ACUTE ANTICHOLINERGIC SYNDROME

    DEFINITION

    Clinical syndrome resulting from antagonization of acetylcholine at
    the muscarinic receptor.

    TOXIC CAUSES

    Antihistamines (especially Promethazine, Trimeprazine,
    Dimenhydrinate)
    Antiparkinsonian drugs (e.g., Benztropine, Biperiden, Orphenadrine,
    Procyclidine)
    Antispasmodic agents (e.g., Clidinium, Glycopyrrolate,
    Propantheline)
    Belladonna alkaloids (e.g., Belladonna extract, Atropine, Hyoscine,
    L-Hyoscyamine sulphate, Scopolamine hydrobromide)
    Cyclic Antidepressants
    Ophthalmic cycloplegics (e.g., Cyclopentolate, Homatropine,
    Tropicamide)
    Phenothiazines
    Plants containing anticholinergic alkaloids (e.g., Atropa
    belladonna, Brugmansia spp, Cestrum spp, Datura spp, Hyoscyamus
    niger, Solanum spp).  The tropane derivatives (alkaloids of
    solanaceous plants and related drugs) are of greatest practical
    importance.

    CLINICAL FEATURES

    The clinical diagnosis is based on the appearance of the
    anticholinergic toxidrome.  This toxidrome has central and
    peripheral components:

    The central anticholinergic signs and symptoms include altered
    mental status, disorientation, incoherent speech, delirium,
    hallucinations, agitation, violent behaviour, somnolence, coma,
    central respiratory failure, and, rarely, seizures.

    The peripheral anticholinergic syndrome includes hyperthermia,
    mydriasis, dry mucosa membranes, dry, hot and red skin, peripheral
    vasodilatation, tachycardia, diminished bowel motility (even
    paralytic ileus), and urinary retention.

    Rhabdomyolysis, cardiogenic shock or cardiorespiratory arrest may
    occur exceptionally.  Patients with closed-angle glaucoma may
    suffer an acute precipitation of the condition.  Patients with
    benign prostatic hyperplasia are particularly prone to develop
    urinary retention.

    DIFFERENTIAL DIAGNOSIS

    Alcohol withdrawal
    Organic delirium (usually secondary to sepsis)
    Psychiatric illness
    Psychedelic drugs
    Sympathomimetic drugs

    RELEVANT INVESTIGATIONS

    Measurement of blood and urine levels of the anticholinergic agents
    are of little or no practical value.
    Other laboratory examinations may be needed as dictated by the
    general condition of the patient. 

    TREATMENT

    Treatment is primarily supportive.  The patient must be protected
    from self-inflicted injury.  This may require physical and/or
    pharmacological restraint.  Respiratory failure may require
    intubation and controlled respiration.  In cases of ingestion,
    decontamination may be considered.

     Diazepam: Administer 5 to 10 mg intravenously over 1 to 3
    minutes.  Repeat this dose as necessary to a maximal total dose of
    30 mg.

    The paediatric dose of  diazepam is 0.25 to 0.4 mg/kg up to
    maximal total dose of 5 mg in children up to 5-years-old and 10mg
    in children over 5-years-old.

     Physostigmine is a specific antidote for anticholinergic
    poisoning and may be used under the following conditions :

         1.   Severe agitation or psychotic behaviour unresponsive to
              other treatments.
         2.   Clinical evidence of both peripheral and central
              anticholinergic syndrome.
         3.   No history of seizures.
         4.   Normal ECG, especially QRS width.
         5.   No history of ingestion or co-ingestion of tricylic
              antidepressants or other drugs that delay
              intraventricular conduction.
         6.   Cardio-respiratory monitoring in place and resuscitation
              facilities available.

    The dose of  physostigmine is 1 to 2 mg (0.5 mg in children) by
    intravenous injection over 2 to 5 minutes.  If necessary, this dose
    can be repeated after 40 minutes.

    CLINICAL COURSE AND MONITORING

    Complete recovery is expected over a period of hours to days.

    In more severe cases of anticholinergic syndrome, cardiac rhythm
    should be monitored and blood pressure frequently measured.  Urine
    output should be monitored so as not to overlook urinary retention.

    LONG TERM COMPLICATIONS

    Nil specific.

    AUTHOR(S)/PEER REVIEW

    Author:        Dr J. Szajewski, Director, Warsaw Poison Control
                   Centre, Warsaw, Poland.

    Peer Review:   Berlin, October 1995: R. Dowsett, J. Pronczuk.