Ricin Exposure Treatment & Management

Emergency department (ED) management begins with universal precautions and the ABCs (airway, breathing, and circulation); a “D” may be added for decontamination (including the removal of garments). If the history and presenting findings suggest that ingestion is possible, gut decontamination should be considered as well.

Treatment depends on the route of exposure. Treatment is supportive, and no antidote for ricin is available. All symptomatic patients should be admitted to the hospital. After ingestion and inhalation, the clinical course typically progresses over 4-36 hours, and monitoring in an intensive care unit (ICU) may be warranted. Children with severe systemic toxicity should be transferred to a center capable of handling critically ill children. This should occur after the child has been stabilized and whole-bowel decontamination initiated.

Because there is no definitive antidote for ricin poisoning, the only effective way of managing ricin toxicity is to prevent it. Candidate vaccines and ricin inhibitors (eg, pteroic acid, neopterin, pterin tautomer, and guanine tautomer) are being investigated either as antidotes or as means of facilitating immunotoxin treatment. Some promising results have been obtained; however, vaccine trials still require additional testing for safety and efficacy.

Universal precautions must be strictly adhered to at all times. The risk of secondary aerosolization is minimal. Protective masks, which are effective in preventing toxicity, should be used when an overt aerosol attack is suspected.

ABCs

The first priority in treating a patient with castor bean poisoning is to establish that the patient’s airway is patent and that breathing and circulation are adequate. Supportive care based on clinical symptoms is the primary therapy.

Any symptomatic patient should be admitted and monitored, and aggressive intravenous (IV) volume resuscitation should be initiated. Hypotension should be treated with isotonic fluids and packed red blood cells as needed. A vasopressor-type agent (eg, dopamine or norepinephrine) should be employed when needed.

Decontamination

Decontamination begins by removing garments and cleaning the body. If available, a 0.5% sodium hypochlorite solution should be used, with a contact time of 15 minutes. It should not be instilled into open abdominal, brain, or spinal cord injuries or into the eyes; however, it can be instilled into noncavity wounds and then removed via suction into disposable containers. This discarded solution is neutralized and nonhazardous in 5 minutes.

To make a 0.5% sodium hypochlorite solution, mix 1 part bleach and 9 parts water. Make it fresh daily with a pH in the alkaline range. In the absence of this solution, copious amounts of soap and water may be used.

Care with specific routes of exposure

For dermal exposure, a weak sodium hypochlorite solution (0.1-0.5%), soap and water, or both typically suffice to decontaminate the skin.

For gastrointestinal (GI) exposure, institute gastric decontamination with superactivated charcoal and volume replacement. Laboratory evaluation should include chemistry panels, a complete blood count (CBC), a liver function panel, blood urea nitrogen (BUN) and creatinine levels, urinalysis, and blood type and screening.

For percutaneous exposure, treatment should be based on excision of the injection site, if possible, within the shortest amount of time. Baseline laboratory information should be obtained, including arterial blood gas values and fibrinogen. Although antibiotics play no role in the treatment of ricin, withholding such therapy in an acutely septic-appearing patient would be difficult. Antibiotics may serve to prevent infection resulting from the percutaneous mechanism. Tetanus immunization status should be updated if unknown.

For aerosol or pulmonary exposure, standard critical care treatment should be directed toward acute lung injury and pulmonary edema. A low threshold should be maintained to secure the patient’s airway and ensure adequate oxygenation and ventilation. A chest radiograph, which may show infiltrates, should be obtained. The clinical course progresses despite antibiotic therapy.

The only post-exposure measure that is effective against pulmonary ricinosis is passive immunization with anti-ricin neutralizing antibodies. The efficacy of this antitoxin treatment depends on antibody affinity and the time of treatment initiation within a limited therapeutic time window. Small-molecule compounds that interfere directly with the toxin or inhibit its intracellular trafficking may also be beneficial against ricinosis. Another approach relies on the co-administration of antitoxin antibodies with immunomodulatory drugs, thereby neutralizing the toxin while attenuating lung injury. Immunomodulators and other pharmacological-based treatment options should be tailored according to the particular pathogenesis pathways of pulmonary ricinosis. ^[16]

Whole-bowel irrigation

In theory, rapid elimination of the bean from the GI tract before erosion of the outer shell may decrease or prevent the release of potent toxins. Accordingly, whole-bowel irrigation (WBI) has been suggested as a means of ensuring rapid and complete decontamination of the GI tract; however, the clinical use of WBI has not been demonstrated.

WBI is accomplished by continuously instilling a polyethylene glycol electrolyte lavage solution through the GI tract until the effluent from the rectum is clear or all of the beans have been recovered. Inserting a nasogastric tube and setting a continuous flow rate will accomplish WBI best. Irrigation rates vary according to age, as follows:

• Age 0-5 years - Flow rate, 500 mL/h
• Age 6-12 years - Flow rate, 1000 mL/h
• Age > 12 years - Flow rate, 1500-2000 mL/h

It is advisable to consult with a medical toxicologist at the nearest regional poison control center before undertaking WBI.

Further inpatient care

IV fluids should be continued at a rate that maintains adequate hydration and replacement of electrolytes. Beans should be counted to ensure complete recovery. Patients should remain under observation for at least 4-6 hours; after this period, they may be safely discharged if they are asymptomatic. Antispasmodics, such as loperamide, are contraindicated.

Surgical consultation for local excision and removal is warranted for parenteral exposures when a retained foreign body is located.

All exposures should be reported to the regional poison control center. The American Association of Poison Control Centers (AAPCC) is the only national organization currently tracking all potentially poisonous ingestions and may be helpful in bean identification. Expert consultation with a trained toxicologist is also recommended and can be obtained at the regional poison control center.

To minimize the risk of accidental ingestion of plant toxins such as ricin, efforts should be made to keep all potentially poisonous and injurious plants and plant-related products away from children. Homes should be purged of all potentially toxic plant items, just as they are purged of medications and cleaning supplies. In addition, children should be specifically instructed never to eat wild plants, beans, or berries.

For a biologic attack involving ricin, the only effective management is prevention; unfortunately, no prophylaxis exists. In an aerosol attack, protective masks are effective in preventing toxicity and should be used.

Currently, investigations of vaccines are ongoing. Candidate vaccines include RVEc (developed by the US Army Medical Research Institute of Infectious Diseases) and RiVax (Soligenix, Princeton, NJ). ^{[17, 18, 19, 20]} RVEc has been tested in human volunteers, who subsequently developed antibodies to the toxin. However, two of the 10 volunteers experienced severe adverse reactions. The study was discontinued and a reliable method of determining antigen concentration is under development. ^[21]

RiVax been found to be safe in healthy human volunteers, in whom they stimulated the production of antibodies. ^{[22]   [23]} A Phase 1B study of RiVax has also been successully completed. ^[24] In animal testing, rhesus macacques vaccinated with RiVax were protected against ricin aerosol exposure. ^[25] Further human testing is necessary.

Ricin inhibitors are also being studied. Certain 6-substituted pterins (eg, pteroic acid) have shown promise in this setting. A study by Pruet et al suggested that 7-carboxy pterin and derivatives thereof may prove useful as part of a program to make effective ricin toxin A chain inhibitors. ^[26]

O’Hara et al found that passive administration of 10 µg of GD12—a murine monoclonal immunoglobulin G (IgG) antibody to an epitope on the A chain of ricin toxin—or a chimeric derivative (cGD12) to mice via intraperitoneal injection protected the animals against a systemic ricin challenge. ^[27] After exposure, the two antibodies, administered up to 6 hours after toxin challenge, were each capable of rescuing mice from toxin-induced death, suggesting that GD12 might have both prophylactic and therapeutic potential for ricin intoxication.