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3rd National Congress of Emergency Medicine




MERCURY POISONING:
An Experience in HUSM



    Dr. Rashidi Ahmad. MD (USM), Mmed (USM)
     Lecturer/Consultant Emergency Physician
            School of Medical Sciences
          USM Health Campus, Kelantan                 1
                  17th Nov 2007
Mercury the Metal




                    2
Environmental Sources of Mercury




• Natural Degassing of the earth
• Combustion of fossil fuel
• Industrial Discharges and Wastes
• Incineration & Crematories
• Dental amalgams

   Hg0      Hg2+       CH3Hg+
                                                    3
The Mercury Cycle




              4
5
Mercury pollution in the Amazon




• Gold mining—sediments of a river are
  run through sluice boxes with mercury
  in them. The gold sticks to the mercury
  and then the mercury-gold goop is
  cooked over a fire to drive off the
  mercury, leaving the gold
• Mercury goes to water and air
• Altered vision in study of children along
  Rio Tajapos river in Brazil

 ? Similarly it can happens at Rusila, Terengganu
                                                             6
The many forms of mercury




         ORGANIC                             INORGANIC

SHORT CHAIN           ARYL               ELEMENTAL         MERCURIC
   ARKYL            COMPOUND                                 SALT

        LONG CHAIN
          ARKYL


   * Methyl mercury (organic) – most toxic
                                                                         7
Mercury




• Toxic in any forms
• The difference lies in how it is absorbed,
  the clinical signs and symptoms, and
  the response to treatment modalities.
• Mercury poisoning can result from vapor
  inhalation, ingestion, injection, or
  absorption through the skin.


                                               8
Historical awareness




“Mad as a Hatter”




                        9
10
Outbreaks of MeHg Poisoning



Place         Year          Cases
Minamata    1953-60            1000
Nigata      1964-65             646
Guatemala   1963-65              45
Ghana         1967              144
Pakistan      1969              100
Iraq          1956              100
Iraq          1960            1,002
Iraq          1971          40,000
                                              11
On-going      2001              ???
Organic Mercury Poisoning




• Minimata, Japan, 50 years
  ago…

• Seafood from the bay was
  polluted with mercury from an
  industrial source

• Neurotoxicity – CP


                                       12
Seed Grain Outbreaks




• Mercury compounds
  applied as antifungal
  agent to seed grains

• Iraq—made bread directly
  from treated seed grain




                                13
Iraq mercury contaminated seed grain – CP




                                            14
Neurobehavioral Effects




• Blindness – Deafness

• Cerebral Palsy – Seizures

• Retarded motor development

• Visual and Auditory Deficits

• Delayed motor development



                                   15
Hg and Heart Attacks




• Case-control study showing higher
  mercury in men who had heart attacks
  vs. controls

       “Mercury, Fish Oils, and the Risk of Myocardial
     Infarction”. New England Journal of Medicine. 2002




                                                          16
The harmful effects




• Organic mercury - Most devastating to
  the CNS
   – Short-chained (methylmercury) - Affects the CNS
   – Long-chained - Subacute/chronic effects similar to that
     of inorganic mercury exposure


• Elemental mercury - Primary neurologic toxicity

• Inorganic mercury salts
   – Acute - Severe corrosive gastroenteritis, acute tubular
     necrosis
   – Subacute or chronic - GI, neurologic, and renal
                                                               17
     dysfunction
Introduction




• Mercury poisoning is usually
  misdiagnosed [insidious onset, nonspecific s/sx & lack
  of knowledge within the medical profession]



• Most recently, 2 areas have caused
  public concern regarding mercury
  toxicity
  - the potential risk associated with eating fish, especially
  when dealing with pregnancy
  - the use of dental amalgams, or fillings, by dentists.

                                                                  18
                  Mercury poisonong. www.e-medicine.com
Pathogenesis




• Unclear
• Induce auto-immunity
• High affinity towards sulfur group
  –   Haemoglobin
  –   IgG, helper CD4+ cells, NK cells
  –   Mitochodrial function esp in neurons
  –   Inhibit transport proteins



          The Journal of Immunology, Vol 140, Issue 3 750-754        19
Accidental Mercury Inhalation:
   An Experience in HUSM




                                 20
Learning objectives




• To highlight the possible clinical
  features and possible complications

• To describe the effects of elemental
  mercury vapor

• To highlight salient points from various
  literatures pertaining to the
  management of mercury poisoning.

                                                    21
17th August 2006 – 3 pm at ED HUSM


• 17 employees of pharmaceutical factory
  were rushed to HUSM after alleged
  inhalational mercury poisoning.
• Mercury contained thermometer broke in
  a beaker with boiled water in a closed
  laboratory environment.
• Released mercury vapor was inhaled by
  the lab staff.
                                            22
Demographic Data




Gender       15 female, 2 male
Mean age     30.6 years
Premorbid    PID – 1
             Pregnancy – 2 (33/52 & 28/52
             POA)
Race         Malay
Occupation   Lab technicians

                                               23
Symptoms




  Sore throat      7
Chest discomfort   1
   Dizziness       3
 Eye itchiness     1
     N&V           2
 Metallic taste    2
      SOB          1
 Asymptomatic      2


                              24
Physical examination




•   Anxious, tachypneic
•   No skin manifestation
•   1 patients showed intention tremor
•   1 patient had reddish sclera of the R eye
•   7 patients had injected throat
•   Lungs – clear
•   CVS – S1S2, no murmur
•   Per abdomen – soft non-tender

                                                       25
Triage parameters




•   Conscious, alert, tachypneic, pink
•   Normal blood pressure and heart rate
•   SaO2 97 – 99%
•   Afebrile




           Fast track – assigned isolated
                       ward
                                              26
Investigations




•   FBC – Normal
•   BUSE /RFT/ LFT– Normal
•   ABG (n = 2) - Normal
•   ECG – Normal sinus rhythm
•   Whole blood mercury level : 0.5 – 7.3μg/L


Normal mercury levels are considered to be less
  than 10 mcg/L in the blood and less than 20
              mcg/L in the urine

                                                          27
28
29
Management




• All patients were treated symptomatically
• Observed in OW for 24 hours with all
  symptoms resolved
• Discharged with TCA 1 week to A&E and
  planned ante-natal clinics.
• Rx – T. Prednisolone 50 mg daily x 3/7


All patients were asymptomatic upon 1/52 follow-up without
       any clinical signs. Repeated CXR were all normal.
                  All patients were discharged
                                                                30
31
Elemental mercury



 • Inorganic, Quicksilver (exist in liquid)
 • Occurs naturally in soil and in the
   atmosphere from volcanic emissions
 • Mercury is extracted and used in
   industry, then enters air or water from
   pollution
 • 13.6 times the weight of water
 • Evaporates at room temperature
 • Lipid soluble; excreted in urine
 • Bacteria change to Methylmercury

  US Department of Health and Human Services, Public Health        32
Service, Agency for Toxic Substances and Disease Registry, 1989;
                publication no. ATSDR/TP-89/16
Elemental Mercury




• Very toxic to the nervous system, also to
  kidneys
• But….very poorly absorbed by the GI tract
  Inhalation route gives higher exposure
• Mercury in fillings is inorganic
• Alloys with other metal called Amalgam
• Many Industrial uses ( drugs, chemicals,
  thermometers, batteries, gold mining)


                                                33
Mercury inhalation




• 80% of inhaled Hg can be absorbed in blood
  (~ t1/2 3 days for single exposure)
• 80-100% lung absorption (WHO, 1991); <1%
  GI
• Oxidized to Hg2+ easily binds to sulfhydryl
  group on enzymes and other proteins and
  membrane disulfide bonds
• Concentrated 10 x higher in brain than
  equivalent dose of inorganic mercuric salts

      Cases of mercury exposure, bioavailability, and absorption
 Michael Gochfeld Environmental and Community Medicine,March 2003    34
Effect of acute inhalational of elemental Hg




                                              Sore throat                7
Shortness of breath
Metallic taste                                  Chest                    1
                                              discomfort
Pleuritic chest pain
                                               Dizziness                 3
Lethargy
                                            Eye itchiness                1
Confusion
                                                 N&V                     2
Nausea & vomitting
                                             Metallic taste              2
Tremors
                                                 SOB                     1
                                            Asymptomatic                 2


Young J: Mercury. In: Goldfrank LR, ed. Goldfrank's Toxicology Emergencies.
              Vol 74. New York: McGraw-Hill; 1994:1051-62.                      35
Inhalational mercury respiratory toxicity




• Erosive bronchitis and
  bronchiolitis with interstitial
  pneumonitis
  (WHO,1991)


• Atelectasis, emphysema,
  haemorrhage and
  pneumothorax
  (Winship, 1985)


• Mild respiratory symptoms
  (Wallach, 1972; Janus and Klein, 1982;
  Tsuji et al, 1970)

                                                                              36
Long term effect- neurotoxicity




    Adult                               Fetus/children

•   Memory loss                    •   Cerebral palsy
•   Ataxia                         •   Mental retardation
•   Dysarthria                     •   Autism
•   Hypoasthesia                   •   Late walking
•   Finger tremor
•   Alzheimer’s disease


        Low dose mercury toxicity and human health, March 2005


                                                                         37
Pathogeneis of mercury neurotoxicity




• Selectively accumulates in hippocampus,
  basal ganglia, cerebral cortex
• Prevents presynaptic serotonin release and
  inhibits serotonin transport; causes
  calcium disruptions
• Causes demylinating neuropathy
• Causes abnormal neuronal
  cytoarchitecture; disrupts neuronal
  migration, microtubules, and cell division

      Clarkson, T. The toxicology of mercury. Crit
                                                                     38
         Rev Clin Lab Sci 1997; 34(3): 369-403
Pregnancy – the risky group




• 117 first term pregnancies in the
  mercury exposed group
• Spontaneous abortion (19 cases)
• Stillbirth (3 cases)
• Congenital malformations (5 cases of
  spina bifida and 1 case of intra-atrial
  defect)


                 Sikorski et al, 1987
                                                       39
Few words on investigation




• Blood mercury is only useful within 3
  days of exposure and it is more reliable
  in methylmercury (high concentrations
  in RBCs)
• A 24-hour urine specimen is a good
  indicator for inorganic mercury
  poisoning
• Hair mercury level has no role in acute
  Hg toxicity
                        WHO, 2002
                                                     40
Treatment of inhalational mercury




• No role of inducing emesis

• Oral steroid is a common practice but
  without substantial evidence

• Hemodialysis is used in severe cases of
  toxicity when renal function has declined

                                    (ATSDR, 2002)


                                                        41
• Most inhalational form are self limited –
  recovery without sequalae but fibrosis,
  empyema and fatal ARDS has been
  reported

      Taueg C, et al. Acute and chronic poisoning from residential exposures to
   elemental mercury-Michigan, 1989-1990. J Toxicol Clin Toxicol 1992; 30(1): 63-7




                                                                                     42
• Use chelating agents: symptomatic,
  systemic absorption is anticipated,
  increased mercury blood or urine levels
  – dimercaprol (BAL) d-penicillamine
    (DPCN)
  – 2,3-dimercaptosuccinic acid
    (DMSA)

                                            43
The identification of mercury
Summary
          poisoning is difficult due to vague
          toxidrome.

          Major target organ in inhalational
          mercury poisoning is brain and lung

          Pregnant ladies are considered high
          risk group

          Inhalational elementary mercury
          poisoning is self-limited with few
          sequelae.

          The use of oral steroids in mild
          inhalational elemental mercury
          poisoning is non-substantial

          Only manage severe poisoning in
          institutes with well fitted           44
          decontamination facilities
Conclusion




Mercury distribution and
exposure is a global problem




                                      45

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Mercury Poisoning

  • 1. 3rd National Congress of Emergency Medicine MERCURY POISONING: An Experience in HUSM Dr. Rashidi Ahmad. MD (USM), Mmed (USM) Lecturer/Consultant Emergency Physician School of Medical Sciences USM Health Campus, Kelantan 1 17th Nov 2007
  • 3. Environmental Sources of Mercury • Natural Degassing of the earth • Combustion of fossil fuel • Industrial Discharges and Wastes • Incineration & Crematories • Dental amalgams Hg0 Hg2+ CH3Hg+ 3
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  • 6. Mercury pollution in the Amazon • Gold mining—sediments of a river are run through sluice boxes with mercury in them. The gold sticks to the mercury and then the mercury-gold goop is cooked over a fire to drive off the mercury, leaving the gold • Mercury goes to water and air • Altered vision in study of children along Rio Tajapos river in Brazil ? Similarly it can happens at Rusila, Terengganu 6
  • 7. The many forms of mercury ORGANIC INORGANIC SHORT CHAIN ARYL ELEMENTAL MERCURIC ARKYL COMPOUND SALT LONG CHAIN ARKYL * Methyl mercury (organic) – most toxic 7
  • 8. Mercury • Toxic in any forms • The difference lies in how it is absorbed, the clinical signs and symptoms, and the response to treatment modalities. • Mercury poisoning can result from vapor inhalation, ingestion, injection, or absorption through the skin. 8
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  • 11. Outbreaks of MeHg Poisoning Place Year Cases Minamata 1953-60 1000 Nigata 1964-65 646 Guatemala 1963-65 45 Ghana 1967 144 Pakistan 1969 100 Iraq 1956 100 Iraq 1960 1,002 Iraq 1971 40,000 11 On-going 2001 ???
  • 12. Organic Mercury Poisoning • Minimata, Japan, 50 years ago… • Seafood from the bay was polluted with mercury from an industrial source • Neurotoxicity – CP 12
  • 13. Seed Grain Outbreaks • Mercury compounds applied as antifungal agent to seed grains • Iraq—made bread directly from treated seed grain 13
  • 14. Iraq mercury contaminated seed grain – CP 14
  • 15. Neurobehavioral Effects • Blindness – Deafness • Cerebral Palsy – Seizures • Retarded motor development • Visual and Auditory Deficits • Delayed motor development 15
  • 16. Hg and Heart Attacks • Case-control study showing higher mercury in men who had heart attacks vs. controls “Mercury, Fish Oils, and the Risk of Myocardial Infarction”. New England Journal of Medicine. 2002 16
  • 17. The harmful effects • Organic mercury - Most devastating to the CNS – Short-chained (methylmercury) - Affects the CNS – Long-chained - Subacute/chronic effects similar to that of inorganic mercury exposure • Elemental mercury - Primary neurologic toxicity • Inorganic mercury salts – Acute - Severe corrosive gastroenteritis, acute tubular necrosis – Subacute or chronic - GI, neurologic, and renal 17 dysfunction
  • 18. Introduction • Mercury poisoning is usually misdiagnosed [insidious onset, nonspecific s/sx & lack of knowledge within the medical profession] • Most recently, 2 areas have caused public concern regarding mercury toxicity - the potential risk associated with eating fish, especially when dealing with pregnancy - the use of dental amalgams, or fillings, by dentists. 18 Mercury poisonong. www.e-medicine.com
  • 19. Pathogenesis • Unclear • Induce auto-immunity • High affinity towards sulfur group – Haemoglobin – IgG, helper CD4+ cells, NK cells – Mitochodrial function esp in neurons – Inhibit transport proteins The Journal of Immunology, Vol 140, Issue 3 750-754 19
  • 20. Accidental Mercury Inhalation: An Experience in HUSM 20
  • 21. Learning objectives • To highlight the possible clinical features and possible complications • To describe the effects of elemental mercury vapor • To highlight salient points from various literatures pertaining to the management of mercury poisoning. 21
  • 22. 17th August 2006 – 3 pm at ED HUSM • 17 employees of pharmaceutical factory were rushed to HUSM after alleged inhalational mercury poisoning. • Mercury contained thermometer broke in a beaker with boiled water in a closed laboratory environment. • Released mercury vapor was inhaled by the lab staff. 22
  • 23. Demographic Data Gender 15 female, 2 male Mean age 30.6 years Premorbid PID – 1 Pregnancy – 2 (33/52 & 28/52 POA) Race Malay Occupation Lab technicians 23
  • 24. Symptoms Sore throat 7 Chest discomfort 1 Dizziness 3 Eye itchiness 1 N&V 2 Metallic taste 2 SOB 1 Asymptomatic 2 24
  • 25. Physical examination • Anxious, tachypneic • No skin manifestation • 1 patients showed intention tremor • 1 patient had reddish sclera of the R eye • 7 patients had injected throat • Lungs – clear • CVS – S1S2, no murmur • Per abdomen – soft non-tender 25
  • 26. Triage parameters • Conscious, alert, tachypneic, pink • Normal blood pressure and heart rate • SaO2 97 – 99% • Afebrile Fast track – assigned isolated ward 26
  • 27. Investigations • FBC – Normal • BUSE /RFT/ LFT– Normal • ABG (n = 2) - Normal • ECG – Normal sinus rhythm • Whole blood mercury level : 0.5 – 7.3Îźg/L Normal mercury levels are considered to be less than 10 mcg/L in the blood and less than 20 mcg/L in the urine 27
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  • 30. Management • All patients were treated symptomatically • Observed in OW for 24 hours with all symptoms resolved • Discharged with TCA 1 week to A&E and planned ante-natal clinics. • Rx – T. Prednisolone 50 mg daily x 3/7 All patients were asymptomatic upon 1/52 follow-up without any clinical signs. Repeated CXR were all normal. All patients were discharged 30
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  • 32. Elemental mercury • Inorganic, Quicksilver (exist in liquid) • Occurs naturally in soil and in the atmosphere from volcanic emissions • Mercury is extracted and used in industry, then enters air or water from pollution • 13.6 times the weight of water • Evaporates at room temperature • Lipid soluble; excreted in urine • Bacteria change to Methylmercury US Department of Health and Human Services, Public Health 32 Service, Agency for Toxic Substances and Disease Registry, 1989; publication no. ATSDR/TP-89/16
  • 33. Elemental Mercury • Very toxic to the nervous system, also to kidneys • But….very poorly absorbed by the GI tract Inhalation route gives higher exposure • Mercury in fillings is inorganic • Alloys with other metal called Amalgam • Many Industrial uses ( drugs, chemicals, thermometers, batteries, gold mining) 33
  • 34. Mercury inhalation • 80% of inhaled Hg can be absorbed in blood (~ t1/2 3 days for single exposure) • 80-100% lung absorption (WHO, 1991); <1% GI • Oxidized to Hg2+ easily binds to sulfhydryl group on enzymes and other proteins and membrane disulfide bonds • Concentrated 10 x higher in brain than equivalent dose of inorganic mercuric salts Cases of mercury exposure, bioavailability, and absorption Michael Gochfeld Environmental and Community Medicine,March 2003 34
  • 35. Effect of acute inhalational of elemental Hg Sore throat 7 Shortness of breath Metallic taste Chest 1 discomfort Pleuritic chest pain Dizziness 3 Lethargy Eye itchiness 1 Confusion N&V 2 Nausea & vomitting Metallic taste 2 Tremors SOB 1 Asymptomatic 2 Young J: Mercury. In: Goldfrank LR, ed. Goldfrank's Toxicology Emergencies. Vol 74. New York: McGraw-Hill; 1994:1051-62. 35
  • 36. Inhalational mercury respiratory toxicity • Erosive bronchitis and bronchiolitis with interstitial pneumonitis (WHO,1991) • Atelectasis, emphysema, haemorrhage and pneumothorax (Winship, 1985) • Mild respiratory symptoms (Wallach, 1972; Janus and Klein, 1982; Tsuji et al, 1970) 36
  • 37. Long term effect- neurotoxicity Adult Fetus/children • Memory loss • Cerebral palsy • Ataxia • Mental retardation • Dysarthria • Autism • Hypoasthesia • Late walking • Finger tremor • Alzheimer’s disease Low dose mercury toxicity and human health, March 2005 37
  • 38. Pathogeneis of mercury neurotoxicity • Selectively accumulates in hippocampus, basal ganglia, cerebral cortex • Prevents presynaptic serotonin release and inhibits serotonin transport; causes calcium disruptions • Causes demylinating neuropathy • Causes abnormal neuronal cytoarchitecture; disrupts neuronal migration, microtubules, and cell division Clarkson, T. The toxicology of mercury. Crit 38 Rev Clin Lab Sci 1997; 34(3): 369-403
  • 39. Pregnancy – the risky group • 117 first term pregnancies in the mercury exposed group • Spontaneous abortion (19 cases) • Stillbirth (3 cases) • Congenital malformations (5 cases of spina bifida and 1 case of intra-atrial defect) Sikorski et al, 1987 39
  • 40. Few words on investigation • Blood mercury is only useful within 3 days of exposure and it is more reliable in methylmercury (high concentrations in RBCs) • A 24-hour urine specimen is a good indicator for inorganic mercury poisoning • Hair mercury level has no role in acute Hg toxicity WHO, 2002 40
  • 41. Treatment of inhalational mercury • No role of inducing emesis • Oral steroid is a common practice but without substantial evidence • Hemodialysis is used in severe cases of toxicity when renal function has declined (ATSDR, 2002) 41
  • 42. • Most inhalational form are self limited – recovery without sequalae but fibrosis, empyema and fatal ARDS has been reported Taueg C, et al. Acute and chronic poisoning from residential exposures to elemental mercury-Michigan, 1989-1990. J Toxicol Clin Toxicol 1992; 30(1): 63-7 42
  • 43. • Use chelating agents: symptomatic, systemic absorption is anticipated, increased mercury blood or urine levels – dimercaprol (BAL) d-penicillamine (DPCN) – 2,3-dimercaptosuccinic acid (DMSA) 43
  • 44. The identification of mercury Summary poisoning is difficult due to vague toxidrome. Major target organ in inhalational mercury poisoning is brain and lung Pregnant ladies are considered high risk group Inhalational elementary mercury poisoning is self-limited with few sequelae. The use of oral steroids in mild inhalational elemental mercury poisoning is non-substantial Only manage severe poisoning in institutes with well fitted 44 decontamination facilities