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Consultant on Call Internal Medicine / Critical Care Peer Reviewed

Ivermectin Toxicosis in Dogs

Adesola Odunayo, DVM, MS, DACVECC


University of Tennessee

Marie E. Kerl, DVM, MPH, DACVECC & DACVIM (Small Animal)


University of MissouriColumbia

P Profile

Definition
When ivermectin, a macrocytic lactone, is present in sufficiently high concentrations to cross Dogs on farms or in
the bloodbrain barrier, it can cause neurologic signs in dogs.
rural settings are at
Toxicity may occur with products administered orally, topically, or parenterally.
The same dose will be absorbed faster when administered parenterally than when adminis- greater risk for
tered topically, but signs of toxicity can be seen in all routes with high enough doses. ivermectin toxicosis, as
Signalment they may be exposed to
No gender or age predisposition. products formulated for
Very young animals may have an increased risk because of their immature bloodbrain barriers.
Dogs with a mutation in the multidrug resistance gene (ABCB1, formerly MDR1) are especially
large animals.
sensitive to ivermectin.1,2
Dogs with an ABCB1 mutation are also predisposed to increased sensitivity to moxidectin,
loperamide, milbemycin, and chemotherapeutic agents.
Common breeds with this mutation include the border collie, Australian shepherd, long-
haired whippet, silken windhound, rough- and smooth-coated collies, and associated mixed
breeds.
In sensitive breeds, ivermectin toxicosis can be seen in doses as low as 100 g/kg, although doses
of 6 g/kg have been shown to be safe in nonsensitive breeds.
In nonsensitive breeds, a dose of >2000 g/kg is required to produce signs of toxicosis.3,4

Risk Factors
Most cases of ivermectin toxicosis result from administration
of ivermectin-containing products.
Ivermectin Dose by Indication
Dogs on farms or in rural settings are at greater risk for iver- Heartworm..........................................6 g/kg
mectin toxicosis because they may be exposed to products Sarcoptic mange.................................300 g/kg
formulated for large animals.
Demodectic mange ............................400600 g/kg
Dogs can also be exposed to ivermectin through ingestion
of feces from treated cows, horses, or pigs.

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December 2012 clinicians brief 63


Consultant on Call

Pathophysiology Examination Findings


The primary mechanism of action for Altered mentationobtundation,
ivermectin is to potentiate glutamate- stupor or coma.
gated chloride receptors and g- Ataxia.
Key Point aminobutyric acid (GABA)gated Bradycardia.
chloride channels. Hypersalivation.
Although ivermectin toxicosis At low concentrations, ivermectin Mydriasis.
typically does not induce pain in potentiates the effect of glutamate. Absense of menace response.
animals, increased vocalization At higher concentrations, gluta- Vomiting.
caused by anxiety or altered mate-gated chloride channels are Respiratory depression.
mentation may be difficult to opened directly.5,6 Tremors.
discern from a pain response. When ivermectin binds to the recep- Seizures.
tors, the chloride channels open
slowly and irreversibly, resulting in
Diagnosis
prolonged hyperpolarization or depo-
larization of the neuron or muscle
Definitive
cell, causing rapid paralysis.5
History and examination findings are
vital.
Signs
Measurement of serum ivermectin
History
concentration can confirm diagnosis,
Ataxia.
but usually results are not available
Mydriasis.
immediately.
Altered mentation (obtundation,
Testing for the ABCB1 gene mutation
stupor, coma).
is available at Washington State Uni-
Hypersalivation.
versity Veterinary Clinical Pharmacol-
Vomiting.
ogy Laboratory, Gribbles Veterinary
Blindness.
Services in Australia, and Genetic
Tremors.
Counseling Services in The Netherlands.
Seizures.
pCO2 = partial pressure of carbon dioxide
Differential
Exposure to other toxicants (eg, ethyl-
ene glycol, methanol, heavy metals,
hallucinogens, marijuana, barbiturates,
opioids, benzodiazepines, mycotoxins).
Infectious, inflammatory, traumatic, or
neoplastic intracranial diseases.
Metabolic diseases (eg, renal failure,
hepatic dysfunction, diabetic ketoaci-
dosis, electrolyte abnormalities).
Other causes of extracranial neurologic
disease.

Laboratory Findings
CBC, serum biochemistry profile, and
urinalysis are usually nonspecific but
may be helpful.
Hemoconcentration has been seen.
Patients with topical ivermectin toxicosis should be washed with Hypoglycemia may be present if
tremors/seizures are prolonged.
mild dishwashing detergent and water before treatment is Prerenal azotemia may occur if patient
initiated. is adipsic or vomiting.

64 cliniciansbrief.com December 2012


Nonspecific elevations in liver
enzymes may be present. Alternative Treatments
Urinalysis may help differentiate
between renal and prerenal azotemia. Physostigmine, an anticholinesterase agent, may be administered at 1
Venous blood gas analysis is recom- mg/dog IV q12h; may cause temporary improvement in neurologic status. The
mended if the patient is moderately drug acts for a short time, but may be helpful to wake the patient for feeding.
obtunded.
Results are typically transient and inconsistent, but beneficial effects may
Respiratory acidosis caused by
help confirm ivermectin toxicosis.
hypoventilation may be present. Partial
pressure of carbon dioxide (pCO2) Potentially toxic adverse effects include seizures, excessive salivation,
>60 mm Hg is diagnostic. tremors, urination, defecation, and lacrimation.

Picrotoxin, a GABA antagonist, may cause rapid improvement in neurologic

Treatment status; however, it should be used cautiously, as it may contribute to seizure


activity.
There are no specific antidotes for iver- IV lipids have seen success in the treatment of ivermectin and other
mectin toxicosis. macrocytic lactone toxicoses, but more research needs to be conducted. IV
Oral: lipids have relatively few adverse effects and may be worth considering as a
Ivermectin is recirculated in the GI therapeutic option.7
tract.
If ingestion occurred <14 hours
before presentation:
Emesis should be induced with

apomorphine (0.03 mg/kg IV Plasmalyte-148 [baxter.com], 0.9% at home for at least 1 week, as more
or subconjunctivally once) or saline solution). extensive therapy may be indicated.
hydrogen peroxide (0.5 mL/kg If hypovolemia (tachycardia,
PO up to 2 times). hypotension, pale mucous mem- Supportive Treatment
Activated charcoal should be branes, prolonged capillary refill Primary treatment for ivermectin toxi-
administered (12 g/kg PO once) time) is present, circulating fluid cosis is mainly supportive.
with/without cathartic; subse- volume should be replaced by External heat support if patient is
quent doses without cathartic at administering crystalloid fluid via unable to maintain body temperature
0.51 g/kg q8h. 20 mL/kg bolus, then reassess vital >99F.
Monitoring electrolyte concen- signs. Affected animals are usually
trations, especially sodium, is Bolus may be repeated up to 4 obtunded and unable to move away
important. times. Colloids (Hetastarch from heat, so care should be taken to
If oral ingestion occurred within [hydroxyethyl starch; HES]) at 5 avoid thermal burns. Provide circu-
2436 hours before presentation: mL/kg concurrently may help lating warm water or air blankets
Activated charcoal should be correct hypovolemia. instead of lamps or heating pads.
administered once at 12 g/kg Endotracheal intubation and Patient should be rotated q48h if
PO; subsequent doses at 0.5 mechanical ventilation should be obtunded, stuporous, or comatose.
1 g/kg q8h. initiated for hypoventilation (pCO2 Consider sterile indwelling urinary
All routes: >60 mm Hg). catheter and closed collection system
Patients with topical ivermectin tox- Consider referral for mechanical

icosis should be washed with mild ventilation if unavailable at pri-


dishwashing detergent and water mary receiving practice. Intubate Affected animals are usually
before initiating additional treat- patient and begin manual ventila- obtunded and unable to move
ments. tion for transportation to spe-
cialty practice.
from heat, so care should be
Crystalloid fluid therapy should be
initiated for maintenance require- Progression of clinical signs may be taken to avoid thermal burns.
ments and any ongoing losses (lac- slow. Exposed animals should be
tated Ringers solution, monitored closely in the hospital or

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December 2012 clinicians brief 65


Consultant on Call

to maintain hygiene if patient is non- week following exposure.


ambulatory or obtunded. Patients may not be fully ambulatory
Endotracheal intubation is indicated if on discharge, so owners may need to
patient does not have a gag reflex and assist the patient in walking and with
is unable to protect its airway. hygiene.
Replace sterilized endotracheal tube
q24h (minimum). Endotracheal
tube should be suctioned and
changed more frequently if excessive
secretions are present.
* In General

Relative Cost
Seizure control can be provided with Most dogs respond well to supportive
phenobarbital, pentobarbital, propofol, therapy.
and etomidate. Benzodiazepines may Depending on the level of care
also be considered, although they may required, treatment ranges from rela-
potentiate the effects of ivermectin. tively inexpensive ($$) to very expen-
Eyes should be lubricated q4h if blink sive ($$$$$).
reflex is absent or diminished because
Key Point of mentation.
Consider enteral nutrition via oral Cost Key
Prognosis is usually very good
feeding, nasogastric tube, or
if aggressive supportive care $ = up to $100
esophagostomy tube early in treat-
is initiated early. However, $$ = $101$250
ment. If patient is high risk for aspira-
treatment can be prolonged, $$$ = $251$500
tion, consider providing total or partial
depending on how much was
parenteral nutrition. $$$$ = $501$1000
ingested.
$$$$$ = more than $1000

Follow-up

Patient Monitoring Prognosis


Respiratory rate and ventilation status Prognosis is usually very good if
should be monitored carefully. aggressive supportive care is initiated
Venous or arterial blood gas analysis early.
should be completed to evaluate pCO2; Depending on the dose ingested and
mechanical ventilation is indicated if the susceptibility of the exposed ani-
pCO2 is >60 mm Hg. mal, treatment may be prolonged.
In intubated patients, CBC and tho- Clinical signs may take several
racic radiographs should be obtained if weeks to resolve.
aspiration pneumonia is suspected. Prognosis may be guarded if the dose
Neurologic status should be assessed ingested is >5 mg/kg in dogs without
q8h for progression or resolution of the ABCB1 mutation.8 cb
signs.
See Aids & Resources, back page, for
At-Home Management references & suggested reading.
A relapse should not be expected, but
owners should be instructed to con-
tinue monitoring neurologic signs for
progression, especially during the first

pCO2 = partial pressure of carbon dioxide

66 cliniciansbrief.com December 2012