Transcript Z06-Bunchman Intox PCRRT4 - Pediatric Continuous Renal

TREATMENT OF
INTOXICATIONS WITH RENAL
REPLACEMENT THERAPY
Timothy E. Bunchman
Professor Pediatric Nephrology & Transplantation
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INTRODUCTION
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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
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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
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Peritoneal Dialysis
Hemodialysis
Hemofiltration
Charcoal hemoperfusion
Considerations
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Volume of Distribution (Vd)/compartments
molecular size
protein/lipid binding
solubility
PHARMOCOKINETIC COMPARTMENTS
ELIMINATION
I
N
P
U
T
Distribution
Re-distribution
kidney
blood
Peripheral
liver
GI Tract
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GENERAL PRINCIPLES
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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
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Impaired
metabolism
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high probability of
significant
morbidity/mortality
 progressive clinical
deterioration
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INDICATIONS
 severe intoxication
with abnormal vital
signs
 complications of
coma
 prolonged coma
 intoxication with an
extractable drug
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PERITONEAL DIALYSIS
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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
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optimal drug characteristics for removal:
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relative molecular mass < 500
water soluble
small Vd (< 1 L/Kg)
minimal plasma protein binding
single compartment kinetics
low endogenous clearance (< 4ml/Kg/min)
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(Pond, SM - Med J Australia 1991; 154: 617-622)
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Intoxicants amenable to Hemodialysis
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vancomycin (high flux)
alcohols
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diethylene glycol
methanol
lithium
salicylates
Ethylene Glycol Intoxication
Rx with Hemodialysis
900
800
700
600
500
Pt 1
Pt 2
400
300
200
100
0
0
2
4
Duration of Rx (hrs)
6
Vancomycin clearance
High efficiency dialysis
membrane
250
Rx
Rx
Rx
200
Rebound
Rebound
150
Pt 1
Pt 2
100
50
0
0
3
12
15
Time of therapy
27
30
High flux hemodialysis for
Carbamazine Intoxication
Rx
35
30
Mic/ml
25
20
CBZ level
(nl < 12)
15
10
5
0
0
5
10
15
20
25
30
Hrs from time of ingestion
35
40
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CHARCOAL HEMOPERFUSION
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optimal drug characteristics for removal:
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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)
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(Pond, SM - Med J Australia 1991; 154: 617-622)
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Intoxicants amenable to Charcoal
Hemoperfusion
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Carbamazepine
phenobarbital
phenytoin
theophylline
paraquat
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HEMOFILTRATION
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optimal drug characteristics for removal:
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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)
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(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
Albumin Hemofiltration
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Serum half-life (hr) Valproic Acid
Total Unbound
Total
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Baseline 10.3
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CVVHD
7.7
4.5
0.12
CVVHD
+Albumin
4.0
3.0
0.32
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10.0
SievingCoefficient*
Carbamazine Clearance
Clearance with
Albumin Dialysis
Askenazi et al, Pediatrics 2004
Natural
Decay
CVVHD following HD for Lithium poisoning
L 6
i
HD started
5
CVVHD started
m 4
E
q 3
/
2
L
Pt #1
Pt #2
Li Therapeutic range
0.5-1.5 mEq/L
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
1
0
Hours
24
12
6
5
0
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Intoxicants amenable to Hemofiltration
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vancomycin
methanol
procainamide
hirudin
thallium
lithium
methotrexate
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Plasmapheresis / Exchange Blood
Transfusions
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Plasmapheresis
(Seyffart G. Trans Am Soc Artif Intern Organs 1982;
28:673)
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role in intoxication not clearly established
most useful for highly protein bound agents
Exchange Blood Transfusions
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Pediatric experience > than adult
Methemoglobinemia
overall very limited role in poisoning
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OTHER ISSUES
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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 Hemofiltration
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Novel Approaches to facilitating intoxicant removal
during hemofiltration
Addition of albumin to dialysate
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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