Low Toxicity

Red squill is a botanic cardiac glycoside derived from the plant Urginea maritima, or sea onion. It is marketed as Deathdiet, Rat Snax, Rat Nip and has a very bitter taste. Toxicity is related to the ability to block sodium-potassium adenosine triphosphatase. Duration of onset is from 30 min to 6 h. Because of its potent emetic properties, patients present with nausea, protracted vomiting, diarrhea, and abdominal pain. Massive ingestion causes hyperkalemia, ventricular irritability with dysrhythmias, and death.

Treatment is similar to that for digoxin toxicity using antiarrhythmics and atropine as indicated. In severe poisoning, an infusion of 10 vials of digitalis-specific antibody (Fab) is recommended. Activated charcoal should be given.

Warfarin-type (3a-acetonylbenzyl-4-hydroxy-coumarin) anticoagulants (Kill-Ko, Rat Busters) were the first rodenticides. They are commonly disguised as yellow corn meal or rolled oats and are among the most commonly ingested substances in the United States. It is important to differentiate these from the more toxic superwarfarins. Most warfarin ingestions are insignificant accidental poisonings and do not cause any bleeding problems.

A single acute exposure results in virtually no bleeding in children or adults. Toxicity requires large amounts in a single exposure or a repetitive exposure over several days. Lipid solubility of the individual anticoagulant determines its elimination half-life. Warfarin's biologic half-life is approximately 42 h. These anticoagulants inhibit, almost immediately, the synthesis of Vitamin K.,-dependent clotting factors II, VII, IX, and X. Coagulopathy develops when the level of at least one critical coagulation factor falls to 25 percent of normal.26 This time interval is approximately 12 to 18 h.

Ingestion of a single mouthful is usually nontoxic, and therapy is not necessary. If potential toxicity is suspected, therapy consists of activated charcoal and a cathartic, with baseline prothrombin time (PT) and partial thromboplastin time (PTT) determinations to be repeated in l2 to 24 h. If the PT is greater than twice normal and the risk of bleeding exists, vitamin K1 (phytonadione) administration is indicated. The suggested oral dose is 1 to 5 mg in children and 20 mg in adults administered two to four times daily due to its short half-life and a PT is checked every 4 h initially, then every 24 h until stable.

Second-generation superwarfarins and the indandione derivatives were introduced when rodent resistance to warfarin began to appear. They are responsible for approximately 80 percent of human rodenticide exposures reported in the United States.1 Their mechanisms are the same as those of the warfarins, but they are more potent, have more prolonged anticoagulant activity, and therefore have the potential to be highly toxic. Poisonings involving the indandione derivatives pindone, diphacinone, and chlorophacinone have toxic and clinical characteristics similar to those of the superwarfarins.

The superwarfarins include the 4-hydroxy-coumarins brodifacoum, diphenacoum, and bromadiolone. These are readily available over the counter as grain-based bait. Since the biologic half-life of brodifacoum is approximately 120 days, a single ingestion may result in marked anticoagulation effects from weeks to months. Acute intentional or repeated ingestions can cause severe bleeding. After intentional ingestions, adults often develop a coagulopathy within 24 to 48 h. 24

A single ingestion usually does not result in immediate toxic effects, and an ingestion may or may not be identified by history. Small children and depressed patients having an unexplained coagulopathy should elevate the index of suspicion. Clinical findings of toxicity consist of ecchymoses, hematuria, uterine or gastrointestinal bleeding, gingival hemorrhage and epistaxis, hematomas, and hemoptysis. Their onset, however, may be delayed for several days, and they may persist for several days.

An abnormal PT may identify chronic ingestions or patients who present hours or days after exposure to a long-acting warfarin. Specific serum assays for superwarfarins are available in reference laboratories. Superwarfarins are not detected by warfarin assays. Initial differential diagnosis in the patient with an elevated PT and PTT includes disseminated intravascular coagulation, liver failure, pathologic inhibitors of coagulation, acquired vitamin K deficiency, or ingestion of a vitamin K antagonist. Warfarin abuse must be suspected when no other cause of vitamin K deficiency can be found.

Resuscitation of acute hemorrhage consists of oxygen administration and repletion of volume losses with normal saline or transfusion. Fresh-frozen plasma should be used if bleeding is severe or unresponsive to vitamin therapy. Vitamin K1 can be diluted and administered by slow intravenous infusion, less than 1 mg per minute, to minimize the risk of an anaphylactoid reaction and cardiovascular collapse. Oral absorption takes approximately 2 to 3 h. Because of the extended half-life of the anticoagulant, prolonged therapy with high doses of vitamin K1 may be required to maintain hemostasis. Doses of vitamin K1 should be titrated to effect. Initial doses of 1 to 5 mg in children and 20 mg in adults have been recommended, but doses up to 100 mg per day for 10 months have been reported. 27 The PT is followed every 4 h and then every 24 h.

Treatment of acute ingestion consists of gastrointestinal decontamination. Recent ingestion of amounts greater than 0.1 mg/kg necessitates activated charcoal and a cathartic. Of 110 children having ingested long-acting anticoagulants, only 8 were found to have an elevated PT, but history was not predictive. 24 Hence any patient with a superwarfarin exposure needs PT determinations at 24 and 48 h. If the PT is elevated, high-dose vitamin K 1 is initiated for at least 6 weeks. Discontinuation of vitamin K1 therapy is followed by serial PT determinations to ensure that further therapy is not needed. After initial parenteral therapy, prolonged oral administration for several months may be required as the PT normalizes.

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