Toxic Gases from Fermentation
รศ.พญ.สุดา วรรณประสาทภาควิชาเภสัชวิทยา
หนวยเภสัชวิทยาและพิษวิทยาคลินิก ภาควิชาอายุรศาสตรคณะแพทยศาสตร มหาวิทยาลัยขอนแกน
Confined space
HypoxiaSimple asphyxiants
Chemical
Asphyxiants
ชองวางหรือบริเวณปด ที่เกิดการสะสมของกาซพิษ ไอน้าํฝุน หรือภาวะออกซิเจนต่ํา โดยอาจเกิดจากการกอสราง ที่ตั้งหรือสภาพแวดลอมภายในเอง
• Displace oxygen from ambient air
• Reduce fraction of oxygen in air or FIO2
(<21%)
• Have no pharmacological activity
• High concentration of asphyxiants in ambient air
• Working in confine spaces
Simple Asphyxiants
FiO2 (%) Symptoms/signs
16-12 Tachypnea, hyperpnea, (resultant hypocapnia), tachycardia, reduced attention and alertness, euphoria, headache, mild incoordination
14-10 Altered judgment, incoordination, muscular
fatigue, cyanosis
10-6 Nausea, vomiting, lethargy, air hunger, severe incoordination, coma
<6 Gasping respiration, seizure, coma, death
Clinical Findings Associated with Reduction of Inspired Oxygen
Specific agent
• Noble Gases: helium, neon, argon, xenon
• Short-chain aliphatic hydrocarbon gases:
methane, ethane, propane, butane
• Carbon dioxide (CO2)
• Nitrogen (N2) gas
Treatment
• Immediate removal from exposure and ventilatory assistance
• Oxygen supplement
Chemical asphyxants
• Cyanide
• Carbon monoxide
• Hydrogen sulfide
• Nitrogen oxide
Hydrogen sulfide
Decaying organic matter
Sulfur containing proteins
Fish
Sewage
Manure
Hot, humid weather→ ↑microbial metabolism and gas production
Rubber vulcanization
Synthetic fabric & paper production
Leather tanning
potent inhibition of cytochrome oxidase
binds to ferric (Fe3+) moiety of
cytochrome a3 oxidase complex
higher affinity than cyanide
inhibition of oxidative phosphorylation
produces cellular hypoxia and anaerobic
metabolism
Mechanism of action
Hydrogen sulfide, cyanide, carbon monoxide
Mechanism of action
Hydrogen sulfide
Colorless gas
More dense than air
Irritating gas→ “rotten eggs” (low)
Olfactory nerve fatigue and paralysis (high)
Effect Concentration (ppm)
Detectable odor 0.2
Eye and respiratory irritation 50
Olfactory nerve paralysis 150
Exposure may cause pulmonary edema 250
Systemic symptom occur in ½ hr 500Quickly unconscious; death without rescue 750Rapid collapse; respiratory paralysis 1,000
Immediate date 5,000
Effects of hydrogen sulfide gas on humans
Fuller DC.JOEM 2000;939
When to suspect hydrogen sulfide poisoning
Person rapidly loses consciousness knocked downRotten eggs odorRescue from enclosed space, such as sewer or manure pitMultiple victims with sudden death syndromeCollapse of a previously healthy worker at work site
Management
1. Supportive carePrehospital- Attempt rescue only if using SCBA- Move victim to fresh air- Administer 100% oxygen- During extrication, consider traumatic
injuries from falls- Apply ACLS protocols as indicated
Emergency department
- Maximize ventilation and oxygenation
- Consider PEEP for ALI
- Treat acidosis based on arterial pH
and serum bicarbonate analysis
- Administer crystalloid and vasopressors for hypotension
cytc2+ cytc3+
cyta3+ cyta2+
cyta32+ cyta3
3+
1/2O2+2H+ H2O
OxyHb
MetHb
SulMetHb
Sodium nitrite
H2S
OxyHb+SOX
Sodium nitrite
Sodium thiosulfate
OxyHb
MetHb
CyanoMetHb
Thiocyanate
Rhonanese
CN
2. Antidote- Sodium nitrite (3%NaNO2) IV over 2-4 min 10 mL (300 mg)
Caution:HypotensionMethmoglobinemia
- Hyperbaric oxygen
• Nitrogen oxides→ Oxidized nitrogenous compounds
• Irritant gas
• Low water solubility
• Heavier than air → collect just above silage
Nitrogen dioxide
NO Nitric oxideNO2 Nitrogen dioxideN2O Nitrous oxideN2O2 Nitrogen Peroxide
N2O3 Dinitrogen trioxideN2O4 Dinitrogen tetroxide
N2O5 Dinitrogen Pentoxide
Nitrogen Oxides
Crops
Silo
Fermentation
CO2, nitrogen oxide
NO, NO2, N2O4
Silo Filler’s disease
NO2Low water solubility
No symptom in upper airway
Irritant effect in bronchi, terminal bronchioles and alveoli
Pathophysiology
NO2
Free radical
Protein oxidationLipid peroxidation
Cell membrane damage
NO, HNO3, HNO2 Distal airway
Direct toxic effect
Type1 pneumocytes
ciliated airway cells
Delay onset ofchemical pneumonitis
Clinical manifestration
• Depend on intensity and duration of exposure
• Lost of consciousness, Sudden death →Hypoxia
• Delay respiratory symptoms
Acute Phase
• No upper respiratory irritation (low level)
• Upper respiratory symptom (high level)
• Methemoglobinemia
• CXR normal → do not rule out ALI
Delayed Phase
• Symptom free interval 3-24 hr follows acute phase
• Then develop chemical pneumonitis
or ALI
• Dyspnea, tachycardia, hemoptysis, bronchospasm, rales and hypoxia
• CXR: perihilar infilatration
progress to ALI
Subacute Phase• Develop brochiolitis obliterans
• 2-4 wk after delay phase
• Acutely ill with fever and chills, cough, dyspnea, rales, wheezing, hypoxia
• CXR: ALI, multiple discrete nodule (miliary pattern)
• Pulmonary function test: obstructive and restrictive defects
Gurney JW. RidoGraphics 1991;625
Management• Prehospital care
- removal from source of exposure- supplement oxygen
• Emergency department care- supportive therapy to correct hypoxia, ventilatory failure, secondary infection- High dose steroid suggested in treatment of pulmonary manifestation- Methylene bule
Clinical feature and Management of H2S&NO2H2S
(manure pit)NO2
(silo)Property Rotten egg
irritantLow water soluble
Mechanism Inhibit cytochromeoxidase
Direct toxic alveolar cell, free radical
Signs & symptoms
Mucous membrane irritationRespiratory irritationCellular hypoxia
Laryngospasm, brochospasm, ARDSRespiratory arrest
Management Extrication/resuscitation/supportiveSodium nitrite
Bronchodilator, steroids
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