Toxicities are a common reason for small animals to be presented for emergency care. The ASPCA Animal Poison Control Center reported the top 10 toxicities of 2018 to be:
1. Over the counter medications
2. Human prescription medications
3. Food
4. Chocolate
5. Veterinary products
6. Household items (e.g., glue, cleaning products)
7. Rodenticides
8. Insecticides
9. Plants
10. Garden products
The clinical presentation for animals exposed to toxins can be variable, with recent exposure or ingestion in currently asymptomatic animals requiring a different approach to symptomatic patients. Likewise, the approach to treatment will be influenced by the quantity ingested, the pharmacokinetic profile of the toxin, and the organ systems that will be affected. This session will review traditional and emerging therapeutic options for toxicities in animals.
Lipid Rescue
In the last decade, there has been growing interest and experience in the use of intravenous lipid emulsion administration (ILE) for toxicities in both human and small animal medicine. A 20% lipid solution is most commonly used in veterinary patients, which is a convenient product to stock given its long shelf life and ability to be stored at room temperature. The exact mechanism of ILE is not known with certainty. The most popular theory describes the creation of a lipid sink within the plasma component. Lipophilic drugs are able to sequester into this lipid sink and thereby reducing the effect concentration of the toxin in tissues. The lipophilicity of the drug, therefore, strongly impacts the effectiveness of ILE based on this theory. An alternative mechanism of action relates to improved myocardial performance by providing a readily available source of free fatty acids, the preferred substrate for the myocardium. A large number of drugs may be amenable to ILE, including, but not limited to, local anesthetic agents, beta blockers, calcium channel blockers, NSAIDs, parasiticides, and some chemotherapeutic agents. The ILE dosing scheme frequently used in the veterinary literature is an initial bolus of 1.5 mL/kg IV and then a constant rate infusion of 0.25–0.5 mL/kg/min for 30–60 min. If the patient remains symptomatic, an additional dose may be provided if gross lipemia is not appreciated on a spun down hematocrit tube. Potential adverse effects of ILE in people include fat emboli and ‘fat overload syndrome,’ characterized by hypocoagulability, hyperbilirubinemia, hyperlipidemia, and hepatosplenomegaly. The current evidence base suggests that ILE is well tolerated by dogs and cats, with few serious adverse effects being described. It is important, however, to administer ILE with strict asepsis given the higher potential for ILE to support bacterial growth.
Extracorporeal Drug Removal
In patients with ingestion of severe drug overdose, immediate decontamination should be recommended if possible. Due to the high oral bioavailability and the rapid gastrointestinal absorption of many drugs, however, decontamination may not be effective if performed not immediately following ingestion. Extracorporeal drug removal would then represent a valuable intervention for severe overdoses. The use of extracorporeal purification specifically for drug poisoning has existed in the veterinary clinical practice for over 30 years. Unfortunately, the evidence remains mostly limited to reviews, opinions, and case reports, which are susceptible to biases and confounders. Randomized trials and comprehensive systematic reviews are inexistent, and this limits the interpretation of the effect of extracorporeal treatments. Also, it is important to recognize, however, that dialyzability of a drug and clinical improvement following treatment do not always correlate. Despite the uncertainty of the efficacy of ECT for many drugs and poisons the use in veterinary medicine of ECT (including hemodialysis, hemofiltration, hemoperfusion, therapeutic plasma exchange) in poisoning and drug overdoses is rapidly increasing.
Hemodialysis (HD) and charcoal hemoperfusion (HP) are methods used to eliminate different substances from a patient’s blood stream. Theoretically, ideal pharmacokinetic properties of a drug for removal with hemodialysis (HD) alone are small apparent volume of distribution (<1 L/kg), low plasma protein binding, and low molecular weight. When treating toxicity from agents that do not meet those criteria, the drug clearance by hemodialysis (HD) is reduced. Hemoperfusion (HP) on the other hand, works by direct adsorption on activated charcoal. Hemoperfusion (HP) can remove any drug or toxin with affinity to charcoal independently from molecular weight and plasma protein binding, until saturation of the adsorptive capacity of the filter is reached. Using in-series charcoal hemoperfusion and hemodialysis (HP/HD) there is a decrease in the potential for negative complications of hemoperfusion while maintaining the functionality of the toxin binding.
Drugs with a low volume of distribution (Vd) and/or a high rate of protein binding are most likely to be removed during plasma exchange. Some authors have proposed that plasma exchange is useful only when plasma protein binding of a substance is greater than 80% and when the Vd is less than 0.2 L/kg. That stated, others have included the exchanged plasma volume, intercompartment equilibration, and endogenous clearance as important determinants of the ability of plasma exchange to effectively remove a given drug. Interestingly the removal of drugs with plasma exchange might be compared to the removal of immunoglobulin M. Aspirin and many other NSAIDs has high protein-binding affinity (80–90% bound to albumin) and a low Vd of 0.1–0.2 L/kg. These properties make them prone to the elimination effect of plasma exchange.
Determination of the efficacy of ECT in overdoses is often determined by estimation of clearance rather than measurement of amount removed in the dialysate or plasma removed. The latter are the most reliable methods to estimate the extent of drug extraction with dialysis and plasma exchange. This amount should be the primary parameter used to assess the effect of ECT on drug disposition. Resorting to calculations of clearance may lead to erroneous conclusions about the ability to remove drugs. Some drugs equilibrate slowly between the peripheral and central compartments during plasma exchange, as with hemodialysis. In these cases, a considerable rebound will occur in drug concentrations after plasma exchange, and estimation of removal with ECT may be artificially high, depending on when it was determined. The discrepancy between clearance and the total amount of drug removed may be because serum concentrations decline faster than tissue levels and clearance do. In the absence of reliable data, knowledge of Vd and protein-binding characteristics of the drug in question, as well as the time when ECT is started relative to dose administration, may be helpful in predicting the effect of the procedure on drug extraction.
References
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