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Occupational Toxicology & Chemical Asphyxiants

Occupational Toxicology & Chemical Asphyxiants. Sultana Qureshi, PGY-2 Dr. Ingrid Vicas January 18, 2007. Bernardino Ramazinni (1633-1714). Considered the father of Occupational Medicine wrote De Morbis Artificum Diatriba ( Diseases of Workers ) in 1700

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Occupational Toxicology & Chemical Asphyxiants

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  1. Occupational Toxicology & Chemical Asphyxiants Sultana Qureshi, PGY-2 Dr. Ingrid Vicas January 18, 2007

  2. Bernardino Ramazinni (1633-1714) • Considered the father of Occupational Medicine • wrote De Morbis Artificum Diatriba (Diseases of Workers) in 1700 • 1st comprehensive text discussing the relationship between disease and workplace hazards • Ramazzini's essential contribution - the addition of a question to the medical history: "What occupation does the patient follow?" • Altogether Ramazzini described diseases associated with 54 occupations, incl: • hydrocarbon poisoning in painters • mercury poisoning in mirror makers • pulmonary diseases in miners

  3. Occupational History

  4. Who was Sir Percivall?

  5. Sir Percivall Pott (1714-1788)Hero of Occupational Toxicology • In 1775, Sir Percivall Pott proposed the first association between workplace exposure and cancer when he noticed a high incidence of scrotal cancer in English chimney sweeps. • Pott's belief that the scrotal cancer was caused by prolonged exposure to tar and soot was confirmed by other investigation in the 1920s, indicating that the polycyclic aromatic hydrocarbons contained in coal tar (including benzo[a]pyrene) are carcinogenic

  6. Overview • Simple Asphyxiants • Chemical Asphyxiants • Carbon Monoxide • Cyanide • Hydrogen Sulfide

  7. Asphyxiants

  8. Case • A 50-year-old medical researcher was discovered dead in a small refrigerated room that contained 10-cubic-inch blocks of dry ice. Fifteen newly arrived blocks of dry ice were placed in the refrigerated room (39.2°F [4°C]) at approximately 9 AM on the day of the scientist's death. The researcher was last seen at approximately noon, suggesting that at least 3 hours had elapsed between the initial dry ice storage and his first exposure. Scene analysis suggested that at the time of his death, the decedent was crouching several inches from the ground to store samples in a container. There were no signs of struggle, and the decedent had no history of psychiatric disorders, recent personal crises, or medical illnesses.

  9. Case • Differential? • Type of asphyxiant?

  10. Simple Asphyxiants i.e. CO2, nitrogen Inert gases Produce toxicity by displacing oxygen and lowering Fio2 Exposed patients remain asymptomatic if the Fio2 is normal Symptoms of hypoxia = slower onset Chemical Asphyxiants i.e. CO, CN, H2S Prevents O2 uptake or metabolism by cells Fast onset (e.g. H2S = suddenly pass out) Simple vs. Chemical

  11. Simple Asphyxiants

  12. Case • 38F c/o vomiting, loose stools, light-headedness, and headache • Her husband had similar symptoms • The couple arrived 2 days earlier at a resort town after a 3-hour flight on which they ate turkey sandwiches of “questionable quality” • No sig. PMHx. No Meds. No All. • No ill contacts or recent travel

  13. Chemical Asphyxiants Carbon Monoxide

  14. Introduction • Colourless, Odourless, non-irritant gas • Most common cause of acute poisoning death in U.S. • Most common cause of fire-related death • Generated through incomplete combustion of virtually all carbon-containing products • Most significant problem is long term neurologic morbidity (not mortality) • No existing predictors of poor outcome, so all exposures need to be treated aggressively with HBO

  15. Endogenous Hemolytic Anemia Sepsis Normal heme catabolism Exogenous Any hydrocarbon combustion source Heating and cooking sources Propane (especially indoor vehicles) Smoke inhalation Methylene chloride (paint solvents)* Cigarette smoke Industrial sources Sources of CO

  16. Diagnosis • Co-oximetry (arterial or venous sample) • Normal 0-5% • PPD Smokers 6-10% • CO Toxicity >15%

  17. Etiology of exposure (U.S. Data) • Suicides = 46% • Involving fires/burns = 28% • Unintentional = 21% • Of Unintentional, most common sources: • Auto exhaust and housefires • Of consumer products: • Indoor heating systems (71%) • Stoves and other appliances (10%) • Charcoal grills (9%) • Camp stoves (8%) • Water heaters (4%) 1988 study 1998 study

  18. From Goldfrank’s Toxicologic Emergencies. 8th Edition

  19. Case • 71 y/o retired male, smoker • Presents ED vague H/A, malaise, intermittent RSCP with exertion • Working in garage restoring chest of drawers for granddaughter going off to college • 4 hrs in garage with paint stripper • Thoughts?

  20. CHR ED CO PoisoningsJanuary - December 2004 From Dr. Clint Drever’s presentation on CO Poisoning, 2005.

  21. Pathophysiology

  22. Goldbaum et al • Dogs breathing 13% CO died within 1 hour after achieving COHb levels of 54% to 90% • Exchange transfusion with blood containing 80% COHb to otherwise healthy dogs resulted in no toxic effects despite resultant COHb levels of 57% to 64% • Suggesting that CO toxicity is not dependent on COHb formation alone

  23. Pathophysiology…simplified • 3 main mechanisms: • 1) Formation of COHb • Decreased O2 carrying capacity • Shifts O2 saturation curve to left resulting in less O2 delivery to tissues • 2) Cellular Toxin • COHB interacts with myoglobin = rhabdo • COHb inhibits cytochrome in mitochondria (like CN) causing switch to anarobic respiration and cell death • Formation of free radicals/NO • 3) Lipid Peroxidation • Neurological Sequelae (Also combined with hypoxic insult and re-perfusion injury)

  24. Pathophysiology

  25. Clinical Features From Goldfrank’s Toxicologic Emergencies. 8th Edition

  26. Clinical Features • Mild CO Poisoning • Non-specific, mild-mod symptoms • Headache, flu-like • Severe CO Poisoning • Identical to CN poisoning • ALOC(coma and seizures), extremely abnormal vital signs (hypotension and cardiac arrest), metabolic acidosis • Delayed Neurologic Sequelae • Frequency varies from 12% to 50%, • Develop neuro abnormalities after 2 to 40 days • 2 Types: • Primarily neurologic syndromes (ie focal deficits, seizures) • Primarily psychiatric or cognitive findings (e.g., apathy, memory deficits) • Since most patients survive, prevention of delayed neurologic and neuropsychiatric sequelae is the predominant goal of therapy

  27. Determinants of Severity of CO Intoxication • Inhaled CO concentration • Duration of exposure • Individual susceptibility • minute ventilation • pregnancy (fetal Hb), extremes of age • Comorbidity • cardiac and pulmonary diseases • ED COHb not predictive • Late changes on CT Head (new lesions after 24 hours)

  28. Diagnosis • High index of suspicion!!! • Why is pulse oximetry not useful? • What is co-oximetry? • What would you expect on the ABG? • Early vs late ABG

  29. Diagnosis • Co-oximetry (arterial or venous sample) • Normal 0-5% • PPD Smokers 6-10% • CO Toxicity >15%

  30. Neuroimaging • Acute changes on CT visible w/i 12 hours of exposure • Usually appear as lucencies within basal ganglia • Findings on CT after 24 hours usually assoc. w/ poor prognosis

  31. Management • ABCDs • 100% O2 • HBOT • Aggressive supportive care • Consider co-intoxication (ie. CN in fire victims) • Serial neuro/Mini-mental exams

  32. CO Half Life

  33. Disposition • Duration of treatment is unclear • Usual guidelines are to treat until resolution of symptoms (+/- CoHb <5%) • Remember mini-mental!

  34. CHR ED CO PoisoningsJanuary - December 2004 From Dr. Clint Drever’s presentation on CO Poisoning, 2005.

  35. Case • 71 y/o retired male, smoker • Presents ED vague H/A, malaise, intermittent RSCP with exertion • Working in garage restoring chest of drawers for granddaughter going off to college • 4 hrs in garage with paint stripper • Thoughts?

  36. Hyperbaric Oxygen Therapy

  37. Hyperbaric Oxygen Therapy • Enhanced elimination of COHb • Improved tissue oxygenation • Enhanced dissociation of CO from cytochrome oxidase • Inhibition of B2 integrin adhesion to vascular endothelium • Prevention of CNS lipid peroxidation

  38. From Goldfrank’s Toxicologic Emergencies. 8th Edition

  39. Hyperbaric oxygen for carbon monoxide poisoning.Cochrane Database of Systematic Reviews. 4, 2006. • Existing RCTs provide conflicting results • All have limitations that may threaten and invalidate their conclusions • Based on trials, HBO cannot routinely be recommended for treatment of CO poisoning • Some patients may benefit from treatment • Multicenter, randomized controlled trial needed

  40. Scheinkestel et al. Med J Aust 1999;170:203-10 • DB RCT • Referred patients, all severity of poisoning • Cluster randomization to HBO ( n=104 ) vs NBO ( n=87 ) • Excluded: pregnant, burn pt. & children • 73 % with severe poisoning • Psychometric testing : 0 and 1 month

  41. Scheinkestel et al. Med J Aust 1999;170:203-10 • Daily Rxs x 3 days 60 % O2 daily in between Rx • HBO :100 % O2 x 60 min at 2.8 atm • NBO : 100 % O2 x 100 min at 1.0 atm • Patients with abnormal clinical evaluation or poor psychometric testing had 3 more txs (28% HBOT, 15% NBOT)

  42. Scheinkestel et al. Med J Aust 1999;170:203-10 • Outcomes: • neuropsych testing & PE after therapy & at 1/12 • HBO patients required more txs • HBO patients had worse outcome in learning test • Greater % of severely poisoned patients in HBO group had a poor outcome at end of tx

  43. Scheinkestel et al. Med J Aust 1999;170:203-10 Limitations: - Only 46 % had 1 month follow up - Baseline O2 x 3 days different from other studies - 44 % with possibility of co-ingestants - High proportion of depressed/suicidal patients - Mean delay to treatment 7.1 hours ( 95 % CI 1.9-26.5) -Large number of severely poisoned patients

  44. Weaver et al. N Engl J Med 2002;347:1057-67 • DB RCT • Patients presenting <24 hours post exposure with symptoms or elevated COHb • Patients received a total of three treatments of either HBOT or NBO • HBOT = 60 min at 3.0 ATA, followed by 60 min at 2.0 ATA for the first session, followed by 120 min of HBOT at 2.0 ATA 6 to 12 hours apart for two more sessions (n  =  76). • NBO = 120 to 150 minutes of 100% NBO 6 to 12 hours apart, administered in the HBOT chamber (“sham” HBOT) (n  =  76).

  45. Weaver et al. N Engl J Med 2002;347:1057-67 • Outcomes: • Neuropsychometric testing performed after the first and third treatments, 2 weeks, 6 weeks, 6 months, and 1 year • PE before the first and after the third treatments • Questionnaires were administered at 2 weeks and 6 weeks • Cognitive sequelae were diagnosed based on having at least one abnormal neuropsychometric subtest at 6 weeks • Cognitive sequelae less frequent in the HBO group at 6 weeks (odds ratio 0.39, 95% confidence interval 0.2–0.78, P  =  .007)

  46. Weaver et al. N Engl J Med 2002;347:1057-67 • Considered the most rigorous and well-controlled study performed to date • Criticism: • Small number of intubated patients • Lack of functional performance as an outcome measure (no change in ADLs) • Increased incidence of cerebellar dysfunction in the NBO group at randomization • Choice of neuropsychometric testing • Inclusion of patients with exposure to gases other than CO • Using a nonstandard HBOT protocol

  47. Weaver et al. N Engl J Med 2002;347:1057-67 • In a subgroup analysis, HBOT was found to improve outcome specifically in patients with loss of consciousness, metabolic acidosis, CO-Hgb level greater than 25%, and age older than 50 • Number needed to treat to prevent 1 negative cognitive sequelae is 5

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