jeffrey brent, m.d., ph.d. toxicology associates university of colorado health sciences center...
TRANSCRIPT
Jeffrey Brent, M.D., Ph.D.Toxicology Associates
University of Colorado Health Sciences CenterAurora, CO
USA
32 y/o male was working along the side of a railroad tanker car filled with liquid Cl2 when the hose broke and a cloud of yellow-green gas was released.
He immediately developed shortness of breath and intense eye and throat irritation.
On presentation to the hospital he was in moderate respiratory distress, 119/62, 28,110, 100% on 2 L by mask.
His eyes were red and tearing and he had diffuse rales, expiratory wheeze, ↑ E/I ratio.
How would you treat him? What is his prognoses?
Generally effects of gases depend on their aqueous solubility
Highly soluble gases: Affect mostly eyes and oro/naso pharynx Ex.: Ammonia
Low solubility gases Mostly deep pulmonary structures (alveoli) Ex. NOX
Chlorine has intermittent solubility
Many descriptions published All are uncontrolled case series No pre-exposure PFTs When PFTs are done they have varying
degrees of quality control Dose assessments rare
Release of 180,000 kg Cl2 over 5 minutes 15,000 French troops exposed
800 fatalities 2,500 -3,000 incapacitated Majority were able to return to duty Reports of long-term disability confounded by:
Smoking TB
Later releases were mixed Cl2/phosgene
Cite Event N FU
LoVecchio, 2005 Poison Center series (mostly household)
298 Days
Guloglu, 2002 Chlorine tank release
106 None
Agabiti, 2006 Swimming pool accident
236 1 month
Moulick, 1992 Acute release 82 1 month
Abhyanker, 1989 Acute release 14 6 months
Jones, 1986 Train derailment 116 6 yrs
Charan Broken hose/railcar 19 2 yrs
Barrett, 1984 Acutely exposed workers
129 1 month
Hasan, 1983 Leaking storage tank/HVAC
18 5 months
Kaufman, 1971 Storage tank release
22 5 yrs
Weil, 1969 Railcar puncture 12 7 yrs
Kowitz, 1967 Longshoreman 156 2.9 yrs
Joyner, 1962 Train derailment 12 7 yrs
Chassis, 1947 Subway system 208 16 months
50 – 2,000 ppm X 30 min→ labored breathing
At highest doses → severe muc memb injury & bronchospasm If lived 3-5 days: acute pul inflammation, lobar
pneumonia, abscesses & necrosis Autopsies of survivors
@ 5-15 days: organizing pneumonia & bronchiolitis @ 6 months: emphysema, patchy BO
Massive exposures (similar to Underhill high dose)
Early deaths mostly due to upper airway injury
Later deaths due to pneumonia Even later deaths due to bronchiolitis
8 healthy non-smokers Exposed for 4 or 8 hours to 0, 0.5, & 1
ppm @ 1 ppm:
↓ FEV1
↓Peak exp flow rate ↓FEF25 – 75
↑ Airway resistance
Rapidly fatal acute necrotic pulmonary edema and tracheobronchitis (human experience)
This tends to occur at > 1,000 ppm Most pts who survive exposure initially
have abnormal PFTs
Diverse patterns of abnormalities ? Related to exposure Rarely have pre-exposure PFTs
Most common pattern is obstructiveTypically resolves in weeks to months
Not a highly soluble gas But, affects eyes, nasopharynx, and
upper respiratory tract Requires > 50 ppm to show significant
lower airway effects Thus tends to act like a high solubility
gas
Solution lies chlorine’s chemical properties dictating its toxicokinetic/dynamic profile
Early theories of toxicity 1. Hydration of chlorine →HCl → acid injury
However, chlorine 35X more toxic than HCl fumes in mice (Barrow 1977)
2. “Oxidative injury” – nonspecfic re chemical/mechanism
Cl2 + H20 OCl- + 2 H+ + 2Cl- HOCl + HCl
This reaction completely explains chlorine’s toxicological properties
Cl2 + H20 OCl- + 2 H+ + Cl- HOCl + HCl
NO2
Nitrite-chlorine complexes
Nitration injury
Chlorination injury:Reacts with –NH2 groups
Thus, due to the rapid hydration of Cl2 it theoretically assumes the properties of a highly soluble gas.
•O
Oxidative injury
Irritation
Copyright ©1999 American Physiological Society
Nodelman, V. et al. J Appl Physiol 86: 1984-1993 1999
Fig. 4. Regression of diffusion model to Cl2 distribution data obtained during nasal breathing in 1 subject
Copyright ©1999 American Physiological Society
Nodelman, V. et al. J Appl Physiol 86: 1984-1993 1999
Fig. 6. Pooled distributions for 10 subjects
Copyright ©1999 American Physiological Society
Nodelman, V. et al. J Appl Physiol 86: 1984-1993 1999
Fig. 8. Pooled compartmental Cl2 absorption for 10 subjects
Cl2 + H20 OCl- + 2 H+ + Cl- HOCl + HCl
Why is it that if hypochlorite is mixed with an acid chlorine gas is liberated?
Answer: Because the release of chlorine gas formed keeps the [Cl2] very low.
Stop exposure Don’t forget ocular decontamination
General supportive care Bronchospasm ALI/ARDS No reported beneficial effect of
corticosteroids
Almost all reported individuals eventually recover without significant long-term sequelae
Recovery may take months, sometimes > 1 year
32 y/o male was working along the side of a railroad tanker car filled with liquid Cl2 when the hose broke and a cloud of yellow-green gas was released.
He immediately developed shortness of breath and intense eye and throat irritation.
On presentation to the hospital he was in moderate respiratory distress, 119/62, 28,110, 100% on 2 L by mask.
His eyes were red and tearing and he had diffuse rales, expiratory wheeze, ↑ E/I ratio.
RADS = reactive airway dysfunction syndrome
Caused by an acute exposure to a pulmonary irritant
< 12 cases of chlorine induced RADS, almost all in smokers, ex-smokers, or subjects c atopic disease
Thank you very much for your attention … I hope it was interesting
If you have any questions or would like a copy of these slides please contact me at : [email protected]