Download Treatment of Intox - Pediatric Continuous Renal Replacement Therapy

TREATMENT OF
INTOXICATIONS WITH
CONTINUOUS RENAL
REPLACEMENT THERAPY
Patrick D Brophy MD FRCPC
University of Michigan
June 23, 2000
1st annual PCRRT, Orlando, FL
(p. brophy)
• 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
(p. brophy)
• 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
(p. brophy)
• Extracorporeal Methods
– Peritoneal Dialysis
– Hemodialysis
– Hemofiltration
– Charcoal hemoperfusion
• Considerations
– Volume of Distribution (Vd)/compartments
– molecular size
– protein/lipid binding
– solubility
(p. brophy)
PHARMOCOKINETIC COMPARTMENTS
ELIMINATION
I
N
P
U
T
Distribution
Re-distribution
kidney
blood
Peripheral
liver
GI Tract
(p. brophy)
• 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)
(p. brophy)
• 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
(p. brophy)
• 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
(p. brophy)
• 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)
(p. brophy)
• Intoxicants amenable to Hemodialysis
– vancomycin (high flux)
– alcohols
• diethylene glycol
• methanol
– lithium
– salicylates
(p. brophy)
High Flux Dialysis for
Vancomycin Overdose
250
200
150
Vanco Level (ug/ml)
100
50
0
0
3
15
18
30
33
(p. brophy)
• 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)
(p. brophy)
High Flux Dialysis for
Tegretol Overdose
35
30
25
20
15
10
5
51
35
30
28
25
16
7
0
0
(p. brophy)
• Intoxicants amenable to Charcoal
Hemoperfusion
–
–
–
–
–
Carbamazepine
phenobarbital
phenytoin
theophylline
paraquat
(p. brophy)
• 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)
(p. brophy)
• 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
(p. brophy)
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
(p. brophy)
• Intoxicants amenable to Hemofiltration
–
–
–
–
–
–
–
vancomycin
methanol
procainamide
hirudin
thallium
lithium
methotrexate
(p. brophy)
• 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
(p. brophy)
• 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
(p. brophy)
• DIALYZE EARLY ! DIALYZE OFTEN !
• “PHYSIOLOGY ? ITS GOT NOTHING
TO DO WITH PHYSIOLOGY ! HELL,
THIS IS CHEMISTRY”
– T. Bunchman - 1999
(p. brophy)
• ACKNOWLEDGEMENTS
–
–
–
–
–
–
–
TIMOTHY BUNCHMAN
DIANE HILFINGER
ANDREE GARDNER
JOHN GARDNER
THERESA MOTTES
TIM KUDELKA
LAURA DORSEY & BETSY ADAMS