Hemodialysis and
Hemofiltration in
Pediatrics: An Approach
to Intoxication
Karen Papez MD
University of Michigan
Pediatric Nephrology, Dialysis &
Transplantation
3rd annual PCRRT, Orlando, FL
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 <3 yrs: 39% of all human exposures
Children <6 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
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.
Treatment Measures Available
for Poisonings

Enhance Elimination (Cont.)

Extracorporeal Methods
 Hemodialysis
 Standard
 High
Efficiency/High Flux
 Hemofiltration
 Hemoperfusion
 Exchange Transfusion
 Plasma exchange
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

HEMODIALYSIS

Optimal drug characteristics for removal:
 Relative
molecular mass < 500 Daltons
 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

HEMOFILTRATION

Optimal drug characteristics for removal:
 Relative
molecular mass less than the cut-off of the
filter fibres (usually < 40,000 daltons)
 Small Vd (< 1 L/Kg)
 Single compartment kinetics
 Low endogenous clearance (< 4ml/Kg/min)
Pond, SM - Med J Australia 1991; 154: 617-622
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.
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.
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

Laboratory Analyses
148
5.4
121 13
7 2.1
9.4
4.8
11.7
4.0
16.8
50.4
98
38
59
0.3
143
163
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
βhCG negative
Salicylate <1
Acetaminophen <10
Ethylene glycol 24.2
Osmolality (mosm/K)
Calculated Osmolality with Dialysis
in Ethylene Glycol Intoxication
Calculated
osmolality
Serum
osmolality
HD Started
315
CVVHDF
Started
CT-190
295
Prisma dialyzer Multiflo-100
BFR -HD 250 ml/min
-CVVHDF 180 ml/min
PO4 based dialysate
275
24
27
34
36
Hours After Ingestion
40
53
- 4L/1.73m2/hr
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.
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
Laboratory Analyses
133 107 31
4.3 22 1.2
6.8
10.5
12.1
34.4
73
7.0
35
4.1
25
0.6
215
176
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
βhCG negative
Salicylate <1
Acetaminophen <10
Lithium 7.34
EKG First degree heart
block, PR 188 ms,
prolonged QTc 520 ms
Lithium Concentration (mEq/L)
Lithium Clearance on Dialysis
Lithium
8
7
HD
Started
6
5
4
3
CVVHD
Started
CVVHD
Stopped
2
1
0
0
3
4
5
6
11 15 20 23 25 30 33 36
Time After Presentation (Hours)
CT-190
Prisma dialyzer
Multiflo-100
BFR -HD 250 ml/min
-CVVHDF 180
ml/min
PO4 based dialysate
- 4L/1.73m2/hr
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 Goldfrank’s Toxologic Emergencies, 7th Ed. 2002
Hemofiltration May Attenuate Rebound Phenomenon!
Pt #1
Pt #2
Pt #3
Li Therapeutic range
0.5-1.5 mEq/L
HD started
10
CVVHD started
8
6
4
2
0
Hours After Presentation
24
12
6
5
0
Lithium concentration (mEq/L)
CVVHD Following HD for Lithium Poisoning
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)
Drug
MW
[Daltons]
H2O
Sol
% Prot
Bound
Vol of Distrib
[L/kg]
Endogenous
Clearance
Lithium
7
Yes
0
0.6-1.0
0.4 ml/min/kg
Methanol
32
Yes
0
0.7
0.7 ml/min/kg
Ethylene
Glycol
62
Yes
0
0.6
2.0 ml/min/kg
Salicylates
138
Yes
90%*
0.15-0.2
0.88 ml/min/kg
Valproic acid
144
No
90%*
0.19-0.23 Tot
1.3 Free
0.13 ml/min/kg
1.1 ml/min/kg
Theophylline
180
Yes
55%
0.4-0.7
0.65 ml/min/kg
Phenobarb
232
No
24-60%
0.5
0.1 ml/min/kg
Carbamazepine
236
No
75%
0.8-1.6
1.3 ml/min/kg
Vancomycin
1486
Yes
10-50%
0.47-1.1
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 patient’s needs.

ACKNOWLEDGEMENTS
THERESA MOTTES
 TIM KUDELKA
 BETSY ADAMS
 TAMMY KELLY
 ROBIN NIEVAARD
 DAVID KERSHAW
 PATRICK BROPHY


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

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]