TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY

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TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL
REPLACEMENT THERAPY

• Patrick D Brophy MD FRCPC
• University of Michigan
• June 23, 2000
• 1st annual PCRRT, Orlando, FL

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• 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

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• 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

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

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ELIMINATION
I N P U T
Distribution
Re-distribution
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• 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)

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• INDICATIONS
• gt48 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

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• PERITONEAL DIALYSIS
• 1st done in 1934 for 2 anuric patients after
  sublimate poisoning (Balzs et al Wien Klin Wschr
  193447851 )
• 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

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

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

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

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

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

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• 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

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

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• Plasmapheresis / Exchange Blood Transfusions
• Plasmapheresis (Seyffart G. Trans Am Soc Artif
  Intern Organs 1982 28673)
• role in intoxication not clearly established
• most useful for highly protein bound agents
• Exchange Blood Transfusions
• Pediatric experience gt than adult
• Methemoglobinemia
• overall very limited role in poisoning

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• 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

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• DIALYZE EARLY ! DIALYZE OFTEN !
• PHYSIOLOGY ? ITS GOT NOTHING TO DO WITH
  PHYSIOLOGY ! HELL, THIS IS CHEMISTRY
• T. Bunchman - 1999

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• ACKNOWLEDGEMENTS
• TIMOTHY BUNCHMAN
• DIANE HILFINGER
• ANDREE GARDNER
• JOHN GARDNER
• THERESA MOTTES
• TIM KUDELKA
• LAURA DORSEY BETSY ADAMS