Evaluation of using adjunct therapy options for most successful outcomes
After receiving an appropriate 37.5 mg dose of carprofen for suspected osteoarthritis the night before, a 12-year-old female Pembroke Welsh corgi ingested the contents of the entire bottle. She consumed 4463 mg (223mg/kg), which is approximately 50 times the recommended dosing at 4.4mg/kg. This case study presented in the Journal of Veterinary Emergency and Critical Care1 demonstrates a successful treatment of carprofen toxicity combining recommended agents and the less proven strategy of manual therapeutic plasma exchange (TPE).
When consumed at the proper dosage, carprofen is a safe, effective treatment for canine osteoarthritis and general pain control. Carprofen is a non-steroidal anti-inflammatory drug (NSAID) that is a selective inhibitor of cyclooxegenase-2 (COX-2) which is responsible for prostaglandin synthesis involved in inflammation. When consumed at high doses, carprofen may cause significant neurologic, gastrointestinal, renal, and hepatic toxicities.
Upon presentation to the veterinarian, the patient received 2 doses of apomorphine in an unsuccessful attempt to force emesis. Treatment escalated to include activated charcoal, lipid emulsion, and supportive care. The decision to begin manual TPE was based on the severity of the toxicity. The combination of these therapies resulted in a 57% reduction in carprofen levels.1
Machine TPE is already proven as an effective adjunct for NSAID toxicity treatment. However, its use is limited by access to laboratory equipment and expertise only found at select hospitals and specialty locations. Manual TPE is a potential alternative option when machine TPE is not accessible because it is technically simpler and uses commonly found equipment. A downside of manual TPE is that it is time and labor consuming.
Manual TPE involves removing a safe percentage of whole blood, centrifuging the sample to remove the drug-containing plasma, and returning the remaining cellular components to the patient along with replacement volume of crystalloids. The patient experienced hematochezia (bloody stools) and hypovolemia as a complication of manual TPE but was treated appropriately and made a full recovery. Other potential complications can include vomiting, hypocalcemia, systemic clotting, infection, and technical problems.
In this case study, the veterinary staff successfully performed manual TPE alongside routine decontamination techniques with minimal complications. It is not possible to attribute the success of this recovery solely to the use of manual TPE due to the use of additional interventions. However, this example demonstrates a comparable reduction in carprofen (57%) to a previously reported use of machine TPE that documented a 51% reduction.
This example can be used as a reference for veterinary staff managing NSAID toxicities who may not have access to sophisticated machine TPE equipment or expertise but are attempting to manage a severe level of toxicity.
Using additional agents in the setting of an acute NSAID toxicity may change the patient’s likelihood of experiencing certain complications, however the ideal combination of agents has not been identified.
A multicenter, retrospective study presented in the Journal of Veterinary Internal Medicine2 evaluated the outcomes of dogs who received intravenous fluids (IVF) alone, or with TPE, lipid emulsion (ILE), or TPE and ILE in treatment of NSAID toxicities. Using records from 4 veterinary teaching hospitals and a private emergency and referral hospital, researchers collected data like body weight, NSAID type, maximal NSAID dose, clinical signs at presentation, and clinical values at baseline and discharge. They assessed the dogs’ outcomes in relation to the treatment regimen they received and evaluated data pertaining to gastrointestinal, kidney, and central nervous system dysfunction.2
The evaluated data showed fewer incidences of acute kidney injury (AKI) when dogs were treated with TPE and the addition of ILE to IVF was associated with a lower maximal creatinine concentration. Neurological symptoms were overrepresented among the dogs treated with TPE, however this was determined to reflect the severity of their toxicity rather than intervention because all TPE treated dogs originally presented with neurologic issues.
Induction of emesis was associated with the development of fewer clinical signs throughout hospitalization. Charcoal administration in hospital was associated with lower odds of AKI development when compared to patients that did not receive charcoal, but the association did not continue when assessing the populations across the multiple variables. Overall, the study was able to establish that IVF, TPE, and ILE were all safe, contributed to the clinical recovery of the dogs, and should be considered in the management of severe NSAID toxicity.2
Ms Bechtold is a 2024 PharmD candidate at the University of Connecticut.