Signs, Symptoms, Management & Prevention of Sarin War Gas Poisoning

Introduction

It is now being alleged that the Mainstream media (MSM)-propagated Sarin Gas attack may not have been an actual attack by the deadly war gas. It is stated by alternative media that this was just another ploy to lay all the blame on Mr. Assad and another excuse for direct intervention in Syria. And rightly so, USA attacked Syria the next day.

This blog addresses for the general public the signs and symptoms of Sarin war gas poisoning along with its management and prevention. At the end, a short scientific analysis whether the Sarin Gas Attack was factual or not.

Sarin War Gas

Sarin is one of the Organophosphorus compounds used as a war gas due to its horrific effects on the human body when exposed to the gas. Other similar gases include soman and tabun.

It is a colorless odour-less gas which can be lethal even at very low concentrations, where death can occur within one to ten minutes after direct inhalation of a lethal dose.

Organophosphorus Compounds

These are a group of indirectly acting cholinomimetics (drugs mimicking the actions of acetylcholine, a natural neurotransmitter acting on different tissues in the body including many smooth muscles, heart, skeletal muscles and exocrine glands).

They do this by irreversibly inhibiting the enzyme that breaks down acetylcholine, acetylcholinesterase. By inhibiting the enzyme, this causes excess of acetylcholine and thus an increase in its actions on various tissues.

There are about 50, 000 thousand Organophosphorus compounds.

Some clinically important ones include

  • Some previously useful agents like Ecothiophate for glaucoma
  • Some Insecticides like malathion, parathion, isofluorophate etc
  • War Gases like Sarin, Soman and Tabun

Organophosphorus Compound (OPC) Poisoning

The causes include

Occupational: Dealing with insecticides

Accidental: Home accidental ingestion

Suicidal

War: Exposure to war gases

Signs & Symptoms of OPC Poisoning

The signs and symptoms are due to excessive cholinergic (caused by acetylcholine activity), easily remembered by this mnemonic:

DUMBBELS

      D   Diarrhea

      U   Urination

      M   Miosis/muscle weakness

      B   Bronchoconstriction

      B Bradycardia

      E Emesis

      L Lacrimation

      S Salivation/sweating

The above are mainly due to actions of acetylcholine on Muscarinic receptors.

There are other more lethal effects due to effects of acetylcholine on nicotinic receptors especially on the skeletal muscles and CNS

Features due to overstimulation of nicotinic acetylcholine receptors in the sympathetic system

  • Tachycardia
  • Mydriasis
  • Hypertension
  • Sweating

Features due to overstimulation of nicotinic and muscarinic acetylcholine receptors in the CNS

  • Confusion
  • Agitation
  • Coma
  • Respiratory failure

Features due to overstimulation of nicotinic acetylcholine receptors at the neuromuscular junction

  • Fasciculations
  • Muscle weakness
  • Paralysis

Major cause of Death is Respiratory failure due to paralysis of respiratory muscles

These drugs cause muscle paralysis due to persistent prolonged depolarization at the motor end plate at the neuromuscular junction.

sarin

The LD50 of Sarin Gas

LD50 of a drug is defined as the dose of drug that causes death in 50 % of the population tested/exposed to the drug.

The LD50 of Sarin gas is about 100 mg/min/m3

This means that 50 % of victims, within an environment for one full minute when there is 100 mg/m3 of sarin in the air, will die.

If the victims are instead in an environment for 10 minutes where there is a density of sarin of 10 mg/m3, they will also receive a lethal dose of 100 mg/min/m3

This means that not only the amount of sarin exposure may cause death, but also the duration of exposure may also lead to death.

Management of OPC Poisoning

Treatment has to be started as early as possible due to seriousness of the condition and that death occurs within minutes of exposure.

The management team has to wear gas masks and gloves to avoid exposure which can be fatal. Sarin goes through the skin.

Symptomatic Treatment

  • Remove soiled clothes, wash skin
  • Clear the mouth, nose and throat with fingers or suction
  • Maintain vital signs especially airway, breathing and circulation
  • Oxygenate and insert airway/intubate;
  • Perform gastric lavage

Drug Treatment

1.  Atropine

This is anti-cholinergic drug that will only antagonize the muscarinic actions of organophosphorus compounds but is insufficient because it will not able to antagonize the Nicotinic actions of organophosphorus compounds

May have to be given repeatedly until dry mouth and reversal of miosis occurs

2. Diazepam or other Benzodiazepine

This is given for treatment and even prevention of seizures

3. Cholinestrase Enzyme Regenerators: Oximes

These are drugs that regenerate the enzyme (acetylcholinesterase) that is irreversibly inhibited by the OPCs, thus inhibiting the breakdown of acetylcholine, leading to excess cholinergic activity.

These are mainly given to treat/reverse the Nicotinic actions of Acetylcholine, especially on the skeletal muscles.

Oximes combine with the phosphoryl groups of OPCs to form soluble complexes. This results in regeneration of the enzyme.

Names of Oximes

Pralidoxime, Diacetylmonoxime and Obdidoxime

Only Obdidoxime can cross the blood brain barrier and enter the brain, so also useful in reversing CNS effects of OPCs

This is a picture of a combat kit containing atropine plus pralidoxime (PAM)

Picture1

Ageing

  • The phosphorylated enzyme undergoes aging i.e. breaking of one of the Oxygen-Phosphorus bonds of inhibitor (and thus a loss of functional group-alkyl group); this causes further strengthening of the Phosphorus-Enzyme bond.
  • At this point (after ageing) it becomes irreversible and even Oximes are ineffective in regenerating the enzyme
  • Aging starts within minutes in case of war gases, 30-40 Minutes for the insecticide difluorophosphate (DFP) and 4-6 Hours for Malathion.
  • This is also why war gases are the most dangerous chemical weapons

Other Treatments

  • Magnesium sulphate blocks ligand-gated calcium channels, resulting in reduced acetylcholine release from pre-synaptic terminals, thus improving function at neuromuscular junctions, and reduced CNS overstimulation
  • The alpha2-adrenergic receptor agonist clonidine also reduces acetylcholine synthesis and release from presynaptic terminals.
  • Sodium bicarbonate is sometimes used for treatment of organophosphorus poisoning in place of oximes
  • Butyrylcholinesterase scavenges organophosphorus in plasma, reducing the amount available to inhibit acetylcholinesterase in synapses

How can anticipated OPC War Gas Poisoning be Prevented?

  • In case of anticipated chemical war:
  • Pretreatment (Prophylaxis) with reversible inhibitors of cholinestrase to prevent binding of the irreversible organophosphorous compounds like war gases
  • Pyridostigmine, Neostigmine or Ambenonium keep the enzyme occupied for some time (2-6 hours) and thus will not allow the organophosphorus compounds to bind with enzyme during this time.
  • These drugs are preferred because major cause of death due to OPC poisoning is respiratory failure
  • Pyridostigmine is preferred because it has a slightly longer duration of action than Neostigmine.
  • The protection is limited to the peripheral nervous system because pyridostigmine or neostigmine do not readily enter the central nervous system

 Supposed Sarin Gas Attack in Syria

With the above scientific facts, a short analysis of the supposed Sarin Gas is presented:

The gas may not have been sarin. How can we say? Very simple. The so-called first responders handled the victims without gloves, as shown in the picture. If this had been Sarin, they would have died. Sarin on the skin will kill you.

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The people are handling the corpses of victims without sufficient safety gear, most particularly with the masks mostly used , as well as no gloves. Although this may seem insignificant, understanding the nature of sarin gas that the opposition claim was used, only opens questions.

Within seconds of exposure to sarin, the effects of the gas begins to target the muscle and nervous system. There is an almost immediate release of the bowels and the bladder, and vomiting is induced. When sarin is used in a concentrated area, it has the likelihood of killing thousands of people. Yet, such a dangerous gas, and the White Helmets are treating bodies with little concern to their exposed skin. This has to raise questions.

It must be questioned why there are people around sarin gas without any protective gear, and not affected at all when it can begin attacking the body within seconds?

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Conclusion:

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For more details and other useful information on Pharmacology

Read ‘Nauman’s Textbook of Pharmacology’ (3rd Edition)

https://drnaumanshad.wordpress.com/2016/07/22/naumans-textbook-of-pharmacology/

For many more MCQs (4500 MCQs) divided into units, chapters, and topics read:

‘Learning Pharmacology from Nauman’s MCQS’

https://drnaumanshad.wordpress.com/2016/11/26/learning-pharmacology-from-naumans-mcqs/

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