（体外膜肺ECMO课件）-Inhalational-Poisoning.ppt

1、Inhalational PoisoningRama B.Rao,MDBellevue Hospital Center/NYU Medical CenterNew York City Poison Control CenterClasses Simple asphyxiants Pulmonary irritants Particulates Mitochondrial toxinsSimple Asphyxiants Alveolar displacement O2 Non-irritating No direct mitochondrial toxicitySimple Asphyxian

2、ts Methane Carbon dioxide(CO2)Helium Nitrogen Nitrous oxideLake Nyos:Carbon DioxideNitrogenNitrous OxideSimple Asphyxiants:Symptoms Loss of consciousness Minimal warning Non-irritating Sustained exposure Hypoxia Cardiovascular collapseSimple Asphyxiants:Treatment Safe rescue 100%oxygen Evaluation fo

3、r other injuries Supportive carePulmonary Irritants Can behave in part like simple asphyxiants Mucosal irritation Acid or base formation Some free radical formationMethyl IsocyanatePulmonary Irritants:Water Solubility Highly water soluble:Ammonia Sulfur dioxide Hydrogen chloride Chloramine Rapid ons

4、etTime of Symptom Onset(hours)Water SolubilityWater Solubility vs Symptom Onset*AmmoniaPhosgene*Dependent on gas concentrationPulmonary Irritants:Intermediate Solubility Chlorine Exposure better tolerated initially Increased duration exposure Subsequent acid formation in upper and lower airways Dela

5、yed effects Acute lung injuryPulmonary Irritants:Low Solubility Include Phosgene Nitrogen dioxide Prolonged exposure Delayed Pulmonary edema Acute lung injuryPulmonary Irritants:Treatment Removal from exposure Oxygen Nebulized bronchodilators For acid forming agents:Nebulized sodium bicarbonate 1 pa

6、rt NaHCO3 to 3 parts saline or water Primarily for symptomatic reliefPulmonary Irritants:Treatment Supportive care Admission:Severely symptomatic patients Low and intermediate solubility exposures Arrange follow-upParticulates and Aspirants Gas exchange impaired Supportive therapy Intubation ECMO Br

7、onchoaveolar lavage Can be fatal in childrenHydrocarbon Aspiration Surfactant disruption Higher severity:Agents Low viscosity Surface tension High volatility 30 mL exposuresHydrocarbon Aspiration:Symptoms/Signs Cough Choking Dyspnea Rales Hypoxia May progress to ALI Assess for evidence of aspiration

8、 Clinical Radiographic For asymptomatic patients without clinical evidence of aspiration Observe 6 hours Radiograph at 6 hours Admit if signs or symptoms aspirationHC Aspiration:ManagementWare LB,N Engl J Med.2000;342(18):1334-49.NADHNAD+NADHNAD+FADH2FADHNADHNAD+Acetyl-CoACoA-SHKrebsCycle(mitochondr

9、ial matrix)QCyto CNAD+NADHH2OO2Electron Transport Chain(inner mitochondrial membrane)ATPIIIIIVGlucosePyruvateGlycolysis(cytosol)Pyruvate dehydrogenasecomplexLactateNAD+NADHNADHNAD+Cori CycleATPADP+Inhibited byCO,CN,H2SImpaired byhypoxemia NADHNAD+NADHNAD+FADH2FADHNADHNAD+Acetyl-CoACoA-SHKrebsCycle(m

10、itochondrial matrix)QCyto CNAD+NADHH2OO2Electron Transport Chain(inner mitochondrial membrane)ATPIIIIIVGlucosePyruvateGlycolysis(cytosol)Pyruvate dehydrogenasecomplexLactateNAD+NADHNADHNAD+Cori CycleATPADP+Inhibited byCO,CN,H2SImpaired byhypoxemia MITOCHONDRIAL TOXINSMitochondrial Toxins Carbon mono

11、xide Cyanide Hydrogen sulfideCarbon Monoxide Incomplete combustion Fires Vehicular exhaust Methylene chloride Leading cause of poisoning deaths in the U.SToxicity CO Displacement O2 Alveoli Hemoglobin binding sites(OCC)Impaired O2 Delivery Utilization100Normal%SaturationTissue pO2 mmHg2040608010050%

12、Anemia50%COHb7550250NADHNAD+NADHNAD+FADH2FADHNADHNAD+Acetyl-CoACoA-SHKrebsCycle(mitochondrial matrix)QCyto CNAD+NADHH2OO2Electron Transport Chain(inner mitochondrial membrane)ATPIIIIIVGlucosePyruvateGlycolysis(cytosol)Pyruvate dehydrogenasecomplexLactateNAD+NADHNADHNAD+Cori CycleATPADP+Inhibited byC

13、O,CN,H2SImpaired byhypoxemia NADHNAD+NADHNAD+FADH2FADHNADHNAD+Acetyl-CoACoA-SHKrebsCycle(mitochondrial matrix)QCyto CNAD+NADHH2OO2Electron Transport Chain(inner mitochondrial membrane)ATPIIIIIVGlucosePyruvateGlycolysis(cytosol)Pyruvate dehydrogenasecomplexLactateNAD+NADHNADHNAD+Cori CycleATPADP+Inhi

14、bited byCO,CN,H2SImpaired byhypoxemia CO Poisoning:Acute Signs and Symptoms Headache Myalgias Dyspnea Nausea,Vomiting Loss of Consciousness Chest pain HypotensionCO Toxicity:Delayed Events Delayed neurological/neuropsychiatric sequelae 2-40 days post-exposure Risks Age Loss of consciousnessSigns and

15、 SymptomsDementiaAmnesiaConfabulationMemory impairmentAtaxiaChorea Cortical blindnessIncontinenceParalysisHypokinesia ParkinsonismTremorCO+Hb COHb (1.displaces O2 from Hb 2.shifts O2 dissociation curve)BloodMuscleCO+Mb COMbMitochondriaCO+cytochrome oxidaseInhibits electron transport(inhibits O2 deli

16、very to myocyte)ATP and O2 utilizationO2-and H2O2 generationBP and CBFN2+O2 2NONOSVasodilation(endothelium,platelets)PlateletsCO binds to heme-containingplatelet proteinsCO-PlateletsNOAffects b2-integrinsXanthine dehydrogenase Xanthine oxidaseFree radicalsLipid peroxidationProteasesONOO-NMDAactivati

17、onPMNs adhere to vascular endotheliumPMNS(inhibitors:tungsten,allopurinol)cGMPPhysiology: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 Peroxi

18、dation Impaired e transport Functional HypoxiaCarbon 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 exami

19、nationCarbon Monoxide Levels Venous sampling 10%abnormal Levels correlate poorly with severity of exposurreCOHb levels(%)Symptoms1-2Normal 5-10Smokers 10-20“Flu-like”symptoms30-40Fatigue;Severe headache40-50Confusion;loss of consciousness60-70Coma SeizuresCV collapseDeath70Rapidly fatalHyperbaric Ox

20、ygen Decrease COHb half life Displaces CO from tissues Improves oxygen carrying capacity Limits lipid peroxidation Improves dissolved oxygenHyperbaric Oxygen Variable outcomes in literature 2:Definition of DNS Timing and duration of therapy Co-exposures Inability to define equivalent exposures Patie

21、nt variability Hyperbaric OxygenWeaver LK,et al:Hyperbaric oxygen for acute carbon monoxide poisoning.N Engl J Med 2002;347:1057-67Hyperbaric Oxygen:Indications Neurological damage Cardiovascular events Loss of Consciousness Persistent symptoms COHb 25%(some centers use 40%)COHb 15%in pregnant woman

22、 Ideally within 6 hours of exposureCyanide Salts used in:Electroplating Mining extraction Photography Jewelry Nitroprusside Amygdalins Jim Jones,The Peoples TempleCyanide Similar mechanism as CO Mitochondrial toxin Acute exposure Rapid onset Lactic acidosis Vomiting,seizures,comaCyanide Salts Alkali

23、ne liquid Gas War CombustionZyklon B,WWII AuschwitzCyanide Antidote KitCyanide Antidote KitCyanideMethemoglobinCyanomethemoglobinSodium ThiosulfateCyt a-a3MitochondriaSodiumThiocyanateHemoglobinNitritesRhodaneseTreatment:Cyanide Antidote Kit Known or suspected cyanide poisoning Metabolic acidosis En

24、d organ damageNitrites for CNHemoglobinMethemoglobinAmyl nitrite,sodium nitriteCyanomethemoglobinCytochrome-CNCytochromeSodium thiosulfateSodium thiocyanateRhodaneseCNHemoglobinMethemoglobinAmyl nitrite,sodium nitriteCyanomethemoglobinCytochrome-CNCytochromeSodium thiosulfateSodium thiocyanateRhodan

25、eseCNCaution if diagnosis is uncertain or if COHb is also suspected.Can omit nitrites if uncertain exposure.CautionHydroxocobalamin for CNHydroxocobalamin Kit Sodium Thiosulfate 8 gm IV Hydroxocobalamin 4 gm IV Under investigation Anaphylactoid reaction May interfere with some lab assaysHydrogen Sulfide