Tox lecture 4
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| Fire Immediate Effects (4) | Mucosal Irritation (acids, soot)
Oxygen consumption » Hypoxia
Heat Stress
Smoke density - limits visibility
Chemical asphyxiants (CO.CN.metHgB)
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| Smoke Inhalation Combustion toxicology (7) | Carbon monoxide
Cyanide -
Hydrochloric acid -
Phosgene -
Acrolein -
Nitrogen oxides -
80 % of fire related deaths are due to smoke inhalation
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| Carbon monoxide | - burning wood (Carbon)
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| Cyanide - | burning plastics, rubber, wool, silk (Nitrogen)
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| Hydrochloric acid - | burning chloride cmpds, thick smoke
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| Phosgene - | thermal degradation of PVC.delayed injury
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| Acrolein - | toxic aldehyde, deep lung/tissue penetration
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| Nitrogen oxides - | potential metHgB inducer
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| Smoke Inhalation Signs | Soot in airway
Carbonaceous
Sputum
Hoarseness
Altered LOC
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| CO Epidemiology | Leading case of death by poisoning in US
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| 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
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| 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
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| Pulse Oximetry | Measures saturation of hemoglobin
Carboxyhemoglobin is "detected" by sensor as saturated hemoglobin
New Product measures CoHgb and MetHgb by pulse ox
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| New Pulse oximeter | Measures by 7 wavelengths:
• Oxy Hgb
• CO Hgb
• MetHgb
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| 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
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| Carboxyhemoglobin | Carbon monoxide (CO) binds competitively at oxygen (02) binding sites.
CO impairs 02 transportation and delivery
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| CO Toxicology | Toxic effects similar to cyanide
• Inhibits mitochondrial respiration
• Oxygen cannot be utilized to generate ATP
• Cells shift to anaerobic metabolism = LACTIC ACIDOSIS
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| 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
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| 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
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| 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.
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| 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
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| Cyanide Toxicology Absorption | Well-absorbed from inhalation and ingestion pathways of exposure
Limited warning signs (inhalation)
Fallacy of the "bitter almond" smell
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| 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
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| Cyanide: Effects Initially | Initially, non-specific
Sense of doom,
increased resp. rate
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| Cyanide: Effects Within minutes: |
abnormal mental status,
depressed cardiac output,
bradycardia, sudden collapse,
metabolic acidosis
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| 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
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| Cyanide antidote kit | Three components: 1) Amyl nitrate pearls
only until IV access established
produces methemoglobinemia
(MetHb)of~5%
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| 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
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| Sodium thiosulfate | -Converts cyanide to thiocyanate
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| Nitrites | (inhaled = amyl nitrite)
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| IV = | Sodium Nitrite
Induces methemoglobinemia: (decreased oxygen carrying capacity)
Redistributes CN- away from mitochondria
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| 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
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| Cyanide Antidote Kit Sodium Thiosulfate | ADULTS: 12.5gmslV
PEDS: 400 mg/kg IV
Should be used alone for smoke inhalation or Nipride toxicity
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| 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
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| 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.
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| 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,
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| 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
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| 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
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| 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
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| Sodium Thiosulfate Side effects | few, occ.
Nausea,
Vomiting,
Pain at injection site
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| 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
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| Human Volunteer Studies HCB Doses | 2.5,
5.0,
7.5,
10.0 GMS
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| 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
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| Human Volunteer Studies HCB Red skin | 95 % at 5 gm dose
100 % at higher doses
Duration 4 to 9 days
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| Human Volunteer Studies HCB Red urine | Duration 7 to 35 days
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| 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.
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| 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
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| 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
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