Acetylcholinesterase inhibitor poisoning
Organophosphate & Carbamate Insecticide Poisoning:
Both organophosphate & carbamate insecticides are acetylcholinesterase inhibitors which are readily absorbed through intact skin or mucosa as well as from the GIT.
Organophosphate inhibition is irreversible lasting months whereas clinical effects of carbamates last little more than 24hrs.
Carbamates poorly pass BBB & thus have less CNS effects cf organophosphates.
Inhibition of acetylcholinesterase leads to rapid accumulation of acetylcholine at the terminal endings of all postganglionic nerves, at both parasympathetic & sympathetic ganglia & myoneural junctions.
In addition, organophosphate poisoning may cause a delayed neurotoxicity - Wallerian degeneration of mainly the large myelinated fibers resulting in a peripheral neuropathy.
Clinical effects of anticholinesterase poisoning:
Classically, symptoms develop over a few hours (less if massive exposures or up to 2days if lipophilic) and present as the “SLUDGE” syndrome:
Salivation, Lacrimation, Urination, Diarrhoea, GIT effects, Everything else;
Patients classically die from inability to aerate whilst drowning in their own secretions.
The route of exposure usually determines the system effected first: inhal. - pulm.; ingested - GIT;
CNS effects are usually late, indicating a more severe ingestion.
Clinical effects of acute exposure:
Stimulation of muscarinic parasymp. receptors:
miosis, bronchoconstriction, wheezing, SOB, nausea, vomiting, diarrhoea, tenesmus, fecal incontinence, urinary frequency & incontinence, excessive lacrimation, salivation, broncorrhoea, sweating, bradycardia, hypotension, ventricular tachycardia;
Stimulation of nicotinic motor & sympathetic receptors:
tachycardia, palor, hypertension, hyperglycaemia, muscle twitching/fasciculations, weakness
CNS effects if penetrate BBB:
emotional lability, restlessness, tremors, headaches, withdrawal & depression, drowsiness, lethargy
If highly toxic exposure, pts can quickly (min-hrs) progress to:
ataxia, generalised weakness, coma, convulsions, resp. depression, CVS depression
In children CNS effects usually predominated by lethargy or coma/stupor;
The predominant symptoms/signs may not be diagnostically useful in young children as:
Classification of severity:
Clinical effects of chronic exposure:
usually occur within 2wks exposure & last several months:
polyneuropathies - paraesthesias, weakness, muscle cramps, altered gait, drowsiness, emotional lability, depression, irritability.
NO long term effects described in children.
Management (last updated 1995):
Staff should be gowned & double-gloved, & should avoid inhaling vapors of vomitus, etc.
ABC's, Oxygen if needed
Decontaminate skin, eyes to prevent ongoing absorption:
thoroughly cleanse skin - at least 2 separate water & detergent washes will remove up to 94% of residual organoP, even if done up to 6hrs after exposure;
consider giving activated charcoal with sorbitol if recent ingestion & no C/I
All pts with suspected exposure, insert IV line & commence atropinisation to minimise bronchorrhoea:
(max 2mg) by slow injection whilst monitoring ECG & obs
0.02-0.05mg/kg (max 2mg) can be given every 10-15min until atropinised:
ie. warm, dry, flushed skin; dilated pupils, dry mouth, tachycardia
for most children 2 doses will be ample but may need much more
further maintenance doses of atropine should be given if signs of atropine excess appear to be reversing, atropinisation should be continued for:
organoP - at least 24hrs with tapering of dose after 12hrs if clinically OK
lipophilic organoP - longer duration Rx
carbamates - shorter duration of Rx
Atropine will not affect nicotinic (skel. muscle & symp. ganglia) receptors.
Take bloods for RBC cholinesterase activity;
Pralidoxime is a cholinesterase reactivator at the NM junction, and is effective for some of the nicotine effects & thus helpful for re-establishing resp. muscle & diaphragm movement, but does not cross BBB & thus CNS dysfunction is not helped.
There is evidence that pralidoxime may increase the toxicity of carbamates & thus should only be used in organoP poisonings, after adequate atropinisation & only if resp. depression or unresponsive cardiac arrhythmias, although some feel it is appropriate to use if more than 2 doses of atropine have been needed in organoP poisonings.
Dose of pralidoxime:
Administration should commence within 36hrs of exposure otherwise it may not work due to a process called “aging” of the organoP-enzyme complex.
Adverse effects of pralidoxime:
dizziness, headache, nausea, blurred vision, muscle weakness.
Summary of Differences between organophosphate & carbamate insecticides:
shorter effect - usually only lasting 24hrs (cf months)
do not pass BBB & thus have less CNS effects
C/I to use pralidoxime as evidence that this makes carbamate toxicity worse!
Highly toxic carbamates:
Moderately toxic carbamates:
Highly toxic (LD50 < 50mg/kg in rats):
tetraethyl pyrophosphate (TEEP)
Moderately toxic organophosphates (LD50 > 50mg/kg rats):
Least toxic organophosphates (LD50 > 1000mg/kg rats):