1 / 58

Managing Chemical Exposure

Managing Chemical Exposure. Kevin O. Rynn, PharmD, FCCP, DABAT Clinical Associate Professor Clinical Pharmacy Specialist Emergency Medicine. Awakening of America. Objectives:. Identify agents potentially used in a terrorist attack Understand the pharmacology and toxicology of these agents

yates
Télécharger la présentation

Managing Chemical Exposure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Managing Chemical Exposure Kevin O. Rynn, PharmD, FCCP, DABAT Clinical Associate Professor Clinical Pharmacy Specialist Emergency Medicine

  2. Awakening of America

  3. Objectives: • Identify agents potentially used in a terrorist attack • Understand the pharmacology and toxicology of these agents • Understand the management of exposed patients • Identify unique potential threats to New Jersey residents • Better appreciate our role as pharmacists

  4. Introduction: Chemical Warfare • Spartans, 429 BC • World War I: Germany • April 22nd 1915: chlorine gas against allies • Belgium, Hundreds killed, troops retreated • July 12th, 1917: Sulfur mustard • Injuries >>> fatalities • World War II: Germany • December 2nd 1943: Mustard bombs destroyed in Italy • Yemen war • Egypt: riot control agents, mustards, nerve agents • Vietnam • US: Tear gas and chemical herbicides

  5. Introduction: Chemical Terrorism • Aum Shinrikyo Cult

  6. Introduction: Chemical Terrorism • Matsumoto: 1994 • Sarin: residential neighborhood • Fatalities: 7 • Hospital visits: 500 • Tokyo: 1995 • Sarin, subway system during rush hour • Fatalities: 12 • Hospital visits: > 5,000 Subway riders injured in Aum Shinrikyo sarin gas attack, Tokyo, March 20, 1995. (AP Photo/Chikumo Chiaki )

  7. Eye Miosis 99% Eye pain 45% Blurred vision 40% Dim vision 38% Tearing 9 % Chest Dyspnea 63% Cough 34% Wheezing 6% Tachypnea 32% ENT Runny nose 25% Sneezing 9% GI Nausea 60% Vomiting 37% Diarrhea 5% Neurologic Headache 75% Weakness 37% Fasciculations 23% Numbness 19% Decreased LOC 17% Vertigo/dizziness 8% Seizures 3% Psychologic Agitation 33% Signs & Symptoms of 111 Moderately or Severely Injured Patients on Admission Okumura T, et al Ann Emerg Med 1996;28(2):129-35

  8. Chemical Weapons

  9. Chemical Weapons

  10. Nerve Agents • Physical characteristics and toxicity • Mechanism: • Cholinesterase inhibitors, excess buildup of Acetycholine (Ach) • Muscarinic effects • Postganglionic parasympathic • Nicotinic effects • Autonomic ganglia • Preganglionic sympathetic & parasympathetic • Neuromuscular junction • Excess Ach in CNS

  11. Muscarinic Diarrhea Salivation Urination Lacrimation Miosis**Urination Bradycardia Defecation Bronchorrhea GI symptoms Bronchospasm Emesis Emesis Lacrimation Nicotinic Tachycardia Hypertension Mydriasis Neuromuscular junction** Fasciculation Weakness paralysis CNS Anxiety, confusion, ataxia, dysarthria Coma, Seizures**, Resp depression** Results of Cholinesterase Inhibition ** Most important after nerve agent

  12. Key Findings Based on Route of Exposure

  13. RBC & Plasma Cholinesterase Levels • Clinical utility limited • Related to clinical effect, but not consistently • Normal value range • Workplace usage • Do not wait on these for treatment!

  14. RBC Difficult assay inhibited preferentially by VX and sarin 2-PAM: regenerates levels Regeneration rate: 1% per day (erythrocyte production) Plasma Easier assay An acute phase reactant (liver protein) Affected by low protein conditions Declines faster acutely and regenerates faster Cholinesterase Levels

  15. Treatment: Decontamination • Selective protective measures • Lipophyllic agents can penetrate latex and vinyl • Nitrile, neoprene, butyl rubber gloves • Leather • Shared Breathing air • Irrigation • Water • Hypochlorite solution • Alkaline soap

  16. Atropine • Competitive MUSCARINIC antagonist • Peripheral > central • Blood brain barrier • Dosing- IV or IM • Initial Adult 2mg Peds 0.02mg/kg (min 0.1mg) • Repeat Every 2 - 5 minutes • Endpoints • Reversal of muscarinic signs of toxicity Mod. to Severe 2-3 times this

  17. Atropine • Dosing in comparison to organic phosphorus insecticide. • Tokyo subway sarin attack (N=111) • Doses > 2mg 18.9% • Max dose administered 9 mg • Adverse effects • Dry mouth&skin, mydriasis, paralysis of accommodation, tachycardia Okumura T. et al Ann Emerg Med 1996;28(2):129-35

  18. Aerosolized Ophthalmic Miosis reversal Causes photophobia and loss of accommodation Glycopyrolate IV administration of EMS sources Opthtalmic Veterinary Powder preparation Atropine: Alternative Routes and Supply Sources

  19. Geller RJ, Lopez G, Cutler S, Lin D, Bachman GF, Gorman SE. Ann Emerg Med 2003;41:453-6. 110 6mg syringes ~ 60 minutes 8 week testing 5˚C: USP standards + 5% Pyrogen free 4 week testing Room Temp: USP standards + 5% Kozak RJ, Siegel S, Kuzma J. Ann Emerg Med 2003;41:685-8. 100 6mg syringes ~ 30 minutes 3 week testing USP standards + 5% microbiologic sterility testing Cost Advantage $11 vs $5,000 Rapid Atropine Reformulation From Bulk Powder

  20. Pralidoxime:Protopam®(2-PAM) • Cholinesterase reactivator • Dosing: IM or IV • Adult: 1-2 gms over 15-20 minutes then q6h for 24 hrs • Peds: 25mg/kg to max 1gm • C.I.: Adult 500mg/hr, peds 25mg/kg/hr • Improves all cholinergic symptoms • Aging • Covalent bond between nerve agent and enzyme • Irreversible dealkylation

  21. Nerve Agent Aging:

  22. Treatment: Continued • Mark 1 Kits • CANA • Convulsion antidote for nerve agents • Diazepam • NAPS • Nerve agent pre-treatment tablets • Pyridostigmine

  23. Nerve Agent Antidote ProgramChemPack

  24. Vesicants

  25. Vesicant Agents: Symptoms

  26. Decontamination Water, hypochlorite solutions Avoid scrubbing and hot water Topical Calamine/other soothing lotions Antibiotics Systemic analgesia Ocular injures Irrigation Mydriatics: homatropine or other anticholinergics Anesthetics Ophthalmic ointments Constant reassurance Respiratory Antitussives: Bronchodilators/mucolytics Antibiotics Intubation Treatment

  27. Treatment: BAL • British Anti-Lewisite: Dimercaprol • Metal chelating agent • BAL combined with lewisite forms stable 5 member ring • Dosing • 3 -5 mg q4hr x 4 doses • Adverse effects • GI, Hypertension, tachycardia • Peanut allergy

  28. Blood Agents: Cyanides • Antiquated term • Carried via blood to exert it’s effect • French • Franco-Prussian war: Napoleon III first to use • WWI: French and British • Hydrogen cyanide and cyanogen chloride used on battlefields • WWII: • German genocidal agent • Iran-Iraq war and Iraq’s suppression of Kurds • Apparent use with mass casualties reported

  29. Cyanide: Tampering • 1982: Chicago Tylenol • 7 deaths • 1988: Yogurt • 1989: Dept of Agriculture • Cyanide traces on fruit from Chile, possible terrorist threat

  30. Cyanide • Routes • Inhalation, ingestion, topical • Primary site of action • Cells rather than blood • Interruption of cellular respiration in mitochondria

  31. Cyanide: Mechanism of Toxicity • Binding of CN- to cytochrome a3 in mitochondria • Stable but not irreversible • CN- has higher affinity for the Fe3+ in methemoglobin • Interruption of oxidative phosphorylation • Decreased aerobic energy production(ATP) • Final results: cellular hypoxia

  32. Cyanide Vapor Exposure

  33. Cyanide • Homicidal and suicidal use • Judicial execution • Combustion of plastics, cigarettes, vehicle exhaust • Household products • Silver polish, acetonitriles • Industry: chemical syntheses • Hospital • Sodium nitroprusside

  34. Cyanide Toxicity: Treatment

  35. Cyanide: Treatment • Healthcare worker protection • Supportive therapy • Antidotal therapy • Displace CN- from cytochrome A3 • Nitrite therapy • Enzymatic conversion of CN- to thiocyanate • Thiosulfate therapy

  36. Sodium Nitrite • Converts Hb(Fe2+ ) to MetHb (Fe3+) • Preferential binding of CN- • Goal MetHb = 20 - 30% • Adverse effects • Excessive methemoglobin production • Vasodilatation: hypotension

  37. Sodium Thiosulfate • Enzymatic (rhodanese) reaction with CN- • Formation of thiocyanate (SCN-) • Irreversible reaction • Renal elimination • Adverse effects - minimal • N/V • Arthralgias

  38. Dosing

  39. Pulmonary Agents: Chlorine and Phosgene • Increased permeability • Delayed pulmonary edema • WWI: Primary chemical agents • Chlorine: yellow-green cloud, pungent • Phosgene: colorless, fresh hay

  40. Pulmonary Agents

  41. Pulmonary agents- Phosgene • Low-solubility = deeper lung penetration • Symptoms within 4 hrs • Worse prognosis • ICU admission • No chest x-ray changes within 8 hours • Acute lung injury unlikely • Delayed serious symptoms • 15 -18 hours

  42. Pulmonary Agents: Treatment • Decontamination • Irrigation of eyes and skin • Oxygen • Endotracheal Intubation • Hoarseness, stridor, upper-airway burns, wheezing, altered mental status • Bronchodilators • Nebulized sodium bicarbonate • Neutralize chlorine derivatives • Efficacy data lacking

  43. Pulmonary Agents: Treatment • Bed rest • Physical exertion exacerbates lung inflammation • Corticosteroids • Moderate to severe exposures • Positive End Expiratory Pressure (PEEP) • Antibiotic prophylactic use • Not recommended

  44. Riot Control Agents • Tear gas or lacrimators • Aerosolized solids • Intense immediate self-limiting symptoms • Prolonged exposure with underlying lung disease • Bronchospasm and acute lung injury

  45. Riot Control Agents • Chloroacetophenone - CN • o-chlorobenzilidene malononitrile - CS • Symptoms • Lacrimation, photophobia, blepharospasm • Chest tightness, wheezing, coughing, secretions • Dermal burning, erythema, vesiculation • Recovery: 15 - 30 minutes post removal

  46. Riot Control Agents: Treatment • Removal from exposure • Remove clothing and placed in airtight bags • Irrigation • Symptomatic treatment • Ophthalmic anesthetics, bronchodilators, antihistamines • Capsaicin-induced dermatitis • Oil immersion

  47. Prevalent New Jersey HazMat Threats • Terrorist attack likely to involve conventional explosives & hazardous materials • New Jersey likely target • Densely populated state • Many companies/manufacturers • Most New Jerseyans live/work within short distances to chemical plants Marcus, S, Ruck B. New Jersey Medicine 2004;101(9):34-43.

  48. New Jersey Department of Environmental Protection (DEP) • New Jersey Toxic Catastrophe Prevention Act (TCPE) • > 100 companies • Implement risk management plan (RMPs) • NJ DEP list chemicals and threshold quantities http://www.nj.gov/dep/rpp/tcpa/

More Related