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    DELIRIUM

    DEFINITION

    An acute reversible alteration in cognitive function and/or behaviour
    that occurs as a direct toxic effect of a substance or secondary to
    some underlying medical condition.

    TOXIC CAUSES

    Substances of abuse 
         Amphetamines
              3,4-Methylenedioxymethamphetamine (MDMA, ecstasy)
              Amphetamine
              Methamphetamine 
         Cocaine
         Lysergic acid diethylamide (LSD)
         Phencyclidine (PCP)
         Solvents e.g. toluene

    Plants and Mushrooms
         Psylocybin-containing (hallucinogenic) mushrooms
         Datura species
         Mescaline
         Nutmeg

    Industrial/Environmental chemicals
         Carbon monoxide
         Bromide
         Mercury (inorganic) 
         Methylbromide
         Solvents

    Pharmaceuticals
         Common causes
              Anticholinergic drugs
                   Antihistamines
                   Atropine
                   Benztropine
                   Scopolamine 
                   Phenothiazines 
                   Tricyclic antidepressants
              Corticosteroids
              Ketamine
              Methylphenidate
              Serotonergic drugs 
              Sympathomimetics 
                   Phenylpropanolamine
                   Pseudoephedrine

         Unusual causes
              Cimetidine 
              Ergotamine 
              Flecainide 
              Ketoconazole 
              Levodopa 
              Mefloquine 
              Non-steroidal antiinflammatories (NSAIDs)
              Ofloxacin 
              Propanolol 
              Salicylates

    NON-TOXIC CAUSES

    Drug withdrawal syndromes
         Ethanol 
         Opiates
         Sedative-hypnotics

    Cerebral disease
         Seizure 
         Trauma
         Tumour
         Vascular

    Environmental
         Hypothermia
         Hyperthermia

    Infection
         CNS infections
         Sepsis

    Metabolic
         Acidosis
         Electrolyte disturbances 
         Hypoglycaemia 
         Hypoxia
         Hypercarbia
         Liver failure
         Thyrotoxicosis 
         Uraemia

    Vitamin deficiency
         Niacin
         Pyridoxine
         Thiamine

    Note:  Some of these non-toxic causes may occur as a complication of
    an intoxication.

    CLINICAL FEATURES

    The clinical features of the altered cognition and behaviour
    associated with delirium are extremely variable in type and severity,
    and may fluctuate with time.  They may include drowsiness, anxiety,
    restlessness, inability to concentrate, impaired memory, poorly-formed
    delusions, agitation, confusion, disorientation, disturbed speech
    content, emotional lability, and visual and auditory hallucinations.

    The disturbance in cognition and behaviour may result in the patient
    causing physical harm to themselves or others.

    Other clinical features of the underlying intoxication (e.g.
    anticholinergic, beta adrenergic, serotonin syndrome) may also be
    noted.

    DIFFERENTIAL DIAGNOSIS

    Acute psychotic illness
    Central nervous system depression
    Dementia
    Malingering

    RELEVANT INVESTIGATIONS

    The major role of biomedical investigations is to exclude or diagnose
    non-toxic causes of delirium.  Investigations should be selected
    according to clinical judgement and may include:

         Arterial blood gases
         Blood sugar level
         Chest X-ray
         CT of the head
         ECG 
         Electroencephalogram
         Pulse oximetry 
         Renal and hepatic function tests
         Serum electrolytes
         Thyroid function tests

    TREATMENT

    Treatment is essentially supportive and should be continued until
    cognitive function and behaviour returns to normal.

    General supportive measures are aimed at alleviating distressing
    symptoms, preventing self-harm and maintaining adequate fluid and
    electrolyte fluid balance.  These measures may include:

         Intravenous fluids (if the patient is not taking oral fluids)
         Provision of a calm environment (no bright lights, no noise, away
           from windows) 
         Reassurance
         Protection of the patient from self-inflicted injury
         Relief of urinary retention (anticholinergic agents)
         Pharmacological sedation

    The delirious patient should never be left unattended.  Physical
    restraint should be minimized to that required to gain initial control
    of an uncooperative patient and to undertake procedures and prevent
    self-harm prior to pharmacological sedation.  When required, physical
    restraint is best accomplished by holding the patient with the
    assistance of several people.  Extremely violent patients should be
    subdued by a team of people who have allocated roles to stabilise each
    limb and the head. The prolonged use of bindings, restraints or other
    restrictive devices should be avoided as they do not necessarily
    protect the patient from injury.

    Pharmacological sedation is best accomplished with a benzodiazepine
    and/or haloperidol. Suggested agents and doses are:

     Diazepam.  Give 5 to 10 mg of  diazepam intravenously over 1 to 3
    minutes.  This dose may be repeated as necessary to a maximal total
    dose of 30 mg.  In children, give 0.25 to 0.4 mg/kg up to maximal
    total dose of 5 mg if under 5 years of age and 10mg if over 5 years of
    age.  Diazepam should not be given intramuscularly.

     Midazolam. Give 0.1 mg/kg intravenously and repeat every 5 to 10
    minutes as required.  If unable to obtain venous access, 0.25 mg/kg
    can be given intramuscularly.  The intramuscular dose should not be
    repeated in less than 1 hour.

     Haloperidol. Give 0.05 to 0.1 mg/kg intravenously and repeat after
    20 minutes if required. Haloperidol may also be given intramuscularly. 
    Intramuscular doses should not be repeated in less than 1 hour.

    The aim is to sedate the patient to the point of being physically and
    mentally calm but still rouseable with stimulation.  If the patient
    cannot be controlled despite sedation with the doses described above,
    further doses should not be used unless facilities for intubation and
    ventilation are available.

    Specific supportive or antidotal therapy may be necessary where the
    delirium is a consequence of a specific toxin or specific complication
    of intoxication (e.g. respiratory failure, hyperthermia, hypothermia,
    hypoglycaemia, hyponatraemia, hypernatraemia, hypomagnesaemia). 
     Physostigmine may be considered in the management of delirium
    associated with poisoning by anticholinergic agents.  The delirium
    associated with serotonin syndrome may be improved by the
    administration of  cyproheptadine or  chlorpromazine.

    CLINICAL COURSE AND MONITORING

    The duration of delirium varies with the intoxication but rarely lasts
    longer than 72 hours.  The patient should be carefully and
    continuously observed until mental status normalizes.  Mental status
    and respiratory function must be carefully monitored after sedation.  

    LONG-TERM COMPLICATIONS

    Rare, provided patients do not injure themselves whilst delirious.  

    Disturbing recurrences of symptoms ("flash-backs") sometimes occur
    following ingestion of LSD or other hallucinogens

    AUTHOR(S)/REVIEWERS

    Authors:       Dr J. Pronczuk, International Programme for Chemical
                   Safety, Geneva, Switzerland.
                   Dr R. Dowsett, Departments of Clinical Pharmacology and
                   Emergency Medicine, Westmead Hospital, Westmead, NSW
                   2145, Australia.

    Reviewers:     Cardiff 3/95, Berlin 10/95: R. Dowsett, J. Pronczuk,
                   Cardiff  9/96 T. Meredith, L. Murray 
                   Birmingham 3/99: T. Meredith, L. Murray, A. Nantel,
                   J. Szajewski.