Lead poisoning from lead-soldered electric kettles RAYMOND NG, MD, CM, FRCP[C]; DAVID J. MARTIN, MB, MRCP, FRCP[C]

Lead poisoning occurred In two Infants, causing lead encephalopathy In one but no symptoms in the other. Both Infants had been fed a formula prepared with water boiled in a lead-soldered electric kettle. The diagnosis was suggested by dense metaphyseal bands In radlographs, Illustrating the Importance of careful examination of "routine" radlographs, particularly In asymptomatic Infants. Un empoisonnement au plomb survenant chex deux b6b6s a caus6 une enc6phalopathie chez l'un mais n'a provoqu6 aucun symptAme chez l'autre. Les deux enfants avalent re.u pour nourriture une formule preparee avec de l'eau boulilie dans une bouillolre electrlque soudee au plomb. Le diagnostic a et6 envisage aprAs l'observation A Ia radlographie de bandes de densite au niveau de Ia ligne de jonction des 6plphyses et des diaphyses; ceci illustre l'importance dexaminer avec precaution les radiographies pratiqu6es syst6matiquement, particulierement chez les enfants asymptomatiques. The sources of lead in our environment are many and varied, and the chief known ones - lead-based paint, exhaust from automobiles using, leadcontaining fuels, and dusts from lead smelters and battery factories - are common causes of lead poisoning. There are also sporadic reports of lead poisoning from such sources as leadglazed pottery,1 lead shot,2 untaxed whisky3 and eye cosmetics.4 Recently it was found that leadsoldered electric kettles can release lead in concentrations exceeding 0.05 parts per million (ppm) (5 .g/d1),5 and in 1974 the Ontario Ministry of Health warned against using water boiled in such kettles in preparing infant formulas.6 The following cases appear to be the first reported in which lead poisoning *has been traced to the ingestion of water boiled in a lead-soldered electric kettle. Case reports Case 1 A 3-month-old girl was transferred to our hospital Nov. 10, 1973 because of convulsions. Delivery had been normal From the departments of pediatrics and radiology, the Hospital for Sick Children, Toronto Reprint requests to: Dr. R. Ng, Department of pediatrics, The Hospital for Sick Children, 555 University Ave., Toronto, Ont. M5G 1X8

508

and at term, and the neonatal period had been uneventful. She had been breast-fed for 6 weeks and then given a commercial formula (Similac) in the usual 1:1 dilution with water, consuming about 2 dl five times daily. Pablum had been added soon after the change to Similac. Projectile vomiting, lethargy and irritability of 1 week's duration had necessitated admission to a local hospital Nov. 8. There she had had repeated generalized convulsions lasting up to 30 minutes despite treatment with diazepam and phenobarbital. There was no history of fever and no signs of meningeal irritation were detected. She was extremely lethargic but well developed and well nourished. Rectal temperature was 37.8 0C. The anterior fontanelle was flat and soft, transillumination of the skull revealed no abnormalities, the fundi were normal, and examination of the central nervous system revealed no localizing signs. All other systems appeared normal. Hemoglobin value was 8.8 g/dl; blood smear showed hypochromia, microcytosis and basophilic stippling. The results of all other laboratory tests, including serum iron concentration and total iron-binding capacity (TIBC), were normal. The infant was treated with ampicillin intravenously until we learned that cultures of blood and cerebrospinal fluid had yielded no growth.

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A brain scan was normal. Radiographs of the skull and chest (Figs. lA and lB. respectively) showed dense metaphyseal bands, splitting of the sutures and increased density of the sutural margins. These findings prompted radiographic examination of the wrists, knees and abdomen, which revealed lines of increased density at the metaphyses (Fig. lC), compatible with heavy-metal poisoning. Blood lead value was 145 i.g/dl and spot testing for urinary coproporphyrins was strongly positive. Chelation therapy with dimercaprol (BAL) and ethylenediamine tetraacetic acid (EDTA) was given for 5 days, during which the infant excreted large amounts of lead and &aminolevulinic acid (ALA) in her urine. At the time of her discharge from hospital her blood lead value was 60 .Lg/dl; d-pencillamine therapy was instituted. The public health authority, which

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FIG. lA-Case 1, November 1973: hone density increased along margins of lambdoid and mendosal sutures.

FIG. lB-Case 1, November 1973: bands of increased density in proximal ends of FIG. iC-Case 1, November 1973: metahumeri and in superior and inferior physeal hands of increased width and borders of scapulae, density in left wrist and knee.

CMA JOURNAL/MARCH 5, 1977/VOL. 116

has been tracing the source of lead responsible for the poisoning, advised us that water boiled in the lead-soldered electric kettle used by the mother in preparing the infant's formula released 120 .'g of lead per decilitre. (The lead content of tap-water in Toronto at that time was 2 .'g/dl.) Thus the infant had been ingesting approximately 600 i.g of lead daily, 12 times the presumed safe maximum amount (50 .'g/dl). At follow-up in March 1975 the child evidenced normal development, normal values of blood lead and free erythrocyte protoporphyrin (FEP) and normal blood smear and radiographs (Fig. 2). Case 2 An infant had been admitted to our hospital May 1, 1975 at 1 day of age for investigation of ambiguous genitalia and severe hypospadias; cystoscopic examination had shown him to be a normal male with penoscrotal hypospadias. He was next admitted Jan. 11, 1976 for treatment of severe seborrheic dermatitis. Since birth his diet had consisted mainly of a commercial formula (Enfalac) in the usual 1:1 dilution with water. Hemoglobin value was 9.3 g/dl; blood smear showed hypochromia and microcytosis but no basophilic stippling. Other laboratory tests, including measurement of serum iron concentration and TIBC, gave normal results. In view of the infant's neglected state, radiography of the skull and long bones was performed in a search for evidence of physical abuse. Dense metaphyseal bands were found (Fig. 3) and heavy-metal poisoning was suspected. Blood lead value was 35 jtg/dl, FEP value was 750 .'g/dl (normal, < 80 ,sg/dl) and ALA-D value was 150 .tmo1 (normal, > 600 b'mol) per decilitre of erythrocytes. In view of the absence of a history of pica and our previous experience (case 1) we question.d the mother concerning preparation of her infant's formula. She stated

that she used water boiled in an electric kettle; a check of the model and serial number with the federal government's published test results7 showed that her kettle released more than S i'g of lead per decilitre and was considered hazardous. The concentration of lead in water boiled in this kettle was 75 .sg/dl. Standard EDTA-mobilization testing after administration to the infant of 200 mg of EDTA (25 mg/kg body weight) revealed 372 #sg of lead in the urine in 24 hours, confirming the diagnosis of lead poisoning. Treatment with d-pencillamine was given for 2 days, then discontinued because of a severe rash, probably drug-induced. Assuming that the infant had consumed approximately 5 dl of boiled water in the formula per day, his estimated daily intake of lead was 375 .g (safe maximum amount, 50 isg/d). With elimination of this source of the metal the patient's blood lead value decreased to normal. When he

was last seen, in June 1976, radiographs of the long bones revealed virtually no trace of "lead-lines"; his FEP concentration (350 .'g/dl) was decreasing toward normal. He had remained asymptomatic. Discussion Traditionally the pediatrician's view of plumbism is that it occurs in children aged 12 to 36 months who have a history of pica and live in old, rundown housing. Recently, however, attention has been directed to those who live close to industrial sources, such as lead smelters and battery factories; blood lead values in these children are inversely proportional to the distance of their dwellings from the industrial sites. Thus, although the relatively protected environment of infants under 1 year of age reduces their likelihood of

FIG. 2-Case 1, March 1975: left knee .* appears normal, with metaphyseal bands FIG. 3-Case 2, January 1976: dense metaphyseal bands, with less dense bone between, of normal density and width. indicating varying exposure to lead.

CMA JOURNAL/MARCH 5, 1977/VOL. 116 509

Vibramycin DOXYCYCLINE

been reported, the significance of which is not known. In clinical efficacy studies to date, VIBRAMYCIN IV. was generally well tolerated. The most frequent side effects reported with the preparation were burning at the site of Infusion, and phlebitis. The frequency and severity of the reactions can be minimized by using dilute solutions of the formulation and by avoiding di ffusion of the solution into surrounding tissues. SYMPTOMS and TREATMENT OF OVERDOSAGE Gastric lavage If necessary.

VIBRAMYCIN PRODUCT INFORMATION Capsules, Oral Suspension and Intravenous A..N VIBRAMYGIN is a broad-spectrum antibiotic and Is active against a wide range of Gram-negative and Gram-positive organisms. VIBRAMYCIN exerts its antimicrobial effect by Inhibition of protein synthesis. INDICATIONS AND CLINICAL USE Oral VIBRAMYCIN Is indicated for the treatment of:-Pneumonia: Single and multilobe pneumonia and broncho-pneumonia due to susceptible strains of Pneumococcus, Streptococcus, Staphylococcus; II. lnfluenzae and Kiebs/ella pneumoniae. Other Respiratory Tract Infections: Pharyngitis, tonsillitis, sinusitis, otitis media, bronchitis caused by susceptible strains of .-hemolytic Streptococcus, Staphylococcus, neumococcus and II. influenzae. Genito-urinary Tract Infections: Pyelonephritis, cystitis, urethritis, gonococcal urethritis caused by susceptible strains of the Klebsiella-Aerobacter group, E. coil, Enterococcus, Staphylococcus, Streptococcus and Nelaserla gonorrhoeae. Skin and Soft Tissue Infections: Impetigo, furunculosis, cellulitis, abscess, wound sepsis, paronychia, caused by susceptible strains of Staphylococcus aureus and albus, Streptococcus, E. coil, and the KIebsiella-Aerobacter group. Gastro-intestinal Infections caused by susceptible strains of Shigella, Salmonella and E. coil. For patients In whom oral therapy may not be feasible for such reasons as dysphagia, nausea, gastro-intestinal intolerance, unconsciousness, lack of cooperation, traumatic or surgical wounds of the gastro-intestinal tract or Intestinal obstruction, VIBRAM YCIN IV. may be used. The clinical efficacy of VIBRAMYCIN IV. has been confirmed In cases of infections caused by E. coli, KIebsiella and Staphylococcus aureus. CONTRAINDICATIONS VIBRAMYCIN is contraindicated In individuals who have shown hypersensitivity to tetracyclines. WARNINGS As with other tetracyclines, VIBRAMYCIN may form a stable calcium complex in any boneforming tissue, though in vitro it binds calcium less strongly than other tetracyclines. Though not observed in clinical studies to date, it should be anticipated that like other tetracyclines the use of VIBRAMYCIN during tooth development (last trimester of pregnancy, during lactation, neonatal period and early childhood) may cause discoloration of the teeth. Though more commonly associated with long term use of tetracyclines, this effect has also been known to occur after short courses. INFUSION OF VIBRAMYCIN IV. SHOULD BE CARRIED OUT AT A RATE NOT TO EXCEED 200 MG. OVER A 30-MINUTE PERIOD. PRECAUTIONS In clinical studies to date, VIBRAMYCIN administration did not lead to increased serum levels nor to an increase in the serum half-life of doxycycline in patients with impaired renal function. VIB RAMYCIN in normal dosage may be used to treat these patients. Although no evidence of increased toxicity has been observed in such patients, the potential for Increased hepatic or other toxicity should be considered until further data on the metabolic fate of doxycycline under these conditions become available. Liver function tests should be carried out at regular intervals on patients receiving high doses for prolonged periods of time. Concurrent administration of VIBRAMYCIN and agents known to be hepatotoxic should be avoided If possible. The use of antibiotics may occasionally result In overgrowth of nonsusceptible organisms; thus, observation of the patient is essential. There i. evidence to suggest that VIBRAMYCIN, may have less effect on the gut flora than other tetracyclines. VIBRAMYCIN should not be administered to pregnant and lactating women or neonates until its safety in such cases has been established beyond all reasonable doubt, unless in the judgment of the physician the potential benefit to the aflent outweighsthe risk to the fetus or child. Certain lye individuals ma develop a photodynamic reaction to sunlight c?'uring treatment with VIBRAMYCIN. If this or any other allergic reaction should occur, medication should be discontinued. Increased intracranial pressure with bulging fontaneiles has been observed in infants receiving therapeutic doses of tetracycline. Although the mechanism of this henomenon is unknown, the signs and symptoms ave disappeared rapidly upon cessation of treatment with no sequelse. ADVERSE REACTIONS As with other broad-spectrum antibiotics, pastro-Intestinal disturbances such as nausea, vomiting and diarrhoea, as well as glossitis, stomatitis and proctitis may occur, but have rarely been sufficiently troublesome to warrant discontinuation of therapy. As with other tetracyclines, elevation of SGOT or SGPT values, anemia, neutropenis, easinophllla, leukopenla or elevated BUN has

DOSAGE AND ADMINISTRATION ORAL: The recommended dosage of oral VIBRAMYCIN in adults for the . infections is a single loading g. the first day of treatment followed by a maintenance dosage of 1 00mg. once daily at the same time each day thereafter. The recommended dosage schedule for children over one month weighing up to 100 pounds is a single loading dose of 2 mg.Ilb. of bodyweight on the first day, followed by a maintenance dosage of 1 mg.IIb. once daily at the same time each day thereafter. As absorption is not significantly affected by food or milk, VIBRAMYCIN should be given with or after a meal thus minimizing the possibility of gastric upset. Antacids and iron preparations impair absorption and should not be given concomitantly to patients taking oral VIBRAMYCIN. In severe infections in adults such as lung abscesses or osteomyalitis, and in chronic urinary tract infections, a single daily dose of 200 mg. may be used throughout. For more severe infections in children, up to 2 mg.Ilb. of bodyweight may be given. Therapy should be continued after symptoms and fever have subsided. It should be noted, however, that effective antibacterial levels are usually present 24 to 38 hours following discontinuance of VIBRAMYCIN therapy. When used in streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis. For treatment of ecute gonococ. cal infections, the recommended dosage is 200 mg. stat. and 100 mg. at bedtime the first day, followed by 100 mg. bid. for 3 days. No alteration In recommended dosage schedule need be made when treating patients with impaired renal function. INTRAVENOUS: INFUSION OF VIBRAMYCIN IV. SHOULD BE CARRIED OUT AT A RATE NOT TO EXCEED 200 mg OVER A 30-MINUTE PERIOD. Rapid administration Is to be avoided. Parenteral therapy is indicated only when oral therapy is not practical. Oral therapy should be instituted when feasible. If intravenous therapy is 9iven over prolonged periods of time, thrombophiebitis may result. The dosage and frequency of administration of VIBRAMYCIN IV. differ from other tetracyclines. Thus therapeutic antibacterial serum activity will usually persist for 24 hours following recommended doses of VIBRAMYCIN IV. Exceeding the recommended dosage may result in accumulation of the drug with an increased incidence of side effects. Adulfs: The dosage of VIBRAMYCIN IV. is 200 mg. on the first day of treatment (administered as a single dose or as 100 mg. every 12 hours) followed by a maintenance dose of 100 mg. per day. In the management of more severe Infections (particularly chronic infections of the urinary tract), 200mg. should be given daily throughout the treatment period. Infusion should be carried out at a rate not to exceed 200 mg. over a 30-minute period. Therapy should be continued beyond the time that symptoms and fever subside. Children: As yet there is no clinical experience with VIBRAMYCIN IV. In children. Careful consideration should be given to the risk-benefit ratio in the pediatric age range. Should use be deemed essential, the suggested dosage schedule for children weighing 100 lb. or less Is 2 mgllb. of bodyweig ht administered as a single or divided dose on the first day of treatment, followed by 1 mg.llb. of bodyweig ht given as a single or divided dose on subsequent days. For more severe Infections, up to2mgIlb. of bodyweight may be considered. For children over 100 lb. the usual adult dose may be used. Oral VIBRAMYCIN dosage forms should be administered for continuing therapy as soon as the patient is able to accept oral medication. Therapy should be continued forat leest 24-48 hours aftersymptoms and fever have subsided. Intravenous solutions should be Injected directly into the vein. They should not be injected intramuscularly or subcutaneously. Caution should be taken to avoid the Inadvertent introduction of the Intravenous solution Into the adjacent soft tissues. DOSAGE FORMS VIBRAMYCIN CAPSULES are available as 100 mg. (blue) hard gelatin capsules containing doxycycline hyclate equivalent to 100 m.. of doxycycline, supplied in bottles of 200, 50 and 2 VIBRAMYCIN FOR ORAL SUSPENSION (doxycycline monohydrate) is available as a dry powder for oral suspension containing, when reconstituted, doxycycline monohydrate equivalent to 25 mg. of doxycyclinel5 ml. (each teaspoonful) with a pleasant raspberry flavor in 50 ml. bottles. VIBRAMYCIN IV. is available as a sterile powder in a vial containing doxycycline hyclate equivalent to 100 mg. of doxycycline with 480 mg.of ascorbic acid. Product Monograph available on request.

PHARMACEUTICAL DIVISION Montreal

512 CMA JOURNAL/MARCH 5, 1977/VOL. 116

Canada

lead poisoning, some may be exposed to increased lead concentrations during their daily outings. In one case in a 6-month-old breast-fed infant the source of lead was hand-to-mouth contact and inhalation of lead-containing dust from the fireplace, where newspapers and magazines were often used as fuel.8 Infants are probably more susceptible than adults to the toxic effects of lead - for example, our second patient had a blood lead value of only 35 ,.tg/dl but the FEP value was greatly increased. Potential sources of lead must be identified and eliminated; since an infant's diet is less varied than an adult's, this can be investigated relatively easily. Boiling liquids in lead-soldered electric kettles releases amounts of lead that are incompatible with good health, and the use of lead solder in canning increases the lead concentration in the can's contents for example, whole milk contains approximately 5 p,g/dl and canned evaporated milk contains about 16 ,.tg/dl. Thus the trend away from breast-feeding introduces the additional hazard of increased lead concentrations in infant formulas, especially if these are prepared with water boiled in a leadsoldered electric kettle. A major problem in the detection of lead poisoning is the nonspecificity of its symptoms and clinical signs. Patients may present with symptoms referable to the central nervous system or gastrointestinal tract, or the condition may be discovered by chance - as in our case 2 and the case reported by Perkins and Oski. Both our cases illustrate that initially the strongest clues may appear in the radiographs. Therefore, physicians who observe dense metaphyseal bands particularly in infants under 1 year of age - should act promptly to confirm or refute the diagnosis of plumbism. References 1. KLEIN

M,

NAMER

R,

HARPUR

E,

Ct

al:

Earthenware containers as a source of fatal lead poisoning. case study and public-health considerations. N Engi .1 Med 283: 669, 1970

2. GREEN5HER J, MOFENSON H., BALAKRISHNAN

C, et al: Lead poisoning from ingestion of lead shot. Pediatrics 54: 641, 1974 3. PALMISANO PA. SNEED RC, CASSADY G: Untaxed whiskey and fetal lead exposure. I Pedjair 75: 869, 1969 4. WARLEY MA, BLACKLEDGE P, O'GoRMAN P: Lead poisoning from eye cosmetic (C). Br Med 1 1: 117, 1968 5. WIGLE DT: Study of lead exposure from electric kettles, in Abstracts, of the International Conference on Heavy Metals in the Environment, Toronto, Oct. 27-31, 1975, University of Toronto, Institute for Environmental Studies, 1975, p B-88 6. CHANT DA, DEMARCO FA, ROBERTSON HR: Effect on Human Health of Lead from the Environment, Toronto, Ontario Ministry of Health, 1974 7. Results of electric kettle tests, in news releases NR-74-37 and NR-74-40, Ottawa, Consumer and Corporate Affairs, 1974 8. PERKINS KC, OSKI FA: Elevated blood lead in a 6-month-old breast-fed infant - role of newsprint logs. Pediatrics 57: 426, 1976

Lead poisoning from lead-soldered electric kettles.

Lead poisoning from lead-soldered electric kettles RAYMOND NG, MD, CM, FRCP[C]; DAVID J. MARTIN, MB, MRCP, FRCP[C] Lead poisoning occurred In two Inf...
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