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Chemical agents

Up Chemical agents Communication Epidemic Terrorism


Cyanide
Phosgene
Ricin

Carolyne Chau

Acute chemical emergencies can occur as a result of:

  • industrial disaster

  • occupational exposure

  • recreational mishap

  • natural catastrophe

  • chemical warfare

  • terrorism

Chemical weapons potentially produce large numbers of casualties and triage is an important consideration.

Properties of toxic agents

Four essential properties of chemical hazard:

  • toxicity

  • latency

    • time between exposure and appearance of features of toxicity

    • short compared to classic biological weapons

  • persistence

    • relates to the ability of a toxic agent to remain in the environment

    • function of the physicochemical properties of the agent

  • transmissibility

Toxicity and latency determine the management of the casualty, whereas persistency and transmissibility determine the management of an incident involving the release of chemical agents.

Pathophysiology of toxic trauma

  • Direct cellular damage and tissue hypoxia leading to cell and organ failure.

  • Systemically, toxic agents may attack the nervous and respiratory systems, producing rapid life threatening respiratory failure

    • eg pesticide and nerve agent poisoning.

    • respiratory system is the most vulnerable to toxic attack, both in terms of structure and function

      • end results on the airways are blockage, increased resistance, and decreased compliance

      • toxic pulmonary oedema causes alveolar diffusion failure and shunting

    • neuromuscular effects lead to impaired ventilation by central and peripheral effects

  • Skin and other epithelial structures may be affected by agents with a longer latency to produce blistering and burning. This is the case with mustard gas exposure. Internal effects of this agent may produce blistering and desquamation in the airways leading to airway blockage.

Diagnosis

Predominant organ failure Class of agents Examples
Central and peripheral nervous system, resulting in ventilatory failure "Nerve gases": organophosphates & carbamates Sarin, soman, tabun, VX
Respiratory   Phosgene, mustard gas
Skin and mucous membranes Vesicants Mustard gas
Cytotoxic tissue hypoxia   Hydrogen cyanide
Multiorgan failure   Ricin

General management principles

  • End exposure

    • evacuating or extricating the affected person

    • thorough decontamination

  • Resuscitate

  • Specific treatment

    • organophosphate and carbamates

    • phosgene

    • mustard gas

    • hydrogen cyanide

    • ricin

Chemical Weapons affecting the Central nervous and Peripheral Nervous Systems

Organophosphate and carbamate compounds

Organic phosphorous pesticides, carbamate pesticides and organophosphorous compounds are developed as weapons known as “nerve agents”. Examples of this group are:

  • Sarin

  • Soman

  • Tabun

  • VX

These agents can be absorbed by inhalation, by ingestion, and through the skin.

 

The Acute Cholinergic Syndrome

Organophosphate (OP) and carbamate compounds affect the central and peripheral cholinergic nervous systems through inhibition of acetyl cholinesterase (AchE), leading to an increase in synaptic acetyl choline and hence cholinergic overstimulation. OP antichholinesterases have effects on type 1 and 2 muscarinic receptors as well as nicotinic receptors at the neuromuscular junction and the anomalous sympathetic system. There are important inhibitory effects on the respiratory centers in the hindbrain. OP also affect gamma-aminobutyric acid (GABA) receptors directly, causing spike discharges and convulsions.

Muscarinic symptoms include profuse exocrine secretions:

  • lacrimation

  • rhinorrhea

  • excess salivation

  • bronchorrhea

  • sweating

Ophthalmic signs and symptoms such as:

  • miosis

  • dim vision

  • eye pain

Exposure to large doses, especially if these are ingested may cause:

  • abdominal cramping

  • nausea

  • emesis

  • diarrhea

  • faecal and urinary incontinence

Nicotinic symptoms include:

  • weakness of skeletal muscle

  • muscle fasciculation

  • initial depolarizing flaccid paralysis

Cardiovascular effects of poisoning are mixed, with an initial tachycardia and hypertension due to nicotinic stimulation which may progress to bradycardia and hypotension. There may be ventricular dysrhymias and prolongation of the QT interval which has been reported as a poor prognostic sign.

Multiple mechanisms can contribute to respiratory failure, eg, hypersecretion, bronchoconstriction, thoracic weakness, and decreased respiratory drive.

 

 

The Intermediate Syndrome

Apart from the acute cholinergic syndrome, the OP intermediate syndrome (IMS) presents a pathophysiological development after OP exposure, which has important consequences for subsequent critical care management. Reparalysis occurs in 10% to 20% of patients at 18 to 24 hours posy OP pesticide exposure after resolution of the acute cholinergic syndrome. There was an apparent change in the nature of neuromuscular blocking with indications of decrementing responses, signifying development of a nondepolarizing block. IMS affects proximal limb, cranial motor, and respiratory muscles. Both neuropathy and myopathy have been suggested as the basis of the pathophysiology of IMS, but current available evidence suggests that the neuromuscular junction is the critical site. At present time, considerations of analogous clinical conditions suggest that it is downregulation of AchR that is responsible.

 

Organophosphate-Induced Delayed Neuropathy

The third stage of clinical presentation of OP intoxication is organophosphate-induced delayed neuropathy, which develops over a long period post-exposure. This is thought to be an action of the OP on the neurotoxic esterase enzyme system and is not related to the anticholinesterase properties of the compound.

 

Treatment of Organophosphate Poisoning

The rationale for treatment is based on airway and ventilatory support and blocking the muscarinic effects and regeneration of AchE at both muscurinic and nicotinic sites. Benzodiazepines have long been used to counter the action of OP on GABA receptors which may cause seizures and convulsion. Benzodiazapines are now available mixed with anticholinergic and enzyme-reactivating drugs for immediate intramuscular injection Anticholinergic Therapy.

Atropine is a key drug in the management of OP poisoning. Its antagonistic action against acetylcholine at the muscarinic synapses allow control of the muscarinic effects, the most severe of which is bradycardia. Atropine at a dosage of 2mg should be given intravenously (paediatric dose 0.02-0.05 mg/kg) with repeated doses every 5 to 10 minutes until papillary dilatation occurs and heart rate rises above 80 beats/min. Atropine infusion may be used for persistent bradycardia in pesticide poisoning.

Oximes are compounds capable of reactivating, in some cases, the complex formed by the OP and AchE. Oximes can bind to the OP-AchE complex and cause the nerve agent molecule to separate from the enzyme. Clinically, this means that they can reverse the actions of OP at the muscarinic and nicotinic receptor. Importantly, unlike atropine, they act at the neuromuscular junction and can thus reduce the degree of paralysis. However, their effectiveness is dependent on the exact nature of the nerve agent involved and on the length of time after the attack before they are given. This is because overtime, organophosphorous-acetylcholinesterase binding becomes irreversibly covalent and resistant to reactivation by oximes, a process known as “aging”. Aging occurs very rapidly in humans after exposure to the nerve agent soman, in a matter of minutes, but sarin ages over a period of 3 to 5 hours. Oximes should never be withheld out of concern that it might be administered too late after exposure.

Oxime therapy should be given simultaneously with atropine. Slow injection of pralidoxime is recommended to prevent laryngospasm, muscle rigidity, and hypertension. Pralidoxime at a dosage of 15 to 30 mg/kg intravenously/intramuscularly is given over 20 minutes for adults and children. This dose may be repeated after 4 hours (or 1 hour if paralysis is worsening). The target therapeutic blood concentration should be 4 micrograms/mL. Sarin is broken down rapidly in the blood by hydrolysis. Oxime treatment in the hospital should continue for as long as atropine is required.

Carbamate insecticides have a more limited penetration of the central nervous system, inhibit acetylcholinesterase reversibly, and result in a shorter, milder course than organophosphorous compounds. Nevertheless, in the treatment of severe cholinergc syndromes, it is prudent to use both atropine and pralidoxime.

 

Chemical Weapons affecting the Respiratory System

 

Pathophysiology

Many toxic agents have direct effects on the airways that cause blockage at all levels. OP cause blockage of large and small bronchi through production of secretions and cholinergically mediated bronchoconstriction. Agents such as mustard gas cause large airway blockage through vesication and desquation as well as chemical bronchiolitis.

Chemical induced pulmonary oedema is a pathophysiological mechanism common to a wide range of compounds used both as chemical industrial intermediates and as chemical weapons. Toxic oedema may be defined as pulmonary oedema occurring after inhalation of toxic gases or vapours. It develops with a variable latent period after exposure and is marked by acute and dramatic collapse of the patient.

Chemical Weapons causing Direct Cellular Disruption (Vesicants)

Chemicals causing blistering of skin and mucous membranes were first used as chemicals weapons during World War I. The most well known is sulfur mustard, commonly known as “mustard gas”. It was used as a disabling agen but has a relatively long latency. Its successor Lewisite is an arsenic-based compound, is more volatile, nd has a short latency and causes immediate eye pain in addition to its vesicant properties.

Although the latency of action of sulfur mustard in cooler climate is 4 hours, information from Iran-Iraq War, the scene of its most recent use, indicates that a higher ambient temperature shorten the latency and causes significant respiratory damage apart from its classic action as a skin vesicant.

 

Time Scale of the appearance of signs and symptoms after mustard gas exposure:

20 – 60 mins: Nausea, retching, vomiting, and eye smarting, sometimes no initial symptoms

1 hr: First appearance of erythema

2 – 6 hrs: Nausea, fatigue, headache, painful eye inflammation, lacrimation, blepharospasm, photophobia, rhinorrhea, face and neck erythema, sore throat, horse or total loss of voice, tachycardia, tachypnea

8 –12 hrs: Raised erythema (oedema)

13 –22 hrs: Inflammation in areas where tight clothing was worn and inner thighs, genitalia, perineum, buttocks, and axillae followed by pendulous blister formation possibly filled with clear, yellow fluid; death within 24 hrs is rare

42 –72 hrs: Maximum blisters or necrosis; coughing appears: muco pus and necrotic slough may be expectorated; intense itching ofskin; increase in skin pigmentation

 

Exposure to high doses produces severe cutaneous injury with necrosis. These burns are susceptible to secondary infection. The bullae characteristic of exposure to mustard agent is filled with a fluid that is not itself corrosive.

The respiratory effects of mustard exposure causes tracheobronchitis with dry cough and horseness at the early stage. Heavy exposure will produce severe damage to the tracheal and main bronchial architecture with necrosis, sloughing, and blockage. It may also cause severe bronchospasm. Lung damage can be severe and permanent with COAD, bronchiectasis, and reactive airway dysfunction syndrome.

At the cellular level mustard agent forms highly reactive sulfonium ions which attack DNA by alkylation of sulfhydryl and amino group. This causes the epithelial manifestations of exposure and also long term carcinogenesis, particularly of skin, pharynx, and respiratory tract. There is also leukopenia evident 3 – 5 days after exposureand reaches lowest point 7 – 9 days after exposure. An exposure that may be fatal is indicated by effects on patient’s airway within 6 hours, burns over 25% of total body surface, and an absolute white cell count of less than 200 per cubic millimeter.

 

Management of Mustard Gas Injuries

Management involve immediate decontamination and eye irrigation. Attending hospital staff should be aware of the potential risk of transmissibility in case of decontamination may not have been thorough.

After immediate contamination and eye irrigation, patients require supportive measures. These may include pulmonary care, specialized ophthalmic treatment, burn care, and critical care. Pain will require analgesia. Overhydration should be avoided. These patients have less fluid loss than patients with thermal burn.

Emerging evidence suggests early treatment with NSAIDS may be beneficial. The use of thiosulfate has been shown t decrease systemic toxicity and mortality in animals.

Granulocyte colony-stimulating factor should be considered for the treatment of severe neutropenia.


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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