PLEASE POST The Blue Ridge Poison Center Tox Talks October 2017 │ A Bulletin for Health Care Professionals Who Manage Poisoned Patients │ www.brpc.virginia.edu

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Director Use of Therapeutic for Poisoning Christopher Holstege, MD In uncommon circumstances, therapeutic apheresis may be useful Nursing Director in the treatment of poisoned patients to remove toxins or support Beth Mehring, MSN certain severe poisonings. Many clinicians are unfamiliar with Medical Toxicologists apheresis; this month's ToxTalks will review both the technique Andy Baer, MD and potential applications to treat patients with overdose, Heather Borek, MD Nathan Charlton, MD envenomation, and other poisonings. Josh King, MD Therapeutic apheresis encompasses a group of extracorporeal Medical Toxicology Fellows therapies including plasma exchange, red cell exchange, Asaad Alsufyani, MD Justin Rizer, MD leukocytapheresis, and others.

Poison Specialists Much like hemodialysis, apheresis removes and returns blood Brenda Beech, RN, CSPI from the body. Unlike hemodialysis, where blood is run across a Andre Berkin, BSN, CSPI Jenni Goodwin, RN, BSN filter and against a dialysate solution which allows for Jennifer Horn, BSN, CSPI normalization of electrolytes, removal of fluid, and removal of Sue Kell, Ph.D, M.Ed, CSPI toxins, in apheresis blood can either run across a filter or is Teresa Kinzie, RN, CCRN, CSPI Christie Lee, RN, CSPI centrifuged. Apheresis can be used for exchange Kathy Mayo, RN, CSPI transfusion, where abnormal red blood cells are removed (e.g., in Scott Wiley, BSN, CSPI sickle cell ) and a large volume of non-diseased blood Steven Yoder, RN, CSPI cells are transfused to the patient. Plasma exchange involves Epidemiologist removal of a patient's plasma, usually to remove antibodies (e.g., Saumitra V. Rege, MS, PhD in thrombotic thrombocytopenic purpura or myasthenia gravis)

Public Health Educator with return of albumin or back to the patient. Kristin Wenger, MT, BS While exchange transfusion and plasma exchange are virtually the only techniques used for treatment of poisoning or Administrative Specialists Heather Collier envenomation, apheresis can also be used to remove excess white Teresa Dorrier blood cells (leukopheresis - e.g., for leukemia), (thrombocytapheresis - e.g., for essential thrombocythemia), To receive this newsletter via email: Kristin Wenger: lipids (lipopheresis - e.g., for primary hyperlipidemia), and stem [email protected]. cells for bone marrow transplantation.

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Plasma exchange has been used for treatment of a variety of poisonings, including amatoxins (from Amanita phalloides, Cortinarius, and similar mushrooms), other plant toxins such as ricin, certain heavy metals, highly protein-bound drugs, and snake and scorpion venom components. Similarly, red cell exchange transfusion has been used for removal of toxins with high degrees of concentration within red blood cells (arsenic, carbon monoxide). A few selected toxins are reviewed in more detail below.

Compared to hemodialysis, the most commonly used extracorporeal therapy for poisoning, apheresis can be used to remove substances of any size, including plasma proteins. The amount of plasma which is filtered in apheresis is significantly lower than the amount filtered in hemodialysis; thus, toxins which are amenable to hemodialysis (toxic alcohols, salicylates, etc.) are better treated with dialysis than apheresis. Unlike apheresis, dialysis is unable to remove very large substances or substances substantially bound to plasma proteins. For both apheresis and dialysis to be used in poisoning, a low volume of distribution (less than 1 L/kg) is needed: neither technique removes substances which are not predominantly in the vascular space.

Of all poisonings which therapeutic apheresis has been used to treat, Amanita phalloides and similar amatoxin-containing mushroom poisoning has the most data behind it, with a total of over 300 published cases. Amatoxins and similar cyclopeptide toxins inhibit RNA polymerase, and may cause severe liver, kidney, and cardiac toxicity; they account for almost all fatalities related to mushroom ingestion. The use of plasma exchange has been shown to improve mortality in severe toxin exposure, although relatively little amatoxin is removed; it is not clear whether this is due to support of patients with liver failure, or direct removal of toxin. If plasma exchange is used in patients with amatoxin poisoning, it is generally recommended within the first 24-48 hours.

Carbon monoxide toxicity accounts for the greatest single number of deaths from environmental poisoning each year, and causes toxicity due to tissue hypoxia. As carbon monoxide has a very high affinity for hemoglobin, exchange transfusion has been used for severe cases of carbon monoxide poisoning. While the number of cases in which exchange transfusion has been used is not great, exchange transfusion has improved neurological outcomes in severe toxicity, and is a consideration if standard therapy is not effective or for extreme toxicity.

Snake envenomation is typically treated within the United States by supportive therapy and antivenin; as almost all envenomations are due to native crotalids (pit vipers), polyvalent antivenom Fab (CroFab) is typically used. In rare situations where antivenin is unavailable for severe envenomation, plasma exchange has been utilized to remove circulating snake or scorpion venom components. The largest case series published, with data on 37 patients from Turkey with native pit viper envenomation, showed significant improvement in coagulopathy and thrombocytopenia following plasma exchange. In a situation where appropriately dosed

Page 2 of 3 ToxTalks October 2017 antivenin is ineffective or unavailable, plasma exchange could be considered as a salvage therapy.

Overall, apheresis is not a common technique, nor does it have a role in caring for the vast majority of poisoned patients. For a select few patients with severe poisoning from selected agents, however, it is a technique which may be employed when other modalities have failed. For questions on the use of apheresis in poisoning, as well as any other questions in the treatment of poisoned patients, we welcome your calls to the Blue Ridge Poison Center at 800- 222-1222.

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Suggested References

Overview of apheresis use and indications: Journal of Clinical Apheresis 31:149–338 (2016)

Apheresis for poisoning in general: Seminars in Dialysis—Vol 25, No 2 (March–April) 2012 pp. 201–206

Exchange transfusion for carbon monoxide: J Clin Apher. 2013 Oct;28(5):337-40

Plasma exchange for liver failure support: Journal of Hepatology 2016 vol. 64 69–78

Plasma exchange for snakebite: Transfusion and Apheresis Science 49 (2013) 494–498

ToxTalks is funded in part through a grant from the U.S. Department of Health and Human Services Health Resources Services Administration.

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