TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY Patrick D Brophy MD FRCPC...
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Transcript of TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY Patrick D Brophy MD FRCPC...
TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL
REPLACEMENT THERAPY Patrick D Brophy MD FRCPC
University of Michigan
June 23, 2000
1st annual PCRRT, Orlando, FL
• 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
kidneybloodPeripheralliverGI Tract
Distribution Re-distribution
INPUT
ELIMINATION
(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 forVancomycin Overdose
0
50
100
150
200
250
0 3 15 18 30 33
Vanco Level (ug/ml)
(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 forTegretol Overdose
0
5
10
15
20
25
30
35
(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)
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
(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
(p. brophy)