Extracorporeal Therapies In Poisoning

Feb 28, 2025

Toxins in Which Extracorporeal Therapy is Tried

Common Indications: ethylene glycol, lithium, and salicylate poisoning.

Agent	Preferred Modality	Other, Acceptable Modalities
Acetaminophen	IHD	IHP, CRRT, Ex
Long-acting barbiturates	IHD	HP, CRRT
Carbamazepine	IHD	IHP, CRRT
Ethylene glycol	IHD	CRRT
Lithium	IHD	CRRT*
Metformin	IHD	CRRT*
Methanol	IHD	CRRT
Phenytoin	IHD	IHP
Salicylates	IHD	IHP, CRRT, Ex
Thallium	IHD	IHP, CRRT
Theophylline	IHD	HP, CRRT, Ex
Valproate	IHD	IHP, CRRT

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Factors Determining Toxin Removal

Generally activated charcoal is given to cleanse the gut
Absorption is prevented
Specific chemical therapy provided
Some toxins require extracorporeal removal, they depend upon :-

Factor	Comments
Molecular weight	< 10 kDa- removed by HD > 40 kDa- HDF, HF
Protein-bound	Once the site is saturated highblood dialysable level
Volume of distribution	Low- easy removal
Compartmentalization	Remote compartment → Proximalcompartment Increasing the frequency of therapy
Contribution of endogenous clearance	Increase total body clearance by30%/ endogenous clearance <4ml/kg/min

Protein Binding

Toxins bound to proteins can't be removed by dialysis
Plasmapheresis is used.
Salicylates are exception
Can be removed easily- Intermittent hemodialysis is done.
Though salicylates have high protein binding

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Techniques Used in Extracorporeal Removal

Technique	Comments
Hemodialysis	First choice The low molecular weight of solutes
Peritoneal dialysis	Not routinely used except in children Because the volume of distribution in children is low
CRRT	Intercompartmental disequilibrium
Hemoperfusion	Charcoal/resin Plasma protein-bound and lipophilic drugs Blood flow < 100-250 ml/min If blood flow is> 250 ml/min - leads to hemolysis Side effect -Thrombocytopenia Performed within 4 hours Example: paraquat poisoning
Plasma exchange	Highly protein bound Amanita Phalloides

Intermittent Hemodialysis

Maximize Qb and dialyzer membrane surface area
Aim for Qb/Qd ratio of >/= 2.5:1 (although diminishing benefits gained from increasing Qd beyond -600 ml/min)
Maximize treatment times to at least 4 hours
Use high-flux (kuf), high- efficiency (KoA) dialyzer, particularly if middle molecular weight solutes (>1000 Da) are to be cleared

Intermittent Hemofiltration/Filtrative Component of Intermittent hemofiltration:

Aim for post-dilution fluid replacement to maximize efficiency with high-flux membrane
Maximize Quf according to filtration fraction

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CRRT (Continuous renal replacement therapies)

Aim for high convective clearance (i.e., post-dilution CVVH with high flux membrane) for larger solutes (> 1000 Da). Aim for high diffusive clearances (i.e., CVVHD) for small solutes (<=1000 Da). For CVVH, maximize Quf according to the filtration fraction. For CVVHD, CVVHDF, maximize Qd up to at least 2.5 L/h for small solutes; For larger solutes (e.g., of an equivalent size to ꞵ2- microglobulin; MVV 11,800) there may be little gain from a Qd > 1.5 L/h

Hemoperfusion

limit Qb to -100 to 250 ml/min. Change cartridge every 3 to 4 hours. Consider the benefits of charcoal vs resin cartridges depending on the poison

Plasma exchange

Aim for two plasma volume exchanges per day
Modify replacement fluid according to poison

Technique	Protein binding	Molecular weight
Plasma exchange	> 90%	> 40 kDa
Hemodialysis	< 80%	< 10 kDa
Hemoperfusion	80-95%	-
Hemofiltration	< 80%	10-40 kDa

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Extracorporeal Therapy in Alcohol Poisoning

Ethylene glycol and methanol used in - antifreeze, de-icing solution cause poisoning

Toxicity is from ethylene glycol→ glycolic acid because of alcohol dehydrogenase

Methanol→ formic acid
- Presentation
- Nausea
- Vomiting
- Abdominal pain
- AKI
Early treatment
- Fomepizole/ ethanol to prevent alcohol dehydrogenase
- To prevent the formation of glycolic acid and formic acid
Indication of fomepizole
- osmolal gap > 10 mosm/kg
- Ethylene glycol/ methanol blood level > 20 msg/dl
Alcohol poisoning
Ideal to be removed by extracorporeal therapy
- Immediate HD when levels > 50 mg/dl
- HD should be continued till pH normalizes and blood level of toxin < 25 mg/dl

Extracorporeal Therapy in Salicylate Poisoning

Salicylate poisoning presents as
- Fever
- Sweating
- Tinnitus
- Vertigo
Severe poisoning leads
- Depression of mental state
- Non-cardiogenic pulmonary edema
- Death
Mixed respiratory alkalosis + metabolic acidosis seen
IV sodium bicarbonate is given to reduce tissue penetration
Salicylates are 90% protein bound
Saturation of binding site → significant free level
Extracorporeal therapy in severe poisoning, level > 100 mg/dl
Intermittent HD-rapid correction of acidemia and electrolytes

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High Yield Questions

Q. Molecular weight of substance/protein binding of substance?

Ans.

Technique	Protein binding	Molecular weight
Plasma exchange	> 90%	> 40 kDa
Hemodialysis	< 80%	< 10 kDa
Hemoperfusion	80-95%	-
Hemofiltration	< 80%	10-40 kDa

Q. Level of alcohol at which extracorporeal therapy should be used?

Ans. > 50 mg/dl

Q. What level of salicylate at which extracorporeal therapy should be used?

Ans. > 100 mg/dl

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