Interpretation
PATIENT MANAGEMENT:
The information on chelation therapy is also available from TOXINZ or the National Poisons Centre. (Guidelines below prepared by Dr. Johan van Schkalkwyk, Auckland Hospital, 2006)
Clinical Examination / Symptoms:
Children: Usually develop symptoms at concentrations >3.0 umol/L. These may include abdominal pain and irritability, followed by lethargy, anorexia, pallor (anaemia), ataxia and slurred speech. Severe poisoning can cause convulsions, coma, and death, and/or renal failure. Lower concentrations (1.5 – 3.0 umol/L) can cause mental retardation, loss of cognitive function and balance, behaviour problems, and poor school performance. Blood lead concentration >= 0.24 umol/L should be investigated, and the environmental exposure reduced if it can be identified.
Adults: Concentrations > 3.2 umol/L may cause abdominal pain, headache and irritability, joint pain, fatigue, anaemia, peripheral motor neuropathy, and loss of short term memory. In some patients, these symptoms develop at lower blood lead concentrations; treatment should be considered if lead concentration exceeds 2.6 umol/L, or at even lower concentrations if symptoms are evident. Chronic long term exposure may not produce high concentrations or clinical symptoms, but may still lead to renal failure, hyperuricaemia, and hypertension.
Management of the Environment:
The first step is to identify the source of environmental exposure and prevent further contact with lead. Occupational Safety and Health (OSH) or the Medical Officer of Health may assist with this process.
Sources of lead that need to be considered are: old lead-based paint being stripped or sanded, lead exposure at work and / or work clothes subsequently contaminating the home, lead based pigments (pottery), using improperly glazed ceramics to hold food or drink, and some herbal remedies, especially Ayurvedic medicines.
Chelation Therapy for Adults:
Chelation therapy must be instituted without delay if the blood concentrations indicate this (see above) and/or if there are any lead toxicity symptoms. The benefit of treating lower concentrations, where there are no clinical signs or symptoms, is still uncertain. (Lead chelation therapy in adults. Dr J M van Schalkwyk. ADHB. Aug 2008)
1. Chelation therapy is generally NOT advised in adults if the whole blood lead level is under 2.4 umol/L AND the patient is completely asymptomatic.
2. Treatment should be considered after discussion with a physician and/or toxicologist with experience in treating lead poisoning if:
a) Whole blood lead levels are 2.4 umol/L or more, OR
b) The patient has symptomatic lead poisoning.
3. Treatment is considered urgent if the patient is encephalopathic, markedly symptomatic, or blood lead levels are very high (e.g. 5 umol/L).
Three agents can be used for treatment:
1. DMSA (meso-2,3-dimercaptosuccinic acid, Chemet)
2. Ca-EDTA (Calcium disodium ethylene diamino tetraacetic acid)
3. BAL (dimercaprol, British Anti-Lewisite, 2,3-dimercapto-1-propanol)
In general, we recommend oral DMSA as the preferred agent unless the patient is severely ill and/or encephalopathic, where combination therapy should be considered. DMSA is available in New Zealand, but must be given under Section 29 of the Medicines Act.
General principles of chelation therapy:
1. Stop the intake of lead. If there is still lead in the gut, consider purging.
2. Maintain good hydration;
3. Check baseline liver function tests, full blood count, urea & electrolytes, and whole blood lead levels. Send a spot urine for porphyrin levels;
4. Ensure regular follow up, noting improvement in symptoms. Repeat the above laboratory tests (as appropriate, but at least on day five and after two weeks);
5. If the patient is very symptomatic and/or blood lead levels are > 5 umol/L, initial inpatient management may be appropriate. Encephalopathic patients may need intensive care management;
6. Recheck whole blood lead levels two weeks after the end of therapy and then monthly for six months, and manage rebound increases in lead levels > 2.4 umol/l.
Specific agents used for chelation therapy
1. DMSA
DMSA is a safe and effective treatment for lead poisoning. In children, it is generally accepted as the treatment of choice. DMSA mobilises lead from brain tissue, can be given orally, and is well-tolerated in almost all patients. Unlike Ca-EDTA, DMSA does not cause substantial depletion of essential elements such as iron and zinc. In well patients DMSA can be given on an out-patient basis (but funding must be justified, which can potentially cause delays). Small numbers of patients with lead encephalopathy have been reported to respond favourably to DMSA administration. DMSA monotherapy is more effective than EDTA in lowering lead blood levels. The drug appears very safe even in overdose. DMSA does not appear to increase gastrointestinal lead absorption.
Dose:
(a) 30mg/kg/day by mouth, in three divided doses for 5 days; then
(b) 20mg/kg/day in two divided oral doses for 14 days
Somewhat lower doses have been used in adults (by some authorities). Shorter regimens are likely to result in more rebound in lead levels following cessation.
Side effects of DMSA are uncommon (liver function test abnormalities in 4%, gastro-intestinal discomfort in 12%, and occasional skin reactions). There have been two reports of substantial toxicity: a mucocutaneous reaction, and haemolysis in association with glucose 6-phosphate dehydrogenase deficiency. Other patients with G6PD deficiency have not experienced haemolysis with DMSA. Occasional reversible neutropaenia makes monitoring of white cell count mandatory.
2. Ca-EDTA
NOTE:
- This is the calcium salt. Use of the sodium salt may precipitate life-threatening hypocalcaemia.
- Do not use in the first trimester of pregnancy unless it is required to save the life of the mother (may be teratogenic).
Ca-EDTA must be given by IV infusion (intramuscular injection is painful), preferably infusion for five days.
Ca-EDTA does not effectively mobilize lead from the brains of experimental animals It may therefore worsen encephalopathy, if this is present, by mobilising lead from bone and allowing re-distribution to brain tissue.
Dose:
(a) 1 – 1.5 g/m2/day (One vial is one gram).
(b) Dilute in 250 – 500 ml sterile isotonic saline or sterile 5% glucose in water. Concentrations over 0.5% cause thrombophlebitis.
(c) Infuse continuously for 5 days. Do not give i.m.
The principle side effect of EDTA is nephrotoxicity, especially in subjects with underlying renal impairment. Good hydration is thus essential. Nephrotoxicity is said to be uncommon at doses under 1.5g/m2/day. Other reported adverse effects include headache, fatigue, myalgia, thirst, fever, nausea and vomiting, sneezing, lacrimation, nasal congestion, rashes, anaemia and hypotension. EDTA depletes whole body iron and zinc which may theoretically worsen lead toxicity. It is believed that EDTA mobilises lead from bone much more effectively than DMSA, but the benefit of this mobilisation (if any) is not clear.
3. BAL
This traditionally favoured therapy should only be administered under the supervision of a responsible expert, and then only (perhaps) in patients with severe encephalopathy. BAL, a toxic, teratogenic drug, is given four hourly IM, dissolved in peanut oil. Major side effects are very common. Even with encephalopathy, the combination of DMSA+EDTA may be a better choice. In children, a head-to head comparison of BAL+EDTA versus DMSA+EDTA showed no difference in the effect on blood lead levels.
Reference Intervals
Lead level
|
For non-occupational i.e. environmental exposure
All whole blood lead levels >= 0.24 umol/L will automatically be reported to the Medical Officer of Health
Report comment
|
| <0.10 umol/L |
Lead not detected in whole blood |
| <0.24 umol/L
(<5 ug/dL) |
Within normal background levels of exposure. Investigation into source of exposure is not normally required unless there is another reason to investigate for a possible environmental lead hazard. NHMRC suggests consider investigating for source of lead exposure in 1st trimester pregnant women with lead level >0.19 umol/L (ref: NHMRC April 2016) |
| 0.24-0.47 umol/L
(5-<10 ug/dL) |
Suggests more than average background exposure. Individuals are unlikely to display noticeable signs or symptoms as a result of lead exposure, however risk rises as lead level increases. Source of lead exposure should be investigated and reduced, particularly in a child or pregnant woman. Repeat the test at 3 months post remediation then 6-12 monthly in follow ups. |
| 0.48-0.96 umol/L
(10-<20 ug/dL) |
This degree of lead exposure may result in health effects, particularly in children. For children when blood lead is 0.72-0.96 umol/L, public health team will notify the child’s general practitioner, discuss need for testing for iron deficiency anaemia and may refer to a paediatrician for an assessment and neurodevelopmental testing. Investigate and adopt abatement strategies to reduce exposure. Repeat the test at least 6 weeks post remediation then 6-12 monthly in follow ups. |
| 0.97-2.12 umol/L
(20-<44 ug/dL) |
This degree of lead exposure may result in health effects, particularly in children. Public health team will consult the child’s general practitioner and refer to a paediatrician for assessment and possible neurodevelopmental testing. Acute lead poisoning symptoms can be seen. Investigate and adopt environmental intervention and abatement strategies to reduce exposure. Repeat the test at least 6 weeks post remediation then 6-12 monthly in follow ups. Consider testing other household or related work members. |
| 2.13-3.33 umol/L
(44-<69 ug/dL) |
Harmful level of lead. For children, public health team will consult the child’s general practitioner and refer to a paediatrician for assessment and possible neurodevelopmental testing. Also for children, when blood lead is >= 2.17 umol/L, an urgent paediatric assessment and chelation therapy is recommended. The information on chelation therapy is available from TOXINZ or the National Poisons Centre. Investigate and adopt environmental intervention and abatement strategies to reduce exposure. Repeat the test at least 6 weeks post remediation then 6-12 monthly in follow ups. Consider testing other household or related work members. |
| >= 3.34 umol/L
( >= 69 ug/dL) |
Medical emergency. Urgent referral to a physician or paediatrician is highly recommended. The information on chelation therapy is available from TOXINZ or the National Poisons Centre. Investigate and adopt environmental intervention and abatement strategies to reduce exposure. Repeat the test at least 6 weeks post remediation then 6-12 monthly in follow ups. Consider testing other household or related work members. |
Note: The table above only includes brief comments based on the Ministry of Health document on “The Environmental Case Management of Lead-Exposed Persons: March 2021”
and the Australian Government NHMRC document on “Managing individual exposure to lead in Australia – A guide for health practitioners: April 2016”.
For further details please refer to the original documents.
The above table is NOT intended to provide guidance in dealing with occupational communities where lead exposure can be endemic. In that instance, please refer to Worksafe NZ guidelines.
For occupational exposure: if you have concerns about an unsafe or unhealthy blood lead level that could cause serious illness, please refer to Worksafe NZ’s guidelines or phone 0800 030 040
In September 2021, Worksafe NZ released a Biological Exposure Index Review document which included proposals to:
-
remove suspension levels for all workers
-
reduce the biological exposure index level from 0.97 umol/L to 0.48 umol/L
-
introduce a Biological Agent Reference Value (BRV) for whole blood lead for females of reproductive capacity at 0.14 umol/L as an indicator that workplace exposure may exist, and should be investigated, as ideally pregnant women, breastfeeding women, or women planning to become pregnant should have no exposure to lead at all
For details, please refer to the link below.
Conversion factors: ug/dL x 0.0483 = umol/L
umol/L x 20.7 = ug/dL
Biological Exposure Index (BEI) review, Lead, September 2021
MoH: The Environmental Case Management of Lead Exposed Persons
NHMRC: Managing individual exposure to lead in Australia – A guide for health practitioners
Worksafe NZ