Picasso, a two-year-old, 4.3-kg exotic shorthaired cat, was presented for respiratory distress beginning 12 hours after ingestion of garbage, which contained two or three Tylenol PM® tablets (500 mg acetaminophen per tablet). Picasso's owner also reported that the cat had two episodes of vomiting, one of which contained a blue coloring similar to that of the acetaminophen tablet, brown urine; and about four hours of increasing lethargy and dyspnea.

Physical examination revealed hyopthermia at 97.3ºF; tachycardia of 240 beats per minute; tachypnea of 80 beats per minute; increased respiratory effort yet normal lung sounds; and cyanotic-brown mucous membranes, pads and nail beds. THe cat was very depressed and cried continuously. Based on the history and physical examination, the diagnosis of acetaminophen toxicosis was made. Picasso had ingested an estimated 500-1500 mg acetaminophen, or 115-355 mg/kg, a level considerably above the reported toxic dose of 50-60 mg/kg in cats.

Acetaminophen Toxicosis

Cats have a limited ability to metabolize xenobiotics because of their relative deficiency of hepatic glucuronyl transferase. Therefore, acetaminophen can be tolerated only in small quantities. Toxicosis occurs with ingested levels of 50-100 mg/kg. When toxic doses are consumed, the glucuronidation pathways in the liver become saturated and the excess drug is converted to toxic metabolites by cytochrome P450. Within two to four hours, these toxic metabolites cause oxidative damage to hemoglobin, converting it to methemoglobin, which is unable to bind and carry oxygen, leading to systemic hypoxia. Within hours to days of toxin ingestion, this oxidative damage can also cause the formation of Heinz bodies, which can lead to hemolysis. Finally, also within hours to days, the toxic metabolites bind covalently to hepatic macromolecules and may induce hepatic necrosis.

The classic clinical signs associated with acetaminophen toxicosis include edema of the face and paws, chocolate-cyanotic mucous membranes, and hyperventilation due to hypoxemia and lactic acidosis. Other nonspecific signs include anorexia, lethargy, vomiting, ptyalism, and stupor. Clinical pathology may reveal anemia secondary to hemolysis, Heinz body formation, methemoglobinemia (chocolate-brown blood), and methemoglobinuria (red-brown urine). Liver enzymes may increase secondary to hepatic necrosis and oxidative injury to hepatocytes, while increases in bilirubin levels can occur from prehepatic and hepatic causes.

Typical treatments for toxin ingestion should be used in any case of acetaminophen toxicosis; these include inducing emesis, administering activated charcoal and cathartics, and performing gastric lavage for recent ingestion. If clinical signs are present, minimal restraint and handling are a must for the most fragile hypoxic patients. A single dose of methylene blue 1.5 mg/kg IV can be used to convert methemoglobin to hemoglobin directly, whilerunningntheeriskt of inducing Heinz body anemia with repeated use. N-acetylcysteine can resolve methemoglobin by reducing the concentration of reactive metabolites of acetaminophen, which in turn secondarily reduces the production of methemoglobin. This treatment may not be rapid enough in severe cases. Vitamin C isthee slowest-acting method of reducing methemoglobin and can be given orally 125 mg four times daily or IV 200 mg/cat t.i.d. Finally, transfusions of whole blood, packed red blood cells, or Oxyglobin® (polymerized bovine hemoglobin glutamer-200) may be used to increase immediately the oxygen-carrying capacity of the blood, while giving the other treatments time to correct the methemoglobinemia.

In general with acetaminophen toxicosis, the ideal treatment is to supply the patient with an adequate quantity of functioning hemoglobin. Although thissupplyy can be provided through whole blood transfusion, in this cat with a packed cell volume (PCV) of 45 percent normal: 30-45), such transfusion was not an option because of the high risk of inducing hyperviscosity.

Oxygen First

Upon admission to the hospital, Picasso was immediately administered oxygen by mask, and minimal restraint was used to place an intravenous (IV) catheter. An IV bolus of 636 mg Mucomyst (N-acetylcysteine) was administered as a five percent solution in 9.0 percent sodium chloride (NaCl) at 15 mL/hr. Total protein of 6.8 mg/dL (normal: 5.7-8.0) and PCV of 45 percent were determined immediately, and a complete blood count (CBC) and chemistry panel were submitted.

After one hour in the oxygen cage, Picasso remained dyspneic, cyanotic, and distressed, generating concern for his survival. It was decided to administer a blood product not currently approved for use in cats, polymerized bovine hemoglobin glutamer-200, toimprovee the oxygen-carrying capacity of the blood. This product is only labeled for use in dogs, so its usage here was offlabel, and the owner's permission was obtained before administration.

Treatment

A total of 50 mL polymerized bovine hemoglobin glutamer-200 was given over 1 ¾ hours, with the option to repeat the dose if desired clinical effects were not obtained. A significant improvement wasnotedd within one hour of administration. Picasso's temperature, pulse, and respiratory rate stabilized, and his mucous membranes and nail beds returned to a normal pink color. In addition, he was no longer distressed and crying but resting comfortably. Additional therapies for acetaminophen toxicosis were prescribed: A regimen of N-acetylcysteine 340 mg every four hours for four additional treatments was continued, and vitamin C was added to the IV fluid to provide 200 mg every eight hours.

With acetaminophen toxicosis, basic supportive care, consisting of fluid administration, oxygen therapy, and control of acid-base balance, should be implemented. Patient monitoring should include serial assessment of vital signs, hydration status, PCV, the appearance of the patient's blood, liver enzymes, bilirubin, and theelectrolytess; clinicians should keep in mind that pulse oximetry will be of no use because the methemoglobin will cause a reading of 85 percent. The prognosis for acetaminophen ingestion is good in the acute stages when emesis and activated charcoal are used to prevent absorption of toxic amounts. The prognosis is poor to guarded once clinical signs occur. Early deaths occur secondary to hypoxemia, whereas late deaths occur secondary to liver toxicosis.

Picasso remained in the hospital for five days. The complete blood count and chemistry panel submitted on presentation were within normal limits. The PV dropped to 31 percent one hour after administration of the treatment; decreased PCV is a known and expected side effect of this product because its oncotic properties cause hemodilution. On day three, Picasso appeared clinically icteric. A PCV of 30 percent eliminated hemolysis as a cause of the icterus, and a liver panel was submitted to investigate a hepatic cause. The alanine transferase (ALT), alkaline phosphatase, and gamma-glutamyl transferase (GGT) levels were normal, while the aspartate aminotransferase (AST) of 246 units/L (normal: 9.2-39.5) and total bilirubin of 0.6 mg/dL (normal: 0.1-0.5) were elevated. The AST was thought to be of muscle origin. Unfortunately, bilirubin is an analyte invalidated by administration of polymerized bovine hemoglobin glutamer-200, so this result could be invalid. The polymerized bovine hemoglobin glutamer-200 itself can also cause a yellow-orange discoloration ofthee mucous membranes, skin, and sclera and could account for the yellow sclera notedduringg physical examination on day 3.

Because of the cat's clinical improvement; normal ALT, AST, and GGT; and minor elevation in the total bilirubin, the decision was made to monitor the cat instead of pursuing more invasive diagnostic testing. Picasso continued to improve over the next two days. His PCV was stable at 29-30 percent, and the yellow sclera resolved, so he was discharged. The dischargeinstructionn included a scheduled recheck in one week for a liver profile and PCV levels; unfortunately, because of poor owner compliance, this follow-up was not completed. Recently, via a phone conversation, Picasso's owner reported that Picasso is doing well and developed no complications after discharge.

In this case, the initial treatment with N-acetylcysteine and oxygen did result in rapid clinical improvement. With the concern for Picasso's survival, polymerized bovine hemoglobin glutamer-200 was sued as a life-saving measure because a whole-blood transfusion was not an option in a cat with a PCV of 45 percent.

Dr Nolte is completing her internship in small-animal medicine at Oradell Animal Hospital, Oradell, New Jersey; Ms. Crovatto is a veterinary technician specializing in emergency and critical care and internal medicine diagnostics at Oradell Animal Hospital.