Hypertonic phosphate enema intoxication in dogs and cats

Hypertonic phosphate enemas (Fleet Enema-Fleet, and generic) contain sodium phosphate and other phosphates, typically at a concentration of 25 to 60 mg/ml, per the package label. They are used for bowel cleansing before a colonoscopy and to alleviate occasional constipation in people. Historically, these were used in veterinary medicine to treat the signs of megacolon in cats and chronic constipation in dogs and cats. But they are not typically recommended any more because of the risk of side effects and the availability of safer and effective alternatives, such as dioctyl sodium sulfosuccinate (DSS) enemas and softgels. 

Typically, pets are exposed due to outdated veterinary recommendations or because the owners are trying at-home treatments. The biggest concerns for toxicosis in dogs and cats are in situations in which a pet has underlying health conditions that predispose the pet to toxicosis, is given an enema orally, or does not defecate after being given the enema rectally.

Pharmacokinetics 

Sodium and phosphorus from the enema are absorbed quickly from the gastrointestinal (GI) tract. Although we don't know the bioavailability in dogs and cats, in humans it is 60 percent. Phosphates are primarily excreted renally (90 percent). In healthy children, the half-life of phosphates is 4.8 to 10.6 hours; with renal insufficiency, the half-life increases to 17 hours.1

Mechanism of action

Phosphate enemas are used in people to relieve occasional constipation and for bowel cleansing prior to a colonoscopy.1 Because phosphate enemas are hypertonic, they cause water to move into the colon and increase the water content of the stool, resulting in evacuation of the bowel within five to 10 minutes.

Excessive absorption of sodium and phosphorus can lead to hypernatremia and hyperphosphatemia. Hyperphosphatemia can lead to hypocalcemia, tetany, muscle stiffness or weakness. Sodium phosphate enemas are also hypertonic, which can cause fluid and electrolyte shifts as well as hyperosmolality. Dehydration and hypotension may occur secondary to GI upset. Hyperglycemia is thought to occur due to stress-induced release of catecholamines.2

Toxicity

Phosphate enema toxicosis is more likely in cats and small dogs, although marked signs have been reported in large-breed dogs. Clinical signs of toxicosis often occur when a retention enema is given or when the enema is given orally. Signs generally occur within 30 to 60 minutes of administration and may include depression, ataxia, vomiting, diarrhea (often bloody), tachycardia or bradycardia, pallor, weakness, tetany, tachypnea and seizures. Laboratory abnormalities may include hyperphosphatemia, hypernatremia, hypocalcemia, hyperkalemia or hypokalemia, hypomagnesemia, hyperglycemia, metabolic acidosis with an increased anion gap (usually < 10 mEq/L) and hyperosmolality.2 Animals with preexisting renal insufficiency, cardiac disease or GI diseases (ulcers, colitis, mucosal erosion, infection) can be at higher risk of severe signs.2

ASPCA Animal Poison Control Center data 

A review of the ASPCA Animal Poison Control Center's toxicology database from 2003 to 2014 identified hypertonic phosphate enema toxicity cases involving nine dogs and 42 cats.3 These cases were single agent (hypertonic phosphate enemas only) and were assessed as medium or high suspect cases based on history of exposure and clinical signs. Of the 42 cats, follow-up information was available in 23 (52%). Eight (18%) recovered with treatment, six (14%) died and three (7%) were euthanized. The remaining four (9%) were still being treated or were showing signs at the time of follow-up.

Of the nine dogs that were showing signs, five weighed less than 22 lb (10 kg) and the remaining four were between 22.1 and 88 lb (10.1 and 40 kg).3 Of the dogs with known follow-up information, one (11%) recovered with treatment, two (22%) died and one (11%) was euthanized. One dog (11%) was still showing signs at the time of follow-up. 

The most commonly reported clinical signs and blood work changes in cats were3

• Depression (n = 29; 69%)

• Hyperphosphatemia (n = 25; 60%)

• Hypocalcemia (n = 22; 52%)

• Vomiting (n = 17; 40%) 

• Hypernatremia (n = 17; 40%)

• Hypokalemia (n = 11; 26%)

• Hyperglycemia (n = 11; 26%)

• Hypothermia (n = 10; 24%)

• Changes in breathing (n = 7; 17%)

• Azotemia (n = 7; 17%)

• Anorexia (n = 7; 17%)

• Hypersalivation (n = 7; 17%)

• Dehydration (n = 7; 17%)

• Weakness (n = 5; 12%)

• Diarrhea (n = 5; 12%)

• Tachycardia (n = 4; 10%)

• Increased alanine transaminase activity (n = 4; 10%)

• Pale mucous membranes (n = 4; 10%)

• Hyperkalemia (n = 4; 10%)

In dogs, the most common clinical signs and blood work changes were3

• Hyperphosphatemia (n = 5; 56%)

• Hypocalcemia (n = 4; 44%)

• Vomiting (n = 4; 44%)

• Diarrhea (n = 4; 44%)

• Lethargy/depression (n =3; 33%). 

Hypokalemia, azotemia, anorexia, tremors and hemoconcentration were present in two (22%) dogs each. Hypernatremia, seizure and acidosis were present in one dog each.3

Monitoring

Monitor electrolyte concentrations and acid-base status until they return to normal. Baseline renal values should be obtained and a urinalysis should be performed to ensure that there is no underlying renal insufficiency. Blood glucose concentrations should also be monitored. The results of a complete blood count are generally unremarkable. Osmolality and osmol gap can provide useful information. Laboratory abnormalities generally return to normal within 24 hours. 

Treatment outline

Treatment is aimed at controlling the electrolyte abnormalities and clinical signs being shown. 

Decontamination. Asymptomatic pets with an oral ingestion can be given aluminum hydroxide. Aluminum salts will bind phosphorus and form insoluble aluminum phosphate. Activated charcoal is contraindicated since it doesn't bind the phosphorus and can potentially contribute to hypernatremia. 

Electrolyte correction. Generally, 5% dextrose or 0.45% sodium chloride in 2.5% dextrose are the fluids of choice for rehydration and the treatment of the associated electrolyte abnormalities at a rate of 1.5 to 2 times maintenance (45 to 60 ml/lb/day), plus fluid deficit and ongoing losses. Oral water should be available and encouraged in patients that are able to safely drink.

Hypernatremia can be treated with the low-sodium fluids. A warm water enema at 5 ml/lb may also be helpful. Animals with chronic hypernatremia (more than 12 hours) will need to have the sodium slowly decreased-no more than 0.5 mEq/hr. Serum sodium concentrations should be monitored every one to four hours until they return to normal.

Hypocalcemia should be treated with calcium gluconate. If hypocalcemia-associated tetany is present, give 50 to 200 mg/kg of calcium gluconate slowly intravenously over 15 to 30 minutes along with electrocardiographic monitoring. If cardiac changes are seen or when improvement in the tetany is seen, the infusion should be discontinued. For stable patients with hypocalcemia, give 150 to 250 mg/kg of calcium gluconate diluted with four times the volume of sterile water subcutaneously every six to eight hours.2

Potassium chloride should be supplemented in fluids of hypokalemic animals, not to exceed 0.5 mEq/hr. Insulin and dextrose therapy can be used to treat severe (> 6 mEq/L) hyperkalemia.4 Hyperglycemia is transient and usually does not warrant treatment. 

Acidosis should be monitored for, but administering sodium bicarbonate is not recommended unless it is severe since the sodium will exacerbate the hypernatremia and hypocalcemia.2 Peritoneal dialysis may be indicated in patients with chronic renal failure, as they will have a decreased clearance of phosphate.5 Hemodialysis can be used to treat hyperphosphatemia, hypernatremia, hypocalcemia and hypomagnesemia.1

Treating clinical signs. Hypotension should be treated with intravenous fluids. Dopamine at a 1 to 3 µg/kg/min constant-rate infusion can be considered in cases that are refractory to fluids alone.6 Seizures can be treated with diazepam. Seizures that are refractory to benzodiazepines can be treated with propofol or barbiturates. Broad-spectrum antibiotic therapy may also be warranted in patients with chronic constipation or megacolon, as they may have compromised gut mucosa and may be at risk for sepsis. 

Summary

Hypertonic phosphate enemas can cause serious and life-threatening signs in cats and dogs such as hyperphosphatemia, hypocalcemia, hypernatremia, cardiac arrhythmias and metabolic acidosis. Intensive care and diligent monitoring are indicated in most cases. Treatment is aimed at correcting electrolyte abnormalities, controlling GI upset, and restoring and maintaining normal hydration. The prognosis in symptomatic animals with preexisting renal or cardiac disease can be poor. 

References

1. POISINDEX editorial staff: Inorganic phosphates. In: POISINDEX System [intranet database]. Version 5.1. Greenwood Village, Colorado: Thomson Reuters Inc, 2014.

2. Donaldson CW. Phosphate enema toxicosis. In: Cote E, ed. Clinical veterinary advisor: dogs and cats. St. Louis: Mosby, 2007;849-850.

3. AnTox Database, Urbana, Illinois: ASPCA Animal Poison Control Center, 2003-2014.

4. Cowgill LD, Francey T. Acute uremia. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. St. Louis: Elsevier, 2005;1745-1746. 

5. Jorgensen LS, Center SA, Randolph JF, et al. Electrolyte abnormalities induced by hypertonic phosphate enemas in two cats. J Am Vet Med Assoc 1985;187(12):1367-1368.

6. Plumb DC. Plumb's veterinary drug handbook. Stockholm: Blackwell, 2008;321-322.

Laura A. Stern, DVM

ASPCA Animal Poison Control Center

1717 S. Philo Road, Suite 36

Urbana, IL 61802

The ASPCA Animal Poison Control Center (APCC) is a 24-hour animal emergency consultation service that provides treatment and diagnostic recommendations to animal owners and veterinarians regarding animal poisoning cases 24 hours a day, 7 days a week, 365 days a year. Since 1978, the veterinary staff at the APCC has experience of handling more than 2 million animal poisoning cases involving pesticides, herbicides, plants, human and animal drugs, heavy metals, and many other potentially hazardous chemicals. A $65 consultation fee may apply. This includes follow-up consultations for the duration of the case. If you think your animal may have ingested a potentially poisonous substance, call (888) 426-4435. Additional information can be found online at www.aspca.org/apcc.