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 O 2 Non-irritating No direct mitochondrial toxicity

4. Simple Asphyxiants Methane Carbon dioxide (CO 2 ) 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

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

12. Methyl Isocyanate

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

15. 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

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

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

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

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

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

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

23. 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 HC Aspiration: Management

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

25. MITOCHONDRIAL TOXINS

26. Mitochondrial Toxins Carbon monoxide Cyanide Hydrogen sulfide

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

28. Toxicity CO Displacement O 2 –Alveoli –Hemoglobin binding sites (OCC) Impaired O 2 –Delivery –Utilization 100 Normal % Saturation Tissue pO 2 [mmHg] 20406080100 50% Anemia 50% COHb 75 50 25 0

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

31. CO Toxicity: Delayed Events Delayed neurological/ neuropsychiatric sequelae 2-40 days post-exposure Risks –Age –Loss of consciousness Signs and Symptoms Dementia Amnesia Confabulation Memory impairment Ataxia Chorea Cortical blindness Incontinence Paralysis Hypokinesia Parkinsonism Tremor

32. CO + HbCOHb (1. displaces O 2 from Hb 2. shifts O 2 dissociation curve) BloodMuscle CO + MbCOMb Mitochondria CO + cytochrome oxidase Inhibits electron transport (inhibits O 2 delivery to myocyte)  ATP and O 2 utilization O 2 - and H 2 O 2 generation  BP and  CBF N 2 + O 2 2NO NOS Vasodilation (endothelium, platelets) Platelets CO binds to heme-containing platelet proteins CO-Platelets NO Affects  2 -integrins Xanthine dehydrogenase Xanthine oxidaseFree radicals Lipid peroxidation Proteases ONOO - NMDA activation PMNs adhere to vascular endothelium PMNS (inhibitors: tungsten, allopurinol)  cGMP

33. 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

34. 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

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

36. COHb levels (%)Symptoms 1-2Normal 5-10Smokers 10-20“Flu-like” symptoms 30-40Fatigue; Severe headache 40-50Confusion; loss of consciousness 60-70Coma Seizures CV collapse Death >70Rapidly fatal

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

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

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

41. 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

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

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

44. Cyanide Salts Alkaline liquid Gas –War –Combustion Zyklon B, WWII Auschwitz

45. Cyanide Antidote Kit

46. Cyanide Methemoglobin Cyanomethemoglobin Sodium Thiosulfate Cyt a-a 3 Mitochondria Sodium Thiocyanate Hemoglobin Nitrites Rhodanese

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

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

49. Hydroxocobalamin for CN

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

51. Hydrogen Sulfide