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TREATMENT OF INTOXICATIONS WITH RENAL REPLACEMENT THERAPY

TREATMENT OF INTOXICATIONS WITH RENAL REPLACEMENT THERAPY . Timothy E. Bunchman Professor Pediatric Nephrology & Transplantation. INTRODUCTION 2.2 million reported poisonings (1998) 67% in pediatrics Approximately 0.05% required extracorporeal elimination

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TREATMENT OF INTOXICATIONS WITH RENAL REPLACEMENT THERAPY

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  1. TREATMENT OF INTOXICATIONS WITH RENAL REPLACEMENT THERAPY Timothy E. Bunchman Professor Pediatric Nephrology & Transplantation

  2. 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

  3. Poison Management • DECONTAMINATION/TREATMENT OPTIONS FOR OVERDOSE • Standard Airway, Breathing and Circulatory measures take precedent • Oral Charcoal • Bowel Cleansing Regimens • Antidotes IV or PO when applicable • IV Hydration

  4. Extracorporeal Methods • Peritoneal Dialysis • Hemodialysis • Hemofiltration • Charcoal hemoperfusion • Considerations • Volume of Distribution (Vd)/compartments • molecular size • protein/lipid binding • solubility

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

  6. 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)

  7. 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

  8. PERITONEAL DIALYSIS • 1st done in 1934 for 2 anuric patients after sublimate poisoning (Balzs et al; Wien Klin Wschr 1934;47:851 ) • Allows diffusion of toxins across peritoneal membrane from mesenteric capillaries into dialysis solution within the peritoneal cavity • limited use in poisoning (clears drugs with low Mwt., Small Vd, minimal protein binding & those that are water soluble) • alcohols, NaCl intoxications, salicylates

  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. CHARCOAL HEMOPERFUSION • optimal drug characteristics for removal: • Adsorbed by activated charcoal • small Vd (< 1 L/Kg) • single compartment kinetics • protein binding minimal (can clear some highly protein bound molecules) • low endogenous clearance (< 4ml/Kg/min) • (Pond, SM - Med J Australia 1991; 154: 617-622)

  15. Intoxicants amenable to Charcoal Hemoperfusion • Carbamazepine • phenobarbital • phenytoin • theophylline • paraquat

  16. 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)

  17. Continuous Detoxification methods • CAVHF, CAVHD, CAVHP, CVVHF, CVVHD, CVVHP • Indicated in cases where removal of plasma toxin is then replaced by redistributed toxin from tissue • Can be combined with acute high flux HD

  18. Albumin 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

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

  20. 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

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

  22. Plasmapheresis / Exchange Blood Transfusions • Plasmapheresis (Seyffart G. Trans Am Soc Artif Intern Organs 1982; 28:673) • role in intoxication not clearly established • most useful for highly protein bound agents • Exchange Blood Transfusions • Pediatric experience > than adult • Methemoglobinemia • overall very limited role in poisoning

  23. OTHER ISSUES • Optimal prescription • biocompatible filters - may increase protein adsorption • maximal blood flow rates (ie good access) • physiological solution (ARF vs non ARF) • ? Removal of antidote • counter-current D maximal removal of toxins

  24. Albumin Hemofiltration • Novel Approaches to facilitating intoxicant removal during hemofiltration • Addition of albumin to dialysate • Enhancement of Valproic Acid removal during CVVHD by the addition of albumin to dialysate • A 6-1/2 month old infant was hospitalized with a serum valproic acid level of 1043 mcg/mL. He received CVVHD (blood flow 80 mL/min; prefilter replacement fluid: 400mL/hr; dialysate: 450 mL/hr) without and with albumin 45 gm/L) in the dialysate. Serial serum levels were obtained before and during dialysis. (PRISMA- M60) • V Chadha et al. pCRRT- Orlando 2002

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