Hemodialysis and Hemofiltration in Pediatrics: An Approach to Intoxication Karen Papez MD University of Michigan Pediatric...
2002 Annual Report of American Association of Poison Control Centers <ul><li>Nearly 2.4 million human exposures reported b...
Enhanced Elimination Techniques for Poisonings <ul><li>Enhanced elimination techniques were used for 1457 cases (0.06%) in...
Treatment Measures Available for Poisonings <ul><li>Enhance Elimination (Cont.) </li></ul><ul><ul><li>Extracorporeal Metho...
Toxin Clearance <ul><li>What effects clearance? </li></ul><ul><ul><li>Volume of distribution </li></ul></ul><ul><ul><li>Wh...
<ul><li>HEMODIALYSIS </li></ul><ul><ul><li>Optimal drug characteristics for removal: </li></ul></ul><ul><ul><ul><li>Relati...
<ul><li>HEMOFILTRATION </li></ul><ul><ul><li>Optimal drug characteristics for removal: </li></ul></ul><ul><ul><ul><li>Rela...
Additional Factors when Considering Enhanced Elimination Methods <ul><li>Drug kinetics should be reviewed </li></ul><ul><u...
Case 1 <ul><li>14 year old female with history of depression, found slurring words, intermittently confused in her bedroom...
Physical Exam at Admission to PICU <ul><li>T 38.8  P 125  RR 32  BP 158/75  Wt  75 Kg </li></ul><ul><li>Generally: GCS var...
Laboratory Analyses <ul><li>148  121  13  98 </li></ul><ul><li>5.4  7  2.1 </li></ul><ul><li>9.4  38  0.3 </li></ul><ul><l...
Calculated Osmolality with Dialysis in Ethylene Glycol Intoxication HD Started CVVHDF Started CT-190 Prisma dialyzer Multi...
Case 2 <ul><li>12 year old female with history of bipolar disorder had started an increased dose of lithium 6 weeks prior ...
Physical Exam at Admission to PICU <ul><li>T afebrile  P  82  RR  23  BP  104/46  Wt 33 Kg </li></ul><ul><li>Generally: Co...
Laboratory Analyses <ul><li>133   107  31  73 </li></ul><ul><li>4.3  22  1.2 </li></ul><ul><li>6.8  7.0  35  0.6 </li></ul...
Lithium Clearance on Dialysis CVVHD Started HD Started CVVHD Stopped CT-190 Prisma dialyzer Multiflo-100 BFR -HD  250 ml/m...
Lithium Redistributes from Intracellular Compartment:  <ul><li>  </li></ul>Arrows indicate beginning and end of HD. A sign...
CVVHD Following HD for Lithium Poisoning HD started CVVHD started CT-190 (HD) Prisma dialyzer -Multiflo-60  (#1,2) -Multif...
0.88 ml/min/kg 0.15-0.2 90%* Yes 138 Salicylates 0.13 ml/min/kg 1.1 ml/min/kg 0.19-0.23  Tot 1.3  Free 90%* No 144 Valproi...
Conclusions  <ul><li>High efficiency hemodialysis and hemofiltration may alter the current “treatment of choice”.  </li></...
<ul><li>ACKNOWLEDGEMENTS </li></ul><ul><ul><li>THERESA MOTTES </li></ul></ul><ul><ul><li>TIM KUDELKA </li></ul></ul><ul><u...
<ul><li>OTHER ISSUES </li></ul><ul><ul><li>Optimal prescription </li></ul></ul><ul><ul><li>Biocompatible filters - may inc...
Specific Antidotes <ul><li>Should be used adjunctively with supportive therapy. </li></ul><ul><li>Examples : </li></ul><ul...
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Hemodialysis and Hemofiltration

  1. 1. Hemodialysis and Hemofiltration in Pediatrics: An Approach to Intoxication Karen Papez MD University of Michigan Pediatric Nephrology, Dialysis & Transplantation 3rd annual PCRRT, Orlando, FL
  2. 2. 2002 Annual Report of American Association of Poison Control Centers <ul><li>Nearly 2.4 million human exposures reported by 64 participating poison centers in 2002. </li></ul><ul><ul><li>4.9% increase from 2001 </li></ul></ul><ul><li>Children <3 yrs: 39% of all human exposures </li></ul><ul><li>Children <6 yrs: 51.6% of all exposures </li></ul><ul><li>*Pediatricians and pediatric subspecialists need to be prepared to handle the majority of poison exposures. </li></ul><ul><ul><ul><li>Watson WA et al. Am J Emerg Med 21: 2003 </li></ul></ul></ul><ul><ul><ul><li>Litovitz TL et al. Am J Emerg Med 20: 2002 </li></ul></ul></ul>
  3. 3. Enhanced Elimination Techniques for Poisonings <ul><li>Enhanced elimination techniques were used for 1457 cases (0.06%) in 2002. </li></ul><ul><ul><li>A near 8% increase over 2001 reports </li></ul></ul><ul><ul><ul><li>Hemodialysis: 1400 [up 9% from 2001] </li></ul></ul></ul><ul><ul><ul><li>Hemoperfusion: 30 [down 33% from 2001] </li></ul></ul></ul><ul><ul><ul><li>Other Extracorporeal Procedures: 27 </li></ul></ul></ul><ul><li>*Pediatric nephrologists and intensivists need to be equipped with advanced techniques to handle such clinical situations. </li></ul>
  4. 4. Treatment Measures Available for Poisonings <ul><li>Enhance Elimination (Cont.) </li></ul><ul><ul><li>Extracorporeal Methods </li></ul></ul><ul><ul><ul><li>Hemodialysis </li></ul></ul></ul><ul><ul><ul><ul><li>Standard </li></ul></ul></ul></ul><ul><ul><ul><ul><li>High Efficiency/High Flux </li></ul></ul></ul></ul><ul><ul><ul><li>Hemofiltration </li></ul></ul></ul><ul><ul><ul><li>Hemoperfusion </li></ul></ul></ul><ul><ul><ul><li>Exchange Transfusion </li></ul></ul></ul><ul><ul><ul><li>Plasma exchange </li></ul></ul></ul>
  5. 5. Toxin Clearance <ul><li>What effects clearance? </li></ul><ul><ul><li>Volume of distribution </li></ul></ul><ul><ul><li>Whether or not the drug is primarily renally excreted (competing pathways) </li></ul></ul><ul><ul><li>Protein binding </li></ul></ul><ul><ul><li>Molecular size of the drug </li></ul></ul><ul><ul><li>Mode of therapy-HD, CVVH vs CVVHD vs CVVHDF </li></ul></ul><ul><ul><li>Hemofilter membrane properties </li></ul></ul><ul><ul><ul><ul><ul><li>Pond, SM - Med J Australia 1991; 154: 617-622 </li></ul></ul></ul></ul></ul>
  6. 6. <ul><li>HEMODIALYSIS </li></ul><ul><ul><li>Optimal drug characteristics for removal: </li></ul></ul><ul><ul><ul><li>Relative molecular mass < 500 Daltons </li></ul></ul></ul><ul><ul><ul><li>Water soluble </li></ul></ul></ul><ul><ul><ul><li>Small Vd (< 1 L/Kg) </li></ul></ul></ul><ul><ul><ul><li>Minimal plasma protein binding </li></ul></ul></ul><ul><ul><ul><li>Single compartment kinetics </li></ul></ul></ul><ul><ul><ul><li>Low endogenous clearance (< 4ml/Kg/min) </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Pond, SM - Med J Australia 1991; 154: 617-622 </li></ul></ul></ul></ul></ul>
  7. 7. <ul><li>HEMOFILTRATION </li></ul><ul><ul><li>Optimal drug characteristics for removal: </li></ul></ul><ul><ul><ul><li>Relative molecular mass less than the cut-off of the filter fibres (usually < 40,000 daltons) </li></ul></ul></ul><ul><ul><ul><li>Small Vd (< 1 L/Kg) </li></ul></ul></ul><ul><ul><ul><li>Single compartment kinetics </li></ul></ul></ul><ul><ul><ul><li>Low endogenous clearance (< 4ml/Kg/min) </li></ul></ul></ul><ul><ul><ul><ul><li>Pond, SM - Med J Australia 1991; 154: 617-622 </li></ul></ul></ul></ul>
  8. 8. Additional Factors when Considering Enhanced Elimination Methods <ul><li>Drug kinetics should be reviewed </li></ul><ul><ul><li>Note: Kinetics may differ in an overdose situation </li></ul></ul><ul><ul><ul><li>Valproic acid: 90% protein bound with nl levels </li></ul></ul></ul><ul><ul><ul><li>Valproic acid: 70% bound at levels of 135 mcg/ml </li></ul></ul></ul><ul><ul><ul><li> : 35% bound at levels of 300 mcg/ml </li></ul></ul></ul><ul><ul><li>*The higher the levels and the more unbound drug that exists, the more effectively it may be removed. </li></ul></ul>
  9. 9. Case 1 <ul><li>14 year old female with history of depression, found slurring words, intermittently confused in her bedroom. </li></ul><ul><li>During period of lucency, told mother she drank something a schoolmate gave her to “get high.” States this was 18 hours before presentation to local ER. </li></ul>
  10. 10. Physical Exam at Admission to PICU <ul><li>T 38.8 P 125 RR 32 BP 158/75 Wt 75 Kg </li></ul><ul><li>Generally: GCS variable, from verbal response to voice to mild response to pain. </li></ul><ul><li>HEENT: Pupils equally round, sluggishly reactive to light, mucous membranes dry </li></ul><ul><li>Resp: Deep, tachypneic, clear to auscultation </li></ul><ul><li>CV: RRR, no murmur, peripheral pulses 2/4 </li></ul><ul><li>Abd: Soft, nondistended, hypoactive bowel sounds </li></ul>
  11. 11. Laboratory Analyses <ul><li>148 121 13 98 </li></ul><ul><li>5.4 7 2.1 </li></ul><ul><li>9.4 38 0.3 </li></ul><ul><li>4.8 4.0 59 143 </li></ul><ul><li>11.7 16.8 163 </li></ul><ul><li>50.4 </li></ul><ul><li>7.24 / 18 / 113 / 8 </li></ul><ul><li>UA SG 1.015, pH 5, normal for all substrates </li></ul><ul><li>AG 20 </li></ul><ul><li>Calc osm 306 </li></ul><ul><li>Serum osm 311 </li></ul><ul><li>CPK 388 </li></ul><ul><li>NH 3 38 </li></ul><ul><li>Ethanol negative </li></ul><ul><li>Urine drug screen negative </li></ul><ul><li>β hCG negative </li></ul><ul><li>Salicylate <1 </li></ul><ul><li>Acetaminophen <10 </li></ul><ul><li>Ethylene glycol 24.2 </li></ul>
  12. 12. Calculated Osmolality with Dialysis in Ethylene Glycol Intoxication HD Started CVVHDF Started CT-190 Prisma dialyzer Multiflo-100 BFR -HD 250 ml/min -CVVHDF 180 ml/min PO4 based dialysate - 4L/1.73m 2 /hr
  13. 13. Case 2 <ul><li>12 year old female with history of bipolar disorder had started an increased dose of lithium 6 weeks prior to admission. </li></ul><ul><li>Was slurring her speech on morning of admission, and had irregular constant movements of her arms and legs. </li></ul>
  14. 14. Physical Exam at Admission to PICU <ul><li>T afebrile P 82 RR 23 BP 104/46 Wt 33 Kg </li></ul><ul><li>Generally: Confused, slurring speech </li></ul><ul><li>HEENT: NC, AT, Mucous membranes moist </li></ul><ul><li>Resp: Clear to auscultation </li></ul><ul><li>CV: Regular rate and rhythm, no murmur </li></ul><ul><li>Abdomen: Soft, normoactive bowel sounds </li></ul><ul><li>Skin: Erythematous rash over abdomen </li></ul><ul><li>Neuro: Athetoid movements as noted in HPI </li></ul>
  15. 15. Laboratory Analyses <ul><li>133 107 31 73 </li></ul><ul><li>4.3 22 1.2 </li></ul><ul><li>6.8 7.0 35 0.6 </li></ul><ul><li>4.1 25 215 </li></ul><ul><li>10.5 12.1 176 </li></ul><ul><li>34.4 </li></ul><ul><li>7.36 / 50 / 28 / 28 </li></ul><ul><li>UA SG 1.010, pH 6.5, pro 1+, ket 2+, LE 1+, otherwise normal </li></ul><ul><li>AG 4 </li></ul><ul><li>CPK 939 </li></ul><ul><li>NH 3 38 </li></ul><ul><li>Ethanol and volatile acids negative </li></ul><ul><li>Urine drug screen negative </li></ul><ul><li>β hCG negative </li></ul><ul><li>Salicylate <1 </li></ul><ul><li>Acetaminophen <10 </li></ul><ul><li>Lithium 7.34 </li></ul><ul><li>EKG First degree heart block, PR 188 ms, prolonged QTc 520 ms </li></ul>
  16. 16. Lithium Clearance on Dialysis CVVHD Started HD Started CVVHD Stopped CT-190 Prisma dialyzer Multiflo-100 BFR -HD 250 ml/min -CVVHDF 180 ml/min PO4 based dialysate - 4L/1.73m 2 /hr
  17. 17. Lithium Redistributes from Intracellular Compartment: <ul><li> </li></ul>Arrows indicate beginning and end of HD. A significant rebound in serum concentration occurred after a 5-hr HD treatment with recurrence of neurologic impairment. An additional 4-hour hemodialysis treatment was then begun. F rom Goldfarb DS in Goldfrank’s Toxologic Emergencies, 7 th Ed. 2002 Hemofiltration May Attenuate Rebound Phenomenon!
  18. 18. CVVHD Following HD for Lithium Poisoning HD started CVVHD started CT-190 (HD) Prisma dialyzer -Multiflo-60 (#1,2) -Multiflo-100 (#3) BFR- HD -pt # 1 200 ml/min -pt # 2 325 ml/min -pt # 3 250 ml/min BFR- CVVHD 200 ml/min - All 3 pts. PO 4 Based dialysate at 2L/1.73m 2 /hr (#1,2) 4L/1.73m2/hr (#3) Li Therapeutic range 0.5-1.5 mEq/L
  19. 19. 0.88 ml/min/kg 0.15-0.2 90%* Yes 138 Salicylates 0.13 ml/min/kg 1.1 ml/min/kg 0.19-0.23 Tot 1.3 Free 90%* No 144 Valproic acid 0.47-1.1 10-50% Yes 1486 Vancomycin 1.3 ml/min/kg 0.8-1.6 75% No 236 Carbamaz-epine 0.1 ml/min/kg 0.5 24-60% No 232 Phenobarb 0.65 ml/min/kg 0.4-0.7 55% Yes 180 Theophylline 2.0 ml/min/kg 0.6 0 Yes 62 Ethylene Glycol 0.7 ml/min/kg 0.7 0 Yes 32 Methanol 0.4 ml/min/kg 0.6-1.0 0 Yes 7 Lithium Endogenous Clearance Vol of Distrib [L/kg] % Prot Bound H2O Sol MW [Daltons] Drug
  20. 20. Conclusions <ul><li>High efficiency hemodialysis and hemofiltration may alter the current “treatment of choice”. </li></ul><ul><li>Pediatric nephrologists need to be aware that more than one treatment option exists for many toxicology situations, and the modality selected should be that tailored to their patient’s needs. </li></ul>
  21. 21. <ul><li>ACKNOWLEDGEMENTS </li></ul><ul><ul><li>THERESA MOTTES </li></ul></ul><ul><ul><li>TIM KUDELKA </li></ul></ul><ul><ul><li>BETSY ADAMS </li></ul></ul><ul><ul><li>TAMMY KELLY </li></ul></ul><ul><ul><li>ROBIN NIEVAARD </li></ul></ul><ul><ul><li>DAVID KERSHAW </li></ul></ul><ul><ul><li>PATRICK BROPHY </li></ul></ul>
  22. 22. <ul><li>OTHER ISSUES </li></ul><ul><ul><li>Optimal prescription </li></ul></ul><ul><ul><li>Biocompatible filters - may increase protein adsorption </li></ul></ul><ul><ul><li>Maximal blood flow rates (i.e. good access) </li></ul></ul><ul><ul><li>Physiological solution (ARF vs non ARF) </li></ul></ul><ul><ul><li>Potential removal of antidote </li></ul></ul><ul><ul><li>Counter-current dialysate maximal removal of toxins </li></ul></ul>
  23. 23. Specific Antidotes <ul><li>Should be used adjunctively with supportive therapy. </li></ul><ul><li>Examples : </li></ul><ul><li>N-acetyl cysteine [for Acetaminophen] </li></ul><ul><li>Benzodiazepines [for Flumazenil] </li></ul><ul><li>Flumazenil [for Benzodiazepines] </li></ul><ul><li>Naloxone [for Opiates] </li></ul><ul><li>Calcium [for Calcium channel blockers] </li></ul><ul><li>Atropine [for Acetylcholinesterase inhibitors] </li></ul><ul><li>Fomepizole [for Ethylene glycol, Methanol, & Diethylene Glycol] </li></ul><ul><li>Ethanol [for Ethylene glycol, Methanol, & Diethylene Glycol] </li></ul>

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