ORGANOPHOSPHATES
Organophosphate poisoning accounts for nearly one third of hospital admissions from poisoning in Sri Lanka. Organophosphorus insecticides inhibit the enzyme acetyl cholinesterase (AChE) at nerve endings by phosphorylation,
40resulting in accumulation of acetyl choline at receptor sites. This
occurs at the neuro-effector junctions, skeletal neuro-muscular
junctions, autonomic ganglia and in the brain.
After ingestion, symptoms can occur almost immediately.
However, symptoms following occupational exposure may be
delayed for a few hours or days.
Certain organophosphates (e.g. methamidophos) can damage the
axons of peripheral nerves, causing weakness or paralysis and
paraesthesia of the extremities. Clinical features appear a few
weeks after the poisoning episode and persist for several months.
No useful therapeutic measures, apart from physiotherapy, are
available for this condition.
CLINICAL FEATURES
Ingestion
Clinical features observed after ingestion can be divided into four
categories.
(a) Muscarinic effects (actions at post-ganglionic parasympathetic
nerve endings): Nausea, vomiting, abdominal cramps, diarrhoea,
tenesmus, involuntary defaecation, sweating, salivation,
rhinorrhoea, lachrymation, small or pin point pupils, blurred vision,
wheezing, rhonchi, crepitations, productive cough, pulmonary
oedema, dyspnoea, cyanosis, tightness of the chest, urinary
frequency and incontinence, bradycardia, cardiac arrhythmias and
conduction defects.
(b) Nicotinic effects (actions at neuro-muscular junction): Muscle
twitching, incoordination, fasciculations, weakness, paralysis, and
cranial nerve palsies. After apparent recovery, sudden respiratory
failure may develop 24 to 96 hours after poisoning with some
organophosphates (intermediate syndrome).
41(c) Central nervous system effects: Headache, general weakness,
giddiness, mental confusion, disorientation, ataxia, convulsions,
coma and depression of the respiratory centre.
(d) Other effects: Hyperglycaemia, acute pancreatitis and rarely
ventricular tachycardia may be present. The ECG may show
prolongation of the QT interval. In 1 to 3 weeks, patients may
develop a polyneuropathy, manifesting as a paralysis of distal
muscles of limbs, numbness, and burning and tingling sensations.
This complication is observed with certain organophosphates only.
Acetylcholinesterase activity
If facilities are available, determine the plasma (pseudo)
cholinesterase and/or red blood cell acetylcholinesterase (RBC
AChE) enzyme activity. Check with the laboratory for the correct
collection technique, as some assays may give misleading results if
incorrectly handled.
The AChE activity may be a useful guide to therapy in a number of
different ways:
• Reduced activity (<80% of the lower limit of normal
range)
confirms
the
diagnosis
organophosphorus/carbamate poisoning.
• The extent of depression roughly correlates with clinical
severity (RBC AChE only). Less than 25% of normal
activity is usually associated with severe toxicity.
• It can be used to monitor the effects of pralidoxime (the
RBC-AChE should increase if the oximes are effective).
• It can indicate when oximes are ineffective (the RBC
AChE will not increase after a dose).
• It can monitor if it is safe to stop oximes (either RBC
42
ofAChE or plasma ChE will fall rapidly if oximes are
stopped too soon – and they can be restarted. If they do
not fall over 6 to 12 hours there is no significant
organophosphorus still present).
• The plasma ChE can also indicate there is no more
organophosphorus present in patients not on oximes
(plasma ChE will rise steadily back to normal over about a
fortnight after the organophosphorus is eliminated).
Inhalation
This can cause cough, difficulty in breathing, bronchitis and
pneumonia.
Eye contact
Irritation or pain, lachrymation, swelling, miosis, blurring of vision
and photophobia may result from eye contact.
MANAGEMENT
Check airway, breathing and circulation. Patients with
respiratory failure that has not responded to antidotes (atropine
and pralidoxime) will require mechanical ventilation.
Consider the need for gastric decontamination once the patient
has been stabilized, and if indicated, atropinised. Do not
perform gastric decontamination until the patient is stable, and if
necessary, intubated.
Ipecac therapy and forced emesis are contraindicated.
Consider gastric lavage or aspiration of ingested liquid poison by
a small flexible nasogastric tube only if it can be performed
within 2 hours of ingestion. (See page 4) If consciousness is
43impaired insert a cuffed endotracheal tube to protect the airway
prior to lavage.
Administer 1gram/kg activated charcoal orally or via nasogastric
tube at the end of the lavage.
Watch for convulsions and treat these with diazepam IV
immediately if they occur.
Atropine
The following features of cholinergic syndrome should be
monitored:
• Poor air entry into the lungs due to bronchorrhoea and
bronchospasm.
• Excessive sweating
• Bradycardia
• Hypotension
• Miosis
Severely poisoned patients are typically covered with sweat, and
have small pinpoint pupils and laboured breathing (often with
marked bronchorrhoea and wheeze).
The presence of pinpoint pupils, excessive sweat, bronchospasm
or crepitations suggests that the patient requires atropine. The
heart rate may be slowed, but normal or even fast heart rates are
common.
If none of these signs are present careful observation is still
required.
Atropine dosing:
44A major priority is to atropinise symptomatic patients. Only
consider the need for gastric decontamination once the patient
has been stabilized, and if indicated, atropinised.
If the clinical presentation is not clear but organophosphorus
poisoning is a possibility, administer atropine 0.6 – 1 mg. A
marked increase in heart rate (more than 20 – 25 beats/min) and
flushing of the skin suggest that the patient does not have
significant cholinergic poisoning and further atropine is not
required.
For an unconscious patient give atropine 1.8 – 3 mg (three to
five of 0.6 mg vials) rapidly IV into a fast flowing IV drip.
Three to five minutes after giving atropine check the five
parameters of cholinergic poisoning. A uniform improvement in
most of the five parameters is required, not improvements in just
one. However, the most important parameters are air entry on
chest auscultation, heart rate and blood pressure.
If after 3-5 min a consistent improvement across the five
parameters has not occurred, then more atropine is required.
Double the dose and continue to double each time that there is no
response.
Once atropinised, a patient will have clear lungs, adequate heart
rate (more than 80 beats/min) and blood pressure (more than 80
mmHg systolic with good urine output), dry skin and pupils no
longer pinpoint, an infusion may be set up if careful monitoring
facilities are available.
In the infusion give 10-20% of the total amount of atropine that
was required to load the patient every hour. If very large doses
(more than 30 mg) were initially required, then less can be used.
45Larger doses may be required, if oximes are not available. It is
rare that an infusion rate greater than 3-5 mg/hour is necessary.
Such high rates require frequent review and reduction of the rate
of infusion as necessary.
Review the patient and assess the five parameters every 15
minutes to see whether the atropine infusion rate is adequate. If
atropinisation is lost, (for example, if there is recurrence of
bronchospasm or bradycardia), give further boluses of atropine
until cholinergic signs disappear and increase the infusion rate.
Target end points for atropine therapy are:
• Clear chest on auscultation with no wheeze.
• Heart rate between 80 – 100 beats/min.
• Pupils no longer pinpoint.
• Systolic blood pressure > 80 mmHg.
• Dry axillae.
The aim of atropine therapy is to clear the chest and reach the
end-points for all five parameters. There is no need to aim for a
heart rate of 120-140 beats/min. This suggests atropine toxicity
rather than simple reversal of cholinergic poisoning.
Tachycardias are not a contraindication for atropine if other
features suggest under atropinisation.
However, such high heart rates will cause particularly severe
complications in older patients with pre-existing cardiac disease
and even myocardial infarctions may result. Tachycardia may
also be caused by hypoxia, agitation, alcohol withdrawal,
pneumonia, hypovolaemia and fast oxime administration.
Pupil dilatation is sometimes delayed and other parameters
usually improve much more rapidly.
46When all the parameters are satisfactory the patient has received
enough atropine and is atropinised.
Once the parameters have settled see the patient half hourly for
the first 6 hours to check that the atropine infusion rate is
sufficient and that there are no signs of atropine toxicity.
Excess atropine causes confusion, urinary retention,
hyperthermia, bowel ileus and tachycardia. The presence of all
these signs suggests that too much atropine is being given. The
infusion should be ceased and the patient reviewed after 30
minutes to see whether the features of toxicity have settled. If
not, continue to review every 30 minutes.
When atropine toxicity settles restart at 70 – 80% of the previous
rate. The patient should then be seen frequently to ensure that
the new infusion rate has reduced the signs of atropine toxicity
without permitting the reappearance of cholinergic signs.
Most ill patients will be catheterized after resuscitation to
observe urinary output. Urinary retention cannot then be used as
a marker of atropine toxicity.
Recurrence of toxicity requiring atropine therapy commonly
occurs after poisoning with fat soluble organophosphates such as
fenthion that leak out of fat over day and even weeks. Recurring
cholinergic crisis may occur with little notice.
Deaths have been reported with atropine overdose where IV
infusions were given without close monitoring in wards.
A febrile patient should receive sedation if there is excessive
agitation and active cooling. Lay a towel soaked with water over
the patient’s chest and place in a fan’s airflow. Cold water
soaked towels can also be placed at points of maximum heat
47loss.
Reduce agitation with diazepam 10 mg IV repeated as necessary
in an adult up to 30 – 40 mg per 24 hours. Tying a nonsedated
agitated patient to the bed is associated with complications,
including death. Such patients struggle against their bonds and
generate excess body heat which may result in hyperthermic
cardiac arrest.
Pralidoxime
Give 30 mg/kg loading dose of pralidoxime over 10 – 20 min
followed by a continuous infusion of 8 – 10 mg/kg per hour until
clinical recovery (for example 12-24 hours after atropine is no
longer required or the patient is extubated) or 7 days which is
later. Less severely poisoned patients can be given intermittent
doses (1 gram 6 hourly by slow IV bolus over10-20 mins)
Oximes are not required for carbamate poisoning.
Respiratory failure
If facilities permit give patients a general anaesthetic and
intubate and mechanically ventilate them. This should reduce
the number of deaths from respiratory complications.
Intermediate syndrome
Watch for early signs of intermediate syndrome. Weakness of
neck flexion is common and the patient has difficulty lifting their
head off the pillow. Subsequent signs include the use of
accessory muscles of respiration, nasal flaring, tachypnoea,
sweating, cranial nerve palsies and proximal muscle weakness in
the limbs with retained distal muscle strength.
48Supportive therapy
Temporary pacing may be necessary to terminate ventricular tachycardias with QT prolongation.
Anticipate and treat bronchopneumonia with appropriate antibiotics. Chest physiotherapy may be necessary.
In severe poisoning management in an intensive care unit can be life-saving. REFERENCES
1. Roberts DM, Aaron CK. “Managing acute