The WHO estimated over 800,000 suicide deaths in 2012, with poisoning a major concern. Three\u2011quarters of suicides occur in low\u2011 and middle\u2011income countries, with an estimated 30% related to pesticides. Organophosphates account for at least 40% of pesticides in India. For non\u2011pesticide overdoses, the Extracorporeal Treatment in Poisoning Workgroup (EXTRIP) has reviewed over 20 drugs and toxins and issued recommendations for extracorporeal therapy.<\/p>\n
Blood purification technology and its evolution<\/p>\n
In 1914, Abel demonstrated salicylate removal in dogs using a dialyser; by 1946, dialysis was clinically applied. In 1958, resin hemoperfusion for barbiturates was described; in 1965, Dunea introduced charcoal hemoperfusion, noting adsorption but also nausea, hypotension, and thrombocytopenia. In 1976, Amberlite XAD\u20114 resin hemoperfusion for lipid\u2011bound drugs demonstrated substantial removal-the first clinical use of styrene divinylbenzene copolymers. By the 1990s, adverse effects were better defined: a study of ~800 patients reported hypotension in 22%, bleeding in 3%, and thrombocytopenia in 31%, with mortality exceeding 44%.<\/p>\n
Skepticism during the 1980s\u20131990s shifted as technologies evolved. Materials progressed from uncoated activated carbon to encapsulated carbon and modern synthetic porous polymer beads designed for blood compatibility, mechanical strength, and thermal stability.<\/p>\n
Current Concepts in Extracorporeal Drug Removal<\/p>\n
Extracorporeal removal depends on molecular weight, protein binding, volume of distribution, solubility, and endogenous clearance.<\/p>\n
Molecular weight: Smaller molecules (<500 Da) pass membranes easily; middle molecules (500\u201340,000 Da) suit hemofiltration. Synthetic resins can have pore sizes up to 60,000 Da.<\/p>\n
Protein binding: The free (unbound) gradient is key. Drug\u2013protein complexes cannot pass filters. With increasing concentration, albumin binding saturates, enabling removal.<\/p>\n
Volume of distribution: Lipid\u2011soluble drugs with low protein binding have a large volume of distribution; tissue removal is limited and occurs only with rapid redistribution. Therapies are applied intermittently. Extracorporeal clearance is useful if it increases endogenous clearance by 30% or if endogenous clearance is low (<4 mL\/kg\/min).<\/p>\n
Evidence for hemoadsorption<\/p>\n
Current evidence: EXTRIP recommends hemoadsorption for acetaminophen, barbiturates, carbamazepine, phenytoin, salicylates, thallium, theophylline, and valproic acid; it is not recommended for CCBs or digoxin.<\/p>\n
CCBs: Current recommendations advise against extracorporeal therapy for CCB poisoning. Charcoal hemoadsorption for diltiazem overdose showed no improvement; diltiazem and amlodipine are protein\u2011bound, lipophilic, and have a large volume of distribution (>1 L\/kg).<\/p>\n
Modern resin cartridges may solve this. Polymer resins adsorb lipophilic substances via van der Waals forces. An ex vivo model demonstrated almost 90% removal of amlodipine within two hours. A case report using the Jafron HA 230 cartridge reversed shock in less than one elimination half\u2011life using two six\u2011hour cycles 18 hours apart. A multicycle approach allows toxin transfer from tissue back into blood.<\/p>\n
A retrospective study in 24 patients with CCB poisoning and shock compared hemoadsorption (n=13) with standard care (n=11). Despite greater initial severity, the hemoadsorption group showed greater improvement in mean arterial pressure during the first 48 hours, faster lactate reduction (14 vs. 4 hours), a trend toward shorter high\u2011dose insulin therapy, and only one death (7.7%).<\/p>\n
Organophosphates: A 2022 meta\u2011analysis identified 11 Chinese studies including 811 patients with acute severe poisoning. Hemoperfusion plus hemofiltration reduced mortality (OR 0.38, 95% CI 0.25\u20130.57), atropine requirements, mechanical ventilation duration, and cholinesterase restoration time, though methodological quality was poor.<\/p>\n
A randomized controlled trial (South Africa) compared hemoadsorption with standard care in 40 patients requiring invasive mechanical ventilation, using two six\u2011hour cycles of the Jafron HA 230 cartridge 12\u201318 hours apart. The hemoadsorption arm showed reduced ICU stay (median 17 to 10 days), lower atropine duration and dose, shorter mechanical ventilation, and savings of over \u20ac7,000 per patient. Severe complications, including death, were significantly lower, with no significant effects on platelets, bleeding, or transfusion.<\/p>\n
A recent observational study of 75 patients found fewer severe complications in the hemoadsorption group despite greater disease severity. Overall, observational data, meta\u2011analysis, and the randomized trial consistently show benefit.<\/p>\n
Suggested care pathway<\/p>\n
A care pathway is proposed: (1) assess poisoning severity; (2) assess physicochemical compatibility; (3) weigh risk versus benefit (vascular access, anticoagulation, infection, low platelets); (4) ensure appropriate setting; (5) initiate hemoadsorption (6\u201312 hours per cycle); (6) terminate based on clinical recovery and biomarker<\/a> improvement (e.g., cholinesterase increase >40%).<\/p>\n Limitations<\/p>\n Only one randomized trial adhered to CONSORT reporting; others lacked randomization, concealment, or blinding. The wide range of toxins creates clinical heterogeneity; different cartridges and protocols create treatment heterogeneity. Observational studies are prone to bias. Sample sizes are limited, and most studies were single\u2011centre.<\/p>\n Conclusions<\/p>\n Recent advances in modern resin bead technology extend hemoadsorption to protein\u2011bound poisons with a large volume of distribution. Using a multicycle approach, it has shown improved outcomes for both CCBs and organophosphate poisoning.<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n