Toxicology of plants (Proceedings)

Lilies (Lilium, Hemerocallis)

Easter lilies (Lilium longiflorum), tiger lilies (Lilium tigrinum), rubrum or Japanese showy lilies (Lilium speciosum and Lilium lancifolium), and various day lilies (Hemerocallis species) have been incriminated in causing acute renal failure and death in cats. The toxic principle is unknown. Even minor exposures (a few bites on a leaf, ingestion of pollen, etc.) may result in toxicosis, so all feline exposures to lilies should be considered potentially life-threatening and should merit aggressive clinical intervention. It should be noted that not all plants with "lily" in the name are members of Liliaceae, e.g. calla lily (Zantedeschia spp. see oxalate-containing plants) or lily of the valley (Convallaria spp., see cardiac glycosides-containing plants).

Affected cats often vomit within a few hours of exposure to lilies, but the vomiting usually subsides after a few hours, during which time the cats may appear normal or may be mildly depressed and anorexic. Within 24 to 72 hours of ingestion, oliguric to anuric renal failure develops, accompanied by vomiting, depression, anorexia, dehydration, and hypothermia; additionally, disorientation, ataxia, facial and paw edema, dyspnea, and seizures have been less commonly reported.

Elevations in blood urea nitrogen (BUN), creatinine, phosphorus and potassium are detectable as early as 12 hours post ingestion. Creatinine elevations may be especially striking, with levels as high as 44 mg/dl reported. In some cases, hypoglycemia and mild liver enzyme elevations may occur. Abundant casts, proteinuria, glucosuria, and isosthenuria are usually detectable on urinalysis within 24 hours of ingestion, reflecting lily-induced damage to renal tubular cells. In severe cases, death or euthanasia due to acute renal failure generally occurs within 3 to 6 days of ingestion.

When initiated within 18 hours of ingestion, decontamination (emesis, oral activated charcoal, and cathartic) and fluid diuresis using lactated Ringer's solution at twice maintenance infusion rate for 48 hours have been effective in preventing lily-induced acute renal failure. Conversely, delaying treatment beyond 18 hours frequently results in death or euthanasia due to severe renal failure. Baseline renal values should be obtained upon presentation and then repeated at 12, 24, 36 and 48 hours.

Because the tubular injury from lily ingestion spares the renal tubular basement membrane, regeneration of damaged tubules may be possible. In severe cases, peritoneal dialysis may aid in managing renal failure until tubular regeneration occurs (10-14 days or longer).

Castor beans (Ricinus communis)

The castor bean plant is used as a decorative plant and oil extracted from the seeds is used in industry and medicine. Other names for castor bean plants are Mole Bean Tree, Wonder Tree, African Coffee Tree, Mexican Weed and Palma Christi; the seeds are sometimes called dog tick seeds. The toxic principle is ricin, a glycoprotein that is one of the most potent plant toxins known.

All parts of the castor bean plant are toxic, but the seeds contain the highest concentration of ricin and are most commonly associated with toxicosis. In humans, ingestion of one to eight seeds is estimated to be potentially lethal. Damage to the seed coat is required in order to allow the ricin to be available for absorption; for this reason, beans that are swallowed whole without being chewed may pass harmlessly through the digestive tract. Because of this, and because ricin has poor oral absorption, deaths from castor bean ingestion are not as common as one would imagine. In a study of the ASPCA National Animal Poison Control Center database between 1987 and 1998, the overall death/euthanasia rate in 98 dogs that ingested castor beans was 9%. The most common clinical signs reported were vomiting (+/- blood; 90%), diarrhea (+/- blood; 51%), depression (45%), anorexia (16%), and abdominal pain (14%). Weakness, hyperthermia, ataxia/tremors/seizures, recumbency/coma, tachycardia, icterus, vocalization and hypersalivation were also noted. Clinical signs generally develop within 6 hours of ingestion, although delays of up to 42 hours post ingestion have been reported. Elevations in hematocrit, WBC, ALT, and/or AST were the most commonly reported clinical laboratory abnormalities; alterations in laboratory values are frequently not seen until at least 12 to 24 hours post ingestion.

Because of the potential for serious toxicosis, any oral exposure to castor beans should be considered an emergency and should treated aggressively. Treatment should include early decontamination (emesis and activated charcoal with cathartic) if possible. Gastrointestinal protectants (sucralfate or kaolin-pectin) should be used as needed. Exposed animals should be closely monitored for at least 24 hours, and fluid therapy using balanced electrolyte solutions should be instituted immediately upon the development of clinical signs. Hypovolemia secondary to massive gastrointestinal fluid and blood losses is possible, so fluid rates should be adjusted as needed based on the severity of clinical signs. Seizures, if present, generally respond to diazepam. Following resolution of gastrointestinal signs, a diet consisting of bland food offered in small, frequent meals should be followed for up to 4 days after vomiting has resolved.

Baseline CBC and serum chemistries should be obtained, and values should be reassessed at 24, 48, and 72 hours in symptomatic animals. Evidence of hepatic damage, based on biochemical values, would indicate that symptomatic therapy for general liver failure (oral antibiotics, lactulose, dietary management, etc) should be instituted. Similarly, significant alterations in renal values should be treated with fluid therapy and supportive care. Repeated monitoring of serum chemistries should be done until values return to normal.

Cycad palms (cycas, zamia)

These ornamental plants are found generally in tropical to subtropical climates, but may also be grown as houseplants in more temperate climates. More recently, 'bonzai' sized cycad palms have been sold in department and home stores throughout the United States, and reports of cycad toxicosis have risen over the last few years. More commonly known as sago palms, the cycads include Cycas revoluta, Cycas circinalis, and Zamia floridana. Of the three known toxins in cycads, cycasin is the one thought to be responsible for the hepatic and gastrointestinal signs generally seen with toxicosis in small animals (neurological syndromes from other toxic principles have been reported in humans and cattle). Most parts of the plant are toxic, but the seeds (nuts) contain a higher concentration of cycasin and are more often associated with toxicosis in small animals. Ingestion of one or more seeds has resulted in severe signs and death in dogs.

In a report of 60 cases of cycad toxicosis in dog, the most common clinical signs included vomiting (+/- blood; 92%), diarrhea (+/- blood; 28%), and neurologic signs (weakness, lethargy, seizures, coma, ataxia; 53%); death or euthanasia occurred in 32% of cases. Similar to castor bean toxicosis, onset of signs may occur as early as a few hours or as late as 3 days. Clinical laboratory abnormalities included elevations in serum bilirubin, ALT, AST, SAP, total protein and WBC, and values may not become abnormal until 24 to 48 hours post ingestion.

Management of ingestion of cycads should be prompt and aggressive, and the protocol is similar to that of castor bean ingestion (i.e. decontamination, g.i. protectants, fluid therapy, monitoring liver/kidney values, etc). Cycad toxicosis carries the potential for significant gastrointestinal blood losses, sometimes necessitating transfusion. Additionally, secondary effects from liver failure, such as hepatic encephalopathy and coagulopathy may develop in severely affected animals. Renal failure has occasionally been reported, most likely as a secondary condition.

Azalea, rhododendron, rosebay (Rhododendron spp.)

Members of the Heath family (Ericaceae) are indigenous to much of North America, especially the eastern U.S, and they include azaleas, rhododendrons, laurels (Kamia spp.), Japanese pieris (Pieris japonica), and Labrador tea (Ledum glandulosum). These plants contain Grayanotoxin (formerly known as andromedotoxins), which affect sodium channels in cell membranes, leading to neurologic, gastrointestinal, and cardiovascular dysfunction. Grayanotoxins are found in the stems, leaves, flowers, and nectar. As few as two leaves may cause serious toxicosis in small animals; humans have been poisoned from honey made from the nectar of these plants.

Clinical signs in dogs and cats include vomiting, diarrhea, abdominal pain, weakness, depression, cardiac arrhythmias, hypotension, shock, cardiopulmonary arrest, pulmonary edema, dyspnea, CNS depression, and seizures. Cardiac arrest is thought to be due to sustained grayanotoxin-induced depolarization in the myocardium. Signs generally occur within 4-12 hours of ingestion and may persist for several days.

Treatment of ingestion of grayanotoxin-containing plants should include decontamination by means of emesis and activated charcoal with a cathartic. When large numbers of leaves have been ingested, gastric lavage may be indicated; some cases of ingestion of large numbers of intact leaves by dogs have necessitated gastrotomy. Careful monitoring of heart rate, heart rhythm, and blood pressure should be instituted. A variety of tachy- and brady-arrhythmias may be observed, so it is imperative in these cases to "treat the patient, not the poison." Atropine at pre-anesthetic doses (i.e. 0.02 mg/kg) should be used in cases of significant bradycardia (heart rate <60 bpm); lidocaine may be needed in cases of sustained tachycardia. Intravenous fluid therapy is important to counter hypotension, and in many cases, IV fluids may be useful in mitigating cardiac arrhythmias. Rarely, dopamine or norepinepherine may be necessary when fluid therapy is ineffective in maintaining normal blood pressure. Seizures generally respond to diazepam. Treatment should be continued until normal neurologic, gastrointestinal, and cardiovascular function return. No significant clinical laboratory abnormalities are expected in animals with no prior health problems.

In cases where confirmation of toxicosis is required, grayanotoxin measurement may be performed on GI contents, urine, and feces; analysis is currently available from the California Veterinary Diagnostic Laboratory System at U-C Davis (530-752-6322).

Chinaberry (Melia azedarach)

Chinaberry trees have worldwide distribution and are particularly common in the southern U.S. and Hawaii. Other names for this plant include white cedar, pride-of-India tree, bead tree, Japanese bead tree, and Texas umbrella tree. The plant produces small berry-like fruit that are most commonly associated with toxicosis, but the bark, flowers and leaves are also toxic. The plant has two toxic principles: a neurotoxin variously termed meliatoxin, azadarin, or mangrovin and an as-yet-unidentified gastrointestinal toxin. Poisonings in humans have occurred following ingestion of as few as 6 fruit, so any reported oral exposure in small animals should be considered an emergency.

Signs of Chinaberry toxicity in dogs include vomiting, hypersalivation, diarrhea (+/- blood), stranguria, abdominal pain, depression, ataxia, seizures, coma and death. Bradycardia, tachycardia, cyanosis, dyspnea, and sudden death have also been reported. Signs generally occur within 1to 8 hours of ingestion. Severely affected animals rarely survive beyond 48 hours after the onset of clinical signs.

Management of Chinaberry ingestion should include aggressive decontamination (emesis or gastric lavage followed by activated charcoal with cathartic) and monitoring of gastrointestinal and cardiovascular status. Gastrointestinal protectants, intravenous fluid therapy, and other supportive care including monitoring of cardiac status should be instituted. Treatment of cardiovascular abnormalities should be done as needed. The use of atropine to treat bradycardia should be done judiciously, as atropine may exacerbate stranguria resulting in urinary tract obstruction. Seizures generally respond to diazepam or barbiturates. Yohimbine has been recommended in cases of profound collapse and coma, but yohimbine should be used with care due the potential for stimulation of seizure activity. Baseline clinical laboratory values should be obtained and repeated in 24 and 48 hours. Symptomatic care for renal or hepatic impairment should be instituted as needed.

Cardiac glycoside-containing plants

Over 400 different cardiac glycosides have been identified in various plants, the most recognizable being digitalis, which is used medicinally. This group includes (but is not limited to) oleander (Nerium oleander), lily-of-the-valley (Convallaria majalis), foxglove (Digitalis purpurea), certain milkweeds (Aesclepias spp.), and squill (Virginea maritima). The list of cardiac glycoside-containing plants includes wild-growing and cultivated plants; some, e.g. foxglove, are widely used as landscaping plants. In most cases, all parts of the plant are toxic, whether green or dry (humans have been poisoned from eating foods cooked over fires fueled by oleander). Because even small amounts of plant material may cause significant clinical signs, all exposures should be dealt with immediately.

Clinical signs generally develop within several hours of ingestion and signs may persist for 1-3 days after removal of plant material from gastrointestinal tract. Signs generally are referable to the gastrointestinal tract and cardiovascular system, although local contact irritation may occur on skin or mucous membranes). Signs include abdominal pain, vomiting, anorexia, diarrhea (+/- blood), weakness, cardiac arrhythmias, hypotension, hypothermia, dyspnea, ataxia, tremors, coma, and death. Alterations in serum potassium levels (increased in early stages of toxicosis, decreased in late stages) have been reported.

Management of cardiac glycoside toxicosis is similar to that for digoxin overdoses. Decontamination via emesis or lavage followed by activated charcoal may be instituted in asymptomatic animals. Animals displaying clinical signs should be treated symptomatically. Fluid therapy will replace fluid losses from vomiting and diarrhea as well as provide cardiovascular support. Tachycardia, bradycardia, or other arrhythmias should be treated as needed. In severe toxicoses, the use of anti-digoxin antibody fragments (FAB, Digibind®) to bind the circulating cardiac glycoside should be considered, as this drug has been shown to be effective in treating foxglove, oleander, lily-of-the-valley and squill poisoning. By removing the glycoside from the circulation, this product can result in rapid improvement of clinical signs in animals displaying serious arrhythmias. Digibind® can usually be obtained from human hospital pharmacies. The main drawbacks are the high price of the drug and the difficulty in calculating the necessary dose of Digibind®, as measurement of serum glycoside levels are usually unavailable (dosage is based on the level of circulating glycoside, not on the size of the animal).

Oxalate-containing plants

Ingestions of plants containing insoluble oxalates are some of the most commonly managed small animal plant "emergencies." Plants involved include Dieffenbachia spp. (dumb cane, mother-in-law's tongue, etc.), Caladium spp. (mother-in-law plant, elephant ear, etc.), Calla palustris (water dragon), Monstera spp. (Swiss cheese plant, cutleaf philodendron, Mexican breadfruit, etc), Philodendron spp. (various philodendrons), Spathiphyllum spp. (Peace lily, spathe flower, snowflower, etc.), Syngonium spp. (African evergreen, arrowhead vine, etc.), Xanthostoma spp. (spoon flower, Indian kale, etc.), and Zantedeschia spp. (Calla lily).

These plants contain calcium oxalate needles (raphides) arranged in bundles within special cells throughout the plant. When the cells are disrupted by chewing, the raphides are forcibly ejected into the adjacent mucous membranes; the irritation from these crystal is enhanced due to release of local release of histamine and kinins in response to proteolytic enzymes released from damaged cells. The result is irritation and edema of the oral mucosa.

Onset of signs is usually immediate, although some cases may have delayed onset of up to a few hours. Signs include hypersalivation, oral and perioral edema, local pruritus, tongue flicking and pawing at the mouth; more severe cases may display vomiting, dysphagia, dysphonia, laryngeal edema (+/- dyspnea), abdominal pain, diarrhea, gastritis and enteritis. Ocular or dermal irritation is also possible. In the vast majority of cases, signs will be relatively mild and serious systemic signs would not be expected. Signs generally resolve with conservative treatment within 2 to 24 hours.

Management includes rinsing of the oral cavity with cold water or milk for mild exposures. Gastrointestinal protectants (e.g. kaolin-pectin, aluminum hydroxide suspension, sucralfate) may be used to help prevent gastric irritation from ingested leaves. Antiemetics (e.g. metaclopramide) may be used to control vomiting, and analgesics (e.g. butorphanol) may be used in cases where oral or abdominal discomfort is pronounced. Fluid therapy is rarely needed, although dehydration from protracted vomiting may necessitate fluid supplementation. In cases with severe oral edema, maintenance of a patent airway is important, and corticosteroids may assist in lessening pharyngeal edema. The prognosis is usually excellent in dogs, cats and birds, although rodents may have more serious effects due to their inability to vomit the offending plant material.

Macadamia nuts (Macadamia integrifolia and M. tetraphylla)

Macadamia nuts are a popular snack and party food that have been associated with toxicosis in dogs following accidental ingestion. The toxic principle is unknown. Clinical signs have occurred in dogs ingesting as little as 3.3 g macadamia nuts per kg body weight. Signs of macadamia nut toxicosis generally occur within 12 hours of ingestion and include depression (31%), vomiting (21%), ataxia (17%), tremor (17%) and hyperthermia (7%). Other reported signs include abdominal pain, rear leg weakness/lameness, recumbency, and muscle rigidity. Signs are generally self-limiting and deaths have not been reported. Treatment should include to decontamination and supportive care. Most dogs return to normal within 48 hours.

Poinsettia (Wuphorbia pulcherrima)

Rumors of the toxic potential of poinsettias have been largely exaggerated. Members of the Euphorbiaceae family have the potential to cause oral and gastrointestinal irritation, but ingestion of these plants rarely results in serious clinical signs. Dogs and cats that nibble poinsettia plants may experience oral discomfort, vomiting and/or diarrhea, but are unlikely to need more than supportive care.

Marijuana (Cannabis sativa)

Because marijuana is an illicit drug in most states, obtaining honest, accurate histories on marijuana exposures can sometimes be challenging. Marijuana contains a large variety of cannabinoids, most notably tetrahydrocannabinol (THC), that produce CNS depression. Small animals are especially sensitive to marijuana, and even relatively small amounts may cause significant signs.

Signs of marijuana intoxication include depression, somnolence, ataxia, mydriasis, nystagmus, bradycardia or tachycardia, tremors, urinary incontinence, hypothermia, and, rarely, coma. Hyperexcitability and seizure have occasionally been reported. Signs frequently persist for 36 hours or more following ingestion.

Treatment consists of decontamination (emesis or lavage followed by activated charcoal and cathartic). Animals should be continuously monitored for hypothermia, cardiac abnormalities, or respiratory depression and treated as indicated. Diazepam is generally helpful in hyperexcitable or seizuring animals. Fortunately, most marijuana exposures are rarely life threatening, and animals generally will make a full recovery when given good supportive care.