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. INTRODUCTION 2.2 million reported poisonings (1998) 67% in pediatrics
(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. Poison Management DECONTAMINATION/TREATMENT OPTIONS FOR OVERDOSE
(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. Extracorporeal Methods
(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. (p. brophy)
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. high probability of significant morbidity/mortality
(p. brophy)
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. (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. HEMODIALYSIS optimal drug characteristics for removal:
(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: )

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

11. (p. brophy)

12. CHARCOAL HEMOPERFUSION
(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: )

13. (p. brophy)

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

15. HEMOFILTRATION optimal drug characteristics for removal:
(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: )

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

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

19. Plasmapheresis / Exchange Blood Transfusions
(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. OTHER ISSUES Optimal prescription
(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. DIALYZE EARLY ! DIALYZE OFTEN !
(p. brophy)
DIALYZE EARLY ! DIALYZE OFTEN !
“PHYSIOLOGY ? ITS GOT NOTHING TO DO WITH PHYSIOLOGY ! HELL, THIS IS CHEMISTRY”
T. Bunchman

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