Docstoc

TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY

Document Sample
TREATMENT OF INTOXICATIONS WITH CONTINUOUS RENAL REPLACEMENT THERAPY Powered By Docstoc
					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
Case Study-2
   There is no hepatic nor renal
    dysfunction
   Lithium level was > 5.1 mmol/l
       (critical > 4)
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


                                        ELIMINATION
I
N                                           kidney
P                                           blood
U                                           Peripheral
T                                           liver
       Distribution   Re-distribution
                                            GI Tract
   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                  INDICATIONS
      >48 hrs on vent              severe intoxication

      ARF                           with abnormal vital
       Impaired                     signs
       metabolism                   complications of


       high probability of          coma
       significant                  prolonged coma

       morbidity/mortality          intoxication with an

      progressive clinical          extractable drug
       deterioration
   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 Intoxication
Rx with Hemodialysis
 900
 800
 700
 600
 500                                  Pt 1
 400                                  Pt 2
 300
 200
 100
   0
       0        2           4     6


           Duration of Rx (hrs)
      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         27        30

                   Time of therapy
         High flux hemodialysis for
         Carbamazine Intoxication
         35                     Rx
         30
         25
Mic/ml




         20
                                                          CBZ level
         15
                                                          (nl < 12)
         10
          5
          0
              0   5   10   15    20   25   30   35   40

              Hrs from time of ingestion
   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 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                   Li Level
          6

          5
                           8 liter CVVHDF
          4                                  4 liter CVVH
Lithium
mmol/l    3

          2                                           2 liter CVVH
          1

          0
              0   1   2   4   6   14   23   27   48
 CVVHD following HD for Lithium poisoning
L 6       HD started            Li Therapeutic range            Pt #1
i                               0.5-1.5 mEq/L                   Pt #2
  5
                       CVVHD started                    CT-190 (HD)
m 4
E                                                       Multiflo-60
                                                        both patients
q 3                                                     BFR-pt #1 200 ml/min
/                                                       HD & CVVHD
  2                                                          -pt # 2 325 ml/min
L
                                                        HD & 200 ml/min
  1                                                                 CVVHD
                                                        PO4 Based dialysate at
  0                                                                 2L/1.73m2/hr
                             Hours
      0



                   5



                                6



                                            12



                                                       24
   Intoxicants amenable to Hemofiltration
       vancomycin
       methanol
       procainamide
       hirudin
       thallium
       lithium
       methotrexate
Albumin augmented Diffusive
Hemofiltration
   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
                                                     Natural
      Carbamazine Clearance                          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

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:13
posted:4/21/2011
language:English
pages:22