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Family poisoned by mercury vapor inhalation
Brief Reports
Family Poisoned by Mercury Vapor Inhalation MICHAEL T. SOLIS, MD,* EDWIN YUEN, MD,† PAUL S. CORTEZ, MD,‡ AND PAUL J. GOEBEL, MD† Acute mercury vapor poisoning is an uncommon but potentially fatal toxicologic emergency. A case series is presented of a family who became exposed to mercury vapor as a result of home gold ore processing. The severity of the poisoning necessitated mechanical ventilation in three of the eight patients who were exposed. Despite aggressive management, two patients died, because their clinical course was dominated by irreversible pulmonary toxicity. The remaining survivors developed varying degrees of mercury toxicity. The pathophysiology, clinical presentation and current treatment guidelines for acute mercury vapor poisoning are emphasized. (Am J Emerg Med 2000;18: 599-602. Copyright r 2000 by W.B. Saunders Company)
Inhalation of mercury vapor can be extremely hazardous, if not fatal. Campbell and Matthes provided early descriptions of the clinical pathophysiology of acute mercury vapor inhalation.1,2 Since then there have been multiple case reports in the literature.3-14 The majority of acute mercury vapor poisonings have involved either industrial exposures with high concentrations of mercury vapor3,6 or home gold ore processing.4,7-9,12-14 A case series involving a family exposed to mercury vapor is presented. CASE SERIES A 45-day-old infant girl and a 13 month-old boy were admitted to Valley Children’s Hospital, Fresno, California with respiratory symptoms and mild hypoxemia (95% on room air). Initial chest radiographs of both children were similar and showed ‘‘bronchial thickening’’ (Figure 1). Within 24 to 36 hours of admission, both children developed signs of respiratory failure necessitating mechanical ventilation. Initial clinical impression suggested a diagnosis of an aggressive atypical pneumonia and an extensive infectious disease work-up was initiated. However, further investigation revealed that the parents were attempting to extract gold ore using liquid mercury 6 hours before the onset of their From the *Department of Emergency Medicine, the †Department of Medicine, and the ‡Department of Pediatrics, University Medical Center—Fresno, Fresno, CA. Manuscript received April 3, 1999, returned April 30, 1999, revision received June 10, 1999, accepted June 19, 1999. Address reprint request to Michael T. Solis, MD, Department of Emergency Medicine, University Medical Center-Fresno, 445 South Cedar Ave, Fresno, CA 93702. Key Words: Family poisoning, acute mercury vapor inhalation, chemical pneumonitis, Heavy metal toxicity. Copyright r 2000 by W.B. Saunders Company 0735-6757/00/1805-0006$10.00/0 doi:10.1053/ajem.2000.4006
children’s symptoms. Both parents and the youngest children were in a poorly ventilated kitchen when this process took place. The remaining four children were in rooms adjacent to the kitchen. Urinary mercury levels proved to be diagnostic of mercury exposure in both children (Table 1). Each child received chelation therapy, with 2,3-dimercaptosuccinic acid (DMSA), which was begun at 10 mg/kg by mouth every 8 hours for the first 5 days and subsequently every 12 hours for the next 14 days. The 45-day-old infant girl’s ventilatory status steadily improved and she was successfully extubated on the 10th hospital day. She recovered from a central venous catheter infection and was discharged on hospital day 25 in excellent condition. One month after discharge, she had no residual pulmonary disease or obvious developmental delay. The 13-month-old boy’s ventilatory status gradually worsened necessitating high FiO2 (1.0) and high peak inspiratory pressures (greater than 60 cm H2O) to maintain oxygen saturations above 90%. He received exogenous surfactant and nitric oxide in an attempt to improve lung mechanics, but developed acute respiratory distress syndrome (ARDS) and multiple pneumothoraces (Figure 2). After a protracted hospital course, he suffered a cardiopulmonary arrest on the 25th day of hospitalization, which was refractory to all resuscitative efforts. Postmortem analysis of the child’s lungs revealed: ‘‘severe chemical pneumonitis’’ and ‘‘alveolar structures filled with a cellular infiltrate.’’ The 38-year-old mother presented to University Medical Center, Fresno, California with a nonproductive cough and severe respiratory distress (48 hours after acute exposure to mercury vapor). The chest radiograph showed ‘‘diffuse bilateral alveolar infiltrates’’ (Figure 3). She was intubated and admitted to the Intensive Care Unit with the diagnosis of ‘‘pneumonia’’ and given empiric intravenous antibiotics. Once the history of mercury vapor exposure was elicited, a spot urine mercury level proved to be elevated (Table 1). She underwent chelation therapy with DMSA, as described previously. Corticosteroids were given as methylprednisolone 125 mg intravenously every 8 hours. Despite maximal supportive therapy, ARDS, sepsis, and multiorgan failure developed and on the 10th day of hospitalization, she died. Postmortem analysis of the lungs revealed ‘‘congestion and thickening of the alveolar septa with denudation of epithelial lining.’’ The 58-year-old father presented to University Medical Center with a sore throat and a nonproductive cough (96 599
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FIGURE 1. Initial chest radiograph of a 45-day-old infant after acute exposure to mercury vapor showing mild bronchial thickening.
hours after acute exposure to mercury vapor). Chest radiograph showed ‘‘heavy interstitial markings bilaterally.’’ He was admitted to the hospital for observation. Although his 24-hour urine mercury level was elevated (Table 1), he refused chelation therapy and was subsequently discharged from the hospital. From telephone interviews with the family it was learned that this patient now has periods of confusion, memory loss, insomnia and a persistent dry cough (signs consistent with mercurialism). The remaining four children who were 3, 7, 10, and 14 years of age were brought to the Valley Children’s Hospital for evaluation after the history of acute mercury vapor exposure was discovered. Six days after exposure, their symptoms included a sore throat, nonproductive cough, and headache. The children were admitted to the hospital for observation. Urine mercury levels were elevated (Table 1). Each child was treated with DMSA, as described previously, and had uneventful hospital courses. On follow-up visit, each child remained asymptomatic 1 month after discharge and had no evidence of chronic mercury toxicity. In the kitchen where the gold ore processing took place, air samples for mercury vapor measured 0.193 mg/m3. The
FIGURE 2. Chest radiograph of a 13-month-old child with severe mercury vapor inhalation showing multiple pneumothoraces and 11 chest tubes.
Agency for Toxic Substances and Disease Registry (ATSDR) has proposed a minimal risk level of 0.00006 mg/m3 for exposure to mercury vapors.15 The local public health agency decontaminated the entire residence. DISCUSSION Elemental mercury, commonly known as quicksilver, is a liquid metal at room temperature. It has a melting point, boiling point, and a vapor pressure of ⫺38.87°C, 356.72°C and 2 ⫻ 10⫺3 mm Hg (25°C), respectively.15 To some extent, mercury can vaporize at room temperature. As the temperature increases, the metal readily forms a vapor that is colorless and odorless. If inhaled, the vapor is absorbed through the alveolar membrane with retention of 74% to 80% of the inhaled dose.15-17 Once absorbed, mercury is transported via the bloodstream to distribute in a variety of tissues, predominantly the central nervous system, kidneys and liver. Toxicity from mercury vapor results from local pulmo-
TABLE 1. Urine and Blood Mercury Levels in Eight Family Members† Case
Age
UHg*
24 h UHg*
Blood Hg
Outcome
1 2 3 4 5 6 7 8
45 days 13 mo 38 yr 58 yr 3 yr 7 yr 10 yr 14 yr
45 mcg/L 190 mcg/L 682 mcg/L
35 mcg/L 120 mcg/L 163 mcg/L 112 mcg/L 161 mcg/L 177 mcg/L 485 mcg/L 107 mcg/L
117 mcg/L 160 mcg/L 322 mcg/L 275 mcg/L
Survived Died Died Survived Survived Survived Survived Survived
210 mcg/L 110 mcg/L 575 mcg/L 27 mcg/L
Abbreviations: UHg, spot urine mercury level; 24 h UHg, 24 hour urine mercury level. *Spot and 24 hour urine mercury levels were obtained on nonconsecutive days. †Not all measurements were made on the same day after exposure.
FIGURE 3. Initial chest radiograph of a 38-year-old mother after acute exposure to mercury vapor showing diffuse bilateral alveolar infiltrates.
SOLIS ET AL 䊏 MERCURY VAPOR POISONING
nary and systemic effects. Postmortem analyses of lungs exposed to mercury vapor have shown severe erosions of the bronchiolar epithelium, necrotizing bronchiolitis with alveolar, and interstitial fluid accumulation.1-3 Airway obstruction and capillary leak may cause alveolar dilation, pneumothorax, and ARDS in severe cases. Systemically, mercury (Hg0 ) is oxidized in vivo to form mercuric ions (Hg2⫹ ) which can bind with sulfhydryl (SH) groups. This may lead to inactivation of enzymes and structural proteins and alteration of cell membrane permeability.23 Numerous case reports have provided us with a uniform description of the clinical features of acute mercury vapor poisoning.3-14 Symptoms which may occur within a few hours include salivation, swollen gingiva, fever, dry cough, shortness of breath, dyspnea, abdominal pain, nausea, vomiting, and diarrhea.2,8,11,12 Some investigators have described mercury vapor inhalation as an evolution of three phases.18,19 The initial phase is typified by a flu-like illness 1 to 3 days after exposure. Subsequently, the patient may develop a chronic bronchiolitis similar to metal fume fever.20,21 The intermediate phase manifests with multisystem findings that are dominated by severe pulmonary toxicity. Complications such as noncardiogenic pulmonary edema, bronchiolitis, pneumonitis, pneumomediastinum, and pneumothorax have all been well described.8,11,13 Rarely will renal, hepatic, hematologic, and dermatologic dysfunction occur.10,22 Death is usually secondary to progressive hypoxia. If the patient survives, the late phase is characterized by gingivostomatatis, tremor and erethism (memory loss, emotional lability, depression, insomnia, and shyness). If the diagnosis of mercury poisoning is suspected, blood and urine mercury levels may be measured. A blood mercury level is a good indicator of a recent acute exposure because elevations in blood levels will precede elevations in urine.22 However, because of tissue redistribution, blood mercury levels are unreliable in predicting toxicity.23,24 Unexposed adults have a blood mercury level of less than 2 mcg/dL.25 Although not absolute, symptoms of toxicity generally occur in individuals with blood mercury levels of 5 mcg/dL or greater.22 Measurement of urine mercury levels may include a 24-hour urine collection or a spot urine level. Normally, urine mercury excretion is less than 50 mcg/L in 24 hours and a spot urine mercury level is less than 10 mcg/L. A spot urine mercury level may be helpful in documenting or excluding an exposure, but has little predictive value, varies considerably between individuals and the 24-hour urine level is quantitatively more useful.26 The lack of correlation between clinical toxicity and mercury levels in both blood and urine is shown by our cases (Table 1). Aggressive supportive care is the cornerstone of therapy after acute inhalational mercury poisoning. Patients with signs of inhalational mercury poisoning should undergo continuous cardiac monitoring and pulse oximetry. Administer supplemental oxygen as needed; mechanical ventilation may be required for those patients with severe exposures. Additionally, there are several chelating agents that can bind mercury and augment its excretion. Historically, British anti-Lewisite (BAL), D-penicillamine (D-PEN) and Nacetyl-D, L-penicillamine (NAP) have been used in mercury
601
TABLE 2. Dosage, Route and Contraindications of Chelating Agents Drug
Dosage
3-6 mg/kg every 4 h ⫻ 2 d, Then 2.5-3 mg/kg every 6 h ⫻ 2 d, Then 2.5-3 mg/kg every 12 h ⫻ 7 d. D-PEN 15-40 mg/kg/day Divided every 6 h ⫻ 3-10 d. DMSA 10 mg/kg every 8 h ⫻ 5 d, Then 10 mg/kg every 12 h ⫻ 14 d.
BAL
Route IM
Contraindications Peanut allergy Liver dysfunction Iron supplementation
PO PO
Renal failure, Pregnancy Penicillin allergy Renal failure
Abbreviations: BAL, British anti-Lewisite; D-PEN, D-Penicillamine; DMSA, 2,3-Dimercaptosuccinic acid.
vapor poisonings.1,2,7-9,11-13 Recently, DMSA has proven to be more effective and less toxic,27,28 but has been used sporadically in mercury vapor poisoning.29,30 The dosages, routes of administration and contraindications of these chelators are provided in Table 2. Although chelation therapy will increase urinary mercury excretion, others have noted a lack of effectiveness in reversing the severe pulmonary toxicity that characterizes acute mercury vapor poisoning.9,13,18 Thus, the goal of chelation therapy in acute mercury vapor poisoning is to decrease the mercury tissue burden and prevent secondary CNS or renal complications. Corticosteroids were used in one of our patients in this series (case 3) and had no clear effect on the eventual outcome. This appears to be consistent with the experience from other case reports.8,9,11,13 To our knowledge, exogenous surfactant and nitric oxide have not previously been used in the treatment of mercury vapor poisoning. These adjunctive therapies31-33 are as of yet unproven benefit in the setting of acute lung injury secondary to mercury vapor. In conclusion, the clinical course and outcome of acute mercury vapor poisoning is both varied and unpredictable as shown in this case series. Diagnosis relies on a thorough history coupled with a high degree of clinical suspicion. Although blood and urine mercury levels are useful to document or exclude an exposure, they are poor predictors of clinical outcome. Although DMSA is not formally approved for mercury poisoning, it is an excellent chelator because of its therapeutic efficacy, diminished side effect profile, and convenience of oral dosing. Adjunctive therapies such as corticosteroids, exogenous surfactant, and nitric oxide require further testing before they can be recommended. REFERENCES 1. Campbell JS: Acute mercurial poisoning by inhalation of metallic vapour in an infant. Can Med Assoc J 1948;58:72-75 2. Matthes FT, Kirschner R, Yow MD, et al: Acute poisoning associated with inhalation of mercury vapor. Pediatrics 1958;22:675688 3. Tennant R, Johnston HJ, Wells JB: Acute bilateral pneumonitis associated with the inhalation of mercury vapor. Conn Med 1961;25: 106-109 4. Hallee TJ: Diffuse lung disease caused by inhalation of mercury vapor. Am Rev Respir Dis 1969;99:430-436
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5. Natelson EA, Blumenthal BJ, Fred HL: Acute mercury vapor poisoning in the home. Chest 1971;59:677-678 6. Seaton A, Bishop CM: Acute mercury pneumonitis. Br J Ind Med 1978;35:258-265 7. Jung RC, Aaronson J: Death following inhalation of mercury vapor at home. West J Med 1980;132:539-543 8. Snodgrass W, Sullivan JB, Jr, Rumack BH, et al: Mercury poisoning from home gold ore processing. Use of penicillamine and dimercaprol. JAMA 1981;246:1929-1931 9. Moutinho ME, Tompkins AL, Rowland TW, et al: Acute mercury vapor poisoning. Am J Dis Child 1981;135:42-44 10. Jaffe KM, Shurtleff DB, Robertson WO: Survival after acute mercury vapor poisoning. Am J Dis Child 1983;137:749-751 11. Lilis R, Miller A, Lerman Y: Acute mercury poisoning with severe chronic pulmonary manifestations. Chest 1985;88:306-309 12. Levin M, Jacobs J, Polos PG: Acute mercury poisoning and mercurial pneumonitis from gold ore purification. Chest 1988;94:554556 13. Rowens B, Guerrero-Betancourt D, Gottlieb CA, et al: Respiratory failure and death following acute inhalation of mercury vapor. A clinical and histologic perspective. Chest 1991;99:185-190 14. Haddad JK, Stenberg E: Bronchitis due to acute mercury inhalation. Am Rev Respir Dis 1953;88:543-545 15. Risher J, DeWoskin R: Toxicological Profile for Mercury. U.S. Department of Health & Human Services. Agency for Toxic Substances and Disease Registry, 1998 16. Hursh JB, Clarkson TW, Cherian MG: Clearance of mercury vapor inhaled by human subjects. Arch Environ Health 1976;31:302309 17. Seiler HG, Sigel H: Handbook on Toxicity of Inorganic Compounds. New York, NY, Marcel Dekker, 1988 18. Lim HE, Shim JJ, Lee SY, et al: Mercury inhalation poisoning and acute lung injury. Korean J Intern Med 1998;13:127-130 19. Ellenhorn MJ, Schonwald S, Ordog G, et al: Ellenhorn’s Medical Toxicology (ed 2). Baltimore, MD, Williams & Wilkins, 1997 20. Offerman PV, Finley CJ. Metal fume fever. Ann Emerg Med 1992;21:872-875 21. Gordon T, Fine JM. Metal fume fever. Occup Med 1993;8:504517
22. Rumack BH, Toll LL, Gelman CR: Toxicologic management of elemental mercury poisoning. Poisondex System. Micromedix Inc. Englewood, CO. Vol. 99, exp 2/28/99 23. Haddad LM, Shannon MW, Winchester JF: Clinical Management of Poisoning and Drug Overdose (ed 3). Philadelphia, PA, WB Saunders, 1998 24. Goldfrank LR, Flomenbaum NE, Lewin NA, et al: Goldfrank’s Toxicologic Emergencies (ed 5). Norwalk, CT, Appleton & Lange, 1994 25. Olson KR: Poisoning and Drug Overdose (ed 3). Stamford, CT, Appleton & Lange, 1999 26. Calder IM, Kelman GR, Mason H. Diurnal variations in urinary mercury excretion. Hum Toxicol 1984;3:463-467 27. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water soluble treatment for heavy metal toxicity. Altern Med Rev 1998;3:199207 28. Heath A, Bluhm RE: 2,3-Dimercaptosuccinic acid (DMSA) vs. N-acetyl-penicillamine (NAP) for the treatment of elemental mercury toxicity. Presented at the 1989 American Academy of Toxicologists, American Association of Poison Control Centers, and Canadian Association of Poison Control Centers Annual Scientific Meeting. Atlanta, GA, Oct 12-15, 1989 29. Bluhm RE, Bobbitt RG, Welch LW, et al: Elemental mercury vapour toxicity, treatment and prognosis after acute intensive exposure in chloralkali plant workers. Part I: History, neuropsychological findings and chelator effects. Hum Exp Toxicol 1992;11:201-210 30. Boyer Hassen LV, Dart RC, Arthur AW, et al: Subacute toxicity in a family exposed to elemental mercury vapor, and the use of dimercaptosuccinic acid in their treatment. Vet Hum Toxicol 1992;34: 353 (abstr) 31. Olivieri D: Corticosteroids in late adult respiratory distress syndrom-towards a better use. Respiration 1998;65:256-257 32. Lutz C, Carney D, Finck C, et al: Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury. Am J Respir Crit Care Med 1998;158:840-845 33. Brett SJ, Hansell DM, Evans TW: Clinical correlates in acute lung injury: response to inhaled nitric oxide. Chest 1998;114:13971404
Family Poisoned by Mercury Vapor Inhalation MICHAEL T. SOLIS, MD,* EDWIN YUEN, MD,† PAUL S. CORTEZ, MD,‡ AND PAUL J. GOEBEL, MD† Acute mercury vapor poisoning is an uncommon but potentially fatal toxicologic emergency. A case series is presented of a family who became exposed to mercury vapor as a result of home gold ore processing. The severity of the poisoning necessitated mechanical ventilation in three of the eight patients who were exposed. Despite aggressive management, two patients died, because their clinical course was dominated by irreversible pulmonary toxicity. The remaining survivors developed varying degrees of mercury toxicity. The pathophysiology, clinical presentation and current treatment guidelines for acute mercury vapor poisoning are emphasized. (Am J Emerg Med 2000;18: 599-602. Copyright r 2000 by W.B. Saunders Company)
Inhalation of mercury vapor can be extremely hazardous, if not fatal. Campbell and Matthes provided early descriptions of the clinical pathophysiology of acute mercury vapor inhalation.1,2 Since then there have been multiple case reports in the literature.3-14 The majority of acute mercury vapor poisonings have involved either industrial exposures with high concentrations of mercury vapor3,6 or home gold ore processing.4,7-9,12-14 A case series involving a family exposed to mercury vapor is presented. CASE SERIES A 45-day-old infant girl and a 13 month-old boy were admitted to Valley Children’s Hospital, Fresno, California with respiratory symptoms and mild hypoxemia (95% on room air). Initial chest radiographs of both children were similar and showed ‘‘bronchial thickening’’ (Figure 1). Within 24 to 36 hours of admission, both children developed signs of respiratory failure necessitating mechanical ventilation. Initial clinical impression suggested a diagnosis of an aggressive atypical pneumonia and an extensive infectious disease work-up was initiated. However, further investigation revealed that the parents were attempting to extract gold ore using liquid mercury 6 hours before the onset of their From the *Department of Emergency Medicine, the †Department of Medicine, and the ‡Department of Pediatrics, University Medical Center—Fresno, Fresno, CA. Manuscript received April 3, 1999, returned April 30, 1999, revision received June 10, 1999, accepted June 19, 1999. Address reprint request to Michael T. Solis, MD, Department of Emergency Medicine, University Medical Center-Fresno, 445 South Cedar Ave, Fresno, CA 93702. Key Words: Family poisoning, acute mercury vapor inhalation, chemical pneumonitis, Heavy metal toxicity. Copyright r 2000 by W.B. Saunders Company 0735-6757/00/1805-0006$10.00/0 doi:10.1053/ajem.2000.4006
children’s symptoms. Both parents and the youngest children were in a poorly ventilated kitchen when this process took place. The remaining four children were in rooms adjacent to the kitchen. Urinary mercury levels proved to be diagnostic of mercury exposure in both children (Table 1). Each child received chelation therapy, with 2,3-dimercaptosuccinic acid (DMSA), which was begun at 10 mg/kg by mouth every 8 hours for the first 5 days and subsequently every 12 hours for the next 14 days. The 45-day-old infant girl’s ventilatory status steadily improved and she was successfully extubated on the 10th hospital day. She recovered from a central venous catheter infection and was discharged on hospital day 25 in excellent condition. One month after discharge, she had no residual pulmonary disease or obvious developmental delay. The 13-month-old boy’s ventilatory status gradually worsened necessitating high FiO2 (1.0) and high peak inspiratory pressures (greater than 60 cm H2O) to maintain oxygen saturations above 90%. He received exogenous surfactant and nitric oxide in an attempt to improve lung mechanics, but developed acute respiratory distress syndrome (ARDS) and multiple pneumothoraces (Figure 2). After a protracted hospital course, he suffered a cardiopulmonary arrest on the 25th day of hospitalization, which was refractory to all resuscitative efforts. Postmortem analysis of the child’s lungs revealed: ‘‘severe chemical pneumonitis’’ and ‘‘alveolar structures filled with a cellular infiltrate.’’ The 38-year-old mother presented to University Medical Center, Fresno, California with a nonproductive cough and severe respiratory distress (48 hours after acute exposure to mercury vapor). The chest radiograph showed ‘‘diffuse bilateral alveolar infiltrates’’ (Figure 3). She was intubated and admitted to the Intensive Care Unit with the diagnosis of ‘‘pneumonia’’ and given empiric intravenous antibiotics. Once the history of mercury vapor exposure was elicited, a spot urine mercury level proved to be elevated (Table 1). She underwent chelation therapy with DMSA, as described previously. Corticosteroids were given as methylprednisolone 125 mg intravenously every 8 hours. Despite maximal supportive therapy, ARDS, sepsis, and multiorgan failure developed and on the 10th day of hospitalization, she died. Postmortem analysis of the lungs revealed ‘‘congestion and thickening of the alveolar septa with denudation of epithelial lining.’’ The 58-year-old father presented to University Medical Center with a sore throat and a nonproductive cough (96 599
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FIGURE 1. Initial chest radiograph of a 45-day-old infant after acute exposure to mercury vapor showing mild bronchial thickening.
hours after acute exposure to mercury vapor). Chest radiograph showed ‘‘heavy interstitial markings bilaterally.’’ He was admitted to the hospital for observation. Although his 24-hour urine mercury level was elevated (Table 1), he refused chelation therapy and was subsequently discharged from the hospital. From telephone interviews with the family it was learned that this patient now has periods of confusion, memory loss, insomnia and a persistent dry cough (signs consistent with mercurialism). The remaining four children who were 3, 7, 10, and 14 years of age were brought to the Valley Children’s Hospital for evaluation after the history of acute mercury vapor exposure was discovered. Six days after exposure, their symptoms included a sore throat, nonproductive cough, and headache. The children were admitted to the hospital for observation. Urine mercury levels were elevated (Table 1). Each child was treated with DMSA, as described previously, and had uneventful hospital courses. On follow-up visit, each child remained asymptomatic 1 month after discharge and had no evidence of chronic mercury toxicity. In the kitchen where the gold ore processing took place, air samples for mercury vapor measured 0.193 mg/m3. The
FIGURE 2. Chest radiograph of a 13-month-old child with severe mercury vapor inhalation showing multiple pneumothoraces and 11 chest tubes.
Agency for Toxic Substances and Disease Registry (ATSDR) has proposed a minimal risk level of 0.00006 mg/m3 for exposure to mercury vapors.15 The local public health agency decontaminated the entire residence. DISCUSSION Elemental mercury, commonly known as quicksilver, is a liquid metal at room temperature. It has a melting point, boiling point, and a vapor pressure of ⫺38.87°C, 356.72°C and 2 ⫻ 10⫺3 mm Hg (25°C), respectively.15 To some extent, mercury can vaporize at room temperature. As the temperature increases, the metal readily forms a vapor that is colorless and odorless. If inhaled, the vapor is absorbed through the alveolar membrane with retention of 74% to 80% of the inhaled dose.15-17 Once absorbed, mercury is transported via the bloodstream to distribute in a variety of tissues, predominantly the central nervous system, kidneys and liver. Toxicity from mercury vapor results from local pulmo-
TABLE 1. Urine and Blood Mercury Levels in Eight Family Members† Case
Age
UHg*
24 h UHg*
Blood Hg
Outcome
1 2 3 4 5 6 7 8
45 days 13 mo 38 yr 58 yr 3 yr 7 yr 10 yr 14 yr
45 mcg/L 190 mcg/L 682 mcg/L
35 mcg/L 120 mcg/L 163 mcg/L 112 mcg/L 161 mcg/L 177 mcg/L 485 mcg/L 107 mcg/L
117 mcg/L 160 mcg/L 322 mcg/L 275 mcg/L
Survived Died Died Survived Survived Survived Survived Survived
210 mcg/L 110 mcg/L 575 mcg/L 27 mcg/L
Abbreviations: UHg, spot urine mercury level; 24 h UHg, 24 hour urine mercury level. *Spot and 24 hour urine mercury levels were obtained on nonconsecutive days. †Not all measurements were made on the same day after exposure.
FIGURE 3. Initial chest radiograph of a 38-year-old mother after acute exposure to mercury vapor showing diffuse bilateral alveolar infiltrates.
SOLIS ET AL 䊏 MERCURY VAPOR POISONING
nary and systemic effects. Postmortem analyses of lungs exposed to mercury vapor have shown severe erosions of the bronchiolar epithelium, necrotizing bronchiolitis with alveolar, and interstitial fluid accumulation.1-3 Airway obstruction and capillary leak may cause alveolar dilation, pneumothorax, and ARDS in severe cases. Systemically, mercury (Hg0 ) is oxidized in vivo to form mercuric ions (Hg2⫹ ) which can bind with sulfhydryl (SH) groups. This may lead to inactivation of enzymes and structural proteins and alteration of cell membrane permeability.23 Numerous case reports have provided us with a uniform description of the clinical features of acute mercury vapor poisoning.3-14 Symptoms which may occur within a few hours include salivation, swollen gingiva, fever, dry cough, shortness of breath, dyspnea, abdominal pain, nausea, vomiting, and diarrhea.2,8,11,12 Some investigators have described mercury vapor inhalation as an evolution of three phases.18,19 The initial phase is typified by a flu-like illness 1 to 3 days after exposure. Subsequently, the patient may develop a chronic bronchiolitis similar to metal fume fever.20,21 The intermediate phase manifests with multisystem findings that are dominated by severe pulmonary toxicity. Complications such as noncardiogenic pulmonary edema, bronchiolitis, pneumonitis, pneumomediastinum, and pneumothorax have all been well described.8,11,13 Rarely will renal, hepatic, hematologic, and dermatologic dysfunction occur.10,22 Death is usually secondary to progressive hypoxia. If the patient survives, the late phase is characterized by gingivostomatatis, tremor and erethism (memory loss, emotional lability, depression, insomnia, and shyness). If the diagnosis of mercury poisoning is suspected, blood and urine mercury levels may be measured. A blood mercury level is a good indicator of a recent acute exposure because elevations in blood levels will precede elevations in urine.22 However, because of tissue redistribution, blood mercury levels are unreliable in predicting toxicity.23,24 Unexposed adults have a blood mercury level of less than 2 mcg/dL.25 Although not absolute, symptoms of toxicity generally occur in individuals with blood mercury levels of 5 mcg/dL or greater.22 Measurement of urine mercury levels may include a 24-hour urine collection or a spot urine level. Normally, urine mercury excretion is less than 50 mcg/L in 24 hours and a spot urine mercury level is less than 10 mcg/L. A spot urine mercury level may be helpful in documenting or excluding an exposure, but has little predictive value, varies considerably between individuals and the 24-hour urine level is quantitatively more useful.26 The lack of correlation between clinical toxicity and mercury levels in both blood and urine is shown by our cases (Table 1). Aggressive supportive care is the cornerstone of therapy after acute inhalational mercury poisoning. Patients with signs of inhalational mercury poisoning should undergo continuous cardiac monitoring and pulse oximetry. Administer supplemental oxygen as needed; mechanical ventilation may be required for those patients with severe exposures. Additionally, there are several chelating agents that can bind mercury and augment its excretion. Historically, British anti-Lewisite (BAL), D-penicillamine (D-PEN) and Nacetyl-D, L-penicillamine (NAP) have been used in mercury
601
TABLE 2. Dosage, Route and Contraindications of Chelating Agents Drug
Dosage
3-6 mg/kg every 4 h ⫻ 2 d, Then 2.5-3 mg/kg every 6 h ⫻ 2 d, Then 2.5-3 mg/kg every 12 h ⫻ 7 d. D-PEN 15-40 mg/kg/day Divided every 6 h ⫻ 3-10 d. DMSA 10 mg/kg every 8 h ⫻ 5 d, Then 10 mg/kg every 12 h ⫻ 14 d.
BAL
Route IM
Contraindications Peanut allergy Liver dysfunction Iron supplementation
PO PO
Renal failure, Pregnancy Penicillin allergy Renal failure
Abbreviations: BAL, British anti-Lewisite; D-PEN, D-Penicillamine; DMSA, 2,3-Dimercaptosuccinic acid.
vapor poisonings.1,2,7-9,11-13 Recently, DMSA has proven to be more effective and less toxic,27,28 but has been used sporadically in mercury vapor poisoning.29,30 The dosages, routes of administration and contraindications of these chelators are provided in Table 2. Although chelation therapy will increase urinary mercury excretion, others have noted a lack of effectiveness in reversing the severe pulmonary toxicity that characterizes acute mercury vapor poisoning.9,13,18 Thus, the goal of chelation therapy in acute mercury vapor poisoning is to decrease the mercury tissue burden and prevent secondary CNS or renal complications. Corticosteroids were used in one of our patients in this series (case 3) and had no clear effect on the eventual outcome. This appears to be consistent with the experience from other case reports.8,9,11,13 To our knowledge, exogenous surfactant and nitric oxide have not previously been used in the treatment of mercury vapor poisoning. These adjunctive therapies31-33 are as of yet unproven benefit in the setting of acute lung injury secondary to mercury vapor. In conclusion, the clinical course and outcome of acute mercury vapor poisoning is both varied and unpredictable as shown in this case series. Diagnosis relies on a thorough history coupled with a high degree of clinical suspicion. Although blood and urine mercury levels are useful to document or exclude an exposure, they are poor predictors of clinical outcome. Although DMSA is not formally approved for mercury poisoning, it is an excellent chelator because of its therapeutic efficacy, diminished side effect profile, and convenience of oral dosing. Adjunctive therapies such as corticosteroids, exogenous surfactant, and nitric oxide require further testing before they can be recommended. REFERENCES 1. Campbell JS: Acute mercurial poisoning by inhalation of metallic vapour in an infant. Can Med Assoc J 1948;58:72-75 2. Matthes FT, Kirschner R, Yow MD, et al: Acute poisoning associated with inhalation of mercury vapor. Pediatrics 1958;22:675688 3. Tennant R, Johnston HJ, Wells JB: Acute bilateral pneumonitis associated with the inhalation of mercury vapor. Conn Med 1961;25: 106-109 4. Hallee TJ: Diffuse lung disease caused by inhalation of mercury vapor. Am Rev Respir Dis 1969;99:430-436
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