Module 5 – Enhanced Elimination and Extracorporeal Therapies

Learning Objectives

1. Understand the principles and techniques of alkaline diuresis, acid diuresis, and dialysis
2. Recognize which toxins are amenable to removal with hemoperfusion vs hemodialysis
3. Appreciate the indications, contraindications, and complications of extracorporeal therapies

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Alkaline Diuresis

– Alkalinizing the urine enhances elimination of weak acids by increasing tubular secretion.

– This is most useful for salicylate poisoning, but can also be used for phenobarbital overdose.

– Administer intravenous sodium bicarbonate to alkalinize plasma and urine to pH >7.5.

– Replace urinary potassium losses and avoid hypokalemia which impairs alkaline diuresis.

– Goal is to achieve urine output of 6 mL/kg/hr in adults or 2-3 mL/kg/hr in children.

– Monitor urine pH hourly along with electrolytes, kidney function, and volume status.

– Avoid fluid overload and recognize that alkalemia may compromise cardiac contractility.

– Discontinue alkaline diuresis once salicylate level drops below toxic range.

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Acid Diuresis

– Acidifying the urine can increase clearance of basic drugs by enhancing ionization.

– This is rarely done given limited efficacy and risks of inducing systemic acidosis.

– Potentially useful for severe poisoning with chloroquine or amphetamines.

– Methods include IV infusion of ammonium chloride or arginine hydrochloride.

– Goal is to reduce urine pH below 5-6 and maintain good urine output.

– Risks include worsening rhabdomyolysis and renal failure. Contraindicated in kidney injury.

– No proven mortality benefit and very rarely used in clinical practice.

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Hemodialysis

– Hemodialysis removes small solutes by diffusion across a semipermeable membrane.

– Effective for small molecular weight toxins (<500 Da) with limited protein binding.

– First-line extracorporeal therapy for severe poisoning from:

•    Salicylates
•    Lithium
•    Methanol
•    Ethylene glycol
•    Valproic acid

– Also useful for uremia, acid-base disorders, electrolyte imbalances.

– Continuous modalities less efficient than intermittent hemodialysis.

– Requires vascular access – prefer venous catheter over peripheral IV access.

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Hemoperfusion

– Hemoperfusion involves passage of blood through a cartridge containing activated charcoal.

– Toxins are removed by adsorption onto the charcoal.

– Used for poisoning by toxins highly bound to proteins:

•  Phenobarbital
•  Theophylline
•  Carbamazepine

– Adsorbs larger molecules compared to hemodialysis.

– Complications include hypocalcemia, thrombocytopenia, and hypotension.

– Limited availability in the US – hemodialysis is typically used instead.

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Plasmapheresis and Exchange Transfusion

– Plasmapheresis separates plasma from blood cellular components. The plasma is discarded and replaced.

– Used for very high molecular weight toxins not cleared by dialysis.

– Rarely used in toxicology – limited to valproic acid overdose unresponsive to HD.

– Complications include bleeding, electrolyte shifts, sepsis, hypocalcemia.

– Exchange transfusion replaces a portion of the patient’s plasma with donor plasma.

– Used in neonates with bilirubin encephalopathy.

– Theoretical utility in severe toxin-induced methemoglobinemia or carboxyhemoglobinemia.

– Limited by small volume of plasma exchanged and lack of high-quality evidence.

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In summary, extracorporeal techniques provide a valuable rescue therapy for selected, severe poisonings not responsive to standard care. Hemodialysis has the widest toxicologic application.