Hasan AÃgin, ÖSebnem ÖCalkavur, Hakan Uzun, Mustafa
Bak
From the Department of Pediatric Emergency, Dr.
BehÖcet Uz Children’s Hospital, Turkey.
Correspondence to: Hasan Agin, Inonu Cad. No: 701/1
D.4, 35350 Poligon/IZMIR, Turkey.
E-mail: hasanagin@mynet.com
Manuscript received: November 25, 2002, Initial
review completed: January 11, 2003;
Revision accepted: September 8, 2003.
Abstract:
Amitraz is an insecticide/acaricide of
formamidine pesticides used worldwide to control ectoparasites in
animals. Amitraz poisoning is a rare disorder characterized by
central nervous system (CNS) and respiratory depression,
bradycardia, hypotension, hypothermia, hyperglycemia, nausea and
vomiting. Poisoning may occur either by oral inhalation and dermal
route. In this study, we present seven pediatric patients with
amitraz poisoning. The initial symptoms were unconsciousness,
dizziness and vomiting; and emerged within 30-150 minutes. The
length of stay in the intensive care unit (ICU) was between 18-62
hours.
Key words: Amitraz, Children, Intensive care unit,
Poisoning.
Amitraz, 1,5 di-(2,4-dimethylphenyl)-3-methyl-1,3,5-tri-aza-penta-1,4
diene is a member of the formamidine pesticides(1). It is an
acaricide and insecticide indicated for the treatment of generalized
demodicosis in dogs, for control of ticks and mites on cattle and
sheep, and to control psylla infestations of pears(2).
Amitraz is a pharmacologically active compound
which has a2-agonist actions. The stimulation effect of
a2-receptors are in part responsible for neurotoxic and
preconvulsant effects(1). Adverse reactions and side effects have
been reported in animals exposed to the product but only a limited
number of human intoxication cases have been published in the
literature. The reported effects include CNS depression,
hypothermia, bradycardia, hypo-tension, hyperglycemia, glycosuria,
vomiting and respiratory failure(3-5).
In Turkey amitraz is available under the
proprietry name Kenaz , 12.5% emulsifable concentrate amitraz. This
paper presents the clinical and laboratory findings and therapeutic
management of the patients with amitraz poisoning admitted to our
intensive care unit.
Subjects and Methods
Seven cases of amitraz poisoning were admitted to
Dr. BehÖcet Uz Children’s Hospital, Emergency Department between
1999-2001 and were evaluated retro-spectively. Cases were analyzed
according to age, sex, the routes and modes of poisoning, first
symptoms, the time to the appearance of first symptoms, clinical and
laboratory findings (state of consciousness in the ICU, pupillary
signs, heart rate, blood pressure, respiratory failure, requirement
for mechani-cal ventilation, body temperature, blood glucose level,
urinary output), therapeutic management, length of stay and
survival.
Results
Age of the patients ranged between 2-6 years.
These included five boys and two girls. Table I shows the
demographic data and clinical and laboratory findings in cases
retrospectively. Six cases were poisoned by oral and one case by
dermal route. Oral poisoning occured by accidental swallowing, and
the ingested amount was 25 mL (3.13 g) in one case and 30 mL (3.75
g) in another, in the rest it was unknown. Dermal poisoning occured
by applying treatment of lice by a parent in one case.
Table I
Please click on to view
Unconsciousness was the predominant initial
symptom, the others being vomiting and dizziness. First symptoms
appeared within 1 h in four cases. Four of the children presented
with coma and two with a somnolent state on admission to the ICU.
Initially, miosis was apparent in three cases. Except for one
hypotensive case, blood pressure levels were unaltered. Respiratory
failure was present in four cases, two of them required mechanical
ventilatory support for less then 10 h. Body temperature was
decreased (<36ºC, axillary) in two cases. A mild increase in blood
glucose level was observed in two cases. Transaminases, blood urea
nitrogen, creatinine, serum electrolyte levels, ECG and urinary
output were within normal ranges in all cases.
Gastric lavage and activated charcoal were
administrated in five cases. Hypotension improved after the
administration of intravenous fluids. Bradycardia and miosis
responded to 1-4 doses of atropine administration. CNS depression
resolved spontaneously within 6-20 h. The length of stay in the ICU
was between 18-62 h. All cases recovered fully within 3 days.
Discussion
Formamidines have toxic effects on both animals
and humans and previous studies have reported the reversible nature
of these effects(3). The present information about amitraz and
formamidine pesticides is frequently built on animal studies because
of the limited human intoxication cases.
The acute oral median lethal dose (LD50) for the
rats is 800 mg/kg(2). Amitraz is a potent inhibitor of rat liver
monoamine oxidase(6).
Animals given amitraz show signs of CNS
depression or CNS stimulation according to the dose level and to
some extent, depending on the species. High doses have a CNS
depressive effect with reduced spontaneous activity, bradycardia,
respiratory depression and hypothermia. Death resulted from
respiratory depression. At low doses CNS stimulation may occur, as
manifest by hyperreactivity to external stimuli such as handling,
considerably increased food consumptions(7). Topical application
amitraz in the dog has been shown to increase plasma glucose and
supress insulin release(8).
Animals that survive after poisoning by
potentially lethal dose of amitraz show complete recovery from all
signs and symptoms in about 7-10 days(9).
The clinical signs reported in previous papers on
human poisonings are CNS depression, drowsiness, vomiting, myosis,
bradycardia, hypotension and hyper-glycemia(10-12). CNS depression,
which is probably attributable to the a2-adrenoceptor
action, was the predominant sign in our cases. In previous studies
the duration of CNS depression has ranged from a few hours to 24
h(3,4). CNS symptoms began within 30-150 minutes and resolved within
6-20 h in our cases.
Co-existence of bradycardia and miosis may
suggest organophosphate poisoning(4). In our series bradycardia was
present in two cases and miosis accompanied one of them.
Cholinesterase levels of this case were documented to be within
normal range; moreover there were no other findings of
organophosphate poisoning.
Amitraz has antipyretic and anti-inflammatory
activity in vivo, and also has been shown to inhibit
prostaglandin E2 synthesis(13). Decreased body temperature was
observed in two of our cases. The basic approach to the patient with
amitraz poisoning includes initial stabilization, treatment to
reduce absorption and measures to improve elimination of the
toxin(14). The medical management is essentially symptomatic and
supportive. There is no specific antidote. Despite life-threatening
symptomatology, all cases may recover completely. In this study we
would like to emphasize that the incidence of poisoning with amitraz
is increasing due to its widespread use in veterinary medicine. In
order to minimize amitraz poisoning, public education should be
given on primary prevention of poisoning and besides, producers
should redesign containers as childproof packagers with warning
labels.
Contributors: SC, HU, MB worked up the cases,
HA diagnosed, reviewed the manuscript and with act as guarantor.
Funding: None .
Competing interests: Nil.
Key
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• Amitraz poisonong is characterized by central
nervous system and respiratory depression.
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