Transcript TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL

RRT and Intoxications
Timothy E Bunchman
Case Study-1
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17 y/o female with poly pharmacy
overdose including risperidone,
stratttera and long acting Lithium
She is not on any medications
chronically
12 hours post overdose she is semi
comatose with QT interval changes on
EKG
Case Study-2
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There is no hepatic nor renal
dysfunction
Lithium level was > 5.1 mmol/l
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(critical > 4)
Thought Process of RRT in
Intoxication
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Is the drug long or short acting
Is there any inhibition of the natural
excretion of the drug
What is the molecular weight?
What is the protein binding?
Is this single or double compartment?
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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
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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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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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)
Hemofiltration
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Can be combined with acute high flux
HD
Indicated in cases where removal of
plasma toxin is then replaced by
redistributed toxin from tissue
Solute Molecular Weight
and Clearance
Solute (MW)
Sieving Coefficient
Diffusion Coefficient
Urea (60)
1.01 ± 0.05
1.01 ± 0.07
Creatinine (113)
1.00 ± 0.09
1.01 ± 0.06
Uric Acid (168)
1.01 ± 0.04
0.97 ± 0.04*
Vancomycin (1448)
0.84 ± 0.10
0.74 ± 0.04**
*P<0.05 vs sieving coefficient
**P<0.01 vs sieving coefficient
HD to Convective HF
High Flux HD
6
5
Lithium
mmol/l
Li Level
8 liter CVVHDF
4 liter CVVH
4
3
2 liter CVVH
2
1
0
0
1
2
4
6
14
23
27
48
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
Albumin augmented Diffusive
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
Conclusion
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RRT with the use of high flux
hemodialysis and convective
hemofiltration may allow for continuous
removal of intoxication
Attention to single or double
compartment kinetics will dertemine the
length of time of excretion