Transcript toxic gases An update on selected EAPCCT Wikitox

An Update on Selected Toxic
Gases in Industry
Stephen W. Borron, MD, MS, FACEP, FACMT
Juan C. Arias, MD
South Texas Poison Center
San Antonio, TX
Acknowledgments and
Conflicts of Interest
• Some material in this presentation was kindly
supplied by Dr. Patrick Conner and the
American Chemistry Council (Diller Registry on
Phosgene Effects)
• The presenter has received research funding
and consulting fees from the manufacturer
and distributers of hydroxocobalamin, a
cyanide antidote
Overview
• Overview of
occupational gas
exposures and injuries
• Epidemiology
• Sources and use
• Clinical case
presentations
• Update on treatments
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•
•
•
•
Carbon monoxide
Hydrogen sulfide
Hydrogen cyanide
Phosgene
Arsine
Occupational deaths & injuries
Fatal
Nonfatal
– Work injuries = 5,703 =
3.9/100,000 workers
– Deaths from exposure
to harmful substances
or environments = 525
(9%)
– Deaths from inhalation
of substances = 58
(11% of exposure
deaths, 1% of deaths)
– Nonfatal exposures
to chemicals =
18,230
• Inhalation = 5, 180
• Confined spaces =
920
54 of 525 deaths
due to exposures
U.S. 2006 Bureau of Labor Statistics
Top 10 reasons it may not pay to
show up for work…
TEN LEADING SOURCES OF FATAL OCCUPATIONAL
INHALATION, UNITED STATES, 1992-1998
NUMBER
%
Carbon monoxide
175
33.5
Sulfur and sulfur compounds
51
9.7
Sewer gas, mine gas, methane
40
7.6
Nitrogen oxides
26
5.0
Coal, natural gas, petroleum fuels and compounds
24
4.6
Smoke, fire gases
21
4.0
Halogens and halogen compounds
20
3.8
Ammonia and ammonium compounds
15
2.9
Acids and alkalis
14
2.7
Aromatics and hydrocarbon derivatives, except halogens
13
2.5
Valent 2002 Chest 121;969-975
CARBON MONOXIDE
Carbon monoxide
• General epidemiology
– 15,000 ED visits/yr for
unintentional, non-firerelated CO
– 500 deaths
– Mostly men (3/4)
• 15 yrs and above
– Attributed to working
with fuel-powered
tools / appliances
U.S. Centers for Disease Control
Carbon monoxide
• Occupational epidemiology
– Study of 1992-1996
– 148 occupational CO
unintentional deaths
– Services industries (25%)
– Manufacturing (14%)
– Construction (14%)
– Agriculture (14%)
– Majority involved motor
vehicle exhaust
Janicak 1998 Compens Work Condition Fall;26-28
Carbon monoxide
• Epidemiology
– AAPCC 2006
• 48 fatal CO exposures (alone/combination);
• 14 fatal occupational CO exposures
– 29% of all CO deaths
– 58% of 24 total occupational fatalities
• Occupational exposures comprise 1.5% of NPDS
Bronstein 2007 Clin Toxicol 45;815-917
Carbon monoxide
• Epidemiology
– 1989-2004: 68 incidents of CO poisoning in hotels
– 772 accidentally poisoned: 711 guests, 41 employees or
owners, and 20 rescue personnel (8% occupational).
– 27 died, 66 had confirmed sequelae, 6 had sequelae
resulting in a jury verdict
– Faulty room heating caused 45 incidents, pool/spa boilers
16, CO entrained from outdoors 5
– Public verdicts averaged $4.8 million per incident
– Poisonings occurred at hotels of all classes
YOU CAN CHECK OUT ANY TIME YOU LIKE, BUT YOU CAN NEVER LEAVE…
Weaver 2007 Am J Prev Med 33;23-27
Carbon monoxide
• Epidemiology
– 167 patients treated for CO poisoning during
US
Consumer Product Safety Commission
hurricanes of 2004 in Florida
estimates a typical
– Portable gas-powered generators responsible in
5-kilowatt
generator
generates
a
nearly all non-fatal and all fatal poisonings
concentration
of
CO
equivalent
to
the
tailpipe
• 48% of generators were outside the home
emissions
between 252 and 572 idling
• 33% in theofgarage
vehicles
• 15% inside the home
• 3% occurred at businesses
Van Sickle 2007 Am J Prev Med 32;340-346
Carbon monoxide
• Case scenario
– 23 y/o commercial coffee roaster entered a 2 x
2.7 meter storage tank to retrieve a tool
– He lost consciousness, retrieved 40 mins later,
dead
– 5 coworkers sent to hospital
– 3 had lost consciousness, 2 were presyncopal
– All rescuers recovered, but 1 hospitalized
– Maximum CO concentrations up to 100,000 ppm
Nishimura 2003 JAMA 290;334
Carbon monoxide
What is and what isn’t
• 150 children with “CO
poisoning”
• Categorized according
to source of CO
• Dramatic differences
in signs / symptoms
and outcomes with
almost no difference
in COHb%
Chou 2000 Pediatr Emerg Care 16;151-155
Carbon monoxide
Treatment: HBO – The intergalactic battle rages on…
• Buckley 2005
• Bentur 2005
• Conflicting evidence
regarding efficacy
• Evidence of bias in
studies
• Firm guidelines
cannot be established
• More research is
needed to define the
role…if any…of HBO
– This review [cannot]
dispel the current
disagreement
• Brent 2005
– HBOT best reserved for
selected patients
• Seger 2005
– I don’t know
Buckley 2005 Toxicol Rev 24;75-92
Carbon monoxide
• Treatment failures…or not
– CO poisoned patients may be successfully
used as donors
• Bentley 2001 Ann Thorac Surg 71;1194-1197
– Two hearts
• Luckraz 2001 Ann Thorac Surg 72:709 –13
– Six hearts, one lung
– One organ failure at 12h  death
H—S—H
HYDROGEN SULFIDE
Hydrogen sulfide
• Product of decomposition
– Petroleum (sour gas)
– Paper pulp industry (Kraft process)
– Decomposing food & waste
• Offal
• Fish scrap
• Manure
• Sewers
• Compost pits
Hydrogen sulfide
• Sources and uses
–Intermediate in production:
• Elemental sulfur
• Sodium sulfide
• Other inorganic sulfides
• Sulfuric acid
• Extreme pressure lubricants and cutting
oils
Hydrogen sulfide
• Epidemiology
– AAPCC 2006
• 5 occupational deaths due to H2S alone or in
combination out of 8 total deaths (62.5%)
• 344 (all causes) treated in HCF with 10 moderate and 1
lethal outcome as single agent
– Valent 2002
• #2 cause of fatal inhalational occupational injuries
• Responsible for 9.7% of these deaths
Bronstein 2007 Clin Toxicol 45;815-917
Valent 2002 Chest 121;969-975
Hydrogen sulfide
• Epidemiology
– Review of 77 deaths related to manure storage
over a 30 year period: 1975-2004
– 34% died while doing repair or maintenance of
manure handling equipment
– 22% died while trying to effect a rescue
– 21% involved persons <16 years of age
– Confined space entry identified as a particular risk
Beaver 2007 J Agromedicine 12;3-23
Hydrogen sulfide
• Case scenario
– 16 y/o male sent to clean a reoxygenation tank in
a fish hatchery known to be contaminated with
H2S after it is drained and the smell dissipates
– As he begins to clean out the sludge in the 5 m
deep tank he collapses. His adult co-worker
attempts to rescue him and dies
– EMS administers oxygen and the youth awakens
– He survives intact after prolonged hospitalization
and rehabilitation
Nikkanen 2004 Pediatrics 113;927-929
Hydrogen sulfide
• Treatment
– Not much new
– Nitrite treatment (induction of
methemoglobinemia?) remains controversial
– HBO therapy…well, you can guess
– Hydroxocobalamin?
• Shown to form sulfitocobalamin with H2S
• Clinical significance remains unknown
Farquharson 1977 Am J Clin Nutr 30;1617-1622
HYDROGEN CYANIDE
Hydrogen cyanide
• Epidemiology
– AAPCC 2006
• 0 pure HCN gas fatalities
• 7 non-gas (cyanide salts) fatalities, all ingestions, none
occupational
• 118 unintentional exposures, 5 major outcomes
– Valent 2002
• Fire smoke is the 6th most common cause of
occupational inhalational fatal injuries accounting for
4% of those deaths
Bronstein 2007 Clin Toxicol 45;815-917
Valent 2002 Chest 121;969-975
Hydrogen cyanide
• Sources and uses
– 1.5 million tonnes / yr used worldwide
– Vast majority used for manufacture of methyl
methacrylate (plexiglas) and adiponitrile (
nylon)
– Other nitrile manufacture (acrylonitrile)
– Gold and silver extraction, electroplating
– Jewelry cleaning
– Vermin extermination
– Fire smoke
Cummings 2004 Occup Med 54;82-85
Hydrogen cyanide
• Case scenario
– 25-year-old male electroplater entered a metal
plating holding tank for excess zinc cyanide to
clean it
– Holding tank had been emptied by a waste
disposal company, but had 2” zinc cyanide sludge
– The victim manually pumped in between 1 and 2
gallons of 1% muriatic acid, then climbed into tank
without respiratory protection
– 4 minutes later, he collapsed
http://www.cdc.gov/niosh/face/In-house/full8833.html
Hydrogen cyanide
• Case scenario, cont’d.
– 4 coworkers entered the tank to attempt to rescue
the victim, none had respiratory protection; all
collapsed
– Additional workers tried to attempt rescue; one
was able to rescue one of the 4 coworkers and
administer CPR
– 5 workers died
– 17 police officers and firefighters received toxic
exposures; 30 total victims were treated
http://www.cdc.gov/niosh/face/In-house/full8833.html
Hydrogen cyanide
• Treatment
– ECETOC is currently studying cyanide antidotes to
determine the most appropriate one(s) for
industry, several EAPCCT members on Task Force
– Hydroxocobalamin has recently been approved by
the EMEA and US FDA
– Cobinamide and various prodrugs of 3mercaptopyruvate are undergoing advanced
studies in the US
Broderick 2006 Exp Biol Med 231;641-651
Nagasawa 2007 J Med Chem 50;6462-6464
PHOSGENE
Phosgene
• Sources and uses
– A high production volume chemical (OECD)
– Phosgene is used in manufacture of:
•
•
•
•
•
•
Polymeric isocyanates (polyurethane, resins)
Polycarbonates (plastics)
Carbamates and related pesticides
Aniline dyes
Perfumes
Pharmaceuticals
– Heating of chlorinated hydrocarbons
Phosgene
• Epidemiology
– AAPCC 2006
• No phosgene exposures reported
– Diller registry (American Chemistry Council)
• Deleted from Wikitox slide set
• Permission not requested or obtained for web
publication
• See ACC website for more information
Bronstein 2007 Clin Toxicol 45;815-917
Phosgene
• Case scenario
– 43 y/o male helping demolish a refrigeration plant
– Cut through a pipe containing
chlorodifluoromethane, noted a musty smell
– Immediate lacrimation, cough, burning in throat
– Later, dyspnea and chest pain
– Admitted to hospital x 24h
– Slow recovery, with lethargy, exertional dyspnea
– Return to work at 2 weeks
Wyatt 1995 J Accid Emerg Med 12;212-213
Phosgene
• Pathophysiology
– Acylation
• Reaction with amino, hydroxyl, and sulfhydryl
groups
• Denaturation of proteins and lipoids
• Irreversible alterations of membrane structures
• Disruption of enzyme and other cell functions
– Hydrolysis
• Less important: formation of HCl
Borak 2000 J Occup Environ Med 43;110-119
Phosgene
• Treatment
– Steroid
• Inhalers
• Prednisolone 250 mg IV
– Ibuprofen
• 25-50 mg/kg
– N-acetylcysteine
• 20 mL of a 20% NAC solution administered by nebulizer
– Positive airway pressure ventilation
– Rest and observation
Borak 2000 J Occup Environ Med 43;110-119
H
As
H
ARSINE
H
Arsine
• Sources and uses
– Production of gallium arsenide
– Dopant in solid-state electronics
– Manufacture of LEDs
– Product of chemical reaction of arsenic salts with
strong mineral acids
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•
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Metal smelting and refining
Arsenical pesticide use
Battery manufacture
Art restoration
Arsine
• Epidemiology
– AAPCC 2006
• No arsine exposures reported
• 1 arsenic death due to ingestion
– Pullen-James 2006
• Approximately 750 reported exposures
• 1/3 lethal
Bronstein 2007 Clin Toxicol 45;815-917
Pullen-James 2006 J Natl Med Assoc 98;1998-2001
Arsine
• Case scenario
– 55 y/o male c/o flank pain radiating into groin for
two hours, with weakness, followed by gross
hematuria
– PMH of testicular cancer
– Developed hypotension during CT to rule out
stone, required vasopressors
– WBC 36k, CPK 546, UA with WBC, 6-8 rbc/hpf, Cr
1.0
– Admitted to ICU with dx of sepsis
Pullen-James 2006 J Natl Med Assoc 98;1998-2001
Arsine
• Case scenario, cont’d
– Deteriorated overnight, developed ARDS
– Skin became beet red, urine black, WBC increased
to 43,000, Hb dropped from 11.2 to 8.8 mg/dl,
Creatinine increased to 2.6 (229.8 μmol/l)
– Occupational history taken on day 2:
• Water detoxification plant
• Removing As from water using an acid preparation
• Recalled smelling garlicky odor above water
– 2 coworkers presented shortly after with
hematuria
Pullen-James 2006 J Natl Med Assoc 98;1998-2001
Arsine
• Signs and symptoms of poisoning
– Concentration-dependent symptom delay
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•
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Headache, vomiting, chills, dyspnea
Pain in chest, lumbar area, abdomen
Fever, tachypnea
Oliguria  anuria
Dark urine, skin tone  jaundice at 24-48h
Leukocytosis, Heinz bodies, basophilic stippling ,
anemia
• Hyperkalemia
• Ur As > 200 mcg/l
Arsine
• Pathophysiology
– Uncertain – definitely involves O2Hb
• COHb is protected
• Oxidation of red blood cells resulting in massive
hemolysis
• Sodium-potassium pump poisoning
• Swelling of RBC
– Renal injury due to hemolysis, direct toxicity
Arsine
• Treatment
– Supportive care
– Plasma exchange
– Antidotes for As not indicated
– Exchange transfusion
– Hemodialysis
– Bicarbonate for hemolysis
– Glutathione (?)
– Dexamethasone (?)
Pullen-James 2006 N Natl Med Assoc 98;1998-2001
Song 2007 Clin Toxicol 45;721-727
Arsine
• Treatment by plasma exchange
Song 2007 Clin Toxicol 45;721-727
Summary
• Toxic gases continue to cause lethal
and injuries in industry
• These exposures account for a small
percentage of fatal occupational
injuries
• Confined space exposures and
unprotected rescue attempts result
in many injuries and deaths
• Treatments continue to slowly
evolve and improve