Page 68 - Cote clinical veterinary advisor dogs and cats 4th

Acetaminophen Toxicosis 11

• History of progressive lethargy, anorexia, increases are typically seen within 24-36 • Supportive care
hours of ingestion.
vomiting, icterus, muddy or cyanotic mucous • Spot test for methemoglobinemia: Place one ○ Oxygen (p. 1146)
VetBooks.ir ness, or paw and facial edema drop of blood on absorbent white paper ○ Blood transfusion may be needed if Diseases and Disorders
○ Fluid therapy to maintain hydration and
membrane color, tachypnea, dyspnea, weak-
electrolyte balance
from affected patient and compare to one
PHYSICAL EXAM FINDINGS
• Most often unremarkable if early in the drop of blood from unaffected patient. If hemolytic anemia develops (p. 1169).
affected patient’s blood appears brown in
clinical course comparison, there is a likely diagnosis of Chronic Treatment
• Lethargy, depression methemoglobinemia. • Ophthalmic cyclosporine until KCS resolves
• Chocolate-colored mucous membranes (typically 4-6 weeks)
(methemoglobinemia) Advanced or Confirmatory Testing • Continue SAMe until liver enzymes return
• Facial and/or paw edema (more common • Acetaminophen levels at human hospital for to normal.
in cats) dogs (ideally run 4 hours after exposure)
• Tachypnea, dyspnea • Methemoglobin levels (not readily available) Behavior/Exercise
• Tachycardia • Schirmer tear test if suspect KCS Restricted activity during treatment
• Icterus • Centrilobular liver necrosis and congestion
• Vomiting on histopathology Drug Interactions
• KCS (rare) (p. 568) Drugs that induce hepatic microsomal systems
TREATMENT (e.g., phenobarbital) may increase acetamino-
Etiology and Pathophysiology phen toxicity due to increased formation of
• When normal biotransformation pathways Treatment Overview hepatotoxic metabolites.
for detoxification (glucuronidation and After exposure but before signs occur,
sulfation) are overwhelmed, an oxidative decontamination with emesis and activated Possible Complications
metabolite (i.e., N-acetyl-p-benzoquinone charcoal is important. Liver protectant and KCS, chronic liver disease
imine [NAPQI]) is formed and binds to antioxidant, N-acetylcysteine, is advised to
cellular macromolecules leading to cellular prevent and treat liver injury and may help Recommended Monitoring
necrosis. If NAPQI is conjugated with with methemoglobinemia. • Monitoring liver enzymes or func-
glutathione, it is detoxified. tion tests every 24 hours for initial 48
• Another metabolite, para-aminophenol Acute General Treatment hours after exposure or until liver injury
(PAP), may be responsible for development • Decontamination, typically most ben- resolves
of methemoglobinemia through oxidative eficial within 2 hours of ingestion (only if • Monitoring for evidence of methemoglo-
damage. asymptomatic) binemia in first 12 hours after exposure,
○ Induction of emesis (p. 1188): Apomor- followed by hemolytic anemia for 72 hours
DIAGNOSIS phine 0.03 mg/kg IV or 0.04 mg/kg IM after exposure
or conjunctivally (canine) • Monitor Schirmer tear test for evidence
Diagnostic Overview ○ Activated charcoal (p. 1087) 1-2 g/kg PO of KCS during initial 72 hours after
Because exposure is usually witnessed or sus- with sorbitol, one dose exposure
pected, determining dose and risk are important. • Liver protectant or antioxidant
If there is doubt regarding recent exposure, ○ N-acetylcysteine (Mucomyst) 140 mg/kg PROGNOSIS & OUTCOME
acetaminophen concentrations (from a human loading dose (or 280 mg/kg in large
hospital) should be considered, although this overdoses), followed by 70 mg/kg every • With prompt and aggressive care, prognosis
test is not sensitive enough for cats. Assess liver 6 hours for 7-17 doses. Oral and intra- is usually good.
enzymes and methemoglobin for suspected venous (IV) formulations are available. • Methemoglobinemia and significant liver
intoxication. Dilute to 5% before giving (dextrose if injury worsen prognosis, as does underlying
PO, replacement fluids if IV). If giving health issues, particularly those involving the
Differential Diagnosis orally, must wait 2-3 hours after admin- liver.
• Hepatic injury: xylitol, aflatoxin, blue-green istration of activated charcoal. May give
algae, cycad palms (e.g., Cycas revoluta, IV N-acetylcysteine concurrently with PEARLS & CONSIDERATIONS
Zamia furfuracea), hepatotoxic mushrooms, activated charcoal.
salicylates ○ S-adenosylmethionine (SAMe) 18-20 mg/ Comments
• Methemoglobinemia: benzocaine (Cetacaine) kg PO q 24h for 2 weeks can be used • Owners may use brand names as generic
in cats, naphthalene, nitrites, chlorates, instead of N-acetylcysteine if liver issues terms for OTC pain relievers. Verify active
phenol, Allium sp., skunk spray are expected but no methemoglobinemia ingredient and strength of what the owner
• Swollen face/paws: insect bite or sting, occurred or after methemoglobinemia has thinks was ingested.
cutaneous adverse drug reaction resolved. • Emesis is not likely to be beneficial for
○ Ascorbic acid (helps reduce methemo- feline patients because acetaminophen is
Initial Database globin to hemoglobin, but efficacy is absorbed very quickly (peak plasma level
• CBC: often unremarkable in initial stages questionable): 30 mg/kg q 6-12h PO of 10-30 minutes). Activated charcoal may
○ Heinz body anemia may occur after or SQ be beneficial if given within 30 minutes of
methemoglobinemia ○ Cimetidine (inhibitor of cytochrome P450) exposure.
• Serum biochemical profile: often unremark- is no longer recommended; its inhibition • Glucocorticoids and antihistamines will
able in initial stages of microsomal enzymes is considered too have no effect on paw and facial edema
○ Progressive increase in liver enzymes slow to be of benefit in dogs. In cats, because they are not due to an allergic
(alanine aminotransferase [ALT], alkaline cimetidine is contraindicated because it reaction.
phosphatase [ALP]) until hepatic function inhibits N-acetyltransferase 1 (NAT1),
declines, then decreases in blood urea which can decrease the conversion of Technician Tips
nitrogen (BUN), cholesterol, and albumin PAP to acetaminophen, putting patients Check for other active ingredients in products
with increasing total bilirubin. Initial at higher risk for methemoglobinemia. because acetaminophen can be combined with

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