Organophosphorous Poisoning

The organophosphorus (OP) pesticides inhibit acetylcholinesterase. Hence acetylcholine accumulates at nerve synapses and neuromuscular junctions, stimulating muscarinic and nicotinic receptors and the central nervous system.

They are used as pesticides but can also be used as "nerve gas". This is prohibited under the Geneva Convention but could be used by terrorists or rogue regimes. There is some suggestion that the use of organophosphate pesticides may have caused some neurotoxicity and be responsible for "Gulf War Syndrome". Certainly insecticides were freely used, as were many other chemicals. The syndrome is inconsistent in sufferers but is neither simply a post traumatic stress disorder nor the result of organophosphorous poisoning.^1,2

There are no accurate figures kept about the incidence of organophosphate poisoning.

• The vast majority of cases are accidental from the use of pesticides. There is a much higher incidence in rural areas of the third world.
• Hospital admissions for intentional OP poisoning are twice as numerous as accidental poisoning. Intentional self-harm tends to involve much higher doses than accidental exposure.
• Fortunately, terrorist or warfare use of OP is rare but the potential exists to expose a great many people at once. Sarin is an organophosphate poison and there are 2 recorded episodes of deliberate release, both in Japan.³ One was in Matsumoto in 1994 and the other was in the Tokyo subway in 1995. Theses two incidents caused 18 deaths. A single drop on the skin can be rapidly fatal.

According to the World Health Organisation, there are about 1 million people a year admitted to hospital with accidental poisoning and 2 million with suicidal intent. It is estimated that there could be as many as 25 million agricultural workers in the developing world suffering an episode of poisoning each year.⁴ The WHO figures appear to be an underestimate and a recent call was made for more reliable data to be collected.⁵

• If symptoms follow spraying, then those who conducted the spraying should know exactly what was being released.
• If people start to get symptoms of poisoning and there is no obvious source then the Health Protection Agency state that intentional release must be considered. They have a diagnostic algorithm that starts with "Could this be cyanide?" and the next suggestion is "Could this be a nerve agent or organophosphate?"
• If there has been an accident and damage to a container, then the container should have the appropriate hazard symbol on the side giving an indication of the contents plus a telephone number to call for further information.
• The affected person may smell of garlic, due to the OP or petrol due to the solvent.

Physical properties

• Organophosphates tend to be colourless to brown liquids at room temperature. Some have a fruity smell but others are odourless.
• They are volatile to varying degrees and can therefore be sprayed or distributed as an aerosol and inhaled.
• The vapours are denser than air and may accumulate in low lying areas and enclosed spaces.
• After the deliberate releases of sarin in Japan in 1994 there were secondary effects in health care workers who treated patients who had not been decontaminated. In emergency medicine departments PPE (personal protective equipment) should be available for use in such cases.

The presentation of organophosphate poisoning depends upon whether the poisoning is mild, moderate or severe. The symptoms are basically those of excessive acetyl choline activity.

Mild

• Small or pinpoint pupils
• Painful, blurred vision
• Runny nose and eyes
• Excess saliva
• Eyes look "glassy"
• Headache
• Nausea
• Mild muscle weakness
• Localised muscle twitching
• Mild agitation

Moderate

• Pinpoint pupils, conjunctival injection
• Dizziness, disorientation
• Coughing, wheezing, sneezing
• Drooling, excess phlegm, bronchorrhoea, bronchospasm
• Breathing difficulty
• Marked muscle twitching or tremors
• Muscle weakness, fatigue
• Vomiting, diarrhoea, urination

Severe

• Pinpoint pupils
• Confusion and agitation
• Convulsions
• Copious excess secretions
• Cardiac arrhythmias
• Collapse, respiratory depression or respiratory arrest
• Coma
• Death

The essential features of this type of acute poisoning are those of excessive cholinergic activity. The HPA algorithm gives a number of other possibilities to consider when deliberate poisoning is suspected:

Could this be cyanide?

Very rapid onset of symptoms in seconds or minutes with gasping, air hunger and acidosis. There is confusion, convulsions, collapse and coma. There is decreased respiratory rate, respiratory arrest or sudden death. Cyanosis is unusual but there may be cherry pink skin (only seen post mortem in carbon monoxide poisoning). Pupils are dilated or normal with no fasciculation and secretions are normal.

Could this be a nerve agent or organophosphate?

Rapid onset of cholinergic symptoms including small or pinpoint pupils, painful dim vision, increased respiratory rate, breathing difficulty and bronchospasm. There are excess secretions, saliva, and sweat. There is muscle twitching, convulsions, coma, arrest.
Carbamates have a similar effect to organophosphates but they are less of a problem as they are more easily reversed.

Could this be lewisite?

Rapid onset of burns or blistering within minutes of exposure.

Could this be mustard?

Burns or blistering usually beginning 2 to 12 hours after exposure.

Could this be phosgene?

No history of exposure to chlorine. Rapid onset eye and/or skin irritation with rapid or delayed respiratory symptoms.

Could this be chlorine, other irritant gas, or a riot control agent?

Exposure to pungent greenish yellow gas (chlorine) or other irritant. Rapid onset eye and/or skin irritation and choking/coughing/wheezing.

Is chemical exposure still a possibility?

Unexplained sudden death in a healthy adult. Unexplained reduction in level of consciousness. Patient reports unusual sight, smell or taste. A number of patients with the same symptoms. Symptoms in family or group with common exposure. Known incident or exposure or cause unknown.

General principles

When aiding those who have or may have been exposed to dangerous chemicals, it is important to consider not just the welfare of the patient but your own safety. It is one of the axioms of disaster management that those who are there to rescue should not add to the problem by becoming victims.

• Ensure either that you are wearing chemical PPE and/or that the patient has been decontaminated.
• Decontaminate the patient in the NHS decontamination unit or decontamination area if this has not already been done. Do not attempt to do in in the A&E department or GP surgery.
• If there has been ingestion of OP or carbamates within the past 2 hours, activated charcoal may be used.
• Stabilise the airway with oxygen by mask, intubate and ventilate if needed, control any haemorrhage and set up IV access if needed.
• Assess the cause, give antidotes if appropriate, reassess, alert the local Health Protection Team (HPT), and seek expert advice if needed from HPT, Toxbase, HPA National Poisons Information Service (HPA NPIS) or HPA Chemical Hazards and Poisons Division (HPA CHaPD).
• Hydrocarbon solvents used with organophosphates often persist after decontamination and can lead to fear that OP is still present. These solvents can lead to symptoms too including headache and nausea.
• Lipophilic compounds can cause delayed or persistent toxicity as they slowly move out of the tissues.

Specific aspects

• If you suspect exposure to a nerve agent or organophosphate, ensure that either they have been decontaminated or that you are wearing PPE.
• Maintain an airway, give oxygen, use suction on secretions.
• Remove the patient's clothing if not already done (place in a double bag, sealed, labelled, and stored securely). Shower, wash down or rinse-wipe-rinse with liquid soap and water, or dilute detergent. Remove any contact lenses if present and irrigate the eyes with lukewarm water or normal saline solution.
• Check triage tags for details of pre-hospital treatment.
• For severe or moderate symptoms, establish IV access, arrange assessment by an anaesthetist and as soon as possible give atropine:
• An adult requires atropine, between 0.6 mg and 4 mg IV and a child needs 20 micrograms per kg IV. Give every 10 to 20 minutes until secretions dry up and the heart rate rises to 80 to 90 per minute. This may need as much as 20 mg to achieve this. Do NOT rely on reversal of pinpoint pupils as a guide to adequate atropine administration. Normalisation of cardiovascular parameters and absence of oro-pharyngeal secretions are better clinical markers of adequate atropine administration.
• Pralidoxime is given at 2g or 30 mg/kg IV for an adult, over 4 minutes. Then continue an the same every 4 to 6 hours or infuse IV at 8 to 10 mg/kg/hour. The rate of fixing of the bond between choline esterase and the OP varies between compounds and so the window of opportunity for pralidoxime varies but is usually between 12 and 36 hours. Pralidoxime may be continued for 7 days or until atropine is not required for 24 hours.
• Diazepam is given at 5 to 10 mg IV for an adult or 1 to 5 mg IV for a child. Repeat as required.
• Intubate and ventilate if there is apnoea or severe respiratory distress but avoid succinyl choline.
• Check arterial blood gases, U&E, and glucose. Monitor the ECG and treat any arrhythmias.
• Contact HPA National Poisons Information Service (HPA NPIS) or HPA Chemical Hazards and Poisons Division (HPA CHaPD) for advice if no response or slow response to antidotes.
• Paralysis may mask seizures. Consider EEG monitoring.
• For mild symptoms only with eye signs but no bronchospasm, bronchorrhoea or fits, observe for 2 hours after exposure, consider atropine or 0.5% tropicamide eye drops for painful or blurred vision and if there is no progression of symptoms, complete a chemical exposure record form and discharge the patient with an information sheet.

Late effects

Between 1 and 4 days after exposure to organophosphates, acute respiratory failure can occur with flaccid paralysis. It is refractory to pralidoxime and ventilation is required.
An intermediate syndrome can occur as proximal weakness presents after resolution of the initial crisis. This is different from a potentially permanent peripheral neuropathy.

A&E departments have been supplied with Toxi-Boxes (Toxicological Analytic Sampling Kits), and these kits should be used, where possible, for toxicological sampling. The HPA gives a long list of guidance for taking samples and the following is just a selection:

• Decontaminate the patient before obtaining any samples
• Collect samples as early as possible, preferably before treatment, but do not delay life-saving treatment to obtain them
• Do NOT clean the venepuncture site with alcohol or proprietary skin wipes or swabs as these contain solvents that can interfere with some assays. Use sterile water or, if the skin is visibly clean, dry cotton wool
• Label all specimens as high risk.

If there is difficulty in obtaining specimens the following are given as order of priority:

1. 10 ml blood in plastic lithium heparin tube, 5 ml for children
2. 5 ml blood in glass lithium heparin tube, may be omitted for children
3. 4 ml blood in EDTA tube, adults and children
4. 30 ml urine with no preservative, adults and children.

Plasma cholinesterase level may be used to screen for exposure. RBC cholinesterase level correlates better with severity and prognosis or a mixed cholinesterase ratio is best for determining if sufficient pralidoxime is being given.

Expert advice may be sought from HPA National Poisons Information Service (HPA NPIS) 0870 600 6266 or HPA Chemical Hazards and Poisons Division (HPA CHaPD) 0870 606 4444

Accurate, contemporaneous notes are essential. The HPA has a chemical exposure record form that should be available to A&E departments and those that may deal with such events. It can also be taken from the HPA website listed at the end. Forward the completed form to HPA Chemical Hazards and Poisons Division (HPA CHaPD), and put a copy of the completed form in the patient's notes. If there are more than 20 victims, the toxicology coordinator will arrange for different records.

• Later effects of acute exposure include EEG changes, poor concentration and memory and post-traumatic stress disorder.⁶
• The respiratory system is often the first to be affected as the agent is usually inhaled but there do not appear to be long term respiratory problems.⁷
• Chronic, usually industrial exposure, gives a lower exposure but for a longer time.
• The long term neuropsychological effects in orchard sprayers in England have been examined and it is difficult to obtain a clear result.⁸ A survey of agricultural workers in the USA found a more clear relationship with cumulative dose of organophosphates.⁹ A survey from Spain was also quite clear about a cumulative dose effect.¹⁰ A study from Birmingham suggested that sheep farmers were at increased risk of neurological abnormalities.¹¹