Inhalation Poisoning

ASPHYXIANTS

INHALATION POISONING

• Inhalation is a major route for both acute and chronic poisonings especially in occupational toxicities.

• Inhalation is a route of poisoning with hazardous poisons

• Absorption through inhalation is very rapid

• Large surface area

• High vascularity

4

ClassificationAccording to

Biological Effects

Asphyxiant gases

Simple asphyxiants

(CO2,methane,ethane,buthane,nitrogen

gases)

Chemical asphyxiants

(CO, CN)

Irritant gasesChlorine, phosgene,

nitrogen compounds

Systematic gasesalcohols &

carbon tetrachloride

Narcotic gasesToluene, benzene

GASES

•Asphyxiants are gases that deprive body tissues of oxygen causing hypoxia

HYPOXIA• Hypoxic Hypoxia (Anoxic Anoxia)

• Anemic Hypoxia

• Cytotoxic Hypoxia (Histotoxic Hypoxia)

• Stagnant Hypoxia

TYPES OF ASPHYXIANTS

1) Simple Asphyxiants

2) Chemical Asphyxiants

SIMPLE ASPHYXIANTS• Displace Oxygen thereby causing

suffocation

• Alveolar displacement O2

• Non-irritating

• No direct mitochondrial toxicity

• CO2

• Nitrogen

• Helium

• Methane

CHEMICAL ASPHYXIANTS

• Interfere with the cellular transit of oxygen

• They react in the human body to interrupt either the delivery or utilization of oxygen

• CO

• Cyanide

CO2

CARBON DIOXIDE

• Carbon dioxide is a colorless, odorless, non-flammable gas at room temperature and is required for plant and animal life.

• Carbon dioxide is produced naturally in the body and during the burning of fossil fuels.

• Carbon dioxide can exist as a liquid or solid depending on the temperature and pressure. Its solid form is called dry ice.

• CO2is present in the atmosphere at 0.035%

SYMPTOMS OF CO2 TOXICITY

CO% Symptoms

2-3 Shortness of breath – Deep breathing

5 Breathing becomes heavy, sweating, pulse quickens

7.5 Headaches, dizziness, restlessness, breathlessness, increased heart rate and blood pressure, visual distortion

10 Impaired hearing, nausea, vomiting, loss of consciousness

15 May be lethal

25 Coma, convulsions, death

TREATMENT

• Removal from site of exposure

• Oxygen therapy

CHEMICAL ASPHYXIANTS

•React in the human body to interrupt either the delivery or utilization of oxygen.

CARBON MONOXIDECO

• Carbon monoxide is a colorless odorless non irritating gas. Its density (0.968 relative to air), allows it to disperse homogeneously within a room as it is released.

Sources

1. Endogenous:

• Normally the body produces small amount of CO during catabolism of protoporphyrin ring of Hb.

• COHb normally dose not exceed 5%.

2. Exogenous:

• Incomplete combustion of carbonaceous materials.

• The major source is motor vehicle exhaust.

• At home, oil and gas heaters, kerosene heaters, charcoal grills all emit CO.

• Tobacco cigarette smoking.

• Fires.

Factors Affecting CO Toxicity:

• Physical factors: CO is tasteless, odorless, colorless and non-irritating so not noticed.

• Duration of exposure.

• Concentration of the gas in the inspired air.

• Muscular activity of the person.

• Decreased PO2 as in high altitude.

• Individuals with cardiovascular or pulmonary diseases tolerate CO intoxication poorly.

• Lowered Hb% as in anemia.

• Neonates and fetus are more liable to CO toxicity because fetal Hb has increased affinity to CO. In addition, fetal elimination of CO is much slower than that of the mother.

Pathophysiology

1- CO has affinity to Hb (200-250 times) greater than O2.

2- CO causes leftward shift of the oxyHb dissociation curve: decrease release of O2 from Hb to tissues.

3- Myoglobin impairment:affinity to CO is 40 times greater than that to O2.

In the heart, carboxymyoglobin causes direct myocardial depression and arrhythmias.

4- Mitochondrial impairment: CO interferes with cellular respiration at the mitochondrial level

Clinical Manifestations

(A) CNS: is most sensitive to CO poisoning

1- Acutely: headache, dizziness and ataxia and slow thinking.

2- Longer exposure: syncope, seizures and coma may occur.

3- Patients may present with symptoms of an acute cerebrovascular accident (CVA).

4- Recurrent symptoms syndrome: Occur in 10-20% of patients with moderate CO toxicity:

Patient may have lucid interval of 1-40 days followed by recurrence of symptoms as headache dizziness, irritability, confusion, disorientation, and memory problems. Patients usually recover over 1-2 months.

Delayed neuropsychiatric sequelae: a severe form of secondary deterioration characterized by appearance of signs of neurologic or psychiatric impairment occur in up to 95% of patients having loss of consciousness in the acute phase of exposure.

Hyperbaric O2 therapy may prevent these sequelae.

(B) Cardiovascular System:

1- Palpitation and chest pain

2- Patchy myocardial infarction with ECG changes of ischemia.

3- Tachycardia is common. Bradycardia occurs in severe cases due to myocardial or CNS hypoxia.

4- Atrial and ventricular arrhythmias.

5- Hypotension.

C. Other Systems:

SKIN

• Cherry red skin is rarely seen

• pallor or cyanosis are more frequent.

• Blisters resembling 2nd degree burn may be seen in severe CO poisoning. These bullae are thought to be due to pressure necrosis and direct effects of CO on the epidermis.

Eye: Blurring of vision, decreased dark adaptation

In severe cases frank blindness due to central effect

Retina: Bright red retinal veins is an early sensitive sign.

Respiratory:

Noncardiogenic pulmonary edema due to fluid shift through alveolar-epithelial junction caused by direct effect of CO on the capillaries.

Cardiogenic pulmonary edema due to myocardial depression.

4. Renal: Oliguric and non oliguric renal failure.

5. Blood: - Disseminated intravascular coagulation (DIC).

6. Metabolic: - Lactic acidosis, hyperglycemia and hypercalcaemia.

7. Muscles: Rhabdomyolysis.

8. GIT: Nausea, vomiting, abdominal pain

Diarrhea (may be misdiagnosed as gastroenteritis or food poisoning specially in children or in a group of patients.

Investigations

1. Carboxy hemoglobin (COHB) level; most helpful diagnostic test

• COHb level is 0-5% in normal individuals.

• Smokers may have COHb levels up to 10%.

• No difference between arterial and venous COHb.

• Measured by cooximeter which spectrophotometrically measures the percentage of total hemoglobin saturated with CO.

2. Arterial blood gases:

PO2 may be normal

O2 saturation is accurate if directly measured and not calculated from PO2.

Pulse oximeter shows falsely elevated O2 saturation.

Metabolic acidosis if present is usually due to lactic acidosis which is a bad prognostic sign.

Management

1- Rapid removal from continued exposure.

2- Secure airway patency.

3- 100% O2 should be provided immediately . 100% O2 shortens CO t 1/2 and increases O2 delivered to tissue in physical solution.

4- Cardiac monitoring and IV access are necessary with rapid treatment of any arrhythmias.

5- Blood samples for COHb level and other lab tests.

6- Rapid assessment of vital signs and treatment of any abnormality.

7- Hypotension improves with fluids but inotropics may be needed for myocardial depression.

8- Do not aggressively treat acidosis with pH above 7.15 as this can increase tissue hypoxia by left shift of oxyhemoglobin dissociation curve.

9- Serial neurologic examination including funduscopy.

10- CT scan and possibly MRI to be done as indicated

TREATMENT1- Rapid removal from continued exposure.

2- Secure airway patency. Rapid assessment of vital signs and treatment of any abnormality.

pulse oximetry is inadequate Oxygen saturation may appear artificially high

3- 100% O2 should be provided immediately . 100% O2 shortens CO t 1/2 and increases O2 delivered to tissue in physical solution.

4-Blood samples for COHb level and other lab tests.

5- Do not aggressively treat acidosis with pH above 7.15 as this can increase tissue hypoxia by left shift of oxyhemoglobin dissociation curve.

6- Serial neurologic examination including funduscopy. CT scan and possibly MRI to be done as indicated

HYPERBARIC OXYGEN

• Decrease COHb half life

• Displaces CO from tissues

• Improves oxygen carrying capacity

• Limits lipid peroxidation

• Improves dissolved oxygen

HYPERBARIC OXYGEN: INDICATIONS

• Neurological damage

• Cardiovascular events

• Loss of Consciousness

• Persistent symptoms

• COHb > 25% ( some centers use >40%)

• COHb > 15% in pregnant woman

• Ideally within 6 hours of exposure

POSTMORTEM APPEARANCE • Cherry red appearance, especially in the areas

of postmortem lividity. In dark people the color can be made out in lips, nail beds, tongue, palms and soles.

• Skin blisters are seen sometimes in calves, buttocks, wrists, and knees.

• Cherry pink color of blood and tissues

• Pulmonary edema

• In delayed deaths; necrosis and cavitation of basal ganglia, especially globus pallidus.

CYANIDE TOXICITY

• Cyanide is one of the most rapidly acting lethal poisons

• A rare source of poisoning.

SOURCES• Salts used in:

• Electroplating

• Mining extraction

• Photography

• Jewelry

• Nitroprusside (iatrogenic)

• Amygdalins: converted into cyanide in the small intestine by bacteria.

• Fires

MECHANISM OF TOXICITY

• It has affinity for ferric iron & is capable of binding to all enzymes and proteins containing iron: Hb, myoglobin, catalase, & cytochrome system

• Its most significant interaction is its binding to ferric iron of the mitochondrial cytochrome oxidase system

• The most sensitive organ systems to cyanide toxicity are CNS and the myocardium.

CLINICAL MANIFESTATIONS

1- Weakness, loss of energy, and pain throughout the body.

2- CNS: headache, dizziness, weakness, confusion

3- Cardiac: Chest pain may be due to myocardial ischemia or pulmonary disease.

Tachyarrhythmias

Bradyarrhythmias have been reported.

5- Respiratory: difficulty breathing.

6- GI: Nausea and vomiting may be due to stimulation of the Vomiting center & direct irritation on GIT

7- Skin & Fundoscopy: cherry red appearance due to increased Hb saturation in venous blood because of inability to utilize O2.

TREATMENT

• Decontamination by removal of the patient from the source, removal of all clothes, and rapid irrigation of the body with copious amounts.

• Adequate intravenous access

CYANIDE ANTIDOTE KIT

Cyanide Antidote Kit

Cyanide

Methemoglobin

Cyanomethemoglobin

Sodium Thiosulfate

Cyt a-a3

Mitochondria

SodiumThiocyanate

Hemoglobin

Nitrites

Rhodanese

TREATMENT: CYANIDE ANTIDOTE KIT

• Known or suspected cyanide poisoning

• Metabolic acidosis

• End organ damage

NITRITES FOR CN

Hemoglobin

Methemoglobin

Amyl nitrite, sodium nitrite

Cyanomethemoglobin

Cytochrome-CN

Cytochrome Sodium thiosulfate

Sodium thiocyanate

Rhodanese

CN

Hemoglobin

Methemoglobin

Amyl nitrite, sodium nitrite

Cyanomethemoglobin

Cytochrome-CN

Cytochrome Sodium thiosulfate

Sodium thiocyanate

Rhodanese

CN

Caution if diagnosis is uncertain or if COHb is also suspected.Can omit nitrites if uncertain exposure.

Caution

HYDROXOCOBALAMIN KIT (CYANOKIT)

• Hydroxocobalamin contains cobalt ion, which is able to bind to cyanide with greater affinity than cytochrome oxidase to form cyanocobalamin (nontoxic), which is excreted in urine.

• Hydroxocobalamin:

• has few adverse effects

• tolerated by critically ill patients

• tolerated by patients with concomitant CO poisoning

• In France, it commonly is used in combination with sodium thiosulfate. Low-dose hydroxocobalamin in combination with sodium thiosulfate has been used successfully to prevent cyanide toxicity due to prolonged sodium nitroprusside infusions.

HYDROXOCOBALAMIN FOR CN

POSTMORTEM APPEARANCE• External

• Odor of bitter almonds

• Brick red color of skin and mucous membranes

• Cyanosis of extremities

• Froth at mouth and nostrils

• Internal

• Hemorrhagic gastritis. Stomach wall may be hardened

• Pulmonary and cerebral edema

• Disseminated petechiae in brain, meninges, pleura, lungs, and pericardium