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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