Veterinary Dermatology 2003, 14, 167176

Effects of propofol-induced sedation on intradermal test reactions

in dogs with atopic dermatitis

Blackwell Publishing Ltd.

LYNELLE F. GRAHAM*, SHEILA M. F. TORRES*, CARL R. JESSEN*, KIM L. HORNE*

and PAULA K. HENDRIX
*Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint
Paul, MN 55108, USA
Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi
State, MS 39762, USA
(Received 6 September 2002; accepted 15 December 2002)

Abstract We compared the effect of propofol and saline control on intradermal test reactions in dogs with atopic
dermatitis undergoing outpatient intradermal testing (IDT). Nineteen dogs were used in this clinical study.
Patients were randomly allocated to receive either intravenous (IV) propofol or IV 0.9% saline, and IDT was performed on the right or left (randomized) lateral thorax. One investigator, unaware of the treatments, interpreted
all IDT results. Injection sites were analysed using a subjective and objective method. A value of P 0.05 was
considered significant. When all injection sites were subjectively analysed for reactions 1+ on all dogs, significantly more positive sites were apparent during propofol sedation than during saline administration. In addition,
the greater number of individual dogs experiencing more positive reactions 1+ during propofol sedation was
significant. When subjectively analysing reactions 2+, the greater number of positive reactions and the greater
number of dogs with more positive reactions observed during propofol treatment was not significantly different
from the saline control. When analysed objectively, the greater number of positive reactions observed during propofol sedation was not significant. A greater number of dogs had higher subjective scores and larger objective
measurements during propofol sedation compared with saline administration. In summary, propofol sedation
was associated with an overall greater number of positive IDT reactions compared with the saline control.
Although not always significant, this difference should be considered when choosing propofol for skin testing
dogs with atopic dermatitis.
Keywords: allergic dermatitis, allergy testing, atopic dermatitis, atopy, dog, intradermal allergy test, intradermal
skin test, intradermal test, propofol, sedation.

INTRODUCTION
Atopic dermatitis (AD), the allergic reaction manifested in response to inhaled or percutaneously
absorbed allergens, is a common skin disease in dogs.
Diagnosis of AD is based on a suggestive history, characteristic clinical signs, elimination of other causative
pruritic skin disorders and at least one positive intradermal testing (IDT) reaction.1 More importantly, IDT
is performed to determine the appropriate allergens
for immunotherapy in dogs with AD.2
Sedation is often necessary to adequately restrain
the patient and minimize stress during IDT. Unnecessary stress associated with physical restraint of patients
for IDT may cause endogenous corticosteroid release,

Correspondence: Lynelle F. Graham, Department of Small Animal

Clinical Sciences, College of Veterinary Medicine/Veterinary
Teaching Hospital, University of Minnesota, 1352 Boyd Avenue
C339, Saint Paul, MN 55108, USA. Tel.: +1 612 625 7744; E-mail:
graha040@umn.edu
2003 European Society of Veterinary Dermatology

accidental subcutaneous injection resulting in no intradermal response, and frustration on the part of the
person conducting the test, all of which may adversely
affect the test results.3,4 Intradermal testing is commonly performed on an outpatient basis. Therefore,
any form of chemical restraint must be short-acting
with minimal residual effects. Several drugs have been
examined as chemical restraint agents for IDT, including acepromazine, oxymorphone, ketamine/diazepam,
ketamine/diazepam/atropine, tiletamine/zolazepam,
xylazine/atropine, medetomidine, thiamylal, methoxyflurane, halothane and isoflurane.3,511 On the basis of
these previous studies, acceptable chemical restraint
agents which do not significantly interfere with IDT
results include ketamine/diazepam, ketamine/diazepam/atropine, tiletamine/zolazepam, xylazine/atropine,
medetomidine, thiamylal, methoxyflurane, halothane
and isoflurane.3,511 Despite the fact that these agents
do not appear to affect the IDT results, each anesthetic
protocol has side effects making it less than ideal.
Propofol is a short-acting, noncumulative drug with
characteristic rapid induction and smooth recovery,
allowing short-term sedation with prompt recovery
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L. F. Graham et al.

for outpatient procedures. Demonstration of a lack

of adverse effects by propofol on IDT would allow
its use as a sedative for outpatient IDT. Although propofol has previously been shown to minimize skin
reactivity to serial intradermal histamine dilutions in
normal dogs, the authors are not aware of any studies
demonstrating the influence of propofol on IDT in
dogs with AD.12 The purpose of this study was to
determine if propofol, compared with saline, had any
effect on IDT results in dogs with AD.

MATERIALS AND METHODS

Animals
Nineteen dogs diagnosed with AD at the time of presentation to the University of Minnesota Veterinary
Teaching Hospital, and candidates for IDT, were
included in the study after written owner consent was
obtained. Diagnosis of AD was based on a compatible
history, suggestive clinical signs and elimination of
other causative pruritic disorders such as cutaneous
adverse food reactions, sarcoptic mange and flea bite
allergy.1 In addition, animals were required to have at
least one positive IDT reaction. Patients with a calm
disposition were required as the IDT needed to be performed accurately in each patient with and without
sedation. Based on history and physical examination
findings, patients were determined to be free of any disease other than the presenting skin condition. Routine
withdrawal periods were observed for drugs commonly
used in the symptomatic therapy of AD.1 The patients
had not received injectable corticosteroids within the
previous 8 weeks, oral corticosteroids within the previous 4 weeks or topical corticosteroids within the previous 3 weeks. In addition, the patients had not received
antihistamines or products/diets containing omega-3/
omega-6 fatty acids within the previous 14 days. The
University of Minnesota Institutional Animal Care
and Use Committee (IACUC) approved this study.
Experimental design
A randomized, single-blind design was used in which
the individual interpreting the IDT results (ST) was
not aware of the treatments. Each patient was covered
with a surgical drape after the IDT allergens were
injected and before the evaluator entered the room.
The evaluator was present for only the brief time it
took to interpret the results of the IDT and was unaware of the sedation status of each dog. The IDT was
performed twice on each dog, once during IV propofol
sedation and once without sedation using 0.9% saline
IV as the control. The two treatments were performed
7 h apart and the order of treatments and the side of
the thorax tested were independently randomized.
Experimental treatments
No premedications were given. A 20 gauge, 45 mm,
over-the-needle, intravenous catheter (Jelco, Johnson
and Johnson Medical, Arlington, TX, USA) was

placed aseptically in the cephalic vein. When the dogs

were randomly assigned to receive the saline control,
they were gently restrained by one individual (LG) and
0.9% saline (0.40.6 mL kg1 IV) was administered in
a volume equivalent to the calculated propofol dose.
Because a calm nature and good temperament were
prerequisites for enrolment in this study, patients tolerated the manual restraint well. When the dogs were
randomly assigned to be sedated, they received propofol (Rapinovet, Mallinkrodt Veterinary Inc., Mundelein, IL, USA) at the dosage of 46 mg kg1 IV (with
25% given every 15 s to desired effect) to cause adequate sedation to perform the test. If necessary, repeated
injections of propofol were given (0.40.6 mg kg1 IV
every 23 min) to maintain an appropriate level of
sedation needed for IDT. The level of sedation was
determined to be adequate if the dog would remain
still with minimal restraint while maintaining a brisk
palpebral reflex, significant jaw tone and spontaneous
respiration. Physical parameters (heart rate, respiratory rate, pulse quality, mucous membrane colour, capillary refill time, palpebral reflex, jaw tone), noninvasive
blood pressure, oxygen saturation and response to the
IDT were monitored and recorded during the period of
sedation.
Intradermal testing
One investigator (KH) performed all IDTs following a
widely used protocol.1 The injection sites consisted of
a positive control (0.05 mL of 1:100 000 histamine
phosphate), a negative control (0.05 mL of sterile saline)
and 58 selected, geographically appropriate allergens
diluted in sterile saline (0.05 mL of each; Appendix 1).
The hair coat on the lateral thoracic wall was clipped
using a # 40 blade. The sites to be used were marked
using a felt tip pen at 1.5 cm intervals to avoid interaction between sites. Twenty-seven gauge, 13 mm intradermal bevel needles were used to administer the
intradermal injections. Seven hours after interpretation
of the first skin test, the alternative treatment (saline
control or propofol sedation) was administered and the
test was repeated on the opposite side of the same dog.
One investigator (ST) interpreted the IDT results
15 min after the intradermal injections. All sites were
evaluated in a subjective and objective manner. The
skin test sites were evaluated subjectively for erythema,
induration and wheal size. For a reaction to be considered positive, erythema and induration similar to the
positive control had to be present. The wheal size was
based on a scale from 1 to 4+ using the positive and
negative controls as references. In this study, subjective
data were analysed using two different minimum end
points ( 1+ and 2+). To provide the objective scale
of interpretation, the horizontal and vertical wheal
diameters of all sites that evidenced erythema and
induration similar to the positive control were measured in millimetres. Any reaction equal to or larger
than the average of the diameters of the positive control (1:100 000 histamine) and the negative control
(sterile saline) was considered positive.1

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Effect of propofol on IDT reactions in dogs

169

Statistical analysis
The database analysed in this study included all of the
allergen injection sites, on each dog, that reacted during the propofol sedation or the saline control. A site
that did not react during one of the treatments, but did
react during the other, was included in the database
and was assigned a value of 0.
The scores assigned in the subjective method of assessment and the objective measurements were statistically
evaluated utilizing the paired t-test (two-tail test). The
number of sites that reacted, including the assigned zero
value for the sites where only one reaction was observed
during the two treatments, were counted and evaluated
with nonparametric statistical procedures. The chi-square
test for heterogeneity and the binomial test were used
under the assumption of equal probability (the null
hypothesis). Wilcoxons signed rank test was also used
on selected count data (one-tail test). Spearmans nonparametric method was utilized for the linear correlation analysis between the subjective and the objective
assessments.
The statistical analyses were performed using
software (SPSS, Version 11.0; Chicago, IL, USA). A
P-value 0.05 was considered statistically significant.

RESULTS
Nineteen client-owned dogs diagnosed with AD at
the University of Minnesota Veterinary Teaching
Hospital were included in the study. Six dogs were
female (three intact) and thirteen were male (three
intact). The ages ranged from 1 to 10.8 years (mean
4.9 years). Body weights were 7.843.4 kg (mean 22.6 kg).
Several breeds were represented, including Labrador
Retriever (3), Bichon Frise (3), Lhasa Apso (2), German Shepherd (2), Australian Shepherd (1), Golden
Retriever (1), Vizsla (1), Sheba Inu (1) and mixed breed
dogs (5).
To achieve a light plane of sedation, the dogs included
in this study required a mean propofol dose of 5.5 mg kg1
IV (range 1.86.6 mg kg1) for initial induction. This
dose was administered in 25% increments every 15 s
to achieve adequate sedation to perform the test. All
dogs required a minimum of four repeated propofol
injections of 0.5 mg kg1 IV (range 0.20.8 mg kg1)
given every 23 min. Four dogs required six repeated
injections to maintain an appropriate level of sedation
needed for IDT. All dogs maintained a palpebral
reflex, significant jaw tone and spontaneous respiration throughout sedation. The values for heart rate,
spontaneous respiratory rate, indirect blood pressure
and oxygen saturation during periods of propofol
sedation were within normal limits in all dogs (data not
shown). The sedation lasted for the time necessary to
complete the IDT interpretation (mean, 19.9 min,
range 12.225.1 min). All dogs recovered smoothly
and uneventfully. Recovery to standing was complete
in all dogs within 20 min after the last propofol
administration.

Figure 1. Total number of subjectively evaluated intradermal test

reactions given a score of 1+ or 2+ in 19 dogs with atopic
dermatitis tested during propofol or saline treatments. The greater
number of positive reaction sites observed during propofol administration, compared with saline, was significant (P 0.05) only for
reactions 1+.

The number of sites reacting positively during both

propofol and saline treatments ranged from 3 to 39 in
the 19 dogs.
When all of the injection sites of the 19 dogs were
subjectively evaluated for positive reactions 1+ during propofol sedation or saline control, 250 sites
reacted during propofol sedation and 226 sites reacted
during administration of the saline control. The
greater number of positive reaction sites (24) during
propofol sedation was significant (P = 0.03; Fig. 1).
When analysing dogs, rather than reaction sites, 12 of
the 19 dogs had more reactions 1+ during propofol
sedation, compared with 4 dogs during saline administration. This difference of eight dogs was significant
(P = 0.03; Fig. 2). The greater number of positive
reactions during propofol ranged from one to eight
sites per dog and during saline ranged from one to
three sites per dog. Three dogs had the same number of
reactions during propofol and saline treatments.
When only the scores 2+ in all 19 dogs were subjectively analysed, 203 positive reactions were observed
during propofol sedation and 194 positive reactions
were seen during saline administration. This difference
was not significant (P = 0.47; Fig. 1). When analysing
dogs, rather than reaction sites, more positive reactions
(17 sites per dog) were noted in seven dogs during propofol sedation, compared with four dogs during the
saline administration (16 sites per dog). This difference

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L. F. Graham et al.

Figure 2. Nineteen dogs with atopic dermatitis showing an equal

number or a greater number of intradermal test reactions given a
score of 1+ by a subjective method of evaluation during propofol
or saline administration. The greater number of dogs showing more
positive reactions during propofol, compared with the saline control,
was significant (P 0.05).

was not significant (P = 0.16; Fig. 3). Eight dogs had

the same number of positive reactions during propofol
and saline treatments.
When the injection sites in all 19 dogs were analysed
using the objective method, 146 reactions were positive
during the propofol sedation, and 131 reactions were
positive during saline administration. This difference
was not significant (P = 0.29; Fig. 4). When analysing
dogs, rather than reaction sites, nine dogs had more
positive reaction sites (19 sites per dog) during the
propofol sedation, compared with six dogs during the
saline administration (14 sites per dog). This difference was not significant (P = 0.15; Fig. 5). Four dogs
had the same number of positive reactions during propofol and saline treatments.
The differences in subjective score and objective
measurement values per reaction site of each individual dog were compared between propofol and saline
treatments. Twelve of the nineteen dogs had higher
score values and nine dogs had larger diameter values
during propofol sedation. This compares with seven
dogs with higher scores and six dogs with larger
diameter values during saline administration. These
differences were not significant (subjective P = 0.10,
objective P = 0.15). Of the 12 dogs with higher score
values during propofol sedation, 4 had significantly
higher values compared with saline control (P < 0.05).
Of the nine dogs with larger diameter values during

Figure 3. Nineteen dogs with atopic dermatitis showing an equal or

greater number of intradermal test reactions given a score 2+ by a
subjective method of evaluation during propofol or saline administration. The greater number of dogs showing more positive reactions during propofol, compared with the saline control, was not
significant (P > 0.05).

propofol sedation, two had significantly higher values

compared with saline control (P < 0.05). One dog had
significantly higher subjective score values during the
saline administration compared with propofol sedation (P = 0.01).
Subjective analysis of only the histamine site showed
no significant difference in the score value between the
propofol sedation and the saline control in each dog
(P = 0.58). Similarly, the objective analysis of the histamine site did not show a significant difference in size
of the reaction between the treatments in each dog
(P = 0.31).
When the positive IDT reactions observed during
propofol and saline treatments were grouped under the
various allergen categories, the greater number of positive reactions observed during propofol sedation was
similarly distributed among the categories of allergens
(data not shown). This was true independent of the
method used for interpreting the reactions.
Correlation analysis using the actual score and diameter values showed a significant association between
the subjective and objective methods of interpreting
IDT reactions within each dog during propofol sedation or saline administration. However, correlation
analysis using the number of positive reaction sites did

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Effect of propofol on IDT reactions in dogs

Figure 4. Total number of positive intradermal test reactions

objectively evaluated during propofol or saline administration in 19
dogs with atopic dermatitis. The greater number of positive reaction
sites observed during propofol sedation, compared with saline
control, was not significant (P > 0.05).

not show a significant correlation between the two

methods during propofol or saline treatment (Table 1).

DISCUSSION
Although some companion animals will tolerate the mild
discomfort of IDT with gentle restraint, IDT is routinely
performed using short-acting sedation because many
dogs require sedation in order to accurately and efficiently complete the test. Many sedative drug combinations used for IDT have long recovery periods, are
controlled substances requiring record keeping, and/or
are associated with adverse physiological effects that may
not be appropriate in certain patients. Because IDT is
most commonly performed on an outpatient basis, a

171

Figure 5. Nineteen dogs with atopic dermatitis showing an equal or

greater number of positive intradermal test reactions evaluated by
the objective method during propofol or saline administration. The
greater number of dogs showing more positive reactions during
propofol, compared with saline, was not significant (P > 0.05).

safe, rapid-acting, short-term sedative with minimal or

no residual effect, such as propofol, would be ideal.
Propofol (2,6-diisopropylphenol) is an intravenous
sedativehypnotic anaesthetic agent, which is highly
effective for use in veterinary patients.13,14 As a FDAapproved sedative for dogs, it provides excellent qualities for outpatient diagnostic procedures such as IDT.
A noncontrolled drug, it is characterized by rapid
onset, short duration, noncumulative effects and fast,
smooth recoveries. Dogs are ambulatory within 20 min
after propofol administration.14 Although designed for
intravenous use, accidental perivascular injection does
not result in tissue trauma.15 Despite its relatively high
cost, propofol can be used at economical low dosages
to provide restraint without necessarily producing

Table 1. Average Spearmans correlation coefficient between the subjective and objective methods of IDT assessment during propofol sedation
or saline control treatment in 19 dogs with atopic dermatitis
Total number of positive reaction sites
Treatment

Scores values vs. diameter values

Scores 1+ vs. diameter

Scores 2+ vs. diameter

Propofol
Saline

r = 0.80*; n = 19
r = 0.87*; n = 19

r = 0.43; n = 16
r = 0.43; n = 11

r = 0.51; n = 18
r = 0.55; n = 19

*In each row, superscript letters indicate significant correlation between variables (P 0.05).
Number of dogs (n) is different from 19 due to inability to compute r when one or more of the variables become constant (e.g. all become equal
to 1).
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L. F. Graham et al.

general anaesthesia. The rapid induction allows for use

without premedication. This characteristic, combined
with the smooth recovery qualities, makes this drug
ideal for outpatient procedures such as IDT. In clinically normal dogs, propofol decreased the mean wheal
size to intradermal injection of serial histamine dilutions.12 However, the effects of propofol on IDT results
in dogs with AD have not been reported previously.
The subjective method of IDT evaluation is most
often used on a clinical basis to determine hyposensitization. Generally, a score 2+ will be considered positive.1,4 However, due to the inherent subjectivity of
individual interpretations of IDT, some discrepancies
in score assignments are possible. Sites that may be
assigned a 1+ rating by one clinician may be considered
a 2+ rating by another and vice versa. Therefore,
because of the subjectivity of this method, the authors
decided to include both interpretive criteria in the data
analysis. When scores 1+ were considered positive,
the difference in the number of positive reactions during propofol sedation compared with saline was significant. However, when only scores 2+ were considered
positive, the number of reactions during propofol
sedation was higher but not significantly different from
the number of reactions under saline. Therefore, the
subjective limit accepted by the individual clinician
may result in a greater number of allergens included in
the hyposensitization therapy if propofol is used for
sedation during IDT.
Owing to the experience needed to reliably interpret
the subjective portion of IDT, the maximal wheal
diameter is considered by some investigators to be a
more accurate indicator of the intensity of an IDT
reaction.16 Also, this objective assessment of wheal size
is the most common method of evaluation used in previous studies investigating the effect of anaesthetic
agents on IDT.5 12 In this study, propofol, compared
with saline, increased the number of positive reactions
assessed by the objective method, but the difference
was not significant.
When considering only dogs, rather than reaction
sites, significantly more dogs experienced more reactions during propofol sedation, and the range of positive reactions was wider. This significant difference
supports the tendency of propofol to increase the reactivity of the IDT. Also, the differences in score and
diameter values per reaction site of each individual dog
were compared between propofol and saline treatments. Although the overall differences were not significant, a greater number of dogs tended to have higher
scores and larger wheal diameters during propofol
sedation.
Previous studies analysing the acceptability of anaesthetic agents used during IDT have been based on the
effect of these agents on serial dilutions of intradermally injected histamine.3,5 12 Because of this precedence, the histamine site in each dog was subjectively
and objectively analysed during propofol and saline
treatments. No significant difference in the score or
wheal size between propofol and saline treatments

was noted, indicating that propofol sedation did not

affect the reaction to intradermally injected histamine
(1:100 000) in dogs with AD included in this study.
These results contradicted a previous study in which
propofol diminished the wheal size of serial intradermal histamine dilutions in normal dogs.12
The greater number of positive reactions observed
under propofol sedation was not associated with any
specific allergen group. This was true whether the reactions were interpreted using the objective or subjective
method.
A significant correlation between the subjective and
objective methods assessing the IDT reactions was
observed in this study only when the actual scores and
diameter values were analysed. These results indicate
that the score and diameter values increased or decreased
in a similar manner. In contrast, when the total number
of positive reactions, subjectively and objectively interpreted, was correlated, as opposed to the actual scores
and diameter values, a poor association was observed
between the methods. Our data showed significantly
more positive reactions with the subjective than the
objective method of interpretation. Because neither
manner of interpreting the reactions has been critically
reviewed and standardized, it cannot be concluded that
the subjective method was associated with falsepositive reactions or that the objective method was
associated with false-negative reactions in this study.
Nevertheless, the results did indicate that the subjective
and objective methods cannot be used interchangeably
in the interpretation of IDT reactions, and future
controlled studies need to be conducted to critically
evaluate both methods.
In this study, the IDT reactions were assigned a
score or were measured only if they presented with
erythema and induration similar to the histamine site.
Therefore, this was the minimal requirement for the
reactions to be evaluated further for wheal size. The
adopted criteria can partially explain the significantly
greater number of positive reactions observed with the
subjective compared with the objective method because
all reactions with erythema similar to the histamine
received a score value and were included in the analysis.
However, for the objective assessment, only the reactions with erythema similar to the histamine that also
had diameters equal to or larger than the average of
the positive and negative controls were included in the
analysis. Regardless of the criteria adopted in this study,
the same parameters of evaluation were strictly applied
when the reactions were assessed during either propofol or saline treatments. Therefore, the method of interpreting the reactions did not influence the final outcome
of the study.
In this study, many steps were taken to minimize the
effects of extraneous factors. The IDT during the two
randomized treatments (propofol sedation and saline
control) were performed 7 h apart. Because the halflife of propofol in the dog is 1.4 h, elimination of the
drug occurred within 7 h, therefore not affecting further
testing.17 This period also allowed the investigators to

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Effect of propofol on IDT reactions in dogs

complete both IDT tests on each dog within one working day, thereby minimizing inherent day-to-day variations in the IDT results, eliminating the need for
overnight hospitalization, avoiding repeated fasting
and minimizing stress to the patient.
Some degree of variability in test results is expected
when the same IDT is performed consecutively on the
same patient. However, the independent randomization of both the order in which the propofol sedation
or saline control was administered and the side of
the thorax used first for the IDT allowed for neutralization of any inherent intertest variation influencing
the effect of either treatment on the IDT results. Therefore, although some variation is expected when performing multiple IDT, every effort was made in this study
to minimize the effect of this variability.
Possible cumulative effects of repeated IDT on the same
patient were also a concern. Nonatopic dogs receiving
weekly IDT were shown to experience induced positive
IDT reactions after three weeks.18 Because cumulative
effects of repeated IDT were not noted until the third
test, it is unlikely that the two tests administered within
the same day in this study resulted in a cumulative
effect. In addition, the randomization of the order of
propofol or saline administration neutralized any possible cumulative effects on the IDT results during
either treatment.
Stress, and the associated increase in endogenous
cortisol levels, may interfere with the reactivity of the
IDT. However, a previous study showed that the significantly increased serum cortisol level observed in
nonsedated dogs did not affect the IDT results.3 In the
design of our study, the inclusion criteria required dogs
that were outwardly calm in an effort to minimize cortisol release associated with physical restraint. It is
therefore very unlikely that stress and/or cortisol release
were associated with the smaller number of positive
reactions during the saline administration.
Although several drugs and drug combinations
other than propofol have been tested for use during
IDT, many drugs are unacceptable and only a few have
been shown to not significantly interfere with skin testing. Morphine and other opioids aggravate histamine
release, potentially causing false-positive IDT results.19
Although intramuscular oxymorphone (0.2 mg kg1)
did not cause any significant differences in the IDT in
one study,6 intravenous oxymorphone (0.05 mg kg1)
did cause a decrease in skin reactivity in another study.5
This discrepancy may be attributable to the differences
in dose and route of administration. Acepromazine,
another common sedative, may cause false-positive
IDT results due to peripheral vasodilation or falsenegative results due to hypotension.5 Acepromazine
also has an antihistaminic effect20 and significantly
diminishes the erythema assessed in subjective assessments and the objective wheal size.5,6
Combinations of dissociatives and benzodiazepines,
such as ketamine/diazepam, ketamine/diazepam/
atropine and tiletamine/zolazepam, are commonly used
intravenously in dogs for IDT.69 The combination

173

of ketamine and diazepam is thought to have antihistaminic effects.5 Benzodiazepinedissociative combinations provide rapid and smooth induction with
adequate cardiopulmonary stability in most patients.
Unfortunately, the dissociative agents, ketamine and
tiletamine, are nonreversible and cause increased sympathetic activity, myotonia and catatonia. Recoveries
are rough, often taking hours before the dog is ambulatory. The decreased tear production and impaired
palpebral reflexes, characteristic of dissociative agents,
can result in corneal ulceration if adequate ocular
lubrication is not provided.21 Perivascular injections
are painful.21 Also, these drugs are controlled substances requiring secure containment and accurate
records. Therefore, the benzodiazepinedissociative
combinations are not ideal agents for outpatient IDT.
Clinically useful alpha-2 adrenergic agonists for IDT
include xylazine/atropine and medetomidine.3,5,10,11
These nonscheduled agents provide reliable sedation,
good muscle relaxation and analgesia, versatility in route
of administration and pharmacological reversibility.
Unfortunately, the use of xylazine has been associated
with increased mortality in small animal practice.22
Alpha-2 agonists have profound cardiovascular effects
including vasoconstriction and initial hypertension,
followed by long-lasting, centrally mediated hypotension.23 Decreased cardiac output, characteristic of
alpha-2 agonists, may be unacceptable in many older
or debilitated patients. Bradyarrhythmias are also common after alpha-2 agonist administration and may
require the administration of an anticholinergic. The
effects of anticholinergics on IDT are unknown,
although the increased intracellular cAMP levels
associated with the use of anticholinergics may stabilize
cells and prevent the release of inflammatory mediators.5 Two studies confirming the use of xylazine for
IDT in dogs have included atropine in the sedation
protocol.3,5 The sedative effects of xylazine and medetomidine last longer than is required for many IDTs.
Although xylazine and medetomidine are reversible,
antagonism increases the risk of rough recoveries and
can increase apprehension.24 Alpha-2 antagonism is
also associated with tachycardia and hypotension due
to alpha-adrenergic blockade, and the antagonist
increases the cost of the sedation.25 Additional adverse
effects of alpha-2 agonist administration include hyperglycemia, osmotic diuresis, emesis and unreliable sedation in some dogs.26,27 Temporary aggressive behaviour
has also been reported in dogs receiving alpha-2 agonists.28,29 For these many reasons, alpha-2 agonists are
most suitable for short-term sedation in young, otherwise healthy patients presenting for IDT.
Barbiturates, specifically thiamylal, do not interfere
with IDT in dogs.6 However, poor recovery quality,
sloughing from extravascular administration, transient
cardiopulmonary depression and the FDA-controlled
status make these drugs less than ideal for outpatient
procedures.
Inhalants including methoxyflurane, halothane
and isoflurane do not adversely affect IDT in dogs.6

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174

L. F. Graham et al.

However, the cost of vaporizers and machine maintenance, negative cardiovascular effects, public health
aspects of inhalant pollution and the difficulty of using
these agents without premedication in dogs make the
routine use of inhalant anaesthetics for IDT difficult
for many practitioners.
Owing to the desirable characteristics discussed
previously, propofol is an ideal sedative drug for IDT.
However, the results of this study showed an overall
trend for propofol to increase the IDT reactivity. Intravenous administration of propofol can cause histamine
release in a variety of species, including dogs.14,3032
Therefore, our results may be attributed to endogenous
release of histamine and known histamine release is the
reason for not using other agents, such as morphine
and meperidine, for sedation during IDT. 19 Paradoxically, propofol was shown to decrease the skin
reactivity to intradermal injections of serial histamine
dilutions in normal dogs.12 However, dogs with AD
may exhibit increased sensitivity to the histaminereleasing effects of propofol, causing an overall trend
towards increasing the IDT reactivity. Also, propofol
has been shown to cause peripheral vasodilation.33,34
This mechanism may also account for the overall trend
towards increasing IDT reactivity during propofol
sedation.
The trend for propofol to increase the number of
positive IDT reactions in atopic dogs may result in
hyposensitization to irrelevant allergens. In normal,
nonatopic dogs, six months of hyposensitization therapy to irrelevant antigens did not significantly change
the IDT reactions of subsequent tests and the dogs
remained asymptomatic.35 However, the long-term
effects of such hyposensitization protocols are not
known at this time.
In summary, this study demonstrated a significantly
greater number of positive IDT reactions during
propofol sedation, compared with the saline control,
only for subjectively evaluated reactions assigned a
score 1. However, results consistently demonstrated a
trend towards greater numbers of positive IDT reactions during propofol sedation. The tendency for propofol to increase the IDT reactivity may not be a
clinically significant problem, when weighed in consideration with the beneficial effects of this sedative over
other options currently available. Nevertheless, this
tendency must be emphasized and considered in subsequent clinical decisions.

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1. Scott, D.W., Miller, W.H., Griffen, C.E. Muller and
Kirks Small Animal Dermatology, 6th edn. W.B. Saunders,
Philadelphia, 2001: 5889.
2. DeBoer, D.J., Hillier, A. The American College of Veterinary Dermatology task force on canine atopic dermatitis (XV): fundamental concepts in clinical diagnosis.
Veterinary Immunology and Immunopathology 2001; 81:
271 6.

3. Frank, L.A., Kunkle, G.A., Beale, K.M. Comparison of

serum cortisol concentration before and after intradermal testing in sedated and nonsedated dogs. Journal of
the American Veterinary Medical Association 1992; 200:
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4. Hillier, A., DeBoer, D.J. The American College of Veterinary Dermatology task force on canine atopic dermatitis (XVII): intradermal testing. Veterinary Immunology
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5. Beale, K.M., Kunkle, G.A., Chalker, L. et al. Effects of
sedation on intradermal skin testing in flea-allergic dogs.
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1990; 197: 8614.
6. Moriello, K.A., Eicker, S.W. Influence of sedative and
anesthetic agents on intradermal skin test reactions in
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7. Codner, E.C., McGrath, C.J. The effect of tiletamine
zolazepam anesthesia on the response to intradermally
injected histamine. Journal of the American Animal Hospital Association 1991; 27: 18991.
8. Codner, E.C., Lessard, P., McGrath, C.J. Effect of tiletamine/zolazepam sedation on intradermal allergy testing
in atopic dogs. Journal of the American Veterinary Medical Association 1992; 201: 185760.
9. Mills, A.C., McKeever, P.J. Comparison of intradermal
skin testing in nonsedated and sedated dogs. In: Abstract
Proceedings of the American Academy of Veterinary Dermatology. American Academy of Veterinary Dermatology
Annual Meeting, Charleston, SC, 1994: 312.
10. Pypendop, B., Verstegen, J. Sedation and skin testing in
the dog. In: Proceedings of the XVII World Small Animal
Veterinary Association World Congress. XVII World Small
Animal Veterinary Association World Congress, Rome,
Italy, 1992: 457.
11. Vogelnest, L.J., Mueller, R.S., Dart, C.M. The suitability
of Domitor (medetomidine) sedation for facilitating
intradermal skin testing in dogs. In: Proceedings of the
14th Annual Meeting of the American Academy of Veterinary Dermatology/American College of Veterinary Dermatology. 14th Annual Meeting of the American
Academy of Veterinary Dermatology/American College
of Veterinary Dermatology, San Antonio, TX, 1998:
378.
12. Kennis, R.A., Robertson, S.A., Rosser, E.J. et al. Effects
of propofol anesthesia on intradermally injected histamine phosphate in clinically normal dogs. American
Journal of Veterinary Research 1998; 59: 79.
13. Morgan, D.W.T., Legge, K. Clinical evaluation of propofol as an intravenous anesthetic in cats and dogs. Veterinary Record 1989; 124: 313.
14. Watkins, S.B., Hall, L.W., Clark, K.W. Propofol as an
intravenous anesthetic agent in dogs. Veterinary Record
1987; 120: 3269.
15. Glen, J.B. Animal studies of the anaesthetic activity of IC
35 868. British Journal of Anaesthesia 1980: 52: 73141.
16. Willemse, A., Van Den Brom, W.E. Evaluation of the
intradermal allergy test in normal dogs. Research in
Veterinary Science 1982; 32: 5761.
17. Plumb, D. Veterinary Drug Handbook, 4th edn. Iowa
State Press, Ames, 2002: 7067.
18. Schmeitzel, L.P. The effects on multiple intradermal skin
tests on skin reactivity. Veterinary Allergist Summer
1986: 4.
19. Robinson, E.P., Fagella, A.M., Henry, D.P. et al.

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Haskins, S.C., Klide, A.M. Precautions when using ketamine for introduction of anesthesia. Veterinary Clinics
of North America Small Animal Practice 1992; 22: 2689.
Dyson, D.H., Maxie, M.G., Schnurr, D. Morbidity and
mortality associated with anesthetic management in small
animals veterinary practice in Ontario. Journal of the
American Animal Hospital Association 1998; 34: 32535.
Klide, A.M., Calderwood, H.W., Soma, L.R. The cardiopulmonary effects of xylazine in dogs. American Journal
of Veterinary Research 1975; 36: 9315.
Hsu, W.H. Effect of yohimbine on xylazine-induced central nervous system depression in dogs. Journal of the
American Veterinary Medical Association 1983; 182:
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Vainio, O. Reversal of medetomidine-induced cardiovascular and respiratory changes with atipamezole in dogs.
Veterinary Record 1990; 127: 44750.
Benson, G.J., Thurmon, J.C., Neff-Davis, C.A. et al.
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formulation of IC 35 868 (2,6-diisopropylphenol). British
Journal of Anaesthesia 1984: 56: 61726.
Kimura, K., Adachi, M., Kubo, K. Histamine release
during the induction of anesthesia with propofol in allergic patients: a comparison with the induction of anesthesia using midazolamketamine. Inflammatory Research
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Stellato, C., Casolaro, V., Ciccarelli, A. et al. General
anaesthetics induce only histamine release selectively
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Robinson, B.J., Ebert, T.J., OBrien, T.J. et al. Mechanisms whereby propofol mediates peripheral vasodilation in humans. Anesthesiology 1997; 86: 6472.
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APPENDIX 1
Allergens included in the intradermal test. Allergen concentrations are 1000 PNU unless specified in parenthesis
A. Controls
Histamine (1:100 000)
Sterile saline
A. Epidermals
Cat epithelia
Mouse epithelia
Sheep epithelia (wool)
A. Grasses
Corn pollen (250 PNU)
Kentucky/June bluegrass
Meadow fesque grass
Orchard grass
Perennial rye grass
Timothy
A. Household pollens and miscellaneous inhalants
Cotton linters
Dust mix (250 PNU)
Feather mix
Grain mill dust mix
House dust
House dust (250 PNU)
Kapok seed
Mixed mites (1:1000)
Pyrethrum
A. Insects
Black ant (250 PNU)
Caddisfly (250 PNU)
Cockroach mix (250 PNU)
Flea (1:1000)
House fly (250 PNU)
Household insect mix (250 PNU)
Mosquito (250 PNU)
Moth (250 PNU)

A. Mould
Alternaria tenuis
Aspergillus mix
Cephalosporium
Cladosporium
Corn smut
Fusarium mix
Helminthosporium
Hormodendrum
Penicillium mix
Rhizopus mix (250 PNU)
Rhodotorula
A. Trees
Ash mix
Black willow
Box elder
Eastern oak mix
Elm mix
Maple mix
Pine mix
Poplar, lombardy
Red cedar
White birch
A. Weeds
Cocklebur
Common mugwort
English plantain
Lambs quarter
Marsh elder/burweed
Nettle
Pigweed mix
Ragweed mix
Russian thistle
Sheep/red sorrell
Yellow/curly dock
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L. F. Graham et al.
Rsum Cette tude a valu les effets du propofol sur les intradermoractions ralises chez des chiens prsentant une dermatite atopique. Dix neuf chiens ont t inclus. Les patients ont reu soit du propofol par voie
intraveineuse soit du solut sal 0.9%. Les tests intradermiques ont t effectus, au hasard, sur la face latrale
droite ou gauche du thorax. Un investigateur, ne connaissant pas le traitement, a interprt les rsultats des tests.
Les sites dinjection ont t cts subjectivement et objectivement. Une valeur p 0.05 tait considre comme
significative. Lorsque les sites dinjection ont t analyss subjectivement pour les ractions 1+ un plus grand
nombre de zones de tests taient positives dans le groupe propofol en comparaison avec le groupe contrle. En
outre, la diffrence tait galement significative pour les chiens prsentant plus de ractions positives. En analysant les ractions juges subjectivement 2+, les diffrences ntaient pas significatives. Avec lanalyse objective,
le plus grand nombre de ractions observes dans le groupe propofol ntait pas significativement diffrent du
groupe contrle. Un plus grand nombre de chiens prsentait des scores subjectifs levs et des mesures objectives
leves pendant la sdation au propofol en comparaison avec le solut sal. En rsum, la sdation avec le propofol
tait associe avec un nombre plus important de ractions intradermiques positives en comparaison avec le contrle. Bien que les diffrences ne soient pas toujours significatives, elles devraient tre envisages si le propofol
est utilis comme sdatif pour tester les chiens prsentant une dermatite atopique.
Resumen El efecto del propofol en las reacciones de los tests intradrmicos fue comparado con la utilizacin
de la solucin control salina en perros no internados con dermatitis atpica en los que se estaba llevando a cabo
las pruebas intradrmicas (IDT). Diecinueve perros fueron utilizados en este estudio clnico. Se seleccionaron al
azar a los pacientes para recibir de forma intravenosa (IV) el propofol o la solucin salina al 0.9% y los IDT fueron
realizados en el trax lateral derecho o izquierdo (seleccionado al azar). Un investigador, desconocedor de los
tratamientos, interpret todos los resultados de IDT. Los sitios de inyeccin fueron analizados usando un mtodo
subjetivo y objetivo. Un valor de p 0.05 fue considerado significativo. Cuando todos los lugares de inyeccin
fueron analizados subjetivamente para reacciones 1+ en todos los perros, un nmero perceptiblemente mayor
de sitios positivos era evidente durante la sedacin del propofol comparada a la administracin salina. Adems,
el nmero superior de perros individuales que experimentaban un nmero mayor de reacciones positivas 1+
durante la sedacin del propofol fue significativo. Cuando se analizaron subjetivamente reacciones 2+, el
nmero mayor de reacciones positivas y el nmero ms grande de perros con un nmero mayor de reacciones
positivas observadas durante el tratamiento con propofol no fueron significativamente diferentes del control
salino. Cuando se analiz objetivamente, el nmero mayor de reacciones positivas observadas durante la sedacin
del propofol no fue significativo. Un nmero mayor de perros tuvo un ndice subjetivo ms alto y medidas objetivas ms grandes durante la sedacin con propofol comparado con la utilizacin de la solucin salina. En
resumen, la sedacin con propofol fue asociada a un nmero total mayor de reacciones positivas en el IDT comparadas al control salino. Aunque no siempre significativa, esta diferencia debe ser considerada en los si se elige
el propofol para la realizacin de tests intradrmicos en perros con dermatitis atpica.
Zusammenfassung Die Wirkung von Propofol auf Intrakutantest- (IKT-) reaktionen wurde bei Hunden mit
atopischer Dermatitis, bei denen ein Hauttest durchgefhrt wurde, mit der von physiologischer Kochsalzlsung
verglichen. Neunzehn Hunde wurden in dieser Studie verwendet. Die Patienten wurden randomisiert und
erhielten entweder Propofol oder IV 0.9%ige Kochsalzlsung intravens (IV) und ein IKT wurde auf dem rechten
oder linken Brustkorb (randomisiert) durchgefhrt. Injektionsstellen wurden objektiv und subjektiv bewertet.
Ein P-Wert von 0.05 wurde als signifikant erachtet. Wenn alle Injektionsstellen bei allen Hunden subjektiv auf
Reaktionen 1+ analysiert wurden, waren signifikant mehr positive Reaktionen whrend der Propofolsedation
feststellbar, verglichen mit den mit Salzlsung behandelten Hunden. Zustzlich war die Anzahl der Hunde mit
einer grsseren Anzahl von positiven Reaktionen 1+ signifikant vermehrt. Wenn subjektiv Reaktionen 2+
bewertet wurden, waren die grssere Anzahl der positiven Reaktionen und die grssere Anzahl von Hunden mit
einer erhhten Anzahl von positiven Reaktionen bei Sedation mit Propofol nicht statistisch signifikant. Wenn
objektiv bewertet wurde, war die whrend der Sedation mit Propofol wahrgenommene grssere Anzahl von positiven Reaktionen nicht signifikant erhht. Eine grssere Anzahl von Hunden hatte hhere subjektive Werte und
grssere objektiv gemessene Reaktionen whrend Sedation mit Propofol verglichen mit der Behandlung mit
Kochsalzlsung. Zusammenfassend war eine Sedation mit Propofol mit einer grsseren Anzahl positiver IKT
Reaktionen verbunden als Kochsalzlsungsbehandlung. Obwohl der Unterschied nicht immer signifikant war,
sollte er bercksichtigt werden, wenn Propofol fr den Hauttest beim Hund mit atopischer Dermatitis verwendet
wird.

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 167176