Treatment of intoxications with renal replacement therapy
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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

Timothy E. Bunchman

Professor Pediatric Nephrology & Transplantation


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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

>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


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  • 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


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  • 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)


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Ethylene Glycol IntoxicationRx with Hemodialysis

Mg/ml

(> 30 mg/ml toxic)

Duration of Rx (hrs)


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Vancomycin clearance High efficiency dialysis membrane

Rx

Rx

Rx

Rebound

Rebound

Vanc level

(mic/dl)

Time of therapy


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High flux hemodialysis for Carbamazine Intoxication

Rx

Mic/ml

Hrs from time of ingestion


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  • 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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  • 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)


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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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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


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Carbamazine Clearance

Natural

Decay

Clearance with

Albumin Dialysis

Askenazi et al, Pediatrics 2004


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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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  • 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


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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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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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