Decontamination Scenarios - Fall 2023 PDF

Short Comments (there are other possible approaches for managing these cases; these comments are not all inclusive of you may choose to do in a given case) Learning Objectives: ==================== Carry out exposure assessment. Explain primary methods for gastrointestinal decontamination....

Short Comments (there are other possible approaches for managing these cases; these comments are not all inclusive of you may choose to do in a given case) Learning Objectives: ==================== Carry out exposure assessment. Explain primary methods for gastrointestinal decontamination. Critique the factors that influence the decisions in decontamination approaches. Explain factors to consider related to residues and public health. Cases and Identifiers ===================== ---------------------- ------------- ---------------- **CASE** **Species** **Identifier** 1 - Ibuprofen Dog K9 1 2 - OP Dairy cows BO 1 3 -- OP Beef cattle BO 2 4 -- Ethylene glycol Cat FE 5 -- Monensin Horses EQ 6 -- Bromethalin Dog K9 2 7 -- Vitamin D Alpacas CAM ---------------------- ------------- ---------------- Case 1 (K9 1): Ibuprofen toxicosis in dogs ------------------------------------------ [Background]: Consistently, human medications have topped the list of toxic exposures in animals accounting for about 17% of all reported exposures (APCC). Pain medications, antidepressants, and heart medications are the most common medications reported. Of these, ibuprofen is the number 1 OTC drug reported to the APCC. Dogs are the most commonly reported species followed by cats. Ibuprofen has 100% bioavailability and is highly protein bound with a low Vd. Ibuprofen undergoes extensive metabolism in the liver with significant enterohepatic recirculation. The plasma half-life is 2 to 2.5 hours. [History]: An owner returns home to find her two dogs having ingested an entire bottle (100 tablets) of Advil™. Each tablet contains 200 mg of ibuprofen. According to the owner, the bottle was new and contained all tablets. The bodyweight of the dogs are 40 pounds (Max, 4 years) and 30 pounds (Spike, 2 years). According to the owner, the dogs ate the contents of the entire bottle of ibuprofen between ½ and 1 hour before she returned home. The owner reports to you over the phone that both dogs appear normal. Toxicity for ibuprofen in dogs is as follows: GI signs: single ingestion of 100-125 mg/kg or greater renal damage: \> 175 mg/kg CNS signs (seizures, ataxia, depression, coma) \> 400 mg/kg [Questions]: 1\. What is the first thing that you want to do? Exposure assessment 2\. Perform an exposure assessment. Toxicity for ibuprofen in dogs is as follows: GI signs: single ingestion of 100-125 mg/kg or greater; renal damage: \> 175 mg/kg, CNS signs (seizures, ataxia, depression, coma) \> 400 mg/kg Approach: Bodyweight in kg: 40 pounds = 18.2 kg; 30 pounds = 13.6 kg 100 tablets x 200 mg of ibuprofen: 20,000 mg of ibuprofen (total dose) Possible max dosage per dog: Max: 20,000 mg/18.2 kg = 1,098 mg/kg; Spike: 20,000 mg/13.6 kg = 1,470 mg/kg 3\. What would you do next? Exposure was very high. Recommend bringing both dogs to the clinic ASAP. If long drive to clinic, induce emesis at home first with hydrogen peroxide (0.5 to 1 ml per pound of 3% H2O2). Once presented in the clinic, time since exposure is likely well over an hour; thus, do not induce vomiting. Give multiple doses of activated charcoal and monitor the dogs (renal function). Clinic will likely also include prostaglandin analogs (e.g., misoprostol), IV fluids, antiemetics, and other gastric protectants. Also consider ILE. Case 2 (BO 1): Organophosphate poisoning in dairy cows ------------------------------------------------------ [Background]: The major mechanism of toxicity of OPs is the inhibition of Acetylcholinesterase (AChE), resulting in a net accumulation of Acetylcholine (ACh) and increased stimulation of cholinergic receptors: muscarinic-receptor induced effects (excessive secretions, miosis, bradycardia) and nicotinic-receptor-induced effects (muscle tremors, convulsions, complete muscle paralysis). Typically, clinical signs in an acute case begin within minutes of exposure. Organophosphorus pesticide poisoning in cattle occurs frequently enough that it should be considered as a differential diagnosis in animals presented with signs consistent with cholinergic toxicity. Phorate, the OP responsible for the deaths of these cows, is a restricted use pesticide because of its high toxicity to birds, fish, and reptiles. The reported oral lethal dose 50 (LD50) in rats is 1.6 mg/kg bodyweight. Phorate is rapidly absorbed and distributed; because of its high lipophilicity, it partitions into brain, liver and fat. [History]: Three hundred Holstein animals of a 600-cow dairy located in Kings County in the Central Valley of California were fed a total mixed ration (TMR; individual commodities not available) one morning after milking. After having fed 167cows, the mixer wagon had a flat tire and feeding of the remaining cows was postponed. When the feeder stepped off the truck, he noted several dead cows in the pen he had fed minutes prior. In addition, other cows that had been fed were showing signs of tremors, foaming at the mouth, weakness, inability to stand, and collapse. [Questions:] 1\. What is the first thing that you want to do if you were called to the case right away? stop further exposure, remove feed, stop feeding, consider AC of animals without signs but that have possibly had access to the feed A quick 'heads-up' call to the state animal health office would be warranted because of the possible food contamination, multiple mortalities, and possible carcass issues. If it's a false alarm, no problem. If it's the real deal, then logistical help (diagnostics, labor and finance) could be started Yes I would consider atropine as an antidote and diagnostic. Atropine sulfate is a competitive antagonist of muscarinic cholinergic receptors. Administering a pre-anesthetic dose of atropine (0.02 mg/kg) IV can be used diagnostically. If there is no response to this test dose (improved respiration, decreased salivation, increasing heart rate), it is likely NOT OP poisoning. OP poisonings will require a higher dose to see an effect and AS dosage must be increased at least 10x. Case 3 (BO 2): Organophosphate poisoning in beef cattle ------------------------------------------------------- [Background]: The major mechanism of toxicity of OPs is the inhibition of Acetylcholinesterase (AChE), resulting in a net accumulation of Acetylcholine (ACh) and increased stimulation of cholinergic receptors: muscarinic-receptor induced effects (excessive secretions, miosis, bradycardia) and nicotinic-receptor-induced effects (muscle tremors, convulsions, complete muscle paralysis). Typically, clinical signs in an acute case begin within minutes of exposure. Organophosphorus pesticide poisoning in cattle occurs frequently enough that it should be considered as a differential diagnosis in animals presented with signs consistent with cholinergic toxicity Dichlorvos, the active ingredient of Vapona™, is a restricted use pesticide that must be diluted prior to application according to the label instructions. The reported oral lethal dose 50 (LD50) in rats is 1.6 mg/kg bodyweight. Vapona is rapidly absorbed through the skin and quickly distributed; because of its high lipophilicity, it partitions into brain, liver and fat. [History]: A group of 50 approximately 8-month-old Hereford-Angus cross steers were power washed and then treated with a pour-on insecticide called Vapona™ at approximately 8 AM. Within 3 hours the steers became bloated, with muscle fasciculations, salivation, and respiratory distress. [Questions:] 1\. What decontamination approach would you initiate if called out right away? Try to corral, give activated charcoal (to trap in GI tract when excreted), wash with water and detergent and hope for the best 2\. Would you consider an antidote? If so, why, and which? Depending on facility, atropine is to be considered if there is suspicion of OP/carbamate poisoning. Unlike docile dairy cows, beef can be difficult and dangerous to handle. Crowding some animals into a chute lead-up might be useful to treat animals showing visible signs of intoxication. Asymptomatic animals can be quietly left alone for continued monitoring. As in the dairy case, I would consider 2-PAM if I was confident aging had not yet occurred. Additional washing with soap and water is strongly recommended. NO POWER WASHER (risk for breaking the skin and enhancing dermal absorption). AC would be useless. This incident was from dermal exposure unless compound is re-distributed to the GI tract (would have to look into PK data) 3\. What would you do with any animal that dies? Unlike the multiple dairy deaths, since all steers were alive, a single dead is very valuable for diagnostics and I would strongly encourage immediate submission of whole fresh carcass to D-lab. That being said, if carcass submission is not possible then whole brain on ice (cholinesterase activity determination), whole blood (cholinesterase activity determination). Equally important to submit are suspected tox sources including feed, rumen contents, feces. More is better so consider collecting 'fist full' of kidney, liver, heart, skeletal muscle and urine for immediate deliver on ice to D-lab 4\. What would you have to consider with any surviving animal? In the short term, all survivors are to be monitored for full recovery. As there is only a 1 day meat withdrawal, there shouldn't be a long term residue concern and these steers can continue feeding and growing out to end point in 10-12 months 5\. What do you think might have happened? Pressure washer compromised the dermal barrier removing skin oils and physically irritating the skin and altered the absorption kinectics. Can't rule out mixing concentration error or other anticholinergic parasiticide that steers were exposed to at an earlier time point- wormer, feed contaminant? Case 4 (FE): Ethylene glycol poisoning in a cat ----------------------------------------------- [Background]: Ethylene glycol poisoning is a very serious and potentially lethal poisoning in cats (and dogs). Ethylene glycol is a small, colorless, odorless, hydrophilic molecule that is the common ingredient of antifreeze. The ready-to-use antifreeze in brake and transmission fluids contains approximately 50% ethylene glycol. EG is rapidly absorbed from the GI tract. Once absorbed, EG is eliminated unchanged in urine; however, some of the EG is metabolized to a number of metabolites that are responsible for the toxic effects. The lethal dose of undiluted ethylene glycol is 1.5 ml/kg. [History]: A 2- year old, spayed female cat weighing 4.1 kg presented after she was found in the garage licking her lips and sitting next to a puddle of radiator fluid that contained ethylene glycol. Before presentation, the owners administered 3% hydrogen peroxide to induce vomiting, but it was unsuccessful. At presentation approximately 1 hour later, the cat was alert and responsive with a normal PE. A point-of-care EG test was positive. [Questions]: 1. What additional decontamination steps would you take in this case? in this case, no additional decontamination steps would be recommended; EG is rapidly absorbed (mostly within 15-20 min) and now ingestion is well over 1 hour in the past; thus emesis and gastric lavage are of no more benefit; AC is of little benefit for alcohols and is not recommended for EG 2. Estimate how much radiator fluid the cat would have had to ingest/lick to consume the lethal dose? Assume a 50% concentration of EG in the radiator fluid. \[lethal dose: 1.5 ml/kg = 6.15 ml for 4.1 kg cat for undiluted =\> 12 ml for 50% fluid. This is about ¾ of a tablespoon which is an possible amount for a cat to ingest\] 3\. Antifreeze products contain a fluorescent dye to help mechanics detect radiator leaks. Would that be helpful to you as a veterinarian? \[Many antifreeze products contain fluorescein (a green or red dye depending on the pH of the medium), which fluoresces UV light. Sometimes the dye may be detected in urine or vomitus using a Wood's lamp and examination of the paws, mouth and face may be useful. This is particularly helpful if there is no good history of exposure\] Case 5 (EQ): Monensin poisoning in a horse ------------------------------------------ Background: Monensin, an ionophore antibiotic, is approved for use by the U.S. Food and Drug Administration as a feed additive for certain classes of ruminants and poultry. Unfortunately, unintended exposure can and does occur in other species with dire consequences. Horses are exquisitely sensitive to monensin; a reported median lethal dose (LD50) of 2--3 mg/kg for horses is substantially lower than the LD50 of 21.9--80 mg/kg that has been estimated for cattle. The pharmacokinetic profile of monensin has been evaluated in several species including cattle and poultry; however detailed information does not exist for horses. Monensin is readily absorbed following oral administration. Following gastrointestinal absorption, monensin is converted to several metabolites by the liver; metabolism rate is slowest in horses. Excretion is almost exclusively in the feces. History: A group of 25 adult Quarter horses broke into a shed and had access to feed that was supplemented with 800 g/ton (880 ppm) of monensin. The horses had free access to approximately 200 pounds of feed. You are called out to the farm within 1 hour of the suspect exposure. At that time, none of the horses show clinical signs. [Questions:] 1. You are called out right away. Explain the initial steps you will take. stop further exposure, remove feed, move horses away from feed; consider AC to all animals assuming all had access on AC: Since toxicant dose is typically unknown, activated charcoal is administered at 1-3 g/kg. In cases of agents that undergo enterohepatic circulation, repeated doses of activated charcoal is indicated at a loading dose of 1-2 g/kg activated charcoal, followed by 0.25-0.5 g/kg every 1 to 6 hours. If activated charcoal is administered with a cathartic, such as sorbitol, the cathartic is not repeated following the initial dose. 2\. Do you have enough information to conduct an exposure assessment? If so, estimate the worst-case scenario. estimate bw of quarter horse: 800 pounds = 363 kg. Estimated ingestion of feed: 3% of bw \~ 10 kg (would be absolute max and unlikely) 800 g/t = 880 ppm. 880 mg/kg à 8,800 mg in 10 kg 8,800 mg/363 kg = 24 mg/kg Alternative approach: assume equal portions consumed by each horse which equals 3.6 kg feed/horse (200lbs feed=91kg.). 3.6 kg of feed contain 3,168 mg of monensin. In a 363 Kg horse that\'s 8.8 mg monensin/kg bw horse. Well above the LD50. 3\. If you decide to give AC, describe how much and how you would administer it. 4\. What would you have to consider with any surviving animal? cardiac abnormalities can persist in horses following recovery from acute ionophore toxicosis Case 6 (KP 2): Bromethalin poisoning in a dog --------------------------------------------- History: A 4-year-old, 25 kg, spayed female mixed breed dog ate one, but possibly 2 bricks of rat bait that contained 0.01% bromethalin. Each brick weighed approximately 1 oz (28.5 g). The owner calls you (her vet) for advice. She lives approximately 1 hour driving distance from your clinic. The bricks were placed in the yard and exact time of exposure is not known. The owner is able to induce partial emesis with 3% hydrogen peroxide at home; the vomitus does contain flecks of green material. Background: The neurotoxic rodenticide bromethalin has become increasingly popular since 2011 when new Environmental Protection Agency regulations went into effect restricting the sale and use of 2^nd^-generation anticoagulant rodenticides. Bromethalin is the active ingredient in many commercial rat and mouse baits (0.01% blocks, pellets, and place packs) as well as worm-shaped mole baits (0.025%). Products include Rampage^®^, Fastrac^®^, Top Gun^™^, Trounce^®^, Victor^®^, and Talpirid^®^. Although the reported minimum lethal dose in dogs is 2.5 mg/kg, the ASPCA case records include a fatality in a dog that ingested 0.95 mg/kg bromethalin. In cats, the reported minimum lethal dose is 0.45 mg/kg. The APCC case records have documented clinical signs of toxicosis in cats ingesting 0.24 mg/kg bromethalin. Bromethalin is rapidly absorbed and then metabolized in the liver; it undergoes considerable enterohepatic recirculation; bromethalin and its primary toxic metabolite are very lipophilic and stored in fat. The half-life of the toxic metabolite is 5 days. Bromethalin targets the central nervous system (CNS) and is associated with two types of presentation: a convulsant syndrome characterized by muscle tremors, hyperexcitability, hyperthermia, and seizures; and a progressive paralytic syndrome involving ascending ataxia/paresis, proprioceptive deficits, and CNS depression. Severely affected animals develop a diminished or absent deep pain response, ascending paralysis, and stupor or coma. High dosages cause rapid onset of signs while lower dosages cause delayed onset of 48 hours or longer. In dogs, higher dosages tend to result in the convulsant syndrome while lower dosages usually cause the paralytic syndrome. Most cats develop the paralytic syndrome regardless of dosage ingested. [Questions:] 1\. Conduct and exposure assessment and interpret the result. Conduct an exposure assessment. 1% = 10,000 mg/kg; 1% = 1 g/100 g; 0.01% = 0.01 g/100 g = 10 mg/100 g 10 mg/100 g = X/28.5 g è 2.85 mg of bromethalin consumed in 1 brick, but possibly 2 bricks 5.7 mg/25 kg = 0.23 mg/kg Asessment: high, potentially lethal exposure 2\. Shortly after arrival in your clinic, the dog defecates, and feces also contain green material resembling the suspect rodenticide. How do you proceed with decontamination? can be assumed that the dog consumed more of the rodenticide much earlier that it already is in feces apomorphine IV at 0.03 mg/kg to produce further emesis; but depends on time since exposure activated charcoal multi-dose is important: 1 mg/kg every 4-6 h for 2-3 days ILE IV: 20% Intralipid: 1.5 ml/kg given over the first 20 min followed by 0.38 ml/kg/min for 60 min. Case 7 (CAM): Vitamin D poisoning in alpacas -------------------------------------------- Background: Vitamin D supplementation to camelids is common practice during periods of reduced sunlight in North America. Vitamin D requirements for alpacas and llamas should be at least 30 IU/kg bodyweight in order to prevent rickets problems. A single parenteral dose of Vitamin D (1,000 to 2,000 IU/kg bw) provides adequate vitamin D to crias for up to 11 weeks. History: An 8-day old, 7.5 kg, male, Suri alpaca cria received 100,000 IU of vitamin D orally daily for the first five days of life by the owner. The cria developed anorexia and was treated with 7,500 IU of vitamin D3 by sc injection, camelid plasma, and antibiotics. The cria did not improve and was presented to the Veterinary medical center for anorexia, lethargy, and anuria. [Questions:] 1. Conduct an exposure assessment. 100,000 IU for 5 days = 500,000 IU total 66,000 IU/kg bw total in 5 days 13,333 IU/kg bw/day for the first 5 days of life Then an additional 7,500 IU of vit D3 on Day 5 (SQ) 7,500 IU : 7.5 kg = 1000 IU/kg This cria received a 36-fold excess above the high end of the currently recommended dosage range. 2. What would be your decontamination approach? Too late for AC (and no oral exposure) Vitamin D metabolism -- by time of presentation likely metabolized Elimination of vitamin D from the body is slow 3. Would you consider ILE? Discuss the properties of vitamin D and whether it would be a suitable candidate for ILE efficacy in removing/redistributing vitamin D. Yes, I would look into the possibility since it has been used for dogs with vitamin D poisoning. logP (25)D3 = 6; based on that it would be suitable for ILE based on the lipid sink theory 4. If you decide on ILE, what dosing regimen would you use? ILE using human or small animal dosage: 1.5 ml/kg IV bolus, followed by 0.25 ml/kg/min IV over 1 h 4\. What is the primary goal of treatment in vitamin D poisoning cases? rapidly decrease hypercalcemia and hyperphosphatemia stimulate urine production can consider steroids, furosemide, bisphosphonates, and phosphate binding agents to treat hypercalcemia, but no data for camelids Basic info for vitamin D: Since North American cria consuming milk likely have limited intake of vitamin D and are rapidly growing, it has been suggested that supplementation during periods of reduced sunlight and UV radiation is necessary to prevent vitamin D deficiency. Van Saun currently recommends daily vitamin D intake of 30 IU/kg to maintain requirements for most camelids. t½ of (25)OH-D3 (calcidiol) is 2-3 weeks (in humans and lab animals; not established for camelids). The long half-life is sustained by cholecalciferol released from stores in muscle and adipose, which reenter the circulation and become 25-hydroxylated. The long half-life of the vitamin D system is also evident by the relatively small, 20% decline in serum calcidiol through the "vitamin D winter", when solar-derived ultraviolet B radiation is minimal through half the year, to the point of not making it impossible to produce vitamin D in the skin (or to sustain or acquire a tan). Hepatic lipidosis is associated with high mortality in camelids and is characterised by lipid accumulation in the liver. Potential precipitating factors include infectious disease, parasitism, stress, poor nutrition and possibly obesity. Disease onset may be acute. **[References:]** (unit error/math error led to this major poisoning! (current paper for the case history) (ILE in dogs with vitamin D tox) **[\ ]** **[References:]** Bolfer, Luiz, et al. \"Treatment of ibuprofen toxicosis in a dog with IV lipid emulsion.\" Journal of the American Animal Hospital Association 50.2 (2014): 136-140. Puschner, B., et al. \"The diagnostic approach and public health implications of phorate poisoning in a California Dairy Herd.\" *J. Clinic. Toxicol* (2013): 2161-0495. Simple overview of EG poisoning in cats: Video of horses with monensin poisoning: Lawsuit was settled in Oct 2018: Gerspach, C., et al. \"Acute renal failure and anuria associated with vitamin D intoxication in two alpaca (Vicugna pacos) cria.\" *Journal of veterinary internal medicine* 24.2 (2010): 443-449. Romano, Megan C., Alan T. Loynachan, Dave C. Bolin, Uneeda K. Bryant, Laura Kennedy, Mike S. Filigenzi, Birgit Puschner, Robert H. Poppenga, and Cynthia L. Gaskill. \"Fatal bromethalin intoxication in 3 cats and 2 dogs with minimal or no histologic central nervous system spongiform change.\" *Journal of Veterinary Diagnostic Investigation* 30, no. 4 (2018): 642-645. Asokan, Vibha R., et al. \"Organophosphate intoxication in 2 dogs from ingestion of cattle ear tags.\" *Journal of Veterinary Emergency and Critical Care* (2019).