participants on the basis of age and only accepted cats older than 26 weeks and 1 year of age, respectively. One rationale for which was to prevent kitten behavioural reactions (Pereira et al., 2016), however no rationale for this exclusion was provided by Van Vetrloo et al. (2021). Studies designed by Argüelles et al. (2021) and Kronen et al. (2006) attempted to control this confounding factor by demonstrating no significant difference in age between treatment groups. Van Vertloo et al. (2021) controlled the confounder using 2x2 factorial design where all cats received all treatments and paired analysis was performed. Additionally, age was included in statistical analysis as a covariate, however no significant difference was found (Van Vertloo et al., 2021). In comparison, median age differed between treatment groups in Pereira et al. (2016) as the median age of the FFPA treatment group was significantly lower. Conti et al. (2017) failed to demonstrate within statistical analysis the presence or absence of significant age difference. Groups in this study were randomised, which reduces the likelihood of confounding bias, however it should be noted that the method of randomisation was not defined.
Regarding randomisation, one reviewed study, by Argüelles et al. (2021), did not employ randomisation to assign treatment groups. This was due to the method of study recruitment, where caregivers were offered the choice to follow a transport protocol when bringing their cat to the clinic for surgery, and therefore enrol their cat in the treatment group (Argüelles et al., 2021). Cats who had been exposed to the protocol, in which the protocol had been applied correctly on the day of surgery, were enrolled in the treatment group (Argüelles et al., 2021). This method of enrolment is likely to have introduced study bias, either through factors influencing caregiver compliance with the low-stress transport protocol such as practical viability, attitudes towards cat welfare, caregiver demographics, or unknown factors. These were not investigated. Conversely, all other studies employed some means of randomisation (Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021). However, methods used were only reported by Kronen et al. (2006), Pereira et al. (2016), and Van Vertloo et al. (2021), who used block randomisation by lottery, simple randomisation based upon order of arrival at the clinic, and simple randomisation based upon random number generator, respectively.
Sample size power calculations were performed by Conti et al. (2017) and Van Vertloo et al. (2021) using data from previous studies, however the mean and standard deviations utilised were not reported. Five individual data sets may have been used by Conti et al. (2017) (Hanås et al., 2009; Lin et al., 2006; Sparkes et al., 1999). Similarly, three data sets were available within the resource used by Van Vertloo et al. (2021) (Sparkes et al., 1999). Consequently, values for both sample size calculations cannot be externally verified, and post-hoc power analysis is typically discouraged (Zhang et al., 2019). Additionally, Argüelles et al. (2021), Kronen et al. (2006) and Pereira et al. (2016) showed no evidence of sample size power calculation and therefore the suitability of their sample sizes cannot be verified.
Behavioural assessment is subjective and interpretations will vary between operators (Wemelsfelder, 1997). Additionally, operator training will influence the ability to recognise and interpret behaviours successfully (Wemelsfelder, 1997). A single-blinded operator was used by Conti et al. (2017) and Pereira et al. (2016), reducing the effect of inter-operator variability. In contrast, Argüelles et al. (2021) used two, Kronen et al. (2006) used five, and Van Vertloo et al. (2021) used an unspecified number of assessors. While none of the studies claimed to have employed an operator specialised in feline ethology, Conti et al. (2017), Kronen et al. (2006), and Pereira et al. (2016) ensured operators were trained for study specific investigations. Although there are difficulties associated with producing accurate and reliable subjective behavioural measurements to quantify stress, observation of behaviour is an important aspect of stress assessment (Lefman & Prittie, 2019).
In terms of study blinding, Argüelles et al. (2021), Kronen et al. (2006), Pereira et al. (2016) and Van Vertloo et al. (2021) included complete descriptions of study blinding, while Conti et al. (2017) did not. Van Vertloo et al. (2021) did not blind operators collecting vocalisation data for practical reasons. This is acceptable however, as the outcome was an objective parameter (Day & Altman, 2000; and Giuffrida et al., 2012). It should also be noted that if placebo composition resulted in concealment of allocation, the effect of blinding upon operators would be nullified (Day & Altman, 2000 Schulz, 2005; and Schulz & Grimes, 2002).
Three of the evaluated studies incorporated a placebo. Conti et al. (2017) used an ethanol 70% spray, Pereira et al. (2016) used an alcohol-based spray, and Kronen et al. (2006) used Feliway Classic™ carrier medium, which according to manufacturers is approximately 90% ethanol (Ceva Animal Health, 2022a). In these situations, placebos may have been distinguishable through either appearance or scent. Kronen et al. (2006) stipulated that identical bottles were used while Pereira et al. (2016) utilised two colourless liquid solutions, visual difference between interventions was not reported by Conti et al. (2017). Humans are unable to detect FFPA by smell (Ceva Animal Health, 2022b; and DePorter, 2016). However, in situations where the composition of placebo differed from the FFPA carrier medium solution, a slight difference in smell may have been discernable. This may have been the case when ethanol 70% was employed by Conti et al. (2017) and an alcohol-based spray of unknown composition by Pereira et al. (2016).
The pheromone product used in all studies was a synthetic F3 fraction of FFPA marketed as Feliway Classic™ with active constituents 100 mg/mL synthetic FFPA and 89.2% ethanol (Argüelles et al., 2021; Ceva Animal Health, 2022a; Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021). UK manufacturer’s instructions state that 8-10 pumps should be applied 15 minutes before the introduction of a cat (Ceva Animal Health, 2022b). A single pump is defined as one depression of the nozzle, with the bottle held vertically (Ceva Animal Health, 2022a). The nozzle is intended to be held at a distance of approximately 10 cm from the intended spray site, and 20 cm above the ground (Ceva Animal Health, 2022a). It should be noted that instructions vary by region. Three to four pumps are recommended in Australia (Ceva Animal Health, 2022c), and a period of 10 minutes is recommended in the USA (Ceva Animal Health, 2021).
In the studies reviewed, a variety of methods were used to apply FFPA. Argüelles et al. (2021) applied four pumps to the carrier, and three to the car 30 minutes before introducing a cat. Distance of the nozzle was not defined, and FFPA diffuser was also used in the consultation room (Argüelles et al., 2021). Conti et al. (2017) applied FFPA throughout the location but did not define a number of pumps. Pumps were applied 10 cm from objects and 20 cm from the floor. A duration of 15 minutes was used before introducing a cat (Conti et al., 2017). Kronen et al. (2006) applied an undefined number of pumps 10 cm from floor 1–1.5 minutes before introducing a cat. A pump was defined as depression of the nozzle for 1–2 seconds (Kronen et al., 2006). Pereira et al. (2016) applied five pumps 15 minutes before exposure at an undefined distance. Van Vertloo et al. (2021) sprayed an undefined number of pumps at an undefined distance onto a towel, which was immediately placed over cat carriers. It is unclear whether cats may have been able to hear application of the spray by Van Vertloo et al. (2021). The spritzing sound may be associated with the sound of hissing by some cats and can cause stress (DePorter, 2016).
This variation in application may have confounded results for a number of reasons. Firstly, time before FFPA exposure is intended to allow scent of the ethanol carrier medium to dissipate (Conti et al., 2017; DePorter, 2016; and Pereira et al., 2016). Cats as a species have a very sensitive sense of smell and it is advised that wherever possible, interference with feline olfactory signals and scent profiles is avoided (Ellis et al., 2013; and Herron & Shreyer, 2014). Insufficient time before exposure may have exposed participants to a pungent alcohol scent, which may have influenced behaviour and confounded results (DePorter, 2016). Secondly, the time of exposure to FFPA before exposure to stressful stimuli was only recorded by Conti et al. (2017), where the environment remained consistent with the addition of FFPA for 10 minutes before veterinary manipulations. Thirdly, the amount of FFPA product administered is likely to have varied between studies. No studies reported the type of spray bottle utilised and whether the bottle design was consistent with commercially available products. Variation in bottle design in terms of shape and nozzle configuration, along with variation in the number of pumps of FFPA applied complicates comparison of results. Finally, no studies reported upon FFPA product storage. Manufacturers recommend that FFPA products be shaken before use and stored below 25 °C in a well-ventilated area with containers tightly closed (Ceva Animal Health, 2022a). Failure to adhere to these guidelines may have led to product degradation and decreased exposure to FFPA when compared to reported levels.
Across the studies, handling methods also varied considerably. Argüelles et al. (2021) employed low-stress protocols at all times and techniques were defined as following the 2011 American Association of Feline Practitioners (AAFP) and International Society of Feline Medicine (ISFM) Feline Handling Guidelines (Rodan et al., 2011). Van Vertloo et al. (2021) ensured all handlers were trained by a certified veterinarian in low-stress handling techniques as defined by Yin (2009). Restraint techniques used during the study were also reported and while minimal restraint was preferred and used where possible, cats were scruffed (Van Vertloo et al., 2021). Handling techniques were not specifically defined by Conti et al. (2017), Kronen et al. (2006), and Pereira et al. (2016) however Conti et al. (2017) stated cats were evaluated from least to most stressful manipulation. Reporting of handling methods influences reproducibility and interpretation of results, particularly in regard to the additive effect of stress.
To minimise handling as a confounding factor, consistency across study participants is imperative. Pereira et al. (2016) ensured all consultations were performed by the same handler. Two handlers were employed by Argüelles et al. (2021) and Conti et al. (2017), the latter of which consistently used the same order of examination. Kronen et al. (2006) employed an undefined number of handlers, some of whom were final-year veterinary students and as such, handling expertise is likely to have varied. Handling techniques of Van Vertloo et al. (2021) varied considerably in terms of scruffing, clipping, headphone use, and towel use. One participant at a single visit was scruffed in 2016 (1/88 (1%), while at 14/68 (21%) of visits participants were scruffed in 2017 when different handlers were employed. Patients were also clipped when required, and thus variations in coat length and thickness may have increased frequency of clipping for some participants across visits. Due to equipment failure, headphone use for Doppler blood pressure measurements was also inconsistent and used more frequently in 2016 than 2017. Finally, towels were placed over carriers in the FFPA treatment group in 2016 but not 2017. These examples of variation in handling throughout studies may have confounded results.
When investigating the effect of FFPA upon acute stress, it is possible that the additive effect of stress associated with the environment coupled with data collection methods may have overcome the protective influence of FFPA and minimised the significance of findings (Argüelles et al., 2021; Van Vertloo et al., 2021). Each study investigated the effect of acute stress, which for the purposes of this review was defined as a stressor lasting a duration of one hour or less (Dickerson & Kemeny, 2004). However, stress is recognised to have an additive effect where animals exposed to several stressors experience a greater stress response than when exposed to a single stressor (Amat et al, 2016). Acute stress within a veterinary context is likely to be multifactorial in nature, and this may have influenced the degree of subject response (Amat et al, 2016; Shu & Gu, 2021; Stella & Croney, 2019).
No adverse effects due to FFPA application were reported in any of the reviewed studies (Argüelles et al., 2021; Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021). Additionally, other investigations into feline pheromonotherapy report that FFPA appears free of side effects and psychopharmacological contraindications (Mills, 2005).
The clinical application of pheromonotherapy may allow clinicians to disseminate positive messages throughout a cat’s environment, influencing their emotional and behavioural responses (DePorter, 2016; Mills, 2005). Formulation for clinical application is an important consideration. The studies investigated predominantly used spray formulations (Conti et al., 2017; Kronen et al., 2006; Pereira et al., 2016; and Van Vertloo et al., 2021), however one study also utilised a diffuser (Argüelles et al., 2021). Spray formulations are portable and allow specific locations to be targeted with pheromone on an as-needed basis (Ceva Animal Health, 2022b; DePorter, 2016). Their primary disadvantage however is logistical in that they must be applied prior to exposure and reapplied often to provide a continuous effect (Ceva Animal Health, 2022b; DePorter, 2016). In situations where pheromone exposure is required in a specific location, electronic diffusers may be more practical (DePorter, 2016). Besides the logistical advantages, diffusers also provide greater preventative protection against acute stress as FFPA provides a greater protective effect if provided while cats are in a lowered state of arousal (DePorter, 2016). Current best practice implementation of pheromonotherapy in clinical veterinary practice for the mitigation of acute stress includes the use of diffusers placed within rooms frequented by feline patients, along with FFPA spray applied to towels and bedding 15 minutes prior to handling or confinement (DePorter, 2016).
Clinical application must also acknowledge the limitations of pheromonotherapy. Pheromone products are designed to influence emotional responses rather than completely control behaviours (DePorter, 2016). Consequently, FFPA should not be used alone as an exclusive measure for stress mitigation (Conti et al., 2017; DePorter, 2016). A best practice clinical approach requires minimisation of environmental stressors through feline friendly clinic design and handling (Conti et al., 2017; Ellis et al., 2013; Herron & Shreyer, 2014; and Yin, 2009).
In conclusion, four of the five studies reviewed found significant improvement in some indicators of acute stress following FFPA exposure. Pereira et al. (2016) showed that FFPA reduced patient stress during routine physical examination, and improved caregiver impression of patient relaxation and ease of handling. Van Vertloo et al. (2021) revealed FFPA decreased vocalisations but had no effect upon systolic blood pressure during physical examination. Argüelles et al. (2021) demonstrated reduced time to sedation and propofol induction dose for routine surgical procedures when a transport protocol incorporating FFPA was applied. Finally, Kronen et al. (2006) determined FFPA calmed but did not reduce struggling during venous catheterisation. Conti et al. (2017) found no significant effect of FFPA upon behavioural or physiologic measures of acute stress during physical examination. Singularly, each finding is not profound however when combined, these findings suggest that the application of FFPA within a clinical veterinary context may provide some benefit toward the mitigation of acute stress in cats.
All studies reviewed were weakened to a degree by various limitations. Consequently, a further study using a calculated sample size of healthy, temperament tested patients, FFPA applied according to manufacturer’s instructions, and a validated stress scale designed for application during acute stress would be beneficial. Additionally, as FFPA diffusers have been identified as the most practical method of application during acutely stressful events, inclusion of diffusers within the study design would be valuable.
Methodology
Search strategy
Databases searched and dates covered: |
CAB Abstracts via Web of Science: 1910–2023 |
---|---|
Search strategy: |
CAB Abstracts: PubMed: Scopus: |
Dates searches performed: |
03 Aug 2023 |
Exclusion / inclusion criteria
Exclusion: |
|
---|---|
Inclusion: |
|
Search outcome
Database |
Number of results |
Excluded – >30 years old |
Excluded – Non-English language publication |
Excluded – Non-experimental design |
Excluded – Not related to PICO question |
Total relevant papers |
---|---|---|---|---|---|---|
CAB Abstracts |
98 |
5 |
8 |
69 |
11 |
5 |
PubMed |
22 |
0 |
0 |
11 |
7 |
4 |
Scopus |
48 |
0 |
4 |
31 |
8 |
5 |
Total relevant papers when duplicates removed |
5 |
ORCiD
Ebony Crump: https://orcid.org/0000-0001-6771-6511
Conflict of interest
The author declares no conflicts of interest.
References
- Amat, M., Camps, T., & Manteca, X. (2016). Stress in owned cats: behavioural changes and welfare implications. Journal of Feline Medicine and Surgery. 18(8), 577–586. DOI: https://doi.org/10.1177/1098612x15590867
- Anseeuw, E., Apker, C., Ayscue, C., Barker, L., Blair, D., Brennan, J., Brooks, S., Case-Pall, D., Caspersen, H., Clark, J., Colson, L., Covill, A., DeLong, J., Dickey, D., Harr, K., Heine, N., Krishna, G., Lynch, K., Maki, J., Malamed, R., McAuliffe, M., McLucas, B., Mengering, C., Mulligan, L., Nicholson, M., Rodan, I., Schobert-Nichols, H., Steele, A. & Young, R. (2006). Handling cats humanely in the veterinary hospital. Journal of Veterinary Behavior. 1, 84–88. DOI: https://doi.org/10.1016/j.jveb.2006.06.003
- Argüelles, J., Echaniz, M., Bowen, J. & Fatjó, J. (2021). The impact of a stress-reducing protocol on the quality of pre-anaesthesia in cats. Veterinary Record. 118(12), e138. DOI: https://doi.org/10.1002/vetr.138
- Beck, A. (2017). Pheromone analogue efficacy in reducing cats’ stress at the veterinary hospital: concerns about the design of a recent study. Journal of Feline Veterinary Medicine and Surgery. 19(2) 251–253. DOI: https://doi.org/10.1177/1098612x16645386
- Carlstead K., Brown, J.L. & Strawn, W. (1993). Behavioral and physiological correlates of stress in laboratory cats. Applied Animal Behaviour Science. 38(2), 143–158. DOI: https://doi.org/10.1016/0168-1591(93)90062-T
- Ceva Animal Health. (2022a). Feliway® Spray [online]. Available at: https://www.ceva.com.au/Products/Products-list/FELIWAY-R-Spray [Accessed 22 February 2022].
- Ceva Animal Health. (2022b). UK Feliway FAQ [online]. Available at: https://www.feliway.com/uk/Products/faq#faq-39747 [Accessed 22 February 2022].
- Ceva Animal Health. (2022c). Australia Feliway FAQ [online]. Available at: https://www.feliway.com/au/Products/faq#faq-39747 [Accessed 22 February 2022].
- Ceva Animal Health. (2021). USA Feliway FAQ [online]. Available at: https://us.feliway.com/pages/faq [Accessed 22 February 2022].
- Conti, L.M.C., Champion, T., Guberman, ÚC., Mathias, C.H.T., Fernandes, S.L., Silva, E.G.M., Lázaro, M.A., Lopes, A.D.C.G. & Fortunato, V.R. (2017). Evaluation of environment and a feline facial pheromone analogue on physiologic behaviour measures in cats. Journal of Feline Medicine and Surgery. 19(2), 165–170. DOI: https://doi.org/10.1177/1098612x15621107
- Da Silva, B.P.L, Knackfuss F.B., Labarthe, N. & Mendes-de-Almeida, F. (2017). Effect of a synthetic analogue of the feline facial pheromone on salivary cortisol levels in the domestic cat. Presquisa Veterinária Brasileira. 37(3), 287–290. DOI: https://doi.org/10.1590/S0100-736X2017000300013
- Day, S.J. & Altman, D.G. (2000). Statistics notes: blinding in clinical trials and other studies. British Medical Journal. 321(7259), 504. Available from: https://www.jstor.org/stable/25225435 [Accessed 25 February 2022].
- DePorter, T.L. (2016). Use of pheromones in feline practice. In I. Rodan & S. Heath (Eds.), Feline Behavioural Health and Welfare: Prevention and treatment (1st Ed., 235–244). Elsevier.
- de Rivera, T.C., Ley, J., Milgram, B. & Landsberg, G. (2017). Development of a laboratory model to assess fear and anxiety in cats. Journal of Feline Medicine and Surgery. 19(6), 586–593. DOI: https://doi.org/10.1177/1098612X16643121
- Dickerson, S.S. & Kemeny, M.E. (2004). Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychological Bulletin. 130(3), 355–391. DOI: https://doi.org/10.1037/0033-2909.130.3.355
- Ellis, S.L.H., Rodan, I., Carney, H.C., Heath, S., Rochlitz, I., Shearburn, L.D., Sundahl, E. & Westropp, J.L. (2013). AAFP and ISFM feline environmental needs guidelines. Journal of Feline Medicine and Surgery. 15(3), 219–230. DOI: https://doi.org/10.1177/1098612x13477537
- Foster, S. & Ijichi, C. (2017). The association between infrared thermal imagery of core eye temperature, personality, age and housing in cats. Applied Animal Behaviour Science. 189, 79–84. DOI: https://doi.org/10.1016/j.applanim.2017.01.004
- Frank, D., Beauchamp, G. & Palestrini, C. (2010). Systematic review of the use of pheromones for treatment of undesirable behaviour in cats and dogs. Journal of the American Veterinary Medical Association. 236(12), 1308–1316. DOI: https://doi.org/10.2460/javma.236.12.1308
- Giuffrida, M.A., Agnello, K.A. & Brown, D.C. (2012). Blinding terminology used in reports of randomized controlled trials involving dogs and cats. Journal of the American Veterinary Medical Association. 241(9), 1221–1226. DOI: https://doi.org/10.2460/javma.241.9.1221
- Griffith, C.A., Steigerwald, E.S. & Buffington, C.A.T. (2000). Effects of a synthetic facial pheromone on behavior of cats. Journal of the American Veterinary Medical Association. 217(8), 1154–1156. DOI: https://doi.org/10.2460/javma.2000.217.1154
- Hanås, S., Tidholm, A., Egenvall, A. & Holst, B.S. (2009). Twenty-four hour Holter monitoring of unsedated healthy cats in the home environment. Journal of Veterinary Cardiology. 11(1), 17–22. DOI: https://doi.org/10.1016/j.jvc.2008.10.003
- Herron, M.E. & Shreyer, T. (2014). The pet-friendly veterinary practice: a guide for practitioners. Veterinary Clinics of North America: Small Animal Practice. 44(3), 451–481. DOI: https://doi.org/10.1016/j.cvsm.2014.01.010
- Hirsch, E.N., Andersson, M., Loberg, J. & Lidfors, L.M. (2021). Development of existing scoring system to assess behavioural coping in shelter cats. Applied Animal Behaviour Science. 234, 105208. DOI: https://doi.org/10.1016/j.applanim.2020.105208
- Kessler, M.R. & Turner, D.C. (1997). Stress and adaption of cats (Felis Silvestris Catus) housed singly, in pairs and in groups in boarding catteries. Animal Welfare. 6(3), 243–254. DOI: https://doi.org/10.1017/S0962728600019837
- Koolhaas, J.M., Korte, S.M., De Boer, S.F., Van Der Vegt, B.J., Van Reenen, C.G., Hopster, H., De Jong, I.C., Ruis, M.A.W. & Blokhuis, H.J. (1999). Coping styles in animals: current status in behaviour and stress-physiology. Neuroscience and Biobehavioural Reviews. 23(7), 925–935. DOI: https://doi.org/10.1016/S0149-7634(99)00026-3
- Kronen, P.W., Ludders, J.W., Erb, H.N., Moon, P.F., Gleed, R.D. & Koski, S. (2006). A synthetic fraction of feline facial pheromones calms but does not reduce struggling in cats before venous catheterization. Veterinary Anaesthesia and Analgesia. 33(4), 258–265. DOI: https://doi.org/10.1111/j.1467-2995.2005.00265.x
- Lefman, S. H. & Prittie, J. E. (2019). Psychogenic stress in hospitalized veterinary patients: causation, implications, and therapies. Journal of Veterinary Emergency and Critical Care. 29(2), 107–120. DOI: https://doi.org/10.1111/vec.12821
- Lin, C. H., Yan, C. J., Lien, Y. H. & Huang, H. P. (2006). Systolic blood pressure of clinically normal and conscious cats determined by an indirect doppler method in a clinical setting. Journal of Veterinary Medical Science. 68(8), 827–832. DOI: https://doi.org/10.1292/jvms.68.827
- Mills, D. (2005). Pheromonatherapy: theory and applications. In Practice. 27(7), 368–373. DOI: https://doi.org/10.1136/inpract.27.7.368
- Mills, D.S., Demontigny-Bedard, I., Gruen, M., Klinck, M.P., McPeake, K.J, Barcelos, A.M., Hewison, L., Van Haevermaet, H., Denenberg, S., Hauser, H., Koch, C., Ballantyne, K., Wilson, C., Mathkari, C.V., Pounder, J., Garcia, E., Darder, P., Fatjó, J. & Levine, E. (2020). Pain and problem behaviour in cats and dogs. Animals. 10(2), 318. DOI: http://dx.doi.org/10.3390/ani10020318
- Pageat, P. & Gaultier E. (2003). Current research in canine and feline pheromones. Veterinary Clinics of North America: Small Animal Practice. 33(2), 187–211. DOI: https://doi.org/10.1016/s0195-5616(02)00128-6
- Pereira, J.S., Fragoso, S., Beck, A., Lavigne, S., Varejão, A.S. & da Graça Pereira, G. (2016). Improving the feline veterinary consultation: the usefulness of Feliway spray in reducing cats’ stress. Journal of Feline Medicine and Surgery. 18(12), 959–964. DOI: https://doi.org/10.1177/1098612X15599420
- Quimby J.M., Smith, M.L. & Lunn, K.F. (2011). Evaluation of the Effects of Hospital Visit Stress on Physiologic Parameters in the Cat. Journal of Feline Medicine and Surgery. 13(10), 733–737. DOI: https://doi.org/10.1016/j.jfms.2011.07.003
- Riemer, S., Heritier, C., Windschnurer, I., Pratsch, L., Arhant, C. & Affenzeller, N. (2021). A Review on Mitigating Fear and Aggression in Dogs and Cats in a Veterinary Setting. Animals. 11(1), 158. DOI: https://doi.org/10.3390/ani11010158
- Rodan, I., Sundahl, E., Carney, H., Gagnon, A., Heath, S., Landsberg, G., Seksel, K. & Yin, S. (2011). AAFP and ISFM feline-friendly handling guidelines. Journal of Feline Medicine and Surgery. 13(5), 364–375. DOI: https://doi.org/10.1016/j.jfms.2011.03.012
- Schulz, K. F. (2005). Assessing allocation concealment and blinding in randomised controlled trials: why bother? Equine Veterinary Journal. 37(5), 394–395. DOI: https://doi.org/10.2746/042516405774479979
- Schultz, K.F. & Grimes, D.A. (2002). Generation of allocation sequences in randomised trials: chance not choice. The Lancet. 359(9305), 515–519. DOI: https://doi.org/10.1016/S0140-6736(02)07683-3
- Siegford, J.M., Walshaw, S.O., Brunner, P. & Zanella, A.J. (2003). Validation of a temperament test for domestic cats. Anthrozoös. 16(4), 332–351. DOI: https://doi.org/10.2752/089279303786991982
- Shu, H. & Gu, X. (2021). Effect of a synthetic feline facial pheromone product on stress during transport in domestic cats: a randomised controlled pilot study. Journal of Feline Medicine and Surgery. 24(8), 691–699. DOI: https://doi.org/10.1177/1098612x211041305
- Sparkes, A.H., Caney, S.M.A., King, M.C.A. & Gruffydd-Jones, T.J. (1999). Inter and intra-individual variation in Doppler ultrasonic indirect blood pressure measurements in healthy cats. Journal of Veterinary Internal Medicine. 13(4), 314–318. DOI: https://doi.org/10.1111/j.1939-1676.1999.tb02187.x
- Stella, J. & Croney, C. (2019). Coping Styles in the Domestic Cat (Felis silvestris catus) and Implications for Cat Welfare. Animals. 9(6), 370. DOI: https://doi.org/10.3390/ani9060370
- Tateo, A., Zappaterra, M., Covella, A. & Padalino, B. (2021). Factors influencing stress and fear-related behaviour of cats during veterinary examinations. Journal of Animal Science. 20(1), 46–58. DOI: https://doi.org/10.1080/1828051X.2020.1870175
- Travnik, I.C., Machado, D., Gonçalves, L.S., Ceballos, M.C. & Sant’Anna, A.C. (2020). Temperament in Domestic Cats: A Review of Proximate Mechanisms, Methods of Assessment, Its Effects on Human-Cat Relationships, and One Welfare. Animals. 10(9), 1516. DOI: https://doi.org/10.3390/ani10091516
- Travnik, I.C. & Sant’Anna, A.C. (2021). Do you see the same cat that I see? Relationships between Qualitative Behaviour Assessment and indicators traditionally used to assess temperament in domestic cats. Animal Welfare. 30(2), 211–223. DOI: https://doi.org/10.7120/09627286.30.2.211
- Urrutia, A., Martínez-Byer, S., Szenczi, P., Hudson, R. & Banszegi, O. (2019). Stable individual differences in vocalisation and motor activity during acute stress in the domestic cat. Behavioural Processes. 165, 58–65. DOI: https://doi.org/10.1016/j.beproc.2019.05.022
- Van Vertloo, L. R., Carnevale, J. M., Parsons, R. L., Rosburg, M. & Millman, S. T. (2021). Effects of Waiting Room and Feline Facial Pheromone Experience on Blood Pressure in Cats. Frontiers in Veterinary Science. 8. DOI: https://doi.org/10.3389/fvets.2021.640751
- Vitale-Shreve, K.R. & Udell, M.A.R. (2017). Stress, security, and scent: The influence of chemical signals on the social lives of domestic cats and implications for applied settings. Applied Animal Behaviour Science. 187, 69–76. DOI: https://doi.org/10.1016/j.applanim.2016.11.011
- Waran, N., Best, L., Williams, V., Salinsky, J., Dale, A. & Clarke, N. (2007). A preliminary study of behaviour-based indicators of pain in cats. Animal Welfare. 16(2), 105–108. DOI: https://doi.org/10.1017/S0962728600031791
- Wemelsfelder, F. (1997). The scientific validity of subjective concepts in models of animal welfare. Applied Animal Behaviour Science. 53(1–2), 75–88. DOI: https://doi.org/10.1016/S0168-1591(96)01152-5
- Yin, S. (2009). Low Stress Handling, Restraint, and Behaviour Modification for Dogs and Cats. pp. 123–394. California: Cattle Dog Publishing.
- Zhang, Y., Hedo, R., Rivera, A., Rull, R., Richardson, S. & Tu, X. M. (2019). Post hoc power analysis: is it an informative meaningful analysis? General Psychiatry. 32(4), e100069. DOI: https://doi.org/10.1136/gpsych-2019-100069
Contribute to the evidence
There are two main ways you can contribute to the evidence base while also enhancing your CPD:
- Tell us your information need
- Write a Knowledge Summary
Either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care.
Learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors
Licence
Copyright (c) 2023 Ebony Crump
Intellectual property rights
Authors of Knowledge Summaries submitted to RCVS Knowledge for publication will retain copyright in their work, and will be required to grant to RCVS Knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so.
Disclaimer
Knowledge Summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. It does not override the responsibility of the practitioner. Informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. Knowledge Summaries are a resource to help inform and any opinions expressed within the Knowledge Summaries are the author's own and do not necessarily reflect the view of the RCVS Knowledge. Authors are responsible for the accuracy of the content. While the Editor and Publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. For further information please refer to our Terms of Use.