rrt and intoxications timothy e bunchman. case study-1 17 y/o female with poly pharmacy overdose...
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RRT and Intoxications
Timothy E Bunchman
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Case Study-1 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
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There is no hepatic nor renal dysfunction
Lithium level was > 5.1 mmol/l (critical > 4)
Case Study-2
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Thought Process of RRT in Intoxication
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• 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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PHARMOCOKINETIC COMPARTMENTS
kidney
blood
Peripheral
liver
GI TractDistribution Re-distribution
INPUT
ELIMINATION
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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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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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Intoxicants amenable to Hemodialysis vancomycin (high flux) alcohols
diethylene glycol methanol
lithium salicylates
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Ethylene Glycol IntoxicationRx with Hemodialysis
0
100
200
300
400
500
600
700
800
900
0 2 4 6
Pt 1Pt 2
Duration of Rx (hrs)
Mg/
ml
(> 3
0 m
g/m
l tox
ic)
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Vancomycin clearance High efficiency dialysis
membrane
0
50
100
150
200
250
0 3 12 15 27 30
Pt 1Pt 2
Time of therapy
Van
c le
vel
(m
ic/d
l)
Rx Rx Rx
Rebound Rebound
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0
5
10
15
20
25
30
35
0 5 10 15 20 25 30 35 40
CBZ level(nl < 12)
High flux hemodialysis for Carbamazine Intoxication
Rx
Hrs from time of ingestion
Mic
/ml
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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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Hemofiltration
Can be combined with acute high flux HD
Indicated in cases where removal of plasma toxin is then replaced by redistributed toxin from tissue
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Solute Molecular Weight and ClearanceSolute (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
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HD to Convective HF
0
1
2
3
4
5
6
0 1 2 4 6 14 23 27 48
Li Level
Lithium mmol/l
8 liter CVVHDF
High Flux HD
4 liter CVVH
2 liter CVVH
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0
1
2
3
4
5
6Pt #1Pt #2
Hours
Li
mEq/ L
CVVHD following HD for Lithium poisoning
HD started
CVVHD started CT-190 (HD)Multiflo-60both patientsBFR-pt #1 200 ml/minHD & CVVHD -pt # 2 325 ml/minHD & 200 ml/min
CVVHDPO4 Based dialysate at
2L/1.73m2/hr
Li Therapeutic range0.5-1.5 mEq/L
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Intoxicants amenable to Hemofiltration vancomycin methanol procainamide hirudin thallium lithium methotrexate
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Serum half-life (hr) Valproic Acid Total Unbound Total
Baseline 10.3 10.0 SievingCoefficient*
CVVHD 7.7 4.5 0.12
CVVHD 4.0 3.0 0.32+Albumin
Albumin augmented Diffusive Hemofiltration
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Carbamazine ClearanceNatural Decay
Clearance with Albumin Dialysis
Askenazi et al, Pediatrics 2004
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Conclusion 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