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Inhalational Poisoning

Inhalational Poisoning. Rama B. Rao, MD Bellevue Hospital Center/NYU Medical Center New York City Poison Control Center. Classes. Simple asphyxiants Pulmonary irritants. Particulates Mitochondrial toxins. Simple Asphyxiants. Alveolar displacement O 2 Non-irritating

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Inhalational Poisoning

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  1. Inhalational Poisoning Rama B. Rao, MD Bellevue Hospital Center/NYU Medical Center New York City Poison Control Center

  2. Classes • Simple asphyxiants • Pulmonary irritants • Particulates • Mitochondrial toxins

  3. Simple Asphyxiants • Alveolar displacement O2 • Non-irritating • No direct mitochondrial toxicity

  4. Simple Asphyxiants • Methane • Carbon dioxide (CO2) • Helium • Nitrogen • Nitrous oxide

  5. Lake Nyos: Carbon Dioxide

  6. Nitrogen

  7. Nitrous Oxide

  8. Simple Asphyxiants: Symptoms • Loss of consciousness • Minimal warning • Non-irritating • Sustained exposure • Hypoxia • Cardiovascular collapse

  9. Simple Asphyxiants: Treatment • Safe rescue • 100% oxygen • Evaluation for other injuries • Supportive care

  10. Pulmonary Irritants • Can behave in part like simple asphyxiants • Mucosal irritation • Acid or base formation • Some free radical formation

  11. Methyl Isocyanate

  12. Pulmonary Irritants: Water Solubility • Highly water soluble: • Ammonia • Sulfur dioxide • Hydrogen chloride • Chloramine • Rapid onset

  13. Pulmonary Irritants: Intermediate Solubility • Chlorine • Exposure better tolerated initially • Increased duration exposure • Subsequent acid formation in upper and lower airways • Delayed effects • Acute lung injury

  14. Pulmonary Irritants: Low Solubility • Include • Phosgene • Nitrogen dioxide • Prolonged exposure • Delayed • Pulmonary edema • Acute lung injury

  15. Pulmonary Irritants: Treatment • Removal from exposure • Oxygen • Nebulized bronchodilators • For acid forming agents: • Nebulized sodium bicarbonate • 1 part NaHCO3 to 3 parts saline or water • Primarily for symptomatic relief

  16. Pulmonary Irritants: Treatment • Supportive care • Admission: • Severely symptomatic patients • Low and intermediate solubility exposures • Arrange follow-up

  17. Particulates and Aspirants • Gas exchange impaired • Supportive therapy • Intubation • ECMO • Bronchoaveolar lavage • Can be fatal in children

  18. Hydrocarbon Aspiration • Surfactant disruption • Higher severity: • Agents • Low viscosity • Surface tension • High volatility • >30 mL exposures

  19. Hydrocarbon Aspiration: Symptoms/Signs • Cough • Choking • Dyspnea • Rales • Hypoxia • May progress to ALI

  20. HC Aspiration: Management • Assess for evidence of aspiration • Clinical • Radiographic • For asymptomatic patients without clinical evidence of aspiration • Observe 6 hours • Radiograph at 6 hours • Admit if signs or symptoms aspiration

  21. Ware LB, N Engl J Med. 2000;342(18):1334-49.

  22. MITOCHONDRIAL TOXINS

  23. Mitochondrial Toxins • Carbon monoxide • Cyanide • Hydrogen sulfide

  24. Carbon Monoxide • Incomplete combustion • Fires • Vehicular exhaust • Methylene chloride • Leading cause of poisoning deaths in the U.S

  25. 100 75 Normal 50% COHb % Saturation 50 50% Anemia 25 0 20 40 60 80 100 Tissue pO2 [mmHg] Toxicity CO • Displacement O2 • Alveoli • Hemoglobin binding sites (OCC) • Impaired O2 • Delivery • Utilization

  26. CO Poisoning: Acute Signs and Symptoms • Headache • Myalgias • Dyspnea • Nausea, Vomiting • Loss of Consciousness • Chest pain • Hypotension

  27. CO Toxicity: Delayed Events • Delayed neurological/ neuropsychiatric sequelae • 2-40 days post-exposure • Risks • Age • Loss of consciousness

  28. Mitochondria Blood Muscle CO + Hb COHb CO + Mb COMb CO + cytochrome oxidase (1. displaces O from Hb (inhibits O delivery to myocyte) 2 2 2. shifts O dissociation curve) 2 Inhibits electron transport ¯ ¯ BP and CBF Vasodilation ¯ ATP and O utilization ­ 2 N + O 2NO cGMP 2 2 NOS (endothelium, platelets) - CO-Platelets O and H O generation 2 2 2 Platelets CO binds to heme-containing NO NMDA - ONOO platelet proteins activation b Affects -integrins 2 PMNs adhere to vascular endothelium Lipid peroxidation PMNS Proteases Xanthine dehydrogenase Xanthine oxidase Free radicals (inhibitors: tungsten, allopurinol)

  29. Physiology: CO Binding • Myocardium • CV impairment  Hypotension • Hemoglobin • Decreased OCC  Functional Anemia • Platelets and PMN • Nitric oxide  Hypotension • Free radicals  Lipid Peroxidation • Mitochondria • Cytochrome oxidase  Lipid Peroxidation • Impaired e transport  Functional Hypoxia

  30. Carbon Monoxide: Management • 100% oxygen • Reduce half-life CO-Hb 6hr to 90 minutes • Assess for pregnancy • Note that pulse oximetry is inadequate • Oxygen saturation may appear artificially high • Assess for end organ damage • VS, ECG, symptomatology, neurological examination

  31. Carbon Monoxide Levels • Venous sampling • > 10% abnormal • Levels correlate poorly with severity of exposurre

  32. Hyperbaric Oxygen • Decrease COHb half life • Displaces CO from tissues • Improves oxygen carrying capacity • Limits lipid peroxidation • Improves dissolved oxygen

  33. Hyperbaric Oxygen • Variable outcomes in literature 2: • Definition of DNS • Timing and duration of therapy • Co-exposures • Inability to define equivalent exposures • Patient variability

  34. Hyperbaric Oxygen Weaver LK, et al: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002; 347:1057-67

  35. Hyperbaric Oxygen: Indications • Neurological damage • Cardiovascular events • Loss of Consciousness • Persistent symptoms • COHb > 25% ( some centers use >40%) • COHb > 15% in pregnant woman • Ideally within 6 hours of exposure

  36. Cyanide • Salts used in: • Electroplating • Mining extraction • Photography • Jewelry • Nitroprusside • Amygdalins Jim Jones, The People’s Temple

  37. Cyanide • Similar mechanism as CO • Mitochondrial toxin • Acute exposure • Rapid onset • Lactic acidosis • Vomiting, seizures, coma

  38. Cyanide • Salts • Alkaline liquid • Gas • War • Combustion Zyklon B, WWII Auschwitz

  39. Cyanide Antidote Kit

  40. Cyanide Antidote Kit Hemoglobin Nitrites Methemoglobin Cyt a-a3 Mitochondria Cyanide Cyanomethemoglobin Sodium Thiosulfate Sodium Thiocyanate Rhodanese

  41. Treatment: Cyanide Antidote Kit • Known or suspected cyanide poisoning • Metabolic acidosis • End organ damage

  42. Nitrites for CN Caution Caution if diagnosis is uncertain or if COHb is also suspected. Can omit nitrites if uncertain exposure.

  43. Hydroxocobalamin for CN

  44. Hydroxocobalamin Kit • Sodium Thiosulfate 8 gm IV • Hydroxocobalamin 4 gm IV • Under investigation • Anaphylactoid reaction • May interfere with some lab assays

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