CHOLINERGIC SYNDROME
DEFINITION
The clinical syndrome that results from excessive stimulation of
acetylcholine receptors. It is characterized by mental status
changes, muscle weakness and excessive secretory activity.
Acetylcholine is the neurotransmitter at all preganglionic autonomic
nerve endings (nicotinic receptors), all parasympathetic and some
sympathetic postganglionic nerve endings (muscarinic receptors), the
neuromuscular junction (nicotinic receptors) and at some CNS synapses.
Acetylcholine undergoes continuous degradation by acetylcholine
esterase. Excessive stimulation of acetylcholine receptors occurs as
a result of inhibition of acetylcholine esterase or direct stimulation
of acetylcholine receptors.
TOXIC CAUSES
Acetylcholine esterase inhibition
Carbamate pesticides
Neostigmine
Organophosphorus pesticides
Organophosphorus warfare agents
Sarin
Soman
Tabun
Physostigmine
Pyridostigmine
Direct stimulation of acetylcholine receptors
Arecholine
Betanechol
Carbachol
Choline
Metacholine
Mushrooms
Boletus sp.
Clitocybe sp.
Inocybe sp.
Pilocarpine
NON-TOXIC CAUSES
None
CLINICAL FEATURES
Clinical manifestations of excessive cholinergic activity may be
divided into muscarinic, nicotinic and central effects. The relative
severity of these effects differs between individual cases.
Muscarinic effects are those of parasympathetic overactivity and
include bradycardia, pinpoint pupils, sweating, blurred vision,
excessive lacrimation, excessive bronchial secretions, wheezing,
dyspnoea, coughing, vomiting, abdominal cramping, diarrhoea, and
urinary and faecal incontinence.
Nicotinic effects are those of sympathetic overactivity and
neuromuscular dysfunction and include tachycardia, hypertension,
dilated pupils, muscle fasciculation and muscle weakness.
Central effects may include agitation, psychosis, confusion, coma and
seizures.
DIFFERENTIAL DIAGNOSIS
The full clinical syndrome usually presents no diagnostic dilemma.
Where particular manifestations of poisoning predominate, the
following conditions may be considered:
Bronchial asthma
Gastroenteritis
Myasthenic crisis
Pulmonary oedema
Status epilepticus of other aetiology
RELEVANT INVESTIGATIONS
Arterial blood gases
Chest X-ray
ECG
Electrolytes, urea and creatinine
Glucose
Oximetry
Serum and/or erythrocyte acetylcholine esterase activity.
Depression of acetylcholine esterase activity is diagnostic of
carbamate or organophosphorus poisoning but is not helpful in the
acute management of the cholinergic syndrome.
TREATMENT
In severe cases, the initial priority is to secure the airway,
maintain ventilation and oxygenation, secure intravenous access and
control seizures with intravenous diazepam.
Decontamination appropriate to the offending agent and route of
exposure should be performed.
Atropine is the specific antidote for the muscarinic effects and
should be administered as soon as the diagnosis is suspected. It has
no effect on nicotinic receptors. The initial dose of 1 to 2 mg
(0.05mg/kg in children) intravenously should be repeated every 5 to 10
minutes until drying of respiratory secretions is achieved. In severe
cases, very large doses of atropine (up to 100 mg) may be required.
Excessive dosing of atropine will manifest itself as agitation and
tachycardia. The patient should remain under close observation and
further doses of atropine should be given as required. Where
intravenous access is not available, atropine may be administered via
the intramuscular, subcutaneous, endotracheal or intraosseous
(children) routes.
In moderate-to-severe cases of cholinergic syndrome due to
organophosphorus pesticide or warfare agent poisoning, an
acetylcholine esterase reactivator should be administered (if
available) following atropine. Either pralidoxime or obidoxime are
suitable. The dose of pralidoxime is 30 mg/kg intravenously followed
by a continuous infusion of 8 mg/kg/hour until clinical recovery is
observed and for at least 24 hours. Alternatively, continued
administration of pralidoxime may be by intermittent intravenous or
intramuscular doses of 30 mg/kg every 4 hours. The dose of obidoxime
is 4 mg/kg intravenously followed by a continuous infusion of 0.5
mg/kg/hour until clinical recovery is observed and at least 24 hours.
Alternatively, continued administration of obidoxime may be by
intermittent intramuscular or intravenous doses of 2 mg/kg every 4
hours. In severely poisoned patients, doses greater than this may be
necessary to achieve enzyme reactivation.
Patients should remain under close observation after cessation of
oxime therapy. Recurrence of clinical manifestations of toxicity
indicates the need for further oxime therapy.
CLINICAL COURSE AND MONITORING
The severity and duration of the clinical syndrome depend on the agent
responsible and the dose. It is usually relatively benign and of
short duration following overdose of a cholinergic drug. More severe
poisoning is usual with carbamate and organophosphorus compounds,
especially following ingestion. The clinical features of poisoning by
carbamate pesticides are usually of shorter duration and less severe
than those of organophosphorus compounds.
Those cases severe enough to require supportive care measures or
antidote therapy require close monitoring and are ideally managed in
an intensive care unit setting. They should not be discharged from
hospital until they remain asymptomatic for at least 24 hours after
the withdrawal of all antidote therapy.
The term "Intermediate Syndrome" is applied to recurrent muscle
weakness occurring some days after the exposure. It may be associated
with inadequate oxime therapy.
Cholinesterase activity often remains low for weeks after the acute
poisoning, despite complete resolution of all symptoms and signs of
toxicity.
LONG TERM COMPLICATIONS
Peripheral neuropathy
Neuropsychiatric sequelae
AUTHOR(S)/REVIEWERS
Authors: Ryszard Feldman & Janusz Szajewski. Warsaw Poisons
Control Centre, Szpital Praski, Pl. Weteranow 4, 03-701
Warszawa, Poland (February, 1998).
Reviewers: Geneva 8/98, D. Jacobsen, L. Murray, J Pronczuk.
Birmingham 3/99: T. Meredith, L. Murray, A. Nantel,
J. Szajewski.