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.