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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

TREATMENT OF INTOXICATIONS WITH RENAL REPLACEMENT THERAPY

Timothy E. Bunchman

Professor Pediatric Nephrology & Transplantation

slide2
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
slide3
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
slide4
Extracorporeal Methods
    • Peritoneal Dialysis
    • Hemodialysis
    • Hemofiltration
    • Charcoal hemoperfusion
  • Considerations
    • Volume of Distribution (Vd)/compartments
    • molecular size
    • protein/lipid binding
    • solubility
slide5

ELIMINATION

I

N

P

U

T

Distribution

Re-distribution

slide6
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)

slide7
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

slide8
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
slide9
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)
slide10
Intoxicants amenable to Hemodialysis
    • vancomycin (high flux)
    • alcohols
      • diethylene glycol
      • methanol
    • lithium
    • salicylates
ethylene glycol intoxication rx with hemodialysis
Ethylene Glycol IntoxicationRx with Hemodialysis

Mg/ml

(> 30 mg/ml toxic)

Duration of Rx (hrs)

vancomycin clearance high efficiency dialysis membrane
Vancomycin clearance High efficiency dialysis membrane

Rx

Rx

Rx

Rebound

Rebound

Vanc level

(mic/dl)

Time of therapy

high flux hemodialysis for carbamazine intoxication
High flux hemodialysis for Carbamazine Intoxication

Rx

Mic/ml

Hrs from time of ingestion

slide14
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)
slide15
Intoxicants amenable to Charcoal Hemoperfusion
    • Carbamazepine
    • phenobarbital
    • phenytoin
    • theophylline
    • paraquat
slide16
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)
slide17
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
albumin hemofiltration
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

carbamazine clearance
Carbamazine Clearance

Natural

Decay

Clearance with

Albumin Dialysis

Askenazi et al, Pediatrics 2004

slide20

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

slide21
Intoxicants amenable to Hemofiltration
    • vancomycin
    • methanol
    • procainamide
    • hirudin
    • thallium
    • lithium
    • methotrexate
slide22
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
slide23
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
albumin hemofiltration24
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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