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Tox lecture 4

Fire Immediate Effects (4) Mucosal Irritation (acids, soot) Oxygen consumption » Hypoxia Heat Stress Smoke density - limits visibility Chemical asphyxiants (CO.CN.metHgB)
Smoke Inhalation Combustion toxicology (7) Carbon monoxide Cyanide - Hydrochloric acid - Phosgene - Acrolein - Nitrogen oxides - 80 % of fire related deaths are due to smoke inhalation
Carbon monoxide - burning wood (Carbon)
Cyanide - burning plastics, rubber, wool, silk (Nitrogen)
Hydrochloric acid - burning chloride cmpds, thick smoke
Phosgene - thermal degradation of PVC.delayed injury
Acrolein - toxic aldehyde, deep lung/tissue penetration
Nitrogen oxides - potential metHgB inducer
Smoke Inhalation Signs Soot in airway Carbonaceous Sputum Hoarseness Altered LOC
CO Epidemiology Leading case of death by poisoning in US
What are the Sources of CO Incomplete Combustion Exhaust fumes: Automobiles -Sleeping in car with engine on -Pick-up truck camper shells Tractors and forklifts indoor Ice resurfacing Machines
Carbon Monoxide Detectors Alarm limits: UL regs Sound at 85 decibels: -70 ppmfor 189 min -150 ppm for 50 min -400 ppm for 15 min -Resets in 6 minutes to realarm once silenced -And it will "ignore" 30 ppm for as long as 30 days & 70 ppm for 1 hour -IDLH = 1200 ppm
Pulse Oximetry Measures saturation of hemoglobin Carboxyhemoglobin is "detected" by sensor as saturated hemoglobin New Product measures CoHgb and MetHgb by pulse ox
New Pulse oximeter Measures by 7 wavelengths: • Oxy Hgb • CO Hgb • MetHgb
Carbon Monoxide: Systemic Asphyxiant Does NOT displace 02 from air Binds to Hgb with 240 times affinity of O2 Changes Oxy-Hgb dissociation curve Decreases O2 release at tissue level Binds to Myoglobin with 40 times affinity of 02 Interferes with cytochrome oxidase a3
Carboxyhemoglobin Carbon monoxide (CO) binds competitively at oxygen (02) binding sites. CO impairs 02 transportation and delivery
CO Toxicology Toxic effects similar to cyanide • Inhibits mitochondrial respiration • Oxygen cannot be utilized to generate ATP • Cells shift to anaerobic metabolism = LACTIC ACIDOSIS
Hyperbaric Oxygen Decreases Half-life of CO-Hgb Increases dissolved 02 in blood 10 fold Accelerates Dissociation of CO from Cytochrome oxidase Prevents lipid peroxidation Prevents leukocyte mediated xanthine dehydrogenase free radical generation
Neurologic testing Baseline neurologic exam and post dive • Statistical monitor Q 50 patients ( anticipated 200 patients to be enrolled) Neuropsychiatry battery at: 2 weeks 6 weeks 6 months 12 months
Interpreting CN Levels Numbers CN 38 umol/L = 1 ug/L Potentially lethal 40 -100 umol/L Likely lethal > 100 umol/L Half-life is 1.2 hours.
Interpreting CN Levels Words And levels decline in blood tube and stored blood. But levels are hard to get, so there is correlation with lactate levels > 10 mmol/L Or decreased pH But also elevated CO in fires
Cyanide Toxicology Absorption Well-absorbed from inhalation and ingestion pathways of exposure Limited warning signs (inhalation) Fallacy of the "bitter almond" smell
Cyanide Toxicology Toxicodynamic effects Toxicodynamic effects similar to sulfide, azide, & phosphine Inhibits mitochondrial respiration Oxygen is present, but cannot be utilized to generate ATP Cells shift to anaerobic metabolism
Cyanide: Effects Initially Initially, non-specific Sense of doom, increased resp. rate
Cyanide: Effects Within minutes: abnormal mental status, depressed cardiac output, bradycardia, sudden collapse, metabolic acidosis
Cyanide Effects: Oxygen and progression Oxygen is present but cannot be utilized Oxygen saturation of arterial, venous blood is similar Rapidly progresses to shock, multi-system organ failure, death
Cyanide antidote kit Three components: 1) Amyl nitrate pearls only until IV access established produces methemoglobinemia (MetHb)of~5%
Cyanide (Lilly) Antidote Kit (CAK) Three Components Nitrites (inhaled = amyl nitrite) IV = sodium Nitrite Induces methemoglobinemia: (decreased oxygen carrying capacity) Redistributes CN- away from mitochondria Sodium thiosulfate -Converts cyanide to thiocyanate
Sodium thiosulfate -Converts cyanide to thiocyanate
Nitrites (inhaled = amyl nitrite)
IV = Sodium Nitrite Induces methemoglobinemia: (decreased oxygen carrying capacity) Redistributes CN- away from mitochondria
Cyanide Antidote Kit Sodium Nitrite ADULTS: 300 mg IV over 5 min. PEDS: 0.33 ml/kg Must reduce dose in anemia in both adults & peds Watch for hypotension !!! Blue skin discoloration Don't use for smoke inhalation
Cyanide Antidote Kit Sodium Thiosulfate ADULTS: 12.5gmslV PEDS: 400 mg/kg IV Should be used alone for smoke inhalation or Nipride toxicity
Problems with Cyanide Kit Less than 25 % of hospital stock it If stocked usually have only one Kit may have passed "expired" date Frequently amyl nitrite pedes missing Instructions missing
Hemoglobin METHEMOGLOBIN: Hemoglobin's (Fe+2) is oxidized to (Fe+3) Oxygen (02) cannot bind to methemoglobin's Fe+3. ^ Water (H20) binds in oxygen's place. Methemoglobin cannot transport 02.
Therapeutic Methemoglobin Production for Cyanide Poisoning Fe Amyl nitrite & sodium nitrite oxidize hemoglobin,'s Fe+2 to produce methhemoglobin's Fe+3, 02 cannot bind to methhemoglobin's, Fe+3 H20 binds in oxygen's place,
Therapeutic Methemoglobin Production for Cyanide Poisoning CN CN preferentially binds to methhemoglobin,'s Fe+3 producing Cyanomethhemoglobin, CN" binds to methhemoglobin, rather than to cytochrome oxidase Cytochrome oxidase activity & aerobic metabolism resume
What about just Sodium Thiosulfate Third component of CAK Does not induce MetHgb Crosses Blood brain barrier Induces enzyme RHODANESE to convert CN into sodium thiocyanate up to 3 times usual rate Thiocyanate is then eliminated by the liver
Sodium Thiosulfate Not well studied alone Few animal models Most human uses are with full CAK or with Hydroxocobalamin Often used alone in suspected smoke inhalation in the US at 12.5 gms IV once
Sodium Thiosulfate Side effects few, occ. Nausea, Vomiting, Pain at injection site
Nithiodote: Two vial version of the classic Cyanide kit (2011) Sodium Nitrite 3 %: 300mg/10mL Do not exceed 5 ml/mi Sodium Thiosulfate: 12.5 grams/50 mL
Human Volunteer Studies HCB Doses 2.5, 5.0, 7.5, 10.0 GMS
Human Volunteer Studies HCB Side Effects Increased BP, in some cases substantial Highest post Rx 188 systolic /125 diastolic Resolved over 4 hours No associated ECG changes in healthy volunteers Red Skin Red Urine
Human Volunteer Studies HCB Red skin 95 % at 5 gm dose 100 % at higher doses Duration 4 to 9 days
Human Volunteer Studies HCB Red urine Duration 7 to 35 days
Hydroxocobalamin Adult - 2.5 grams, repeat once if needed Pediatrics - 50 to 70 mg/kg Packaging 2.5 gm vials Reconstituted in 200 ml saline, give over 30 min.
Hydroxocobalamin - Adverse Effects Increased Blood Pressure Orange or red discoloration of skin, urine and other body fluids Rare allergic reactions Interference with standard laboratory tests - Or, Mg, bilirubin, CPK and LFTs by colorometric tests May overread COHgb
Bottom Line Who do I treat pre-hospital Only Paris Study had specific criteria HOB carries some risks of HTN BEST ADVICE: Persistent altered LOC after removal from fire and administration of 02 Soot in face/airway
Created by: pberriochoa