Full text of DOI:10.1111/j.1751-0813.2001.tb12980.x

Clinical
News
Reactions to tick antitoxin serum and
the role of atropine n treatment of dogs
and cats with tick paralysis caused
Australian
VETERINARY
JOURNAL
i
by Ixodes holocyclus: a pilot survey
C L I N I C A L S E C T I O N
EDITOR
RB ATWELL and FE CAMPBELL
MAUREEN REVINGTON
School of Veterinary Science, The University of Queensland, Queensland 4072
ADVISORY COMMITTEE
ANAESTHESIA
PETER GRAY
AQUATIC ANIMAL MEDICINE AND HEALTH
Objective
To determine the incidence and nature of adverse reactions of dogs
BRADLEY CHADWICK
and cats to tick antitoxin serum and to re-evaluate the role of atropine in the treatment
of tick paralysis.
AVIAN MEDICINE AND SURGERY
SHANE RAIDAL
CLINICAL PATHOLOGY/BIOCHEMISTRY
MARY McCONNELL
Design
A retrospective questionnaire of veterinarians.
CRITICAL CARE/EMERGENCY MEDICINE
ALICIA FAGGELLA
Procedure Questionnaires were posted to 320 veterinarians in tick-endemic
regions of Australia. Questions referred to dogs and cats treated for tick paralysis over
a period of three years: the number treated, treatment protocols and adverse
systemic reactions to tick antitoxin serum. Ninety completed questionnaires were
returned and responses analysed.
EPIDEMIOLOGY
CHRIS BALDOCK
EQUINE MEDICINE AND SURGERY
KATE STEEL
LABORATORY ANIMAL MEDICINE/HEALTH
DAVID PASS
OPHTHALMOLOGY
ZIGRIDA CHESTER
Results Veterinarians reported that approximately 3% of dogs exhibited adverse
reactions immediately following treatment with tick antitoxin serum. Eighteen percent
of these reactions were described as anaphylaxis, with the remaining 82% attributed
to the Bezold-Jarisch reflex. Six percent of cats treated with tick antitoxin serum
reacted adversely and the majority of reactions (63%) were ascribed to the Bezold-
Jarisch reflex. Atropine was used routinely by 10% of responding veterinarians in the
treatment of dogs and cats with tick paralysis. A similar number of veterinarians used
atropine only in selected cases. Most veterinarians (76%) reported that they never
used atropine in the treatment of tick paralysis in either dogs or cats. Within the
survey population, premedication with atropine reduced the number of Bezold-Jarisch
reactions following tick antitoxin administration approximately five-fold in dogs and
four-fold in cats.
PRODUCTION ANIMAL MEDICINE
HELEN CHAPMAN
SMALL ANIMAL MEDICINE
PETER IRWIN
SURGERY
RICK READ
WILDLIFE AND EXOTIC ANIMAL
MEDICINE/SURGERY
RALPH SWAN
EDITORIAL ASSISTANT AND
DESKTOP PUBLISHING
ANNA GALLO
CONTRIBUTIONS INVITED
Conclusions Data from this pilot survey indicate that more cats than dogs have
adverse systemic reactions to tick antitoxin serum and that the majority of these
reactions in both dogs and cats could be related to the Bezold-Jarisch reflex. The
number of reactions to tick antitoxin serum in dogs and cats could be significantly
reduced by the routine use of atropine prior to administration of tick antitoxin serum.
Aust Vet J 2001;79:394-397
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Key words: Tick paralysis, B-J reflex, anaphylaxis, atropine, tick antitoxin serum, cat, dog.
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Bezold-Jarisch reflex
Intravenouslly
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TAS
Tick antitoxin serum
ick paralysis, the condition induced by the Australian paralysis tick, Ixodes
holocyclus, affects some 10,000 dogs and cats along the eastern coast of Australia
every year.1 Treatment involves the use of TAS to neutralise the clinical effects of
T
the tick’s toxin, which acts on the neuromuscular junction to inhibit
neurotransmission.2 However, TAS administration carries with it the risk of possible
adverse systemic reaction that has often been termed anaphylaxis. However, anecdotal
evidence complied by the National Tick Paralysis Forum in 1998 (unpublished)
indicates that there is some confusion concerning TAS reactions and that the term
anaphylaxis may be used inaccurately. If true anaphylaxis occurs rarely, then precautions
and drugs administered to prevent possible TAS adverse reactions may be ill-directed.
The aim of this pilot survey was to determine the incidence and nature of clinical
reactions to TAS in dogs and cats in order to re-evaluate prophylactic protocols.
Editor, AVJ Clinical Section
AVA House, 272 Brunswick Road,
Brunswick, Vic. 3056,
Phone: (03) 9387 2982
Fax: (03) 9388 0112
Email: desktop@ava.com.au
394
Aust Vet J Vol 79, No 6, June 2001

Clinical
Dogs
Materials and methods
Veterinarians reported treating 14,550 dogs for tick paralysis
during the 3-year period and reported an adverse clinical
reaction following TAS administration in 3.3% of these dogs.
Eighty-two percent of adverse reactions to TAS were described
as being clinically characterised by bradycardia, mucous
membrane pallor, hypotension, weakness, depression and
reduced heart sounds. The remaining 18% of adverse reactions
to TAS were clinically characterised by tachycardia, injected
mucous membranes, anxiety or restlessness, piloerection on the
back of the neck, swelling of the lips, cutaneous wheals,
erythema, diarrhoea, vomiting, dyspnoea and coughing. This
equated to 2.7% of all dogs treated with TAS exhibiting clinical
signs consistent with the B-J reflex and 0.6% of all dogs
similarly treated developing anaphylaxis (Table 2).
In the treatment of dogs with tick paralysis, 10% (n=9) of
veterinarians reported that they routinely used atropine, 14%
(n=13) used it occasionally and 76% (n=68) never used
atropine. Dogs that were given atropine before administration
of TAS (n=2,640) had fewer B-J reactions: 0.5% developed a
B-J reaction compared with 2.7% of dogs treated with TAS
alone (P < 0.001).
In December 1999, a retrospective questionnaire was mailed
(with invoices sent by Veterinary Pathology Services, Brisbane)
to 320 veterinarians practising in tick-endemic regions of
Queensland and New South Wales. The survey comprised short-
answer and alternate-answer questions and covered the 3-year
period ending January 2000. The number of dogs and cats
treated annually for tick paralysis by each veterinarian and the
total numbers of reactions to TAS were recorded. Respondents
were asked to provide actual numbers from practice records if
available.
For those animals reacting adversely to TAS, respondents were
asked to specify reactions that could best be described by
bradycardia, mucous membrane pallor, clinical signs of
hypotension, weakness, depression and reduced heart sounds, as
opposed to reactions that involved tachycardia, injected mucous
membranes, anxiety or restlessness, piloerection on the back of
the neck. swelling of the lips, cutaneous wheals, erythema,
diarrhoea, vomiting, dyspnoea and coughing. The first of these
clinical presentations describes the B-J reflex3-6 while the latter
typifies anaphylaxis7-13 (Table 1). No reference was made on the
survey form to the name of each reaction type in order to
minimise inaccurate responses arising from preformed
conclusions.
Cats
Only responses of veterinarians who routinely used atropine
prior to TAS and those who never used atropine were assessed
statistically. Data from respondents (n=11) who administered
atropine at the same time or after administration of TAS, in all
or selected animals, were excluded. This was necessary to assess
more accurately the possible prophylactic effect of atropine
premedication against the B-J reflex. Chi-squared tests were used
to test for association in 2x2 contingency tables. Yates correction
was made for one degree of freedom. Significance was assigned a
P-value of < 0.001.
Surveyed veterinarians recalled treating 6,054 cats for tick
paralysis during the 3 years prior to January 2000. Adverse
systemic reactions to TAS were observed in 6.2% of these cats.
The reactions characterised by clinical signs of bradycardia,
mucous membrane pallor, clinical signs of hypotension,
weakness, depression and reduced heart sounds were described
in 63% of cases, reflecting a 3.9% B-J reaction rate of all cats
treated with TAS. Accordingly, 37% of adverse reactions to TAS
(2.3% of all cats treated) were described by clinical signs of
tachycardia, injected mucous membranes, anxiety or
restlessness, piloerection on the back of the neck, swelling of the
lips, cutaneous wheals, erythema, diarrhoea, vomiting,
dyspnoea and coughing and were considered characteristic of
anaphylaxis (Table 2).
Results
Ninety veterinarians returned completed survey forms. Of
these, 12% were able to provide exact figures from practice
records for the total number of tick paralysis cases treated and 60
to 70% of respondents gave the actual numbers of dogs and cats
that reacted to TAS during the survey period. All other figures
were estimations.
The rate of atropine usage in cats was similar to that in dogs.
The majority of veterinarians (76%; n=68) reported never using
the drug in treatment of tick paralysis, 13% (n=12) used it
Table 1. Summary of differences between the Bezold-Jarisch reflex and anaphylaxis in dogs and cats.
B-J Reflex3-6
Anaphylaxis7-13
Pathophysiologic effects
Physiologic responses
Chemical stimulation of cardiac receptors in
the posterior wall of the left ventricle initiates
a vagally mediated cholinergic response.
Foreign antigens act on mast cells and basophils to cause cellular
degranulation and release of endogenous chemicals that affect
multiple organ systems.
Bradycardia; systemic vasodilation; reduced
total peripheral resistance, and slight, though
insignificant, reduction in myocardial contractility.
Peripheral vasodilation; increased vascular permeability; constriction
of smooth muscle of bronchi, gastrointestinal tract, and coronary
artery; pulmonary vasoconstriction, and increased production of
airway mucus.
Clinical signs
Bradycardia; pale mucous membranes;
hypotension; weakness; depression, and
reduced heart sounds.
Tachycardia; injected mucous membranes; anxiety or restlessness;
piloerection on the back of the neck; swelling of the lips; cutaneous
wheals; erythema; diarrhoea; vomiting; coughing, and dyspnoea.
Treatment
Atropine 0.1-0.2 mg/kg IV
Adrenaline 0.01mL/ kg of 1: 1000 IV or IM up to a maximum of
0.2-0.5 rnL. Repeat every 15 to 20 minutes if needed.
IM = intramuscularly, IV = intravenously
Aust Vet J Vol 79, No 6, June 2001
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Clinical
Table 2. Reported incidence of reactions following TAS administration.
Traditionally, atropine has been used in supportive treatment
of tick paralysis to ease dyspnoea by effecting bronchodilation
and to reduce salivation and pharyngeal pooling, thereby
decreasing the risk of aspiration and airway obstruction.
However, since Ilkiw’s work15,16 the use of atropine as part of
the treatment for tick paralysis has become unpopular. This
trend was seen in the current survey with so few veterinarians
routinely administering atropine. Ilkiw proposed that
sympathetic overdrive and autonomic imbalance were responsible
for the cardiovascular changes documented in dogs with tick
paralysis. It followed that atropine, which would attenuate the
vagal reflex essential for the body to compensate for excessive
sympathetic stimulation, would be contraindicated. However,
Dogs
Cats
Animals treated with TAS (n)
Reactions to TAS (n)
14,550
480
3.3
6,054
375
6.2
Reactions to TAS (%)
TAS reactions attributed to the B-J reflex (% )
Incidence of B-J reactions (%)
82
63
2.7
3.9
Incidence of B-J reactions when premedicated
with atropine (%)
0.5
0.9
TAS reactions attributed to anaphylaxis (%)
Incidence of anaphylaxis (% )
18
37
0.6
2.3
plasma catecho-lamines were not measured to substantiate the
theory and the work was based on only a small group of dogs
(n=10, six of which provided results) that had experimentally
induced tick paralysis and were heavily instrumented. Recent
work on naturally occurring tick paralysis in dogs has not been
able to validate Ilkiw’s hypothesis and suggests no
contraindication for the use of atropine (unpublished).
occasionally and 11% (n=10) routinely administered atropine.
Cats that were given atropine prior to administration of TAS
(n=1,035) had a significantly reduced number of B-J reactions:
0.9% compared with a reaction rate of 3.9% when atropine was
not administered (P < 0.001).
Anaphylaxis occurs when a foreign antigen acts on host cells
to cause release of vasoactive factors. When the rate of release of
vasoactive molecules is greater than the body’s ability to
compensate for the rapid changes in its cardiovascular system, as
occurs with rapid IV injection of antigen, anaphylaxis ensues.
Multiple organ systems are affected resulting in clinical signs
characteristic of anaphylaxis (Table 1).7-13 Amongst the animals
in this survey, the risk of anaphylaxis following TAS
administration was minimal. Only 0.6% of all dogs and 2.3%
of all cats treated with TAS developed clinical signs consistent
with anaphylaxis. The fact that cats were significantly more at
risk of anaphylaxis than dogs is not surprising considering that
TAS is collected from hyperimmune dogs, and is, therefore, a
protein that is foreign to the cat The most important drug in
the prevention and treatment of anaphylaxis is adrenaline. It
acts via beta-receptors to provide positive chronotropic and
inotropic effects and bronchodilation. It also impairs synthesis
and release of some mediators of anaphylaxis. Its alpha-agonist
properties increase systemic vascular resistance and increase
diastolic blood pressure, thereby improving venous return and
cardiac perfusion to increase cardiac output further.7,10
Dogs and cats
Significantly fewer dogs than cats showed clinical signs
consistent with an anaphylactic reaction following TAS
administration (P < 0.001).
Discussion
Most adverse reactions that were reported to follow TAS
administration in both the dog and cat were characteristic of
clinical manifestations of the B-J reflex3-6 (Table 1), which is a
vagally mediated reflex initiated by chemical stimulation of
cardiac receptors in the posterior wall of the left ventricle.3
Bradycardia, hypotension, reduction in total peripheral
resistance and a slight, though insignificant, reduction in
myocardial contractility occurs with activation of these
receptors. The vagal reflex induces bradycardia while
hypotension results from a combination of sympathetic
withdrawal and cholinergic vaso-dilation. The minor negative
inotropic component is solely dependent on the negative
chronotropic response.3 If untreated, persistent bradycardia and
hypotension, together with poor ventricular function, will lead
to a further decline in cardiac output and systemic arterial
pressure, with subsequent induction of circulatory stock.5
Due to the cholinergic nature of the B-J reflex, atropine will
attenuate or abolish its clinical manifestations.3,5 This was
reflected in the survey results in which only 0.5% of dogs
premedicated with atropine developed a B-J reaction following
administration of TAS, which is a five-fold reduction compared
with dogs not receiving atropine and of which 2.7% exhibited a
B-J reaction. Similarly, cats treated with atropine prior to TAS
administration had a B-J reaction rate of 0.9% compared with
3.9% for cats not receiving atropine, which is a four-fold
reduction in association with atropine administration. In
experimental studies, the B-J reflex in dogs was blocked using
0.1 to 0.2 mg/kg IV of atropine.3,5 Although the present study
did not investigate dose rates, the recommended dose rate of
atropine is 0.04 mg/kg.14 If high dose rates block the reflex
more completely, this may explain why a small percentage of the
survey dogs developed a B-J reaction despite premedication
with atropine.
Premawardhena et al17 demonstrated that in humans
receiving treatment for snakebite the use of SC adrenaline
immediately before administration of the antivenom serum
significantly reduced the incidence of anaphylactic reactions to
serum. Similarly, Malik18 routinely uses 3 mL of 1:10,000
adrenaline SC 3 to 4 minutes before IV administration of TAS
to help prevent anaphylaxis in cats.
Anaphylactic reactions to TAS administration should be
treated using 0.01 mL/kg of 1:1000 adrenaline up to a
maximum dose of 0.2-0.5 mL. The dose can be repeated 15 to
20 minutes later if needed.7 Other drugs, such as cortico-
steroids, antihistamines, aminophylline and, in selected cases,
atropine, may ameliorate the consequences of anaphylaxis.
However, the use of these drugs does not eliminate the need for
immediate administration of adrenaline.7,10
There are some obvious limitations to interpretation of the
results of this survey. The sample population of veterinarians
was restricted to one client base, and the data may not be
representative of the general veterinary or animal population.
Veterinarians were asked to provide information about tick
paralysis cases and adverse reactions to TAS administration over
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Clinical
a 3-year period. The majority of respondents submitted exact
numbers of adverse reactions to administration of TAS but
fewer were able to give precise figures for the total number of
cases treated. This resulted in many estimations. Additionally,
only two choices of reaction category were offered and some
mild clinical events following TAS administration may have
been unnecessarily included. Similarly, some overlap between
reaction categories may exist. For example, the injected mucous
membranes accompanying peripheral vasodilation of early
anaphylaxis8,9 may become less injected as shock develops and
as neuroendocrine reflexes stimulate peripheral vasoconstriction
to redirect blood from skin to vital organs.8,12,13 A larger
prospective survey would overcome these problems, but, while
overall figures may vary with a subsequent survey, the
significant trends illustrated are unlikely to change. Moreover,
this survey has highlighted areas for potential improvement in
the treatment of tick paralysis that have not been previously
addressed.
References
1. Stone BF, Aylward JH. Tick toxicosis and the causal toxins: tick paralysis. In:
Gopalakhrishnakone P, Tan CK, editors. Progress in venom and toxin research.
National University of Singapore Press, Singapore, 1987:594-682.
2. Cooper BJ. Studies on the pathogenesis of tick paralysis [PhD Thesis].
University of Sydney, New South Wales, 1976.
3. Zucker IH, Cornish KG. The Bezold-Jarisch reflex in the conscious dog. Circ
Res 1981;49:940-948.
4. Thoren PN. Activation of left ventricular receptors with nonmedullated vagal
afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol
1976;37:1046-1051.
5. Schillingford J, Thomas M. Treatment of bradycardia and hypotension
syndrome in patients with acute myocardial infarction. Am Heart J 1968;75:843-
844.
6. Frink RJ, James TJ. Intracardiac route of the Bezold-Jarisch reflex. Am J
Physiol 1971;221:1464-1469.
7. Mueller DL, Noxon JO. Anaphylaxis: pathophysiology and treatment. Comp
Contin Educ Pract Vet 1990;12:157-170.
8. Brasmer TH. Shock -basic pathophysiology and treatment. Vet Clin N Am
Small Anim Pract 1972;2:219-233.
9. BrasmerTH. The. symposium on shock. Vet Clin N Am Small Anim Pract
1976;6:173-192.
Although only a small percentage of animals that receive TAS
may have adverse reactions, recognition of the clinical nature of
the reaction is vital in order to effectively treat any such
reactions. Adrenaline is the most important drug in the
prevention and treatment of anaphylaxis. However, because
sympathetic withdrawal mediates only a small fraction of the B-
J reflex, adrenaline will be of little, if any benefit in the
treatment of a B-J reaction. Similarly, administration of
atropine prior to administration of TAS will block the B-J
reflex, but will not prevent or attenuate anaphylaxis. With such
a large proportion of adverse reactions to TAS administration
ascribable to the B-J reflex, the routine use of atropine as a
premedication in tick paralysis cases may substantially reduce
the number of adverse clinical reactions to TAS.
10. Cohen RD. Systemic anaphylaxis. In: Bonagura ll, editor. Kirk’s Current
Veterinary Therapy; Small Animal Practice XII. Saunders, Philadelphia,
1995:150-152.
11. Tizard I. Type I hypersensitivity. In: Veterinary Immunology: Saunders,
Philadelphia. 1992:335-350.
12. Clark DR. Circulatory shock: etiology and pathophysiology. J Am Vet Med
Assoc 1979;175:78-81.
13. Morgan RV. Shock. Comp Contin Educ Pract Vet 1981;3:533-539.
14. Adams RH. Veterinary Pharmacology and Therapeutics. Iowa State
University Press, Ames, 1995.
15. llkiw lE. A study of the effects in the dog of Ixodes holocyclus [PhD Thesis].
University of Sydney, New South Wales, 1979.
16. Ilkiw JE, Turner DM. Infestation in the dog by the paralysis tick, Ixodes
holocyclus 5. Treatment. Aust Vet J 1988;65:236-238.
17. Premawardhena AP, de Silva CE, Fonseka MMD, Gunatilake SB, de Silva
HJ. Low dose subcutaneous adrenaline to prevent acute adverse reactions to
antivenom serum in people bitten by snakes: randomised, placebo controlled
trial. Br Med J 1999;318:1041-1043.
Acknowledgments
18. Malik R. Tick paralysis in the cat. In: Clinical Toxicology. University of
Sydney Post Graduate Foundation in Veterinary Science, Proceedings
1998:147-148.
The authors wish to thank Veterinary Pathology Services,
Brisbane, and Dr Ian Hughes, The University of Queensland,
for assistance with statistical analyses.
(Accepted for publication 24 January 2001)
Aust Vet J Vol 79, No 6, June 2001
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