RRT and Intoxications Timothy E Bunchman
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Transcript of RRT and Intoxications Timothy E Bunchman
RRT and Intoxications
Timothy E Bunchman
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
There is no hepatic nor renal dysfunction
Lithium level was > 5.1 mmol/l (critical > 4)
Case Study-2
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?
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
PHARMOCOKINETIC COMPARTMENTS
kidneybloodPeripheralliverGI Tract
Distribution Re-distribution
INPUT
ELIMINATION
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)
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
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)
Intoxicants amenable to Hemodialysis vancomycin (high flux) alcohols
diethylene glycol methanol
lithium salicylates
Ethylene Glycol IntoxicationRx with Hemodialysis
0100200300400500600700800900
0 2 4 6
Pt 1Pt 2
Duration of Rx (hrs)
Mg/
ml
(> 3
0 m
g /m
l to x
i c)
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
v el
(m
i c/ d
l )
Rx Rx Rx
Rebound Rebound
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
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)
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
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
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
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
Intoxicants amenable to Hemofiltration vancomycin methanol procainamide hirudin thallium lithium methotrexate
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
Carbamazine ClearanceNatural Decay
Clearance with Albumin Dialysis Askenazi et al, Pediatrics 2004
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