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RRT and Intoxications: Pharmacological Implications and Treatment Strategies

Explore cases of polypharmacy overdose, indications for hemodialysis and hemofiltration, and drug characteristics influencing removal in toxic states. Understand molecular weight, protein binding, and elimination pathways of intoxicants.

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RRT and Intoxications: Pharmacological Implications and Treatment Strategies

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  1. RRT and IntoxicationsTimothy E Bunchman

  2. Case Study-1 • 17 y/o female with poly pharmacy overdose including risperidone, stratttera and long acting Lithium • She is not on any medications chronically • 12 hours post overdose she is semi comatose with QT interval changes on EKG

  3. Case Study-2 • There is no hepatic nor renal dysfunction • Lithium level was > 5.1 mmol/l • (critical > 4)

  4. Thought Process of RRT in Intoxication • Is the drug long or short acting • Is there any inhibition of the natural excretion of the drug • What is the molecular weight? • What is the protein binding? • Is this single or double compartment?

  5. INTRODUCTION • 2.2 million reported poisonings (1998) 67% in pediatrics • Approximately 0.05% required extracorporeal elimination • Primary prevention strategies for acute ingestions have been designed and implemented (primarily with legislative effort) with a subsequent decrease in poisoning fatalities

  6. ELIMINATION I N P U T Distribution Re-distribution

  7. GENERAL PRINCIPLES kinetics of drugs are based on therapeutic not toxic levels (therefore kinetics may change) choice of extracorporeal modality is based on availability, expertise of people & the properties of the intoxicant in general Each Modality has drawbacks It may be necessary to switch modalities during therapy (combined therapies inc: endogenous excretion/detoxification methods)

  8. INDICATIONS >48 hrs on vent ARF Impaired metabolism high probability of significant morbidity/mortality progressive clinical deterioration INDICATIONS severe intoxication with abnormal vital signs complications of coma prolonged coma intoxication with an extractable drug

  9. HEMODIALYSIS • optimal drug characteristics for removal: • relative molecular mass < 500 • water soluble • small Vd (< 1 L/Kg) • minimal plasma protein binding • single compartment kinetics • low endogenous clearance (< 4ml/Kg/min) • (Pond, SM - Med J Australia 1991; 154: 617-622)

  10. Intoxicants amenable to Hemodialysis • vancomycin (high flux) • alcohols • diethylene glycol • methanol • lithium • salicylates

  11. Ethylene Glycol IntoxicationRx with Hemodialysis Mg/ml (> 30 mg/ml toxic) Duration of Rx (hrs)

  12. Vancomycin clearance High efficiency dialysis membrane Rx Rx Rx Rebound Rebound Vanc level (mic/dl) Time of therapy

  13. High flux hemodialysis for Carbamazine Intoxication Rx Mic/ml Hrs from time of ingestion

  14. HEMOFILTRATION • optimal drug characteristics for removal: • relative molecular mass less than the cut-off of the filter fibres (usually < 40,000) • small Vd (< 1 L/Kg) • single compartment kinetics • low endogenous clearance (< 4ml/Kg/min) • (Pond, SM - Med J Australia 1991; 154: 617-622)

  15. Hemofiltration • Can be combined with acute high flux HD • Indicated in cases where removal of plasma toxin is then replaced by redistributed toxin from tissue

  16. Solute Molecular Weight and Clearance Solute (MW) Sieving Coefficient Diffusion Coefficient Urea (60) 1.01 ± 0.05 1.01 ± 0.07 Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06 Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04* Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04** *P<0.05 vs sieving coefficient**P<0.01 vs sieving coefficient

  17. HD to Convective HF High Flux HD 8 liter CVVHDF 4 liter CVVH Lithium mmol/l 2 liter CVVH

  18. L i m E q / L CVVHD following HD for Lithium poisoning HD started Li Therapeutic range 0.5-1.5 mEq/L CVVHD started CT-190 (HD) Multiflo-60 both patients BFR-pt #1 200 ml/min HD & CVVHD -pt # 2 325 ml/min HD & 200 ml/min CVVHD PO4 Based dialysate at 2L/1.73m2/hr Hours

  19. Intoxicants amenable to Hemofiltration • vancomycin • methanol • procainamide • hirudin • thallium • lithium • methotrexate

  20. Albumin augmented Diffusive Hemofiltration • Serum half-life (hr) Valproic Acid Total UnboundTotal • Baseline 10.3 10.0 SievingCoefficient* • CVVHD 7.7 4.5 0.12 • CVVHD 4.0 3.0 0.32 +Albumin

  21. Carbamazine Clearance Natural Decay Clearance with Albumin Dialysis Askenazi et al, Pediatrics 2004

  22. Conclusion • RRT with the use of high flux hemodialysis and convective hemofiltration may allow for continuous removal of intoxication • Attention to single or double compartment kinetics will dertemine the length of time of excretion

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