Ask the Doctor: Lead Poisoning and Chelation

1
Ask the Doctor Lead Poisoning and Chelation

• Charlene Graves, MD, FAAP
• Indiana State Department of Health
• October 29, 2007

2
Lead is Long-Lasting

• 95 of lead is stored in bone
• Half-life in bone is 20 to 30 years
• Half-life in blood is 1 to 2 months (active
  portion, results in toxicity)
• Pregnancy lead crosses the placenta, uptake is
  cumulative until birth
• Breast-feeding lead is also transmitted
• Toxic effects of lead cannot be reversed!

3
Why Children are At-Risk

• Incomplete development of blood-brain barrier
• Effect on developing nervous system
• Increased absorption, retain more lead than
  adults per body weight
• Hand to mouth behavior
• High metabolic rate

4
Effects on the Developing Brain

• Learning/cognitive abilities memory, IQ
• Highest cord blood lead levels related to lower
  developmental scores (high SES)
• Effect on cognition for at least 2 years, longer
  in some studies
• Behavior inattention, hyperactivity, poor
  teacher ratings

5
Low-Level Exposure Effects

• Lead levels below 10 micrograms/deciliter
• No clinical symptoms in child
• Decline in IQ of 3 to 7 points per 10 mcg of lead
• Early intervention programs can improve IQ
• Effects on behavior activity levels,
  disinterest, social withdrawal

6
What about Symptoms of Toxicity?

• Not medically evident for blood lead level (BLL)
  below 50 mcg/dL
• At higher levels, can affect heart, liver,
  kidneys
• Pregnancy miscarriage, stillbirth, preterm
  birth, LBW, small head size, and hypertension
  during gestation can occur

7
Risk Questions

• 1. Does the child reside in or regularly visit a
  house that was built before 1978?
• 2. Does the child have a sibling or playmate who
  has been diagnosed with lead poisoning?
• 3. Does the child often have contact with an
  adult working in an industry or with a hobby that
  uses lead?
• 4. Is the child a member of a minority, enrolled
  in Hoosier Healthwise, or a recent immigrant?
• 5. Does anyone in the family use ethnic or folk
  remedies or cosmetics?

8
Known Risk Groups

• ALL children enrolled in Medicaid (Hoosier
  Healthwise) or uninsured (poverty)
• ALL racial and ethnic minority children
• Recent immigrants to U.S.
• Children with occupationally exposed parents
• Children living in homes built before 1978,
  especially those built before 1960 that are being
  renovated or remodeled

9
Other Risk Considerations

• Historically, poor children living in urban areas
  with old, dilapidated housing are at great risk
• But renovation and remodeling in upscale homes
  can also result in risk
• General Obtain a blood lead test on all at-risk
  children at ages 1 and 2 years, and on all
  children 36-72 months of age if not tested
  previously

10
Blood Lead Testing

• Capillary vs. Venous Blood Samples
• Capill. Result Confirm w. Venous
• 10 to 19 ASAP, within 2 months
• 20 to 44 ASAP, within 1 week
• 45 to 69 ASAP, within 24 hours
• 70 or higher Immediately (medical emergency)
• Note Child less than 12 months old or rapidly
  rising levels, do confirmatory testing more
  quickly

11
Medical Assessment

• Detailed environmental, behavioral history
• Basic nutritional history
• Physical examination usually normal
• Labs look for anemia
• Abdominal X-ray (flat plate of abdomen) - useful
  if unexpected acute rise in BLL or child not
  responding to case management as expected

12
How Does Chelation Work?

• Lead is stored in bone, but available in soft
  tissues of body and in blood
• Binds lead in soft tissues
• Enhance urinary and biliary excretion of lead
• Also increase excretion of other heavy metals
  mercury, zinc
• Chelating agents CaEDTA, BAL, D-penicilamine,
  succimer (DMSA)

13
Conclusions re Chelation

• Oral chelation treatment (DMSA) indicated only
  for children with confirmed BLL of 45-69 mcg/dL
• If BLL is 70 or higher, consult with pediatric
  specialists (intensive care)
• Rx recommendations for BLL above 70 mcg/dL
  available in Harriet Lane Handbook

14
Considerations re Chelation

• Little/no evidence for clinical benefit when BLL
  is below 45
• Good evidence for benefit IF child is symptomatic
• Large RCT re oral chelation with succimer when
  BLL 20-44 3 year follow-up showed no
  significant difference between Rx group and
  controls in mean IQ, behavior or learning
• BLLs decreased in both the treatment and placebo
  groups no difference _at_ 24 mos.
• Pediatrics 118, No.6, Dec. 2006, NEMJ 2001 344

15
More Evidence re Chelation

• Short-term reductions in BLL when chelation Rx
  combined with environmental interventions, but
  not sustained over time.
• Harmful side effects can occur with chelation Rx,
  if used for BLL below 45 Risks are greater than
  the benefit, so NOT RECOMMENDED.

16
Chelation Basics

• Succimer (DMSA) Chemet given orally
• Outpatient Rx for BLL of 45-69 mcg/dl
• Adequate hydration needed
• Baseline and weekly renal, liver chemistries, CBC
  with differential WBC
• Withdraw or D/C Rx if absolute neutrophil count
  (ANC) below 1200

17
Chelation with Succimer

• Rx for 19 days 350mg/m2/dose OR 10 mg/kg q.8 hrs
  X 5 days. Then same dose q. 12 hrs X 14 days
• Calculate dose to the nearest 100 mg.
• 100 mg capsules opened and contents mixed with
  food (jello, applesauce).

18
Succimer Side Effects

• GI symptoms vomiting, diarrhea
• Fatigue
• Rash, usually transient
• Elevated liver enzymes
• Neutropenia susceptibility to infection is a
  concern if remain neutropenic

19
Treatment Considerations

• After succimer Rx Weekly BLL until stable, labs
  for renal liver function, CBC in 2-4 weeks
• Minimum of 2 weeks between repeated courses
• Rebound Expect to reach BLL of 2/3 of initial
  value _at_ 4-6 weeks post-chelation

20
Venous BLL of 70 or higher

• This is a medical emergency
• Admit to hospital with a Peds ICU
• Complicated treatment regimen with edetate
  disodium calcium
• (CaETDA) consult Harriet Lane Handbook and/or
  Poison Control

21
Chelation Misuses/Dangers

• Chelation regimens sometimes used through
  naturopathy or Rx for autism, but no scientific
  basis for such use! (MMWR, Vol.55, No.8, March
  3,2006)
• Such treatment regimens have resulted in deaths
  (Na2EDTA resulting in hypocalcemia)
• Confusion between CaEDTA and Na2EDTA (do NOT use
  latter!)

22
What about Nutrition?

• Evidence-based review conflicting evidence as to
  whether nutritional interventions are effective
  in lowering BLL.
• Basic, good nutrition is needed
• Adequate calcium, iron, Vitamin C intake desired
  for all children

23
Education and Awareness
Risk Assessment
Remediation
Control Hazards
Abatement
Inspection
EBLL Children
Lead Hazard Reduction
24
Questions?