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(BQ) Part 2 book Pillay modern medical toxicology has contents: Asphyxiant poisons, hydrocarbons and pesticides, miscellaneous drugs and poisons, substance abuse, food poisons, substance abuse, analytical toxicology.
Section Asphyxiant Poisons 26 Toxic gases may be classified as follows: Simple Asphyxiants—These gases displace oxygen from the ambient air and reduce the partial pressure of available oxygen Examples include carbon dioxide, nitrogen, aliphatic hydrocarbon gases (butane, ethane, methane, and propane), and noble gases (argon, helium, neon, radon, and xenon) Respiratory Irritants—These gases damage the respiratory tract by destroying the integrity of the mucosal barrier Examples include acrolein, ammonia, chloramine, chlorine, formaldehyde, hydrogen sulfide, methyl bromide, methyl isocyanate, oxides of nitrogen, osmium tetroxide, ozone, phosgene, and sulfur dioxide Heavy metal-related gases also come under this category (cadmium fumes, copper fumes, mercury vapour, zinc chloride and zinc oxide) Systemic Asphyxiants—These gases produce significant systemic toxicity by specialised mechanisms Examples include carbon monoxide, cyanide, and smoke It must be noted that systemic toxicity may also be observed in the case of some simple asphyxiants and respiratory irritants, though it is not the predominant feature Discussion of toxicity of the examples mentioned under the various categories now follows, while pointing out that some of them have been discussed elsewhere (consult Index) SIMPLE ASPHYXIANTS Carbon Dioxide (CO2) Physical Appearance Colourless, odourless, non-flammable gas which is heavier than air In its solid form (dry ice) it is whitish in colour and acts as a corrosive Uses Fire extinguisher Carbonation of soft drinks Shielding gas during welding processes Synthesis of urea, for dry ice, and organic synthesis Toxic Gases Clinical Features Four stages have been described, depending on the arterial oxygen saturation: YY Indifferent Stage: –– %O2 Saturation: 90% –– Night vision: decreased YY Compensatory Stage: –– %O2 Saturation: 82 to 90% –– Respiratory rate: compensatory increase –– Pulse: compensatory increase –– Night vision: decreased further –– Performance ability: somewhat reduced –– Alertness: somewhat reduced –– Symptoms may begin in those with significant pre-existing cardiac, pulmonary, or haematologic diseases YY Disturbance Stage: –– %O2 Saturation: 64 to 82% –– Compensatory mechanisms become inadequate –– Air hunger –– Fatigue –– Tunnel vision –– Dizziness –– Headache –– Belligerence –– Euphoria –– Visual acuity: reduced –– Numbness and tingling of extremities –– Hyperventilation –– Poor judgement –– Memory loss –– Cyanosis –– Decreased ability for escape from toxic environment YY Critical Stage: –– %O2 Saturation: 60 to 70% or less –– Deterioration in judgement and co-ordination may occur in to minutes or less –– Total incapacitation and unconsciousness follow rapidly 350 Unconsciousness leading to death will occur when the atmospheric oxygen concentration is reduced to to 8% or less Concentrations up to 35% CO2 have an exciting effect upon both circulation and respiration Concentrations above 35% have a depressing effect upon both circulation and respiration Bradycardia progressing to asystole may occur in the absence of signs of cyanosis following inhalation exposure to 99.97% carbon dioxide Investigators suggest hypercapnia and acidosis may contribute to the cause of cardiac arrest Dermal exposure to solid carbon dioxide (“dry ice”) may cause frostbite injury Severe tissue burns have been reported Section 7 Asphyxiant Poisons Diagnosis Arterial blood gases are useful to assess the degree of hypoxaemia Treatment Move patient from the toxic environment to fresh air Monitor for respiratory distress If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis Administer 100% humidified supplemental oxygen, perform endotracheal intubation, and provide assisted ventilation as required If hypoxia has been severe or prolonged, carefully evaluate for neurologic sequelae and provide supportive treatment as indicated Treatment of frostbite: a Freeze injury associated with dermal exposure to “dry ice” is unlike frostbite in that the damage occurs within seconds and rewarming is not beneficial b Some investigators suggest that freeze injuries of this nature should be managed much like a thermal burn c Burn surgeons should be consulted in the more severe cases d Do not institute rewarming unless complete rewarming can be assured; refreezing thawed tissue increases tissue damage Place affected area in a water bath with a temperature of 40 to 420C for 15 to 30 minutes until thawing is complete Some authors suggest that an antibacterial (hexachlorophene or povidone-iodine) be added to the bath water e Correct systemic hypothermia f Rewarming may be associated with increasing pain, requiring narcotic analgesics –– Digits should be separated by sterile absorbent cotton; no constrictive dressings should be used Protective dressings should be changed twice per day –– Perform daily hydrotherapy for 30 to 45 minutes in warm water 400C This helps debride devitalised tissue and maintain range of motion –– The injured extremities should be elevated and should not be allowed to bear weight –– Prophylactic antibiotics are recommended by some investigators –– Topical aloe vera may decrease tissue destruction and should be applied every hours –– Ibuprofen is a thromboxane inhibitor and may help reduce tissue loss Adult dose of 200 mg every 12 hours is recommended Forensic Issues ■■ Most cases are accidental resulting from inadvertent build- up of CO2 in a confined space ■■ Dry ice can generate toxic concentrations of CO ■■ Release of carbon dioxide from rising colder, deep water producing a deadly cloud of gas has been postulated to explain the deaths associated with the Lake Nyos disaster of August 21, 1986, Lake Monoun disaster of August 1984, and Dieng Plateau, Indonesia disaster of February 20, 1979 Survivors of the Lake Nyos disaster in August, 1986 were noted to have superficial blisters which healed rapidly Characteristics of the blisters suggested that they were the result of depriving the skin of oxygen Hospitalised and outpatient survivors had symptoms compatible with exposure to a suffocating gas Many survivors had lost consciousness for hours (6 to 36 hours) after the incident Cough, headache, fever, weakness or malaise, and limb swelling were frequently noted (10% or more incidence) among the victims Evidence after the incident suggested a slow build-up of carbon dioxide deep in the lake, followed by its release as a cold, suffocating aerosol Dogs, cats, cattle, goats, chickens, snakes, and frogs were also found dead in their tracks Insect life was noted to be absent for approximately 24 hours following the incident ■■ Excess levels of carbon dioxide, ammonia, and other asphyxiant gases have been theorised to accumulate at the face of a sleeping infant If the infant is unable to change its position or breathing pattern, sudden infant death syndrome (SIDS) may result from asphyxiation Asphyxia may be due to an excess of CO2 and abnormal reflex actions connected with breathing and swallowing Aliphatic Hydrocarbon Gases Ethane is an odourless gas which is used as a refrigerant and as a component of natural gas It is methane (swamp gas), however, which is the major component of natural gas Both are odourless gases and produce simple asphyxiation at high concentrations Conversion of domestic gas from coal gas (mostly carbon monoxide) to natural gas (mostly methane) has significantly reduced mortality from domestic gas leaks, since methane is much less toxic as compared to carbon monoxide Methane being odourless, a stenching agent (alkyl mercaptan) is deliberately added to domestic gas so that leaks can be immediately recognised It is important to remember that a build-up of methane resulting in 4.8 to 13.5% concentration in air constitutes an explosive mixture which can be ignited by a flame or even a tiny spark Most explosions in mines (as well as homes using natural gas as fuel) occur because of this reason Butane, liquefied petroleum gas, propane, and propylene have a faint petroleum-like odour and may be stenched with mercaptans for transport and storage Butane is used as a raw material for automobile fuels, in organic synthesis, and as a solvent, refrigerant, and aerosol Propane is used as a raw material in organic synthesis, as a component of industrial and domestic fuels, as an extractant, a solvent, and a refrigerant, and in the manufacture of ethylene Incomplete combustion of these agents can release carbon monoxide into the ambient air Butane is often abused by adolescents in the form of inhalation (see “glue sniffing”, page no 576) Liquefied petroleum gas is used as a domestic, industrial, and automotive fuel Propylene is a raw material in polypropylene, isopropyl alcohol, isopropylbenzene, acetone, and propylene oxide manufacturing Most of the aliphatic hydrocarbon gases act as simple asphyxiants (vide supra), in addition to additional specific toxicities RESPIRATORY IRRITANTS Ammonia Physical Appearance ■■ Extremely irritant gas with a penetrating odour ■■ It is highly water soluble (forming ammonium hydroxide which is an alkaline corrosive) ■■ Aqueous ammonia is a colourless liquid with a strong alka- line reaction (pH 11.6) and a penetrating pungent odour When heated to decomposition, it emits toxic fumes of ammonia and oxides of nitrogen Uses ■■ ■■ ■■ ■■ ■■ ■■ Agriculture (fertiliser) Mining Manufacture of plastics and explosives Refrigerant Cleaning and bleaching agent Treatment of syncope in the form of smelling salts (page no 57) ■■ Household ammonia is to 10% Strong ammonia solution is 28% (sold in pharmacies) Clinical Features Inhalation produces such severe upper airway irritation that the victim seldom remains exposed for more than an instant, unless he is trapped Symptoms include lacrimation, cough, dyspnoea, convulsions, coma, and death There is glottic and laryngeal oedema, sloughing of bronchial mucosa, and chemical pneumonitis with pulmonary oedema If recovery from the acute event is incomplete, a chronic condition may set in called reactive airways dysfunction syndrome or RADS This is a persistent, asthma-like syndrome and is also referred to as irritant induced asthma It is different from occupational asthma since there is no evidence of atopy in individuals suffering from RADS, and the agents involved are generally not considered to be immunologically sensitising However it is true that RADS can occur as a chronic occupational condition in people who Usual Fatal Dose ■■ About to 10 ml of liquid ammonia ■■ Inhalation of the gas at concentrations above 5000 ppm can be rapidly fatal Fatalities may also occur from exposure to ammonia concentrations of 2500 to 4500 ppm if inhaled for 30 minutes ■■ Mixing of ammonia with hypochlorite bleach results in the formation of chloramine, which causes a toxic pneumonitis (pulmonary oedema) following inhalation, and may produce residual pulmonary function abnormalities Diagnosis Chest X-ray in dyspnoeic patients Early endoscopy to determine the extent of injury Barium swallow after to weeks to rule out oesophageal strictures Presence of ammonia in an unknown solution, stomach contents, or vomitus can be confirmed by placing an open bottle of concentrate HCl in the vicinity This will produce copious white fumes of ammonium chloride The determination of ammonia in air may be done using an ammoniaspecific electrode, second derivatives spectroscopy, ion chromatography, or colourimetrically 351 Chapter 26 Toxic Gases work with chemicals The inflammatory response of the airways in RADS most probably has a neurogenic aetiology involving the release of substance P from unmyelinated sensory neurons or C fibres Substance P is a well-known culprit in neurogenic inflammation Management is best effected by immediate (and permanent) exclusion from the source of exposure and symptomatic measures, though the response to beta2 adrenergic agonist therapy is not as good as in occupational asthma Ingestion of ammonia solution produces corrosion of the alimentary tract and aspiration pneumonia Nausea and vomiting occur frequently following ingestion Swelling of the lips, mouth, and larynx, and oral or oesophageal burns may occur if concentrated ammonia solutions are ingested Dermal contact can result in deep, penetrating burns Exposure to anhydrous ammonia stored at minus 280 F may produce frostbite injury with thrombosis of surface vessels and subsequent ischaemia and necrosis Ocular exposure can result in immediate and serious chemical burn with rapid penetration into the interior of the eye Conjunctivitis, lacrimation, corneal irritation, and temporary or permanent blindness can result Total corneal epithelial loss may occur Ammonia has greater tendency than other alkalies to penetrate and damage the iris, and to cause burns and cataracts in cases of severe exposure Iritis may be accompanied by hypopyon or haemorrhages, extensive loss of pigment, and severe glaucoma Chronic exposure in workers may lead to initial complaints of chronic cough, dyspnoea on effort, bilateral infiltrates on chest X-ray, and lung function indices reflecting ventilatory and diffusion abnormalities Asthma and laryngitis have been reported in workers chronically exposed to ammonia Section 7 Asphyxiant Poisons 352 Treatment Ammonia blood levels are generally not useful indicators of exogenous ammonia exposure or toxicity It is normally found in human blood at a concentration of 80 to 110 mcg/100 ml There can be a four-fold or greater rise in blood ammonia in some toxic liver diseases because the urease needed to convert ammonia to urea is found only in the liver A serum concentration of 1,000 to 10,000 mcg/100 ml is considered toxic Ocular exposure should be treated with prolonged irrigation with water (30 minutes or more) until the eye reaches neutral pH as tested with a litmus paper in the conjunctival sac Dermal exposure requires washing with soap and water, followed by copious irrigation with water alone Frostbite should be treated in the standard manner (page no 350) Inhalation should be treated with oxygen, PEEP (positive end expiratory pressure), intubation, and bronchodilators Intubation or tracheostomy may be life-saving following severe exposure if stridor, indicating laryngeal oedema, is present Partial liquid ventilation has shown promise in preliminary studies If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents In the case of ingestion, a small quantity of water or milk can be administered as a first-aid measure to dilute the chemical Neutralisation with vinegar or weak acids is not recommended Demulcents can be given Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway Diluents should not be force fed to any patient who refuses to swallow Activated charcoal is of no benefit, and may induce vomiting and obscure endoscopy findings Stomach wash and emetics are contraindicated Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated Antibiotics are indicated only when there is evidence of infection The use of corticosteroids for the treatment of caustic ingestion is controversial Forensic Issues While poisoning with ammonia is not very common, most of the cases reported are suicidal in nature Since the solution or gas even when weak has a distinct irritant smell, accidental poisoning is unlikely Obviously, its properties preclude its choice for murder However, of late ammonia is being used as a spray to incapacitate victims of robbery Serious eye injuries can result Formaldehyde Synonyms Dormol, fannoform, formalin, formalith, formic aldehyde, formol, lysoform, methanal, methyl aldehyde, methylene oxide, morbicid, oxomethane, oxymethylene Physical Appearance Colourless gas with strong pungent smell Formalin is an aqueous solution of formaldehyde containing 37 to 40% formaldehyde and 10 to 15% methanol.* This is however generally referred to as 100% formalin Therefore 10% formalin would actually mean a 1: 10 dilution of such a commercial preparation and contains 3.7% formaldehyde Formalin is a clear, colourless liquid with a pungent odour Some formaldehyde aqueous solutions can be amber to dark brown or even reddish in colour Formaldehyde is also available as a solid polymer, paraformaldehyde, in a powder or flaked form containing from 90 to 93% formaldehyde, and as its cyclic trimer, trioxane Uses and Sources Industrial/Household: Formaldehyde is used in fertilisers, pesticides, sewage treatment, paper-making, preservatives, embalming fluids, disinfectants, foam insulation, urea and melamine resins, artificial silk and cellulose esters, explosives, particle board, plywood, air fresheners, cosmetics, fingernail polishes, water-based paints, tanning and preserving hides, and as a chemical intermediate It is also used as a preservative and coagulant in latex rubber, and in photograph developing processes and chrome printing Medical/Veterinary: Therapeutically, formaldehyde has been used to treat massive haemorrhagic cystitis and hydatid cysts of the liver It has also been used in veterinary medicine Formaldehyde is sometimes used to sterilise dialysis machines Dialysis patients using dialyser machines sterilised with formaldehyde receive a small dose with each treatment The most frequent sequelae is a type of autoimmune haemolytic anaemia; rarely, peripheral eosinophilia may occur Severe hypersensitivity reactions have been observed in a few of these dialysis patients, though the exact relationship of this to formaldehyde-sterilised equipment is unclear Currently other sterilisers are in use such as a mixture of hydrogen peroxide and peracetic acid Formaldehyde is a common contaminant of smoke and is even present to a significant extent in tobacco smoke Burning wood, cigarette smoking, and other forms of incomplete combustion emit formaldehyde Addicts sometimes dip cigarettes of tobacco or cannabis in formaldehyde (“amp” or “dank”) before smoking, in the belief that this produces a hallucinogenic effect and “body numbness” It is a dangerous practice and can result in encephalopathy, pulmonary oedema, rhabdomyolysis and coma * Methanol prevents polymerisation of formaldehyde to paraformaldehyde which precipitates and settles to the bottom as a sediment Other inhibitors of polymerisation used with formaldehyde include ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, and isophthalobisguanamine Mode of Action Formaldehyde is a protoplasmic poison and potent caustic It causes coagulation necrosis, protein precipitation, and tissue fixation Due to conversion in the body to formic acid there is usually profound metabolic acidosis, and this is aggravated by the concomitant presence of methanol (a common additive in formalin solutions) which is also broken down to formic acid Delayed absorption of methanol might occur following ingestion of formalin if the formaldehyde causes fixation of the stomach Clinical Features 353 Usual Fatal Dose About 30 to 50 ml of 100% formalin (liquid) ; more than 100 ppm (gas) Ingestion of as little as 30 ml of 37% (approximately tablespoons) formaldehyde solution (formalin) has been reported to cause death in an adult Exposure to air concentrations as low as ppm can cause eye and upper respiratory irritation Dermal exposure to formalin can result in irritation (acute), or allergic dermatitis (chronic) in susceptible individuals Exposure to solutions of to 10% may result in blisters, fissures, and urticaria Diagnosis Formaldehyde plasma levels are not widely available, but may help in dialysis monitoring Monitor acid base status in symptomatic patients Monitor liver function tests Monitor haematocrit and haemoglobin concentration in dialysis patients repeatedly exposed parenterally to formaldehyde Monitor blood methanol levels after significant formalin ingestion Pulmonary function testing and nasal and bronchial provocation tests may be recommended in patients with signs and symptoms of reactive airways dysfunction following inhalation of formaldehyde The presence of a small amount of endogenously derived formate in human urine is normal; however, formate derived from the metabolism of formaldehyde, several other industrial compounds (methanol, halomethanes, acetone) and some pharmaceutical compounds may elevate the urine formate concentration above the normally expected values Urinary formic acid levels were shown to be subject to a great deal of individual variation and did not correlate with known exposures to formaldehyde Formic acid is not a suitable biomarker for formaldehyde exposure Treatment Acute Poisoning: a Dilution with milk or water as a first-aid measure may help reduce corrosive effects Emesis is contraindicated Activated charcoal may be of benefit b Gentle gastric aspiration with a soft nasogastric tube (if the victim is seen within hour of ingestion) c Sodium bicarbonate IV d Haemodialysis e Ethanol infusion will help counteract methanol toxicity f Monitor electrolytes, fluids, acid-base, and renal function Chapter 26 Toxic Gases Acute Poisoning: a Inhalation—cough, lacrimation, dyspnoea, chest pain, wheezing, rhinitis, anosmia, tracheitis, bronchitis, laryngospasm, pulmonary oedema, headache, weakness, dizziness, and palpitations b Ingestion—severe abdominal pain, vomiting, diarrhoea, haematemesis, tachypnoea, hypotension, cyanosis, altered mental status, and coma Seizures, jaundice, albuminuria, haematuria, anuria, and metabolic acidosis have also been reported Ulceration of mouth, oesophagus, and stomach is common Strictures and perforation are possible delayed complications Renal failure is a frequent complication in severe poisoning Hepatotoxicity has been reported Skin and mucous membrane may appear whitened If the patient survives for more than 48 hours, the prognosis is good c Dermal exposure—dermatitis, brownish discolouration of the skin, urticaria, and pustulovesicular eruptions, may develop from dermal exposure Concentrated solutions can cause coagulation necrosis d Ocular exposure—irritation, lacrimation, and conjunctivitis may develop with exposure to vapours Eye exposure to solutions with high formaldehyde concentrations may produce severe corneal opacification and loss of vision Inhalation or ingestion of formaldehyde has not been found to affect vision in humans or animals Chronic Poisoning: a Formaldehyde is a known carcinogen in animals, and epidemiologic data among humans are mounting in implicating the chemical in human carcinogenesis There are reports of increased incidence of nasopharyngeal cancers in individuals occupationally exposed to formaldehyde Some epidemiologic studies have found a slightly elevated risk for lung cancer mortality with formaldehyde exposure Suggestive association between occupational exposure to formaldehyde and deaths from breast cancer was seen in one case-control study b Asthma and dermatitis in sensitive individuals c Possible disturbances in memory, mood, and sleep; headache, and fatigue Seizures may also be induced d Occupational exposure at recommended limits is not thought to present a reproductive risk Formaldehyde exposure among female hospital workers did not correlate with an increase in spontaneous abortion in one study, but did correlate in another e Formaldehyde is a potent genotoxin and has been reported to be active in many short-term genetic tests, including the Ames Salmonella assay and other assays for mutation using bacteria, chromosome aberrations and sister chromatid exchanges in vitro and in vivo, and many assays detecting direct effects on DNA Section 7 Asphyxiant Poisons 354 g Dopamine or noradrenaline for hypotension h Watch for signs of gastrointestinal haemorrhage and perforation i Early endoscopy to assess the degree of injury j Inhalation exposure: Administer 100% humidified supplemental oxygen, perform endotracheal intubation, and provide assisted ventilation as required Administer inhaled beta adrenergic agonists if bronchospasm develops Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 ml/ kg) is preferred if ARDS develops k Exposed skin and eyes should be flushed with copious amounts of water Patients with ocular exposure to significant concentrations of formaldehyde should be evaluated by an ophthalmologist Chronic Poisoning: a Removal of patient from exposure b Symptomatic measures c Preventive measures include exhaust ventilation at place of work, use of goggles, face shields, gloves, and aprons Autopsy Features Odour of formalin around the mouth and nostrils, and in the stomach contents Inflammatory oedema of oesophagus, larynx, and lungs Stomach (and sometimes the proximal small intestine) may show signs of “fixation” of tissues Histological details may be well preserved Kidneys may reveal microscopic evidence of tubular necrosis Autopsy Diagnosis: To confirm the presence of formaldehyde in the gastric contents, a small quantity of the latter is dissolved in resorcinol in a test tube and sulfuric acid is gently poured along the sides of the tube A red to violet coloured ring will develop at the junction of the two solutions Forensic Issues Most reported cases of acute poisoning are either accidental or suicidal in nature Chronic poisoning is invariably due to occupational exposure Some Indian studies conducted in embalming rooms of medical colleges revealed fairly high formaldehyde concentration of ambient air, stressing the need for fixing standard limits of exposure in work places in India like in the West Hydrogen Sulfide Synonyms Dihydrogen monosulfide, Dihydrogen sulfide, Hydrosulfide, Sulfur hydride, Hydrogen sulfuric acid, Hydrosulfuric acid, Sulfureted hydrogen Physical Appearance Colourless gas, heavier than air, with a strong “rotten egg” odour Because it rapidly paralyses olfactory nerve endings in high concentrations, odour is not a dependable means of detecting this gas Natural gas containing hydrogen sulfide is termed “sour gas” Hydrogen sulfide is a liquid at high pressures and low temperatures, and is shipped as the liquefied material under its own vapour pressure Uses and Sources Decay of organic sulfur-containing products such as fish, manure, sewage, septic tank contents, etc It is produced by bacterial action on sewage effluents containing sulfur compounds when oxygen has been consumed by excessive organic loading of surface water (“sewer gas”) Industrial sources—pulp paper mills, leather industry, petroleum distillation and refining, vulcanising of rubber, heavy-water production, viscose-rayon production and coke manufacture from coal Natural sources—volcanoes, caves, sulfur springs, and subterranean emissions Other sources—burning of wool, hair, and hides can release hydrogen sulfide Hydrogen sulfide is used or encountered in farming (usually as agricultural disinfectants), brewing, tanning, glue making, rubber vulcanising, metal recovery processes, heavy water production (for nuclear reactors), in oil (“sour crude” refinery) and gas exploration and processing, in rayon or artificial silk manufacture, lithography and photoengraving, fur-dressing and felt-making plants, slaughter houses, fertiliser cookers, beet sugar factories, analytical chemistry and dye production Usual Fatal Dose ■■ Exposure to concentrations approaching 250 ppm causes irritation of mucous membranes, conjunctivitis, photophobia, lacrimation, corneal opacity, rhinitis, bronchitis, cyanosis, and acute lung injury ■■ At concentrations of 250 to 500 ppm, signs and symptoms include headache, nausea, vomiting, diarrhoea, vertigo, amnesia, dizziness, apnoea, palpitations, tachycardia, hypotension, muscle cramps, weakness, disorientation, and coma ■■ At concentrations of 750 to 1000 ppm, victims may experience abrupt physical collapse or “knock down” Higher concentrations may also result in respiratory paralysis, asphyxial seizures, and death The mortality rate is in the range of six per cent Toxicokinetics After absorption, H2S is detoxified in the body to thiosulfate and polysulfides by enzymatic and non-enzymatic oxidation of sulfides and sulfur This reaction is catalysed by oxyhaemoglobin As per recent studies, hydrogen sulfide is metabolised by oxidation to sulfate, methylation, and reaction with metalloproteins (responsible for the most serious toxic effects) Mode of Action Like cyanide (vide infra), H2S is a cellular poison and inhibits cytochrome oxidase by disrupting electron transport In fact it is said to be a more powerful inhibitor of cytochrome oxidase than cyanide The resulting inhibition of oxidative phosphorylation produces cellular hypoxia and anaerobic metabolism Anaerobic metabolism further causes lactic acidosis H2S is also a strong respiratory irritant and reacts with the moisture on the surface of the mucous membrane to form sodium sulfide Clinical Features Diagnosis Rotten egg odour in the vicinity of the patient Blackening of copper and silver coins in the patient’s pockets, or darkening of jewellery Measurement of sulfide ion level in the blood by ion-selective electrode in combination with Conway microdiffusion Clinical (Toxic) Features Respiratory arrest can occur Mydriasis, urinary retention, and seizures may occur, especially following large doses of mecamylamine Tremor, hallucinations, and confusion may also follow high dose mecamylamine Treatment Immediate removal of victim from contaminated area to freshair area Rescuers must use self-contained breathing apparatus Immediate supportive care should be given as most fatalities occur at the scene Maximum oxygen flow and supportive care may be sufficient treatment without the need to use nitrites Seizures may have to be controlled with muscle relaxants (i.e succinylcholine) to complete intubation Symptomatic patients must be kept under observation for an average of 48 hours, and monitored closely for acute lung injury, dysrhythmias, peripheral neuritis, or some degree of neurological disturbance High-flow oxygen Hyperbaric oxygen is said to be beneficial Nitrites are antidotal in action in H2S poisoning They induce methaemoglobinaemia Since H2S has greater affinity for methaemoglobin than for cytochrome oxidase, it dissociates from the latter and binds preferentially to the former resulting in the formation of sulfmethaemoglobin Dose: a An amyl nitrite perle is broken and inhaled for 30 seconds every minute until intravenous sodium nitrite can be begun b Sodium nitrite, 10 ml of 3% solution (amounting to 300 mg), is given IV over minutes c Unlike in the case of cyanide poisoning, sodium thiosulfate is not necessary in hydrogen sulfide poisoning because the body spontaneously detoxifies sulfmethaemoglobin Many cases of H2S poisoning have been treated successfully with supportive care and oxygen, without resorting to nitrites 355 Chapter 26 Toxic Gases Acute Exposure: a Low-level exposure: keratoconjunctivitis, corneal ulceration (gas eye), rhinitis, bronchitis, pulmonary oedema Injection of the conjunctivae, seeing coloured halos, ocular pain, corneal bullae, blurred vision and blepharospasm may be noted following exposure to 150 to 300 ppm Olfactory fatigue may occur after to 15 minutes of exposure at 100 ppm Recovery of smell is slow, depends on the extent of exposure, and may require weeks to months b High-level exposure: headache, vertigo, nystagmus, vomiting, dyspnoea, convulsions, sore throat, cardiac dysrhythmias, and conduction defects Inhalation exposure to 500 ppm for 30 minutes produces sweating, somnolence, weakness, amnesia, malaise, confusion, delirium, hallucinations, nystagmus and coma c Pure gas exposure: Death can result in seconds due to respiratory failure if the gas is inhaled in its pure form Characteristics of a fatal exposure are rapid collapse, respiratory depression, tremors, blurred vision, cyanosis, seizures and tachycardia d Skin exposure: may result in severe pain, itching, burning, and erythema, especially in moist areas Cyanosis may be noted Recovery may be associated with neurological sequelae such as memory failure (amnestic syndrome), disorientation, delirium, and dementia There may also be impairment of hearing, vision, and olfaction Basal ganglia damage results in tremor, ataxia, and muscle rigidity Some of these effects are irreversible Chronic Exposure: a Results in headache, weakness, nausea, and weight loss b One report suggests basal ganglia abnormalities— ataxia, dystonia and choreoathetosis c An epidemiological study of Chinese female workers found an increased risk of spontaneous abortions associated with exposure to benzene, gasoline and hydrogen sulfide cells Levels higher than 0.05 mg/L are associated with toxic effects Reliable results are obtained only if the analysis is done within hours of exposure, and the sample had been tested without delay, because sulfide concentrations rise with tissue decomposition Presence of H2S in the air at a scene of poisoning can be detected by exposing a strip of filter paper moistened with lead acetate It will get blackened Monitor vital signs Monitor pulse oximetry and/or arterial blood gases and chest radiograph in patients with respiratory signs or symptoms Measuring blood sulfide and thiosulfate levels or urinary thiosulfate levels may be performed to document the exposure but are not useful for emergency treatment Whole blood sulfide concentration in normal subjects is less than 0.05 mg/L In fatal cases, confirmation of hydrogen sulfide poisoning can be done by measuring both sulfide and thiosulfate levels in blood 356 a Use maximum oxygen flow b Monitor fluid and electrolyte balance c Watch for development of aspiration pneumonia and pulmonary oedema d Treat convulsions with conventional anticonvulsants Refractory seizures may have to be managed by succinylcholine (with ventilatory support) e Treat metabolic acidosis in the usual way Section 7 Asphyxiant Poisons Autopsy Features Greenish discolouration of grey matter of brain, viscera, and bronchial secretions Characteristic odour Pulmonary oedema Generalised visceral congestion with scattered petechiae Decomposition is said to be faster in hydrogen sulfiderelated death Forensic Issues Most cases of poisoning are accidental in nature arising out of industrial or occupational mishaps Cleaning out sewers replete with hydrogen sulfide can pose an occupational risk, which can sometimes be potentially life-threatening Methyl Isocyanate (MIC) Methyl isocyanate (MIC) is one of a group of isocyanates, the others being toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) Physical Appearance Colourless liquid with a sharp odour, which becomes gaseous at 390C It is an extremely reactive chemical and needs to be stored carefully Contact with water results in an exothermic reaction Methyl isocyanate is produced by heating metal cyanates or by heating N,N-diphenyl-N’-methylurea Uses ■■ Manufacture of carbaryl (a carbamate pesticide) ■■ Manufacture of polyurethane articles (plastics, urethane foam, adhesives, etc.) Mode of Action Methyl isocyanate (MIC) is a powerful respiratory irritant Even brief exposure at high concentrations may cause severe injury, burns, or death Usual Fatal Dose At ppm, no odour is generally discernible, but irritation and lacrimation may be noted Symptoms become more marked at ppm and unbearable at 21 ppm Exposures to breathing zone concentrations of 0.5 ppm are likely to produce a respiratory response Clinical Features Inhalation of MIC gas produces immediate lacrimation, photophobia, lid swelling, and corneal ulceration; cough, choking sensation, dyspnoea, chest pain, haemoptysis, pink frothy discharge from nose, and pulmonary oedema; less commonly vomiting, convulsions, and coma Metabolic acidosis has been reported Dermal exposure results in erythema and vesiculation Ocular exposure can cause permanent damage A 40% increased incidence of trachoma, 36% increased risk of other lid infection and 45% increased incidence of irritant symptoms were noted in the exposed population of Bhopal resulting in a “Bhopal eye syndrome” A follow-up study three years after the Bhopal methyl isocyanate exposure demonstrated an excess of eyelid infection, decreased visual acuity, cataracts, and eye irritation among survivors as compared to controls There is conflicting data as to whether methyl isocyanate is foetotoxic; however, it crosses the placental barrier Reports from Bhopal, and animal studies suggest a high degree of adverse reproductive effects and teratogenicity Long-term effects after survival include RADS (reactive airways dysfunction syndrome, page no 351), and pregnancy-related problems: high incidence of spontaneous abortions, and increased perinatal mortality Respiratory function and visual acuity has remained abnormal among the persons exposed in the Bhopal incident for at least two years, and longer in those of close proximity to the 1984 accident Lung function showed mainly restrictive changes with small airway obstruction and interstitial deposits Pulmonary function testing performed 1–7 years after the Bhopal accident demonstrated that deterioration in respiratory function occurred in gas-exposed patients as a consequence of accumulation of inflammatory cells (macrophagus and lymphocytes) The intensity of the inflammatory response was greatest in the most severely exposed patients Treatment Monitor ECG, chest X-ray, pulse oximetry, peak air flows, arterial blood gases, serum electrolytes, and renal and hepatic function in symptomatic patients High-performance liquid chromatography (HPLC) is specific and sensitive for the detection of MIC in blood Decontamination of skin and eyes with saline Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed Topical antibiotics may be useful in secondary infection Severe iritis may be treated with topical atropine or homatropine Ingestion: emesis, activated charcoal Inhalation: covering the face with a wet cloth immediately during exposure may minimise toxicity Move patient from the toxic environment to fresh air Monitor for respiratory distress Observation for 72 hours is advisable to detect delayed onset of acute lung injury If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis ... trends and applications J Assoc Physicians India 20 03;51 :28 0-4 20 Singh B, Singh N, Kumar R Sewer gas poisoning Int J Med Toxicol Legal Med 20 02; 5 :25 -6 21 Vossberg B, Skolnick J The role of catalytic... erythrocyte 2, 3-diphosphoglycerate concentration Chapter 26 Toxic Gases ■■ is 23 0 to 27 0 times greater than that of oxygen Therefore, in spite of adequate partial pressure of oxygen (PO2) in blood,... Toxicol 20 04;46:183-5 Blumenthal I Carbon monoxide poisoning J Roy Soc Med 20 01;94 :27 0 -2 Borak J, Diller WF Phosgene exposure: Mechanisms of injury and treatment strategies J Occup Environ Med 20 01;43:110-9