CASE REPORT lead poisoning
Lead Poisoning in Adults From Renovation of an Older H o m e Presented is the case of a group exposure to lead occurring during the removal of lead-based paint from an older home. One patient had symptoms from the time of exposure to the time of presentation, when he was acutely ill and encephalopathic. The patient was treated successfully with an initial course of British Anti-Lewisite agent and calcium disodium versenate (CaEDTA) chelation, and two subsequent chelations with CaEDTA alone. The other two patients had elevated lead levels but were asymptomatic. They were followed closely, and their lead levels steadily declined over several months. The evaluation and treatment of lead poisoning and excessive lead levels in adults is discussed, as is the need for physicians and the lay public to become aware of the hazards of renovating older homes. [Schneitzer L, Osborn HH, Bierman A, Mezey A, Kaul B: Lead poisoning in adults from renovation of an older home. Ann Emerg Med April 1990;19:415-420.] INTRODUCTION Lead is a well-known toxin, and the spectrum of lead-induced disease has been well described. 1-4 Much attention has been paid to the problem of preventing chronic lead intoxication in inner-city children and to occupational exposure in adults, s-8 Most lead toxicity, especially in children, occurs secondary to oral ingestion. Lead can, however, also be inhaled. Absorption of atmospheric lead by the lung is dependent on particle size. Seventy percent of the fine lead inhaled from the atmosphere is exhaled in the expired air. Of the 30% that is not returned, particles of less than 0.1 u in diameter are absorbed, while particles larger in diameter are trapped in the upper airways and swallowed. 9 It has been shown that excessive lead absorption can occur during the renovation of bridges and other structures containing lead-based paint, lo-13 In this instance, lead dust or fumes are readily absorbed through the respiratory mucosa due to the small particle size involved. When heated, lead vaporizes and precipitates as a fine particulate mist. Any process creating lead dust or fumes presents a significant health hazard. Furthermore, eating in areas where lead dust is present can also lead to intoxication. 1,1 We report three cases of excessive lead absorption in adults resulting from a single massive exposure to lead fumes and dust. This occurred during the sandblasting of paint from the interior of an older house. Guidelines regarding the need for treatment of these patients are discussed.
Leila Schneitzer, MD, FACEP* Boston, Massachusetts Harold H Osborn, MD, FACEPIBronx, New York Arlene Bierman, MD~: New York, New York Andrew Mezey, MD§ Bronx, New York Balkrishena Kaul, PhDII New York, New York From the Emergency Department, Boston City Hospital, Boston, Massachusetts;* Emergency Services, Lincoln Medical College, Bronx, New York;t Department of Medicine, Metropolitan Hospital, New York Medical College, New York, New York;~: Department of Pediatrics, Bronx Municipal Hospital, Bronx, New York;§ and the City of New York Department of Health, Public Health Laboratories, New York, New York.II Received for publication November 8, 1988. Revision received November 27, 1989. Accepted for publication December 12, 1989. Address for reprints: Harold H Osborn, MD, FACER Department of Emergency Medicine, ©ur Lady of Mercy Medical Center, 600 East 233rd Street, Bronx, New York 10464.
CASE REPORTS Case 1 A 33-year old man presented to the emergency department with complaints of headache, fatigue, nausea, crampy abdominal pain, and arthralgias. The patient, a paramedic supervisor, was well until 15 days prior to admission when he sandblasted a thick layer of paint from a fireplace in his 50 year-old home. The patient spent 12 hours doing this work, wore only a surgical mask for protection, and in addition had constructed a "canopy" around the fireplace to protect the rest of the room. The evening of the sandblasting, the patient developed symptoms that persisted and worsened up until the time of presentation. Initially he at-
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LEAD POISONING Schneitzer et al
FIGURE. PbB and EP levels in three patients exposed to lead. Chelation therapy is indicated for patient 1.
BAL
I :aEDTA
100 tributed his symptoms to a viral syndrome. He finally sought medical attention at the urging of his fiancde (patient 3), also a paramedic, who wondered about the possibility of lead poisoning. His medical history was entirely negative, with a recent normal physical examination and a reported blood pressure of 140/90 m m Hg. An environmental and occupational history failed to reveal any other sources of lead exposure. Physical examination revealed a well-developed man in moderate distress, with frequent episodes of vomiting. He was i n t e r m i t t e n t l y lethargic, despite the severe abdominal pain and vomiting. Vital signs revealed a blood pressure of 170/125 m m Hg; pulse, 88; respirations, 16; and temperature, 37 C. Abdominal examination was unremarkable, as was the neurological examination. There was no papilledema or focal motor or sensory deficits. Cerebellar f u n c t i o n i n g was normal, as were deep tendon reflexes. The rest of the physical examination was unremarkable. Chest and abdominal radiographs were normal. An ECG revealed a PR interval of 0.10 seconds and a wide QRS with a delta wave. The h e m a t o c r i t , electrolytes, glucose, liver function tests, calcium, and uric acid level were all within normal limits. His initial blood lead (PbB) level was markedly elevated at 98 ~g/dL ( n o r m a l , < 25 ~ g / d L ) and t h e erythrocyte protoporphyrin (EP) was 68 ~xg/dL (normal, < 35 ~xg/dL). His serum ferritin level was 78 ng/mL (normal, > 15 ng mL). The peripheral blood smear revealed mild basophilic stippling of erythrocytes. Although the patient was quite symptomatic and had elevated PbB and EP levels, there was no sign of anemia, thus indicating that the exposure was an acute one. Blood and urine lead determinations were performed by atomic absorption spectrophotometry, and EP determinations were measured by Piomelli's extraction method.14, is After admission to the ICU, chelation therapy was started with 280 nag of British Anti-Lewisite agent (BAL) 4 mg/kg IM every four hours and 3,300 mg of calcium disodium versenate 114/416
Chelation Treatment
I
Blood Lead Levels
I
I CaEDTA I
[ CaEDTA I
I----I
• Patient 1 [ ] Patient 2 [ ] Patient 3
80 60 40 20 0
Erythrocyte Protoporphyrin Levels 220 180 140 100
60 20
15
16 18
25
36
46
60
69
88
127
187
Days After Exposure
(CaEDTA) 50 mg/kg/IV daily. Within two days, the patient was alert, normotensive, and entirely asymptomatic. A PbB level after 48 hours of treatment was 15 ixg/dL and the EP was 82 ~g/dL. BAL was discontinued after 48 hours, and the CaEDTA alone was given for an additional three days. Fifteen clays after the completion of chelation, PbB and EP levels were 57 ~g/dL and 212 ~g/dL, respectively. At that time a second five-day course of CaEDTA chelation only was given (2g CaEDTA IV per day). Three weeks after the second chelation, PbB and EP levels were 43 ~g/dL and 172 txg/dL, respectively, and a CaEDTA provocation test was performed. One gram of CaEDTA was administered IV twice at 12-hour intervals. The patient's urine was collected for 24 hours and was found to contain 1,610 ixg of lead. The lead excretion ratio (lead excreted [~g]/ Annals of Emergency Medicine
CaEDTA a d m i n i s t e r e d [mg]) was 0.80. The cut-off level considered to mandate treatment is 650 ~g or more of urinary lead in 24 hours16,17 or a lead e x c r e t i o n ratio greater t h a n 0.60. 4 Following the positive provocation test, a third course of chelation therapy was given, again administering 2g CaEDTA IV per day. During the last day of chelation, the 24-hour urinary output of lead was 520 ~g, with a lead excretion ratio of 0.21. Following the last chelation, the patient's lead levels continued to decrease and he remained asymptomatic (Table 1 and Figure). Blood pressure, urinalysis, and serum BUN and creatinine determinations remained normal as well. Case 2 A 32-year-old asymptomatic man who had been sandblasting with pa19:4 April 1990
TABLE 1. Blood and urine FEP and lead levels of patient 1 over a 26-week period
Levels (l~g/dL) Days After Sandblasting
Blood Lead
FEP
15
98
68
Initial presentation to ED Chelation with CaEDTA and BAL begun
16 18
15
82
25 36 40
45 56
95 212
46 60 69
26 45 43
212 186 172
BAL discontinued CaEDTA continued for additional 3 days Five days after chelation Sixteen days after chelation Second course of chelation begun CaEDTA for 5 days Second course of chelation ending Fourteen days after 2nd course of chelation CaEDTA provocation test done (2 g OaEDTA) Serum iron 75 p,g/dL Saturation 23%; total binding capacity, 326 #g/dL Ferritin 78 ng/mL Third course of chelation begun CaEDTA for 5 days Urine collected last day of chelation (2 g CaEDTA per day)
1,610
75
80 520
85 88 127 182
31 30
tient 1 was examined after that patient was admitted to the hospital. He had w o r k e d on the project for only a few hours and did not live in the house. This patient was grossly a s y m p t o m a t i c and his physical exa m i n a t i o n was u n r e m a r k a b l e , although neuropsychiatric testing was n o t performed. All laboratory tests were within normal limits. The patient's initial PbB and EP levels were 66 Ixg/dL and 120 ~g/dL, respectively. A serum ferritin level was 113 ng/dL. Repeat PbB and EP levels one week later w i t h o u t treatm e n t were 54 ~g/dL and 138 ~g/dL, respectively. To assess the body burden of lead, a CaEDTA provocation test was performed on the patient. He received 2 g CaEDTA IM (1 g every 12 hours) and excreted a total of 1,995 ~g of lead in 24 hours with a ratio of approximately 1.0. Treatment was r e c o m m e n d e d but the p a t i e n t declined to u n d e r g o chelation therapy. 19:4 April 1990
Comments
Urine Lead (24 Hours)
94 50
Five days later, PbB and EP levels were 43 ~xg/dL and 147 ~xg/dL, respectively. Another CaEDTA provocation test was done and was considered negative (urinary lead excretion of 666 ~g in 24 hours, and a lead excretion ratio of 0.33). The patient's PbB levels continued to decrease w i t h o u t chelation therapy, and he remained grossly asymptomatic (Figure). Case 3 A 29-year-old w o m a n who lived in the house where the sandblasting had t a k e n place was e x a m i n e d after it was discovered that the two m e n doing the work had elevated lead levels. W h e n questioned, she had no complaints. Her p h y s i c a l e x a m i n a t i o n was unremarkable. Again, neuropsychiatric testing was not carried out. Her initial PbB and EP levels were 24 ~g/dL and 66 ~g/dL, r e s p e c t i v e l y . The patient's serum ferritin level was 26 ng/mL. She did not receive any chelation therapy or CaEDTA provoAnnals of Emergency Medicine
cation tests. Her levels continued to decrease, and she remained grossly asymptomatic (Figure).
DISCUSSION Lead i n t o x i c a t i o n in a d u l t s has been described, but m o s t cases have involved exposure over several weeks to m o n t h s . Lead i n t o x i c a t i o n h a s b e e n r e p o r t e d in p r o f e s s i o n a l deleaders r e m o v i n g lead p a i n t f r o m housing units, ironworkers dismant l i n g e l e v a t e d s u b w a y lines, a n d those renovating old bridges. 1°-12 In 1981, Fischbein reported two cases of lead intoxication in adults secondary to removal of lead paint during h o m e renovation. 13 Both had primary occupations in which no significant lead exposure occurred. One was renovating his own home. The other patient was doing the renovation as a parttime job. The case of patient 1 is unusual in that s y m p t o m a t i c i n t o x i c a t i o n resulted from a relatively brief expo417/115
LEAD POISONING Schneitzer et al
TABLE 2. Symptoms and signs of lead intoxication
Acute Exposure
Mild fiulike nonspecific Complaints (fatigue, headache, arthralgias, weakness) Colicky abdominal pain, anorexia Nausea and vomiting, constipation Diarrhea, dark stools, abdominal radiograph may reveal radiopaque substance following oral ingestion Irritability, headache, poor concentration, insomnia or lethargy Clumsiness, ataxia, convulsions, coma, papilledema
sure, albeit a massive one. Several factors may be involved. The work was done in a small enclosed area without ventilation. Sand used in the process was reused, thus generating an even higher concentration of lead dust. Beverages were ingested during the day near the work area. Work was done in the kitchen where meals were prepared and subsequently consumed. Patient l's symptoms began shortly after exposure. Though these symptoms were typical of lead poisoning, they were nonspecific and more commonly associated with a viral syndrome. Lead i n t o x i c a t i o n affects multiple organ systems. Its presentation is variable and, like carbon monoxide poisoning, the diagnosis can easily be missed unless a history of lead exposure is obtained (Table 2). Jain reported six cases that were all referred to an infectious disease service and subsequently diagnosed as lead intoxication. 18 Schottenfeld and Cullen reported lead poisoning presenting as an organic affective illness with depression, irritability, and loss of libido, all of which disappeared with treatment. 19 Clinical manifestations of lead poisoning tend to be dependent on duration and intensity of exposure, and many of those poisoned may appear grossly asymptomatic. In the 1960s and 1970s when lead poisoning was recognized as a major problem in -~ 116/418
Chronic Exposure Early Nonspecific complaints
Apathy or irritability Anorexia, constipation Metallic taste, nausea Late All the above plus:
Incoordination, disturbance of menstrual cycle, abortion, cranial nerve, abnormalities Impaired nerve conduction Wrist and ankle drop Neurosensory loss in extremities Anemia, basophilic stippling of red cells Long bone radiographs may reveal deposition Chronic nephritis Learning disability, poor psychosocial development, mental and behavioral problems
young children, m a n y undiagnosed cases w e r e f o u n d t h r o u g h m a s s screening programs. Patient l's case is also unusual because he had symptoms compatible with encephalopathy. During the first few hours of his treatment with BAL and CaEDTA, he was lethargic and sleepy despite multiple noxious stimuli. Thirty-six hours following the initiation of treatment, the patient was fully awake, alert, and no longer hypertensive. Acute lead encephalopathy is not u n c o m m o n in children but is extremely rare in adults. We were unable to find any case reports of encephalopathy following such a short exposure time to lead. Although Whitfield reported 23 adults with lead encephalopathy after c o n s u m i n g large a m o u n t s of moonshine whiskey contaminated with lead salts, 91% of the patients were a n e m i c , i n d i c a t i n g a m o r e chronic exposure. 2o Blood lead levels, when elevated, most accurately reflect recent exposure but not toxicity nor the body burden of lead. 21 One can also have only m i l d l y elevated blood lead levels despite a significant exposure, systemic toxicity, and a large chelatable pool once distribution has occurred. Zinc protoporphyrin and free e r y t h r o c y t e p r o t o p o r p h y r i n are markers of lead interference with heme synthesis and thus serve as indicators of lead toxicity but only Annals of Emergency Medicine
when blood lead values are significantly elevated. Like the PbB level, these tests tell nothing about the body burden of lead. ~1 In addition, they are not reliable in documenting an acute lead exposure and are not useful in following a response to treatment. PbB levels and urinary lead excretion values can be used as indicators of a response to treatment. However, blood and urinary lead levels do not measure the lead deposited in the deep bone stores. Because the goal of therapy is to reduce the total body lead burden, the provocation test is the most sensitive parameter of adequacy of treatment, and, in our opinion, can often resolve the question of whether treatment is indicated. A good illustration of this point can be seen in our patients at day 69 following exposure. Of interest is the fact that patients 1 and 2's PbB levels were identical at this time (43 ~g/ dL), but patient l's provocation test was positive (1,610 ~g/lead/24 hours urine) while patient 2's test was borderline (666 ~g/lead/23 hours urine) (Table 1 and Figure). Patient 1 had a greater body burden of chelatable lead and was more toxic, a fact that is reflected in his greater EP level (172 p~g/dL) compared with that of patient 2 (147 Fg/dL). It also underscores the point that one cannot rely on blood lead levels alone without assessing toxicity with EP levels and 19:4 April 1990
the body burden of lead with the provocation test. The most sensitive marker of increased lead stores is the CaEDTA provocation test, which reflects the total body burden of chelatable lead. The test is performed by administering one or two parenteral doses of CaEDTA followed by a 24-hour urine collection. In adults,more than 650 p,g/dL lead/24 hr is considered to represent significantly increased chelatable lead body stores. In renal failure, a 72-hour urine collection is required. A l t h o u g h the p r o v o c a t i o n test was first introduced three decades ago, it is infrequently used in the management of adults exposed to lead, and there is, at present, no agreement on the method.~6,17, zz-26 The recommended exposure limit set by the National Institute for Occ u p a t i o n a l Safety and H e a l t h for workers exposed on the job is a blood lead 60 b~g/100 g of whole b l o o d y Most authorities would recommend t r e a t m e n t above this level. 4 For asymptomatic individuals with PbB levels between 25 and 60 ~xg/dL, the provocation test can be an important guide to therapy. T r e a t m e n t of lead poisoning in adults is s o m e w h a t controversial. However, it is generally accepted that symptomatic patients should be treated with both BAL and CaEDTA. The BAL may be discontinued after two days if symptoms improve and the lead levels are significantly lowered, while CaEDTA is continued for an additional three days. However, o p t i m u m doses have not yet been established. Oral penicillamine is not used in the treatment of acute lead toxicity but has been used after parenteral chelation therapy to lower lead levels once the environmental source of lead is eliminated. It is also used as a primary treatment for asymptomatic patients with elevated lead levels. Its use, however, is limited by the side effects of fever, proteinuria, skin rash, and leukopenia. Finally, a new oral chelator, 2,3 dimercaptosuccinic acid (DMSA), holds great promise. DMSA is a derivative of dimercaprol (BAL) and has been shown in animals to be as effective as conventional chelators even when given orally and is the best tolerated of all chelating agents, zs Clinical reports of its effectiveness are still limited and its application in the treatment of acute 19:4 April 1990
lead i n t o x i c a t i o n r e m a i n s undefined.29,3o The question of whether to chelate an a s y m p t o m a t i c p a t i e n t w i t h a modestly elevated PbB level (similar to patient 2) is a more difficult issue. Of relevance to this question are studies associating low-level exposure to clinical disease of the neurologic, endocrine, reproductive, and renal systems. Correlation between elevated lead levels and decreased performance on n e u r o p s y c h i a t r i c testing in adults has been reported. 31 In a study of exposed foundry workers, Baker found deficits in short-term m e m o r y and verbal intelligence, and significant mood changes associated with lowlevel exposures and modestly elevated (40 to 60 Fg/dL) PbB levels. 32 Bautman and coworkers found a correlation between chelatable lead and nephropathy in patients with renal insufficiency who had PbB and EP levels within normal limits but an abnormal provocation test:~3 Finally, relatively low levels of lead have been shown to affect the reproductive systems of both sexes. 34,35 Debate continues over w h e t h e r there is a threshold or "safe" level of exposure to lead. Although we know that neurophysiologic and enzymatic processes as well as heine synthesis are impaired at PbB levels of 20 ~g/ dL and less, until recently there were few h u m a n studies that addressed the issue of threshold effects on behavior. 36-38 However, two large, prospective cohort studies examining the effect of prenatal exposure to lead on cognitive development have rec e n t l y been concluded.39, 4° Both found significant impairment of cognitive development that persists for years in infants born with elevated cord blood lead levels that were still below the level currently considered safe. Taken together, these studies suggest there may be no clear threshold below which adverse effects do
receiving parenteral CaEDTA represents s o m e o n e with a significant body burden of lead. In light of the current differences in the methodology of the provocation test, we believe there is a pressing need to standardize the test for adults. Because many of the biological effects of lead exposure are poorly understood, and because lead affects a number of important organ systems, we believe a strong argument can be made for treating any asymptomatic adult with an elevated lead level and positive provocation test. Prevention was first addressed in 1977, when a federal law was passed that regulated household paint. Paint cannot contain more than 0.06% (600 parts per million) lead by dry weight. However, the interior surfaces of about 27 million homes are still contaminated with lead paint produced before the regulations were codified. Many people are restoring and r e n o v a t i n g older h o m e s and buildings that contain this paint. Any process that involves sanding, blasting, or burning of paint is especially dangerous. Dust generated by this work is hazardous to those in the home, especially children. Very often those doing this work are unaware of hazards and take few, if any, precautions. Physicians should advise these individuals to take recommended precautions to prevent exposures. 41,42 W h e n possible, p r o f e s s i o n a l deleaders should perform the work. Adequate masks and ventilation should be provided. During the work, all children, pregnant women, and women of child-bearing age should be removed. Furniture and dining implements should be sealed off from exposure. After the work is finished the surfaces should be washed with sodium hexa metaphosphate, a detergent that binds lead.
not
SUMMARY
occur.
In light of these low-level effects we believe that a more aggressive posture toward treatment of adults (particularly m e n and w o m e n of childbearing age) is justified. The CaEDTA provocation test may be useful in helping to decide whether treatment of patients with borderline elevations of PbB and EP levels'is indicated. A patient who excretes an excessive lead load in 24 hours after Annals of Emergency Medicine
These cases underscore the need for emergency physicians to question possible environmental and occupational exposures in their history taking of acute medical problems. It is imperative that lead intoxication be recognized as a possible sequela of renovation work and included in the differential diagnosis in this setting. Interpreting tests for lead and treatment are discussed. 4.19/t17
LEAD POISONING Schneitzer et al
Additional research must be done on the role of provocation testing in the diagnosis and m a n a g e m e n t of lead intoxication in adults. As more is learned, it is possible that current recommendations for diagnosis and treatment will have to be adjusted further.
Lead poisoning from "Do It Yourself" heat guns for removing lead based paint: Report of two cases. Environ Research 1981;24:425-431.
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Treatment of lead poisoning by 2-3 dimercaptosuccinic acid. Lancet 1978;2:1234-1236. 30. Graziano JH, Siris ES, Lolacono N: 2,3 dimercaptosuccinic acid as an antidote for lead int o x i c a t i o n . Clin P h a r m a c o l Ther 1985; 37:431-438.
17. Morgan JM: A simplified screening test for exposure to lead. South Med J 1967;60:435-438.
31. Valciukas JA, Lilis R, Singer R: Lead exposure and behavioral changes: Comparisons of four occupational groups with different levels of lead absorption. A m J Industrial Med 1980; 1:421-426. 32. Baker EL, Feldman RG, White RA, et al: Occupational lead: A behavioral and electrophysiological evaluation. Br Jnl Ind Med 1984;41:352-362.
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18. Jain S, O'Brien B, Pothergill R, et ah Lead poisoning presenting as infectious disease. Practitioner 1970;384:784-786.
33. Bautman VpMaesaka JK, Haddad B: The role of lead in gout nephropathy. N Engl J Med 1981;304:520-523.
3. Hamilton A: Lead, in Finkel AJ (ed): Hami/ton and Hardy's Industrial Toxicology Boston, Wright - PSG, 1983, p 62-87.
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4. Piomelli S, Rosen JF, Chisolm JJ Jr, et ah Management of childhood lead poisoning. J Pediatr 1984;105:523-532.
20. Whitfield CL, Ch'ien LT, Whitehead JD: Lead encephalopathy in adults. A m J Med 1972;52:289-298.
34. Cullen MR, Kayne RD, Robins JM: Endocrine and reproductive dysfunction in men associated with occupational organic lead intoxication. Arch Env Health 1984;39:431-440.
5. Guinee VF: Lead poisoning. A m J Med 1972;52:283-288.
21. Saenger P, Rosen JF: Hydroxycortisol excretion is a non-invasive and sensitive index of chelatable lead stores in children, in: Brown SS, Davis DS (eds): Organ-Directed Toxicity-Chemical Indices and Mechanisms. New York, Pergamon Press, 1981, p 297-303.
1. Cullen MR, Robins JM, Eskenzai B: Adult inorganic lead intoxication: Presentation of 31 new cases and a review of recent advances in the literature. Medicine 1983;62:221-247.
6. Preventing Lead Poisoning in Young Children: A Statement by the Centers for Disease Control. DHEW (CDC) Pub 99-2230. Atlanta, US Department of Health, Education and Welfare, Centers for Disease Control, 1985. 7. Goldfrank LR, Osbom H: Lead The silent epidemic, in Goldfrank LR, Fiomenbaum NE, Lewin NA, et al (eds): Toxicologic Emergencies: A Comprehensive Handbook in Problem Solving. New York, Appleton Century-Crofts, 1982, p 273-280.
15. Piomelli S, Davidow B, Guinee V, et al: The PEP Test: A screening micromethod for lead poisoning. Pediatr 1973;51:254-259.
22. Hansen JP, Dossing M, Paulev PE: Chelatable lead body burden (by calcium disodium EDTA} and blood lead concentration in man. J Occup Med 1982;23:39-43. 23. Lecki WJ, Tombsett SL: The diagnostic and therapeutic use of EDTA in excessive inorganic lead absorption. Q J Med 1958;27:65-70.
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24. Westerman M, Pfidzer E, Ellis LD: Concentration of lead in bone plnbism. N Engl J Med 1965;273:1246-1250.
9. Green VA, Wise GW, Callenbach J: Lead poisoning. Clin Toxicol 1976;9:33-51.
25. Emerson BT, Thielea BR: Calcium versenate in the diagnosis of lead nephropathy. Australia Med J 1960;1:243-246.
10. l:eldman RG: Urban lead mining: Lead intoxication among deleaders. N Engl J Med 1978;298:1143-1t45. 11. Fischbein SA, Daum SM, Davidow B, et al: Lead hazard among ironworkers: Dismantling lead-painted elevated subway line in New York City. NY State J Med 1978;78:1250-1259.
26. Wedeen RP, Malik DK, Bautman V: Detection and treatment of lead nephropathy. Arch Intern Med 1979;139:53-57. 27. National Institute of Occupational Safety and Health Recommendations for Occupational Safety and health standards 1988. MMWR 1988;37:1-8.
12. Landrigan PJ, Baker EL, Himmelstein JS: Exposure to lead from the Mystic River Bridge: The dilemma of deleading. N Engl J Med 1982;306:673-676.
28. Aposhian HV: DMSA and DMPS-water soluble antidotes for heavy metal poisoning. Ann Rev Pharmacol Toxieol 1983;23:193-215.
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35. Rom WN: Effects of lead on the female and reproduction: A review. Mt Sinai J Med 1976; 43:542-552. 36. Hernberg S, Nikkanen J: Enzyme inhibition by lead under normal urban conditions. Lancet 1970;1:63-64. 37. Otto D, Robinson G, Bauman S: Five year follow-up study of children with low-to-moderate lead absorption: Electro-physiological evaluation. Environ Res 1985;38:168-186. 38. Otto D, Bernigus V, Muller K: Effects of low to moderate lead exposure on slow cortical potentials in young children: Two year follow-up study. Neurobehav Toxicol Teratol 1982;4: 733-736. 39. Bellinger D, Leviton A, Waternaux C, et al: Longitudinal analysis of prenatal and post-natal lead exposure and early cognitive development. N Engl J Med 1987;316:1037-1043. 40. McMichael A, Baghurst P, Wigg N, et ah Port Pirie cohort study: Environmental exposure to lead and children's abilities at the age of four years. N Engl J Med 1988;319:468-475. 41. Milar C, Mushak P: Lead contaminated housedust: Hazard measurement, decontamination in Chisolm J, O'Hara D (eds): Lead Absorption in Children. Baltimore, Urban and Schwarzenberg, 1982, p 141-152. 42. Preventdng Lead Poisoning in Young Children. Atlanta, Centers for Disease Control. DHEW publication no. 002629. Washington, DC, US Dept of Health, Education and Welfare, 1978:1-26.
19:4 April 1990
Lead Poisoning in Adults From Renovation of an Older H o m e Presented is the case of a group exposure to lead occurring during the removal of lead-based paint from an older home. One patient had symptoms from the time of exposure to the time of presentation, when he was acutely ill and encephalopathic. The patient was treated successfully with an initial course of British Anti-Lewisite agent and calcium disodium versenate (CaEDTA) chelation, and two subsequent chelations with CaEDTA alone. The other two patients had elevated lead levels but were asymptomatic. They were followed closely, and their lead levels steadily declined over several months. The evaluation and treatment of lead poisoning and excessive lead levels in adults is discussed, as is the need for physicians and the lay public to become aware of the hazards of renovating older homes. [Schneitzer L, Osborn HH, Bierman A, Mezey A, Kaul B: Lead poisoning in adults from renovation of an older home. Ann Emerg Med April 1990;19:415-420.] INTRODUCTION Lead is a well-known toxin, and the spectrum of lead-induced disease has been well described. 1-4 Much attention has been paid to the problem of preventing chronic lead intoxication in inner-city children and to occupational exposure in adults, s-8 Most lead toxicity, especially in children, occurs secondary to oral ingestion. Lead can, however, also be inhaled. Absorption of atmospheric lead by the lung is dependent on particle size. Seventy percent of the fine lead inhaled from the atmosphere is exhaled in the expired air. Of the 30% that is not returned, particles of less than 0.1 u in diameter are absorbed, while particles larger in diameter are trapped in the upper airways and swallowed. 9 It has been shown that excessive lead absorption can occur during the renovation of bridges and other structures containing lead-based paint, lo-13 In this instance, lead dust or fumes are readily absorbed through the respiratory mucosa due to the small particle size involved. When heated, lead vaporizes and precipitates as a fine particulate mist. Any process creating lead dust or fumes presents a significant health hazard. Furthermore, eating in areas where lead dust is present can also lead to intoxication. 1,1 We report three cases of excessive lead absorption in adults resulting from a single massive exposure to lead fumes and dust. This occurred during the sandblasting of paint from the interior of an older house. Guidelines regarding the need for treatment of these patients are discussed.
Leila Schneitzer, MD, FACEP* Boston, Massachusetts Harold H Osborn, MD, FACEPIBronx, New York Arlene Bierman, MD~: New York, New York Andrew Mezey, MD§ Bronx, New York Balkrishena Kaul, PhDII New York, New York From the Emergency Department, Boston City Hospital, Boston, Massachusetts;* Emergency Services, Lincoln Medical College, Bronx, New York;t Department of Medicine, Metropolitan Hospital, New York Medical College, New York, New York;~: Department of Pediatrics, Bronx Municipal Hospital, Bronx, New York;§ and the City of New York Department of Health, Public Health Laboratories, New York, New York.II Received for publication November 8, 1988. Revision received November 27, 1989. Accepted for publication December 12, 1989. Address for reprints: Harold H Osborn, MD, FACER Department of Emergency Medicine, ©ur Lady of Mercy Medical Center, 600 East 233rd Street, Bronx, New York 10464.
CASE REPORTS Case 1 A 33-year old man presented to the emergency department with complaints of headache, fatigue, nausea, crampy abdominal pain, and arthralgias. The patient, a paramedic supervisor, was well until 15 days prior to admission when he sandblasted a thick layer of paint from a fireplace in his 50 year-old home. The patient spent 12 hours doing this work, wore only a surgical mask for protection, and in addition had constructed a "canopy" around the fireplace to protect the rest of the room. The evening of the sandblasting, the patient developed symptoms that persisted and worsened up until the time of presentation. Initially he at-
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Annals of Emergency Medicine
415/113
LEAD POISONING Schneitzer et al
FIGURE. PbB and EP levels in three patients exposed to lead. Chelation therapy is indicated for patient 1.
BAL
I :aEDTA
100 tributed his symptoms to a viral syndrome. He finally sought medical attention at the urging of his fiancde (patient 3), also a paramedic, who wondered about the possibility of lead poisoning. His medical history was entirely negative, with a recent normal physical examination and a reported blood pressure of 140/90 m m Hg. An environmental and occupational history failed to reveal any other sources of lead exposure. Physical examination revealed a well-developed man in moderate distress, with frequent episodes of vomiting. He was i n t e r m i t t e n t l y lethargic, despite the severe abdominal pain and vomiting. Vital signs revealed a blood pressure of 170/125 m m Hg; pulse, 88; respirations, 16; and temperature, 37 C. Abdominal examination was unremarkable, as was the neurological examination. There was no papilledema or focal motor or sensory deficits. Cerebellar f u n c t i o n i n g was normal, as were deep tendon reflexes. The rest of the physical examination was unremarkable. Chest and abdominal radiographs were normal. An ECG revealed a PR interval of 0.10 seconds and a wide QRS with a delta wave. The h e m a t o c r i t , electrolytes, glucose, liver function tests, calcium, and uric acid level were all within normal limits. His initial blood lead (PbB) level was markedly elevated at 98 ~g/dL ( n o r m a l , < 25 ~ g / d L ) and t h e erythrocyte protoporphyrin (EP) was 68 ~xg/dL (normal, < 35 ~xg/dL). His serum ferritin level was 78 ng/mL (normal, > 15 ng mL). The peripheral blood smear revealed mild basophilic stippling of erythrocytes. Although the patient was quite symptomatic and had elevated PbB and EP levels, there was no sign of anemia, thus indicating that the exposure was an acute one. Blood and urine lead determinations were performed by atomic absorption spectrophotometry, and EP determinations were measured by Piomelli's extraction method.14, is After admission to the ICU, chelation therapy was started with 280 nag of British Anti-Lewisite agent (BAL) 4 mg/kg IM every four hours and 3,300 mg of calcium disodium versenate 114/416
Chelation Treatment
I
Blood Lead Levels
I
I CaEDTA I
[ CaEDTA I
I----I
• Patient 1 [ ] Patient 2 [ ] Patient 3
80 60 40 20 0
Erythrocyte Protoporphyrin Levels 220 180 140 100
60 20
15
16 18
25
36
46
60
69
88
127
187
Days After Exposure
(CaEDTA) 50 mg/kg/IV daily. Within two days, the patient was alert, normotensive, and entirely asymptomatic. A PbB level after 48 hours of treatment was 15 ixg/dL and the EP was 82 ~g/dL. BAL was discontinued after 48 hours, and the CaEDTA alone was given for an additional three days. Fifteen clays after the completion of chelation, PbB and EP levels were 57 ~g/dL and 212 ~g/dL, respectively. At that time a second five-day course of CaEDTA chelation only was given (2g CaEDTA IV per day). Three weeks after the second chelation, PbB and EP levels were 43 ~g/dL and 172 txg/dL, respectively, and a CaEDTA provocation test was performed. One gram of CaEDTA was administered IV twice at 12-hour intervals. The patient's urine was collected for 24 hours and was found to contain 1,610 ixg of lead. The lead excretion ratio (lead excreted [~g]/ Annals of Emergency Medicine
CaEDTA a d m i n i s t e r e d [mg]) was 0.80. The cut-off level considered to mandate treatment is 650 ~g or more of urinary lead in 24 hours16,17 or a lead e x c r e t i o n ratio greater t h a n 0.60. 4 Following the positive provocation test, a third course of chelation therapy was given, again administering 2g CaEDTA IV per day. During the last day of chelation, the 24-hour urinary output of lead was 520 ~g, with a lead excretion ratio of 0.21. Following the last chelation, the patient's lead levels continued to decrease and he remained asymptomatic (Table 1 and Figure). Blood pressure, urinalysis, and serum BUN and creatinine determinations remained normal as well. Case 2 A 32-year-old asymptomatic man who had been sandblasting with pa19:4 April 1990
TABLE 1. Blood and urine FEP and lead levels of patient 1 over a 26-week period
Levels (l~g/dL) Days After Sandblasting
Blood Lead
FEP
15
98
68
Initial presentation to ED Chelation with CaEDTA and BAL begun
16 18
15
82
25 36 40
45 56
95 212
46 60 69
26 45 43
212 186 172
BAL discontinued CaEDTA continued for additional 3 days Five days after chelation Sixteen days after chelation Second course of chelation begun CaEDTA for 5 days Second course of chelation ending Fourteen days after 2nd course of chelation CaEDTA provocation test done (2 g OaEDTA) Serum iron 75 p,g/dL Saturation 23%; total binding capacity, 326 #g/dL Ferritin 78 ng/mL Third course of chelation begun CaEDTA for 5 days Urine collected last day of chelation (2 g CaEDTA per day)
1,610
75
80 520
85 88 127 182
31 30
tient 1 was examined after that patient was admitted to the hospital. He had w o r k e d on the project for only a few hours and did not live in the house. This patient was grossly a s y m p t o m a t i c and his physical exa m i n a t i o n was u n r e m a r k a b l e , although neuropsychiatric testing was n o t performed. All laboratory tests were within normal limits. The patient's initial PbB and EP levels were 66 Ixg/dL and 120 ~g/dL, respectively. A serum ferritin level was 113 ng/dL. Repeat PbB and EP levels one week later w i t h o u t treatm e n t were 54 ~g/dL and 138 ~g/dL, respectively. To assess the body burden of lead, a CaEDTA provocation test was performed on the patient. He received 2 g CaEDTA IM (1 g every 12 hours) and excreted a total of 1,995 ~g of lead in 24 hours with a ratio of approximately 1.0. Treatment was r e c o m m e n d e d but the p a t i e n t declined to u n d e r g o chelation therapy. 19:4 April 1990
Comments
Urine Lead (24 Hours)
94 50
Five days later, PbB and EP levels were 43 ~xg/dL and 147 ~xg/dL, respectively. Another CaEDTA provocation test was done and was considered negative (urinary lead excretion of 666 ~g in 24 hours, and a lead excretion ratio of 0.33). The patient's PbB levels continued to decrease w i t h o u t chelation therapy, and he remained grossly asymptomatic (Figure). Case 3 A 29-year-old w o m a n who lived in the house where the sandblasting had t a k e n place was e x a m i n e d after it was discovered that the two m e n doing the work had elevated lead levels. W h e n questioned, she had no complaints. Her p h y s i c a l e x a m i n a t i o n was unremarkable. Again, neuropsychiatric testing was not carried out. Her initial PbB and EP levels were 24 ~g/dL and 66 ~g/dL, r e s p e c t i v e l y . The patient's serum ferritin level was 26 ng/mL. She did not receive any chelation therapy or CaEDTA provoAnnals of Emergency Medicine
cation tests. Her levels continued to decrease, and she remained grossly asymptomatic (Figure).
DISCUSSION Lead i n t o x i c a t i o n in a d u l t s has been described, but m o s t cases have involved exposure over several weeks to m o n t h s . Lead i n t o x i c a t i o n h a s b e e n r e p o r t e d in p r o f e s s i o n a l deleaders r e m o v i n g lead p a i n t f r o m housing units, ironworkers dismant l i n g e l e v a t e d s u b w a y lines, a n d those renovating old bridges. 1°-12 In 1981, Fischbein reported two cases of lead intoxication in adults secondary to removal of lead paint during h o m e renovation. 13 Both had primary occupations in which no significant lead exposure occurred. One was renovating his own home. The other patient was doing the renovation as a parttime job. The case of patient 1 is unusual in that s y m p t o m a t i c i n t o x i c a t i o n resulted from a relatively brief expo417/115
LEAD POISONING Schneitzer et al
TABLE 2. Symptoms and signs of lead intoxication
Acute Exposure
Mild fiulike nonspecific Complaints (fatigue, headache, arthralgias, weakness) Colicky abdominal pain, anorexia Nausea and vomiting, constipation Diarrhea, dark stools, abdominal radiograph may reveal radiopaque substance following oral ingestion Irritability, headache, poor concentration, insomnia or lethargy Clumsiness, ataxia, convulsions, coma, papilledema
sure, albeit a massive one. Several factors may be involved. The work was done in a small enclosed area without ventilation. Sand used in the process was reused, thus generating an even higher concentration of lead dust. Beverages were ingested during the day near the work area. Work was done in the kitchen where meals were prepared and subsequently consumed. Patient l's symptoms began shortly after exposure. Though these symptoms were typical of lead poisoning, they were nonspecific and more commonly associated with a viral syndrome. Lead i n t o x i c a t i o n affects multiple organ systems. Its presentation is variable and, like carbon monoxide poisoning, the diagnosis can easily be missed unless a history of lead exposure is obtained (Table 2). Jain reported six cases that were all referred to an infectious disease service and subsequently diagnosed as lead intoxication. 18 Schottenfeld and Cullen reported lead poisoning presenting as an organic affective illness with depression, irritability, and loss of libido, all of which disappeared with treatment. 19 Clinical manifestations of lead poisoning tend to be dependent on duration and intensity of exposure, and many of those poisoned may appear grossly asymptomatic. In the 1960s and 1970s when lead poisoning was recognized as a major problem in -~ 116/418
Chronic Exposure Early Nonspecific complaints
Apathy or irritability Anorexia, constipation Metallic taste, nausea Late All the above plus:
Incoordination, disturbance of menstrual cycle, abortion, cranial nerve, abnormalities Impaired nerve conduction Wrist and ankle drop Neurosensory loss in extremities Anemia, basophilic stippling of red cells Long bone radiographs may reveal deposition Chronic nephritis Learning disability, poor psychosocial development, mental and behavioral problems
young children, m a n y undiagnosed cases w e r e f o u n d t h r o u g h m a s s screening programs. Patient l's case is also unusual because he had symptoms compatible with encephalopathy. During the first few hours of his treatment with BAL and CaEDTA, he was lethargic and sleepy despite multiple noxious stimuli. Thirty-six hours following the initiation of treatment, the patient was fully awake, alert, and no longer hypertensive. Acute lead encephalopathy is not u n c o m m o n in children but is extremely rare in adults. We were unable to find any case reports of encephalopathy following such a short exposure time to lead. Although Whitfield reported 23 adults with lead encephalopathy after c o n s u m i n g large a m o u n t s of moonshine whiskey contaminated with lead salts, 91% of the patients were a n e m i c , i n d i c a t i n g a m o r e chronic exposure. 2o Blood lead levels, when elevated, most accurately reflect recent exposure but not toxicity nor the body burden of lead. 21 One can also have only m i l d l y elevated blood lead levels despite a significant exposure, systemic toxicity, and a large chelatable pool once distribution has occurred. Zinc protoporphyrin and free e r y t h r o c y t e p r o t o p o r p h y r i n are markers of lead interference with heme synthesis and thus serve as indicators of lead toxicity but only Annals of Emergency Medicine
when blood lead values are significantly elevated. Like the PbB level, these tests tell nothing about the body burden of lead. ~1 In addition, they are not reliable in documenting an acute lead exposure and are not useful in following a response to treatment. PbB levels and urinary lead excretion values can be used as indicators of a response to treatment. However, blood and urinary lead levels do not measure the lead deposited in the deep bone stores. Because the goal of therapy is to reduce the total body lead burden, the provocation test is the most sensitive parameter of adequacy of treatment, and, in our opinion, can often resolve the question of whether treatment is indicated. A good illustration of this point can be seen in our patients at day 69 following exposure. Of interest is the fact that patients 1 and 2's PbB levels were identical at this time (43 ~g/ dL), but patient l's provocation test was positive (1,610 ~g/lead/24 hours urine) while patient 2's test was borderline (666 ~g/lead/23 hours urine) (Table 1 and Figure). Patient 1 had a greater body burden of chelatable lead and was more toxic, a fact that is reflected in his greater EP level (172 p~g/dL) compared with that of patient 2 (147 Fg/dL). It also underscores the point that one cannot rely on blood lead levels alone without assessing toxicity with EP levels and 19:4 April 1990
the body burden of lead with the provocation test. The most sensitive marker of increased lead stores is the CaEDTA provocation test, which reflects the total body burden of chelatable lead. The test is performed by administering one or two parenteral doses of CaEDTA followed by a 24-hour urine collection. In adults,more than 650 p,g/dL lead/24 hr is considered to represent significantly increased chelatable lead body stores. In renal failure, a 72-hour urine collection is required. A l t h o u g h the p r o v o c a t i o n test was first introduced three decades ago, it is infrequently used in the management of adults exposed to lead, and there is, at present, no agreement on the method.~6,17, zz-26 The recommended exposure limit set by the National Institute for Occ u p a t i o n a l Safety and H e a l t h for workers exposed on the job is a blood lead 60 b~g/100 g of whole b l o o d y Most authorities would recommend t r e a t m e n t above this level. 4 For asymptomatic individuals with PbB levels between 25 and 60 ~xg/dL, the provocation test can be an important guide to therapy. T r e a t m e n t of lead poisoning in adults is s o m e w h a t controversial. However, it is generally accepted that symptomatic patients should be treated with both BAL and CaEDTA. The BAL may be discontinued after two days if symptoms improve and the lead levels are significantly lowered, while CaEDTA is continued for an additional three days. However, o p t i m u m doses have not yet been established. Oral penicillamine is not used in the treatment of acute lead toxicity but has been used after parenteral chelation therapy to lower lead levels once the environmental source of lead is eliminated. It is also used as a primary treatment for asymptomatic patients with elevated lead levels. Its use, however, is limited by the side effects of fever, proteinuria, skin rash, and leukopenia. Finally, a new oral chelator, 2,3 dimercaptosuccinic acid (DMSA), holds great promise. DMSA is a derivative of dimercaprol (BAL) and has been shown in animals to be as effective as conventional chelators even when given orally and is the best tolerated of all chelating agents, zs Clinical reports of its effectiveness are still limited and its application in the treatment of acute 19:4 April 1990
lead i n t o x i c a t i o n r e m a i n s undefined.29,3o The question of whether to chelate an a s y m p t o m a t i c p a t i e n t w i t h a modestly elevated PbB level (similar to patient 2) is a more difficult issue. Of relevance to this question are studies associating low-level exposure to clinical disease of the neurologic, endocrine, reproductive, and renal systems. Correlation between elevated lead levels and decreased performance on n e u r o p s y c h i a t r i c testing in adults has been reported. 31 In a study of exposed foundry workers, Baker found deficits in short-term m e m o r y and verbal intelligence, and significant mood changes associated with lowlevel exposures and modestly elevated (40 to 60 Fg/dL) PbB levels. 32 Bautman and coworkers found a correlation between chelatable lead and nephropathy in patients with renal insufficiency who had PbB and EP levels within normal limits but an abnormal provocation test:~3 Finally, relatively low levels of lead have been shown to affect the reproductive systems of both sexes. 34,35 Debate continues over w h e t h e r there is a threshold or "safe" level of exposure to lead. Although we know that neurophysiologic and enzymatic processes as well as heine synthesis are impaired at PbB levels of 20 ~g/ dL and less, until recently there were few h u m a n studies that addressed the issue of threshold effects on behavior. 36-38 However, two large, prospective cohort studies examining the effect of prenatal exposure to lead on cognitive development have rec e n t l y been concluded.39, 4° Both found significant impairment of cognitive development that persists for years in infants born with elevated cord blood lead levels that were still below the level currently considered safe. Taken together, these studies suggest there may be no clear threshold below which adverse effects do
receiving parenteral CaEDTA represents s o m e o n e with a significant body burden of lead. In light of the current differences in the methodology of the provocation test, we believe there is a pressing need to standardize the test for adults. Because many of the biological effects of lead exposure are poorly understood, and because lead affects a number of important organ systems, we believe a strong argument can be made for treating any asymptomatic adult with an elevated lead level and positive provocation test. Prevention was first addressed in 1977, when a federal law was passed that regulated household paint. Paint cannot contain more than 0.06% (600 parts per million) lead by dry weight. However, the interior surfaces of about 27 million homes are still contaminated with lead paint produced before the regulations were codified. Many people are restoring and r e n o v a t i n g older h o m e s and buildings that contain this paint. Any process that involves sanding, blasting, or burning of paint is especially dangerous. Dust generated by this work is hazardous to those in the home, especially children. Very often those doing this work are unaware of hazards and take few, if any, precautions. Physicians should advise these individuals to take recommended precautions to prevent exposures. 41,42 W h e n possible, p r o f e s s i o n a l deleaders should perform the work. Adequate masks and ventilation should be provided. During the work, all children, pregnant women, and women of child-bearing age should be removed. Furniture and dining implements should be sealed off from exposure. After the work is finished the surfaces should be washed with sodium hexa metaphosphate, a detergent that binds lead.
not
SUMMARY
occur.
In light of these low-level effects we believe that a more aggressive posture toward treatment of adults (particularly m e n and w o m e n of childbearing age) is justified. The CaEDTA provocation test may be useful in helping to decide whether treatment of patients with borderline elevations of PbB and EP levels'is indicated. A patient who excretes an excessive lead load in 24 hours after Annals of Emergency Medicine
These cases underscore the need for emergency physicians to question possible environmental and occupational exposures in their history taking of acute medical problems. It is imperative that lead intoxication be recognized as a possible sequela of renovation work and included in the differential diagnosis in this setting. Interpreting tests for lead and treatment are discussed. 4.19/t17
LEAD POISONING Schneitzer et al
Additional research must be done on the role of provocation testing in the diagnosis and m a n a g e m e n t of lead intoxication in adults. As more is learned, it is possible that current recommendations for diagnosis and treatment will have to be adjusted further.
Lead poisoning from "Do It Yourself" heat guns for removing lead based paint: Report of two cases. Environ Research 1981;24:425-431.
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