Lead Dr Mark Little Clinical Toxicologist and Emergency Physician NSW Qld WA Poisons Information Centre March 2011
Aim Discuss Toxicology of lead Symptomatic childhood poisoning Asymptomatic childhood poisoning - why the concern Medical management My recommendations
Lead - history One of first metals smelted & used Lead based ochre paints Neanderthal era (40 000BC) Lead artifacts found in sites from Turkey 6200 BC Ancient Hebrews and Egyptians used lead Romans used lead for pipes, ceramic glazes, cooking utensils.
Lead today Most widely used non ferrous metal Global production 9 million tons pa Uses: Waterproofing, electrical & radiation shielding Batteries Telephone cables Solder Ammunition Paint Fuel additive
Human poisoning due to lead Greek physicians 2BC CNS effects “mind gave way” Pliny warned of the danger of inhaled lead fumes from smelting Benjamin Franklin (1763) described “dry gripes” = abdominal colic “dangles” = wrist drop In tinkers, painters and typesetters
Toxicology Absorption: Inhalation: <1mcm in alveoli Ingestion: adults 10-15% children 50% deficiency Fe, Zn increases absorption calcium reduces absorption Transplacental: readily crosses
Toxicology Distribution: 99% bound to RBC Deposited Bone Teeth Soft tissue CNS prefers grey matter
Toxicology Excretion: Mainly urine (65%) and bile (35%) Miniscule amount in hair Vit C may enhance excretion
How does lead cause toxicity? Lead binds to sulfhydryl groups effecting numerous enzymatic, receptors and structural proteins Similar to calcium so interfers with multiple metabolic pathways
Lead No known physiological role for lead Any lead found in the body fluids represents environmental contamination
BLL (mcg/dL) Effect in adults 100 Life threatening encephalopathy 80 Anaemia Impaired kidney function 60 Reduced fertility females 40 Impaired conduction peripheral nerves 30 Hypertension Reduced testicular function
Who is at risk from lead Children - especially under 4 Pregnant women - unborn baby Breast feeding mothers Those working with lead
Investigations Measure of body lead load Blood lead level used as primary biomarker Urine is insensitive Hair in unreliable Shed teeth is used in research
Level of concern BLL > 10 mcg/dL Recommended by NHMRC, CDC, WHO, AAP However we should aim for a BLL as low as possible
Variation in BLL with age Age Mean BLL mcg/dL 6 months 3.4 24 months 9.7 61 months 5.8 Canfield et al NEJM 03
Mt Isa Blood Lead Survey July 2007: children 1 - 4 years 60 Mean 5.8 mcg/dL 50 Median 5 mcg/dL 40 Number (n = 328) 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 -10 Rounded Blood Lead mcg/dl
WHO SHOULD GET TESTED IN MT ISA Everyone
CHILDHOOD LEAD POISONING
Childhood poisoning Lead paint poisoning recognised in Brisbane (Aust Med Gaz 1897) Law passed banning lead paint for houses 1914 USA only passed similar law 1961! Children recovering from symptomatic lead poisoning frequently left with neurological sequelae and intellectual impairment (Am J Dis Child 1943)
Childhood poisoning Symptomatic paediatric lead poisoning commonly seen in 1950/60’s in USA and effective chelation protocols developed (Paeds 1957, J Paed 1966) Recognition & quantification of more subtle neurocognitive impairment due to subclinical poisoning in 1970/80’s (NEJM 1972)
Clinical effects in children Symptomatic 1. Acute lead encephalopathy [SEVERE] (BLL>70mcg/dL) Presentation: altered LOC, seizures, vomiting, change behaviour, ataxia, change in developmental skills, CN palsies Anaemia
Clinical effects in children 2. Subencephalopathic [MODERATE] (BLL>50mcg/dL) Often difficult to diagnose 1- 5 yo “terrible two’s” Irritable, intermittent lethargy, constipation, intermittent vomiting, abdominal pain & anorexia Often not recognised until after chelation
Asymptomatic child with elevated blood lead levels Children with elevated lead burden but without overt symptoms the largest group of persons at risk from chronic lead toxicity Numerous studies demonstrate a correlation between elevated lead levels and:- Increased rate learning disabilities Lower IQ Lower class rank
Relationship between BLL and neurocognitive impairment Goldfrank’s Clinical Toxicology 7th ED ? Blood lead level (mcg/dL)
TREATMENT
Antidote Succimer = 2,3dimercaptosuccinic acid [DMSA] Oral agent SAS drug S/E: • Transient LFT abnormalities Neutropenia (rare) GIT upset Hypersensitivity
Indication Adults Symptomatic BLL >60 mcg/dL Children Symptomatic BLL > 45 mcg/dL [Has been used to chelate mercury, arsenic, bismuth, antimony, copper - limited experience]
Summary 780 children with BLL 20 - 45 mcg/dL Randomised double blind placebo controlled trial 3 x 25 days of succimer
Conclusion Those treated with succimer reduced BLL No improvement in cognition, behaviour or neuropsychiatric testing Succimer is NOT indicated in these children
Conclusion “…Suggests that as there is no effective treatment for children with moderate lead levels the collective evidence argues for shift toward primary prevention of lead exposure…”
Controversies
Many factors influence cognitive development in children Genetic Prenatal factors Socioeconomic factors Nutrition Smoking/drugs Parent and family nuturing
Effects on children with bll< 10 mcg/dL
Method 172 children BLL measured 6,12,18,24,36 mo Stanford Binet intelligence scale at 3 and 5 yrs Regression modelling
Results For 101 children with BLL < 10mcg/dL IQ dropped by 7.4 pts for lifetime average BLL <10 mcg/dL
Effects of early childhood lead exposure on academic performance and behaviour of school aged children Arch Dis Child 2009 582 children at 30 months had BLL Developmental behavioural and standardised educational outcomes at 7 - 8 yrs
Results 488 cases had all data on confounders Regression analysis
Distribution of BLL
Conclusion Exposure to lead early in childhood even at low levels is harmful on behaviour and school performance Reduce level of concern to 5 mcg/dL
Household interventions
To determine the effectiveness of household interventions in reducing lead exposure Only 12 studies All in the USA
Conclusion No evidence of effectiness of household interventions for education or dust controls Insufficient evidence for soil abatement Further trials required to establish the most effective intervention for the prevention of lead exposure
What do I recommend?
Toxicologist take home points Lead is here in Mt Isa Children absorb more lead that adults Children around 2 years seem to have the highest BLL Children probably absorb most of the lead through ingestion
Know the potential sources of lead Dust Lead paint and home renovations Contaminated people, clothes cars or items Rain water
Reduce the exposure Wash hands (especially children) before eating Wet wipe and mop Those working with lead shower and change before coming home Shoes/work gear outside Reduce exposure to potentially contaminated soil
Diet Regular meals Diet high in iron, zinc, calcium and vit C
Blood lead levels Aim for BLL < 10 mcg/dL The lower the better Everyone should be tested Opportunity to explain lead and its toxicity/reduction of exposure
If BLL > 10 mcg/dL Test entire family Involve Public Health Unit CDC
Summary of medical management BLL is best measure of lead body load BLL < 45 mcg/dL Not use chelating drug Seek enviromental source and limit Asymptomatic child BLL > 45mcg/dL Seek source Chelate with succimer dw toxicologist/PIC Symptomatic or BLL > 70 mcg/dL Admit Immediate chelate - dw Toxicologist/PIC
Conclusion Lead poisoning humans for centuries Elevated BLL indicates environmental contamination Main concern is in children and the risk of cognitive development Major management [BLL < 45 mcg/dL] is removal from the lead source
Mt Isa Will have an ongoing lead exposure Need to have an ongoing process of education of community to reduce exposure to children Need to test the entire population
Need more help with medical management of patients Clinical Toxicologists available through the Poisons Information Centre system Ph 13 11 26 any time and ask for a toxicologist
Questions?
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