Hemoperfusion: A brief history, current considerations, and future applications

Explore hemoperfusion, its potential benefits for pets, and the current understanding of reintroducing this treatment into practice.

Hemoperfusion is a technique that emerged several decades ago, gaining popularity for its ability to filter out toxins from the blood. While its use declined over time due to advancements in other dialytic therapies, recent technological improvements and a better understanding of its potential have brought hemoperfusion back into consideration in the veterinary field.

Let's explore hemoperfusion, its potential benefits for pets, and the current understanding of reintroducing this treatment into practice.

A chocolate Labrador retriever undergoing hemoperfusion in a hospital setting.
Kallie, a one-year-old female spayed Labrador that ingested ~650mg/kg ibuprofen
undergoing treatment on direct hemoperfusion. Photo courtesy Tufts University Cummings School of Veterinary Medicine

What is hemoperfusion?

Hemoperfusion is an extracorporeal blood purification technique that involves circulating blood through a cartridge filled with adsorbents, such as activated carbon or synthetic polymers.1 These adsorbents trap various substances on their surface as the blood passes through. Unlike absorption, where substances are taken up into a material, adsorption works by binding substances on the surface of the sorbent, allowing the blood to return to the body without unwanted molecules.

Hemoperfusion was first employed utilizing plant-derived charcoal, often made from materials, such as coconut shells.2,3 While effective, these early adsorbents had drawbacks; irregular shapes with rough edges that could damage blood cells, release of microparticles, and risk of blood clotting. This led to complications, such as hemolysis (destruction of red blood cells) and thrombocytopenia (reduction in platelet count).3 As dialysis and other blood-filtering technologies advanced, the use of hemoperfusion waned.

Today, newer adsorbents, such as synthetically derived activated carbon or polymer beads, are available in veterinary medicine, making the technique safer and more tailored to remove a broad range of toxic substances from the blood while mitigating the unintended effects of legacy sorbents.2,3 These are also more effective than activated charcoal due to their higher surface area and engineered porous structure.

For example, the activated carbon used in modern hemoperfusion is manufactured to create controlled pore sizes, allowing for targeting molecules associated with different conditions.3 These features make it capable of binding a wide range of molecules, from small molecules (protein-bound, or non-protein bound protein-bound or non-protein-bound molecules) to larger inflammatory proteins and possibly even relatively massive immunoglobulins.

Given these advances in technology, hemoperfusion has become an emerging therapy in veterinary medicine for treating poisoning or drug overdose.4–6 It also shows potential for other diseases that create harmful substances in the blood, such as infections or organ failures.1

When is hemoperfusion used?

Extracorporeal blood purification methods, including hemoperfusion, are most effective when clearing substances that stay primarily in the bloodstream. Similar to other blood purification methods, they become less efficient as substances spread more widely throughout the body.6 Thus, hemoperfusion works best for toxins bound to blood proteins or otherwise tend to stay in plasma.

Hemoperfusion can remove both fat-soluble and water-soluble substances. Longer treatment times can sometimes help reduce the overall amount of substance with a wider distribution in the body.3,6

One application of hemoperfusion is in the treatment of severe acute poisoning.4–7 For example, dogs and cats that have ingested toxic substances, such as certain medications, may benefit from this therapy. Carbon hemoperfusion (cHP) has been successfully applied to nonsteroidal anti-inflammatory drug (NSAID) intoxication in dogs and cats.5,8

In a recent case series of 18 dogs with severe NSAID intoxication, cHP lasting an average of two hours significantly reduced plasma NSAID concentrations by an average of 58 percent (32 percent - 95 percent). The half-lives of NSAIDs during cHP were markedly shortened compared to previously reported half-lives of therapeutic dosages in dogs, suggesting the efficacy of cHP.

Another study in a larger group of dogs treated with cHP for neurotoxic or nephrotoxic NSAID intoxication,8 27 percent (10/37) developed mild to moderate acute kidney injury (AKI): one dog (3 percent) had AKI classified as IRIS grade I; five dogs (14 percent) as grade II, and four dogs (11 percent) as grade III. The dogs were hospitalized for a median of 1.7 days (interquartile range: 1 to 2.5 days), and AKI resolved in 80 percent (8/10) of affected dogs before discharge.

The overall survival rate of dogs treated with cHP was 94 percent (34/36), suggesting cHP should be considered for the management of severe NSAID intoxication when accessible within a suitable time frame.

Further investigations are underway to gain a deeper understanding of the pharmacokinetics of NSAIDs during cHP, to determine the efficacy of cHP, and compare the outcomes in dogs treated with cHP to those treated with different modalities, such as therapeutic plasma exchange.

Limitations and other applications

Hemoperfusion is not limited to treating acute intoxications. It holds potential for managing other conditions involving unwanted blood components.1

Modern hemoperfusion is being studied for its role in conditions such as sepsis, a serious inflammatory response to infection. During sepsis or severe inflammatory conditions, cytokines (proteins that signal inflammation) can elevate significantly, creating a "cytokine storm" that can damage organs. Some experimental studies and human clinical studies suggest hemoperfusion, with its ability to adsorb these cytokines, could help regulate inflammation and improve recovery.1,9 While the evidence for this in veterinary patients is still developing, preliminary findings from experimental studies suggest that this therapy shows evidence of clinical benefit.

How is hemoperfusion performed?

Hemoperfusion requires vascular access, typically achieved by placing double-lumen hemodialysis catheters or large-bore central venous catheters, depending on the patient's size.6

The patient is typically heavily sedated but does not necessarily need to be anesthetized for catheter placement. Blood is drawn from the patient through the catheters, passed through the hemoperfusion cartridge, where toxins bind to the adsorbent material, and then returned to the patient. Anticoagulation is typically maintained by constantly administering unfractionated heparin via dialysis machines or dedicated hemoperfusion machines, monitored by activated clotting times or activated partial thromboplastin time.

Several extracorporeal platforms are available that can perform hemoperfusion by incorporating hemoperfusion columns into their circuits, enabling in-series hemoperfusion and hemodialysis . This strategy effectively maximizes clearance by utilizing both modalities.10

Additionally, specific equipment designed for standalone hemoperfusion is currently available on the market, simplifying its use in clinical settings.

Sedation can be administered to keep patients on the table during the hemoperfusion treatment, but often, manual restraint using a harness is sufficient to keep the patient still. During the treatment, careful monitoring of hemodynamic stability, clotting parameters, and kidney function is essential during the procedure.

Challenges and considerations

While hemoperfusion presents an exciting opportunity in veterinary medicine, it is not without challenges, including the potential for a drop in platelet count during treatment.3 This thrombocytopenia is well-documented and may occur due to the interaction between blood components and the adsorbent surface. While this effect is often temporary, it can increase bleeding risks in some patients, necessitating careful monitoring of patients during and after hemoperfusion.

Hypothermia is another concern, particularly in small animals with a higher extracorporeal circuit volume.4,6 Extracorporeal therapies can lead to a drop in body temperature, making measures, such as external warming devices or blood warmers, necessary to prevent hypothermia.

Other complications include blood loss in the event of circuit clotting. While effective anticoagulation strategies can help mitigate these issues, they may still occur, especially with slower blood flow and prolonged circuit transit times. Effective training for veterinary professionals is essential to ensure the safe and efficient use of hemoperfusion, including proper catheter placement and maintenance of vascular access.

A final limitation of hemoperfusion is the column filled with adsorbents becoming saturated, rendering further hemoperfusion ineffective. Previous case studies have described saturation occurring in cases of significant intoxication, typically during the early stages of treatment.11,12 Replacing the saturated filter with a fresh one can help continue the removal process.

Conclusion

Once overshadowed by other blood purification methods, hemoperfusion is experiencing renewed interest due to advancements in material science and device design. Its potential benefits for treating pets in critical conditions, such as severe acute intoxication and severe inflammation, make it a promising addition to veterinary care.

While challenges such as platelet count management and technical training persist, ongoing research and improved technology may soon position hemoperfusion as a standard treatment option. For veterinary professionals, staying informed about these developments will be essential for improving enhance patient care and outcomes.


Jiwoong Her, DVM, MS, DACVECC, is an associate professor in Small Animal Emergency and Critical Care, Nephrology and Extracorporeal Services at the North Carolina State University (NCSU). Dr. Her earned his DVM from the Chungnam National University in South Korea and completed evaluated clinical experience at the Louisiana State University. After an ECC internship at Chesapeake Veterinary Referral Center in Columbia, Md., Her completed a master's degree and residency in Small Animal Emergency and Critical Care at Auburn University in 2020. He then served as an Assistant Professor of Small Animal Emergency and Critical Care at the Ohio State University (OSU) before joining NCSU in 2024. During his faculty appointment at the OSU, he completed Hemodialysis Academy and a fellowship in Extracorporeal Therapies. He is currently a member of the inaugural class of the American College of Veterinary Nephrology and Urology (ACVNU).

Jeff Barnes is the vice president of Business Development with ImmutriX Therapeutics, Inc., which developed and manufactures a hemoperfusion system intended for use in human and veterinary medicine. He is also president of the veterinary division AimaLojic Animal Heath. Barnes has more than 30 years of experience in the medical device industry and has played a role in developing and adopting the technology used in LASIK surgery, femtosecond cataract surgery, and various ophthalmic diagnostic devices. Due to personal family experience, he was led to the development of the ImmutriX / AimaLojic hemoperfusion system in 2012. Barnes is passionate about developing technology driven by clinical applications to solve unmet medical needs.

References

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  3. Barnes J, Cowgill LD, Diaz Auñon J. Activated Carbon Hemoperfusion and Plasma Adsorption. Advances in Small Animal Care. 2021;2:131-142. doi:10.1016/j.yasa.2021.07.010
  4. Londoño L. Extracorporeal Therapies in the Emergency Room and Intensive Care Unit. Advances in Small Animal Care. 2023;4(1):61-70. doi:10.1016/j.yasa.2023.05.004
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  6. Foster JD. Extracorporeal Therapies in the Emergency Room and Intensive Care Unit. Veterinary Clinics of North America - Small Animal Practice. 2020;50(6):1215-1236. doi:10.1016/j.cvsm.2020.07.014
  7. Haire LE, Vitalo AD, Gonçalves RP, Lanaux TM. Case report: Manual carbon hemoperfusion for the treatment of meloxicam toxicity in a cat and suspected ibuprofen toxicity in a dog. Front Vet Sci. 2024;11. doi:10.3389/fvets.2024.1395967
  8. Her J, Gordon D, Spillane A, Finstad J, Langston C. Outcomes of Non-Steroidal Anti-inflammatory Drug toxicosis treated with carbon hemoperfusion in dogs. Abstracts from the International Veterinary Emergency and Critical Care Symposium and the European Veterinary Emergency and Critical Care Annual Congress 2024. Journal of Veterinary Emergency and Critical Care. 2024;34(S2):516-517. doi:10.1111/vec.13420
  9. Putzu A, Schorer R, Lopez-Delgado JC, Cassina T, Landoni G. Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials. Anesthesiology. 2019;131(3):580-593. doi:10.1097/ALN.0000000000002820
  10. Her J, Gordon D, Riggs A, Venner L, Cooper E, Langston C. Successful treatment of a severe 5-hydroxytrytophan intoxication using carbon hemoperfusion, hemodiafiltration, and mechanical ventilation in a dog. Journal of Veterinary Emergency and Critical Care. 2024;34(2):186-192. doi:10.1111/vec.13368
  11. Tauk BS, Foster JD. Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog. Journal of Veterinary Emergency and Critical Care. 2016;26(6):787-792. doi:10.1111/vec.12544
  12. Fick ME, Messenger KM, Vigani A. Efficacy of a single session in-series hemoperfusion and hemodialysis in the management of carprofen overdose in two dogs. Journal of Veterinary Emergency and Critical Care. 2020;30(2):226-231. doi:10.1111/vec.12931

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