Hemodialysis and Hemofiltration in Pediatrics: An Approach to Intoxication

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Hemodialysis and Hemofiltration in Pediatrics An
Approach to Intoxication

• Karen Papez MD
• University of Michigan
• Pediatric Nephrology, Dialysis Transplantation
• 3rd annual PCRRT, Orlando, FL

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2002 Annual Report of American Association of
Poison Control Centers

• Nearly 2.4 million human exposures reported by 64
  participating poison centers in 2002.
• 4.9 increase from 2001
• Children lt3 yrs 39 of all human exposures
• Children lt6 yrs 51.6 of all exposures
• Pediatricians and pediatric subspecialists need
  to be prepared to handle the majority of poison
  exposures.
• Watson WA et al. Am J Emerg Med 21 2003
• Litovitz TL et al. Am J Emerg Med 20 2002

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Enhanced Elimination Techniques for Poisonings

• Enhanced elimination techniques were used for
  1457 cases (0.06) in 2002.
• A near 8 increase over 2001 reports
• Hemodialysis 1400 up 9 from 2001
• Hemoperfusion 30 down 33 from 2001
• Other Extracorporeal Procedures 27
• Pediatric nephrologists and intensivists need to
  be equipped with advanced techniques to handle
  such clinical situations.

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Treatment Measures Availablefor Poisonings

• Enhance Elimination (Cont.)
• Extracorporeal Methods
• Hemodialysis
• Standard
• High Efficiency/High Flux
• Hemofiltration
• Hemoperfusion
• Exchange Transfusion
• Plasma exchange

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Toxin Clearance

• What effects clearance?
• Volume of distribution
• Whether or not the drug is primarily renally
  excreted (competing pathways)
• Protein binding
• Molecular size of the drug
• Mode of therapy-HD, CVVH vs CVVHD vs CVVHDF
• Hemofilter membrane properties
• Pond, SM - Med J
  Australia 1991 154 617-622

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• HEMODIALYSIS
• Optimal drug characteristics for removal
• Relative molecular mass lt 500 Daltons
• Water soluble
• Small Vd (lt 1 L/Kg)
• Minimal plasma protein binding
• Single compartment kinetics
• Low endogenous clearance (lt 4ml/Kg/min)
• Pond, SM - Med J
  Australia 1991 154 617-622

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• HEMOFILTRATION
• Optimal drug characteristics for removal
• Relative molecular mass less than the cut-off of
  the filter fibres (usually lt 40,000 daltons)
• Small Vd (lt 1 L/Kg)
• Single compartment kinetics
• Low endogenous clearance (lt 4ml/Kg/min)
• Pond, SM - Med J
  Australia 1991 154 617-622

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Additional Factors when Considering Enhanced
Elimination Methods

• Drug kinetics should be reviewed
• Note Kinetics may differ in an overdose
  situation
• Valproic acid 90 protein bound with nl levels
• Valproic acid 70 bound at levels of 135 mcg/ml
• 35 bound at levels of 300
  mcg/ml
• The higher the levels and the more unbound drug
  that exists, the more effectively it may be
  removed.

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Case 1

• 14 year old female with history of depression,
  found slurring words, intermittently confused in
  her bedroom.
• 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.

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Physical Exam at Admission to PICU

• T 38.8 P 125 RR 32 BP 158/75 Wt 75 Kg
• Generally GCS variable, from verbal response to
  voice to mild response to pain.
• HEENT Pupils equally round, sluggishly reactive
  to light, mucous membranes dry
• Resp Deep, tachypneic, clear to auscultation
• CV RRR, no murmur, peripheral pulses 2/4
• Abd Soft, nondistended, hypoactive bowel sounds

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Laboratory Analyses

• 148 121 13 98
• 5.4 7 2.1
• 9.4 38 0.3
• 4.8 4.0 59 143
• 11.7 16.8 163
• 50.4
• 7.24 / 18 / 113 / 8
• UA SG 1.015, pH 5, normal for all substrates

• AG 20
• Calc osm 306
• Serum osm 311
• CPK 388
• NH3 38
• Ethanol negative
• Urine drug screen negative
• ßhCG negative
• Salicylate lt1
• Acetaminophen lt10
• Ethylene glycol 24.2

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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/1.73m2/hr
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Case 2

• 12 year old female with history of bipolar
  disorder had started an increased dose of lithium
  6 weeks prior to admission.
• Was slurring her speech on morning of admission,
  and had irregular constant movements of her arms
  and legs.

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Physical Exam at Admission to PICU

• T afebrile P 82 RR 23 BP 104/46 Wt 33 Kg
• Generally Confused, slurring speech
• HEENT NC, AT, Mucous membranes moist
• Resp Clear to auscultation
• CV Regular rate and rhythm, no murmur
• Abdomen Soft, normoactive bowel sounds
• Skin Erythematous rash over abdomen
• Neuro Athetoid movements as noted in HPI

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Laboratory Analyses

• 133 107 31 73
• 4.3 22 1.2
• 6.8 7.0 35 0.6
• 4.1 25 215
• 10.5 12.1 176
• 34.4
• 7.36 / 50 / 28 / 28
• UA SG 1.010, pH 6.5, pro 1, ket 2, LE 1,
  otherwise normal

• AG 4
• CPK 939
• NH3 38
• Ethanol and volatile acids negative
• Urine drug screen negative
• ßhCG negative
• Salicylate lt1
• Acetaminophen lt10
• Lithium 7.34
• EKG First degree heart block, PR 188 ms,
  prolonged QTc 520 ms

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Lithium Clearance on Dialysis
HD Started
CVVHD Started
CVVHD Stopped
CT-190 Prisma dialyzer Multiflo-100 BFR -HD 250
ml/min -CVVHDF 180
ml/min PO4 based dialysate - 4L/1.73m2/hr
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Lithium Redistributes from Intracellular
Compartment

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. From Goldfarb DS in Goldfranks Toxologic
Emergencies, 7th Ed. 2002
Hemofiltration May Attenuate Rebound Phenomenon!
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CVVHD Following HD for Lithium Poisoning
Li Therapeutic range 0.5-1.5 mEq/L
HD 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. PO4 Based
dialysate at 2L/1.73m2/hr (1,2)
4L/1.73m2/hr (3)
CVVHD started
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Conclusions

• High efficiency hemodialysis and hemofiltration
  may alter the current treatment of choice.
• 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 patients needs.
  

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• ACKNOWLEDGEMENTS
• THERESA MOTTES
• TIM KUDELKA
• BETSY ADAMS
• TAMMY KELLY
• ROBIN NIEVAARD
• DAVID KERSHAW
• PATRICK BROPHY

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• OTHER ISSUES
• Optimal prescription
• Biocompatible filters - may increase protein
  adsorption
• Maximal blood flow rates (i.e. good access)
• Physiological solution (ARF vs non ARF)
• Potential removal of antidote
• Counter-current dialysate maximal removal of
  toxins

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Specific Antidotes

• Should be used adjunctively with supportive
  therapy.
• Examples
• N-acetyl cysteine for Acetaminophen
• Benzodiazepines for Flumazenil
• Flumazenil for Benzodiazepines
• Naloxone for Opiates
• Calcium for Calcium channel blockers
• Atropine for Acetylcholinesterase inhibitors
• Fomepizole for Ethylene glycol, Methanol,
  Diethylene Glycol
• Ethanol for Ethylene glycol, Methanol,
  Diethylene Glycol