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Role of r.r.t in toxicology modalities and indications

Role of r.r.t in toxicology modalities and indications. Dr sunil Karanth md, fnb , edic , fcicm Chairman of critical care service Manipal health enterprises (p) ltd Manipal hospital, bangalore Adjunct prof in critical care medicine Manipal university.

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Role of r.r.t in toxicology modalities and indications

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  1. Role of r.r.t in toxicology modalities and indications Dr sunil Karanth md, fnb, edic, fcicm Chairman of critical care service Manipal health enterprises (p) ltd Manipal hospital, bangalore Adjunct prof in critical care medicine Manipal university

  2. Poisoning and overdose not uncommon in an intensive care unit • Extracorporeal therapy one of the methods of elimination of a toxin • First conceptualized in 1950 by doolan • Showed elimination of salicylates by dialysis • Resulted later in Jorgensen publishing a paper on dialyzable poisons • To date 142 dialyzable poisons

  3. Data and evidence on the use of rrt in toxicology • Factors affecting dialyzability of drugs and toxins • Discuss different extracorporeal treatment modalities • Review the role of r.r.t in management of specific poisons

  4. Removal of drugs and toxins by extracorporeal therapies Justified if there is an indication of severe toxicity Determined by different physico-chemical properties

  5. Extracorporeal treatment modalities

  6. INTERMITTENT HEMODIALYSIS

  7. CONTINUOUS RENAL REPLACEMENT THERAPY

  8. Ihd vs cvvhf • diffusion • Rapid initial clearance • Risk of rebound phenomena • Good experience – familiarity and hence preferred • Convection • Slow initial clearance • No rebound phenomena • Case reports and series only present

  9. hemoperfusion • Passage of anticoagulated blood through a cartridge with adsorbant material • Water soluble and lipid soluble • 100-40000 daltons • Specially useful for highly protein bound drugs

  10. Rrt in specific poisonings

  11. Ethyleneglycol Methanol + + Alcoholdehydrogenase Glycolaldehyde Formaldehyde Toxic alcohol ingestion + + CNS SYMPTOMS Aldehyde dehydrogenase Glycolateoxidase Formicacid(toxic) Glycolicacid + Folicacid Glyoxylicacid Pyridoxine CO H O + 2 2 + Glycine Lactatedehydrogenase Oxalicacid(toxic) Thiamine Alpha-hydroxy- Calciumoxalate • Methanol, ethylene glycol • High anion gap with increased osmolar gap • Later stages only high anion gap – lactate induced beta-ketoadipate RETINAL TOXICITY ACUTE KIDNEY INJURY

  12. Isopropylalcohol Alcoholdehydrogenase + Acetone Toxic alcohol ingestion Acetonemonooxygenase + Acetol L-Propane-1,2-diol Alcoholdehydrogenase + Acetonemonooxygenase + Methylglyoxal L-Lactaldehyde Formate+Acetate Aldehyde Glyoxylase + + dehydroxygenase D-Lactate L-Lactate • Isopropyl alcohol • Normal anion gap • Increased osmolar gap • Ketones positive • Rrt rarely needed Glucose

  13. Toxic alcohol ingestion • Fomipazole or ethanol • Competitive blockade of alcohol dehydrogenase • Rrt very effective • Readily dialyzable • Useful in the presence of aki, metabolic acidosis • If unstable consider crrt • Rrt if levels of parent alcohols > 50mg% • In case of ethylene glycol, hd even for glycolic acid clearance • Formic acid not cleared by dialysis • Monitor osmolality and acid-base balance for 12-36 hours in view of the risk of redistribution

  14. Salicylate toxicity Aspirin, bismuth salicylate Inhibition of cyclooxygenase pathway – decreased production of prostaglandins Higher doses – uncoupling of oxidative phosphorylation Hemodialysis most appropriate

  15. Other indications for rrt • Pulmonary edema • Hypoxemia • Altered mental status indicating high cns concentration • Acute kidney injury

  16. Lithium toxicity

  17. Valproic acid poisoning • Favourable molecular weight and volume of distribution for hemodialysis • High protein binding at therapeutic concentrations • Supratherapeutic concentrations – decreased protein binding due to saturation of stores • Amenable to hemodialysis • Cvvhf can be considered • Unstable hemodynamics • Hyperammonemia • End point for dialysis – valproate levels < 100 mg%

  18. Metformin poisoning • Rapid removal by hemodialysis despite large volume of distribution • Low protein binding • Low molecular weight • Rapid transport from cell to serum • CVVHF • If hemodynamically unstable • Lactic acidosis

  19. Dabigatron poisoning • Predominantly excreted by the kidneys • Intermittent hemodialysis seemed to be superior to crrt • Risk of rebound levels • Recently role of rrt limited in view of the development of a monoclonal anti-body idarucizumab

  20. Miscellaneous drugs • Many other drug toxicities may benefit from hemodialysis – in severe toxicities only • Anticonvulsants like • Carbamezapine Phenytoin Phenobarbital • Calcium channel blockers • Beta blockers • Theophylline • Dapsone • Inh • Cefipime, metronidazole • Hemodialysis may be most appropriate • Limited data with other modes • Crrt used if unstable hemodynamically

  21. In summary • Rrt could be considered • Drug toxicity • Specially – toxic alcohol, salicylates, lithium, metformin, valproate • May have a role in other drugs based on the pharmacokinetic profile • Support for organ dysfunction • Aki • Hepatic dysfunction • Most circumstances ihd can be used • Crrt is a suitable alternative with limited experience

  22. Thank you

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