TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY

1. TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY Patrick D Brophy MD FRCPC University of Michigan June 23, 2000 1st annual PCRRT, Orlando, FL

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

5. (p. brophy) 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) (p. brophy)

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 (p. brophy)

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

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12. (p. brophy) • 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)

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14. (p. brophy) • Intoxicants amenable to Charcoal Hemoperfusion • Carbamazepine • phenobarbital • phenytoin • theophylline • paraquat

15. (p. brophy) • 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)

16. (p. brophy) • 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

17. (p. brophy) 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

18. (p. brophy) • Intoxicants amenable to Hemofiltration • vancomycin • methanol • procainamide • hirudin • thallium • lithium • methotrexate

19. (p. brophy) • 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

20. (p. brophy) • 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

21. (p. brophy) • DIALYZE EARLY ! DIALYZE OFTEN ! • “PHYSIOLOGY ? ITS GOT NOTHING TO DO WITH PHYSIOLOGY ! HELL, THIS IS CHEMISTRY” • T. Bunchman - 1999

22. (p. brophy) • ACKNOWLEDGEMENTS • TIMOTHY BUNCHMAN • DIANE HILFINGER • ANDREE GARDNER • JOHN GARDNER • THERESA MOTTES • TIM KUDELKA • LAURA DORSEY & BETSY ADAMS