Microsoft word - delirium and sleep disturbances final.doc

Clinical Guideline
Delirium and sleep disturbances in critical care —
pharmacological management
CONTENTS
Pharmacological management of delirium
Background
Table 1 Drugs commonly associated with delirium Table 2 Commonly used medications with anticholinergic activity and possible alternatives Pharmacological management of sleep disturbances
Management of sleep disturbances flow chart Acknowledgements- Dr. R Bourne (Clinical pharmacist, STH NHS Foundation trust)
(Elements of this guideline are derived from STH NHS Foundation trust guidelines.)
Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 Pharmacological management of delirium
Background
Delirium is acute brain failure in critical care patients secondary to systemic disease. It is very common,
occurring in up to 80% of mechanically ventilated patients during the course of their illness. It contributes to
increased patient morbidity and mortality, which persists even after patients have been discharged from
hospital. 1,2 Three motor subtypes exist - hypoactive, hyperactive and mixed types. The hypoactive form is
the most common subtype and is often missed, or misdiagnosed.

All patients in ICU are at a high risk of developing delirium and therefore should be screened for delirium
frequently (once every shift, or sooner if suspected). A daily checklist should be filled out to address all the
precipitating and augmenting factors. In addition to prevention and non-pharmacological techniques
appropriate drug management is an important adjunct in management of patients with delirium.
Drug treatment should be considered when other non-pharmacological measures have failed or patient has
distressing symptoms.3 Patients may be screened for the presence of delirium using tools such as the
Confusion Assessment Method (CAM), a specific screening tool has been developed for use on critical care
which is called CAM ICU. NICE recommend the use of CAM ICU, the flow chart can been found at:
www.icudelirium.org . Nursing staff on critical care will be trained in the use of CAM ICU and will assess all
patients daily. It should be noted that CAM-ICU is only 70% sensitive and delirium is fluctuant so that even
patients with troublesome delirium can have lucid intervals. Therefore screening should be carried out
several times a day, but a clinical suspicion of delirium should be trusted more than a single test which is
known to have a significant false negative rate.
Regular drug treatment should be commenced for patients who are CAM ICU positive and reviewed daily for
efficacy and adverse effects. When delirium symptoms resolve, antipsychotic medication can be withdrawn
over 48 to 72 hours. Only short treatment courses (less than a week) should be used.3
The incidence of delirium is higher if benzodiazepines are used for sedation, and therefore their primary
indication is treatment of withdrawal delirium e.g. alcohol withdrawal. 4.5 However, they remain a treatment
option in patients with severe hyperactive delirium who pose a risk to themselves and/or staff.
Sleep disturbances are often regarded as a precipitating factor for causing delirium, the cause and effect
relationship is not straightforward and therefore delirium status should be accounted for when attempting to
improve nocturnal sleep quantity in critical care patients. For this reason guidelines on the pharmacological
management of delirium and sleep disorders are included in the same document.
Further information on the pharmacological management of delirium is also available from the following links:


NICE CG 103, Delirium- diagnosis, prevention and management
Vanderbilt University Medical Center delirium resource website
UK delirium resource website
Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 MANAGEMENT OF DELIRIUM
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk Review drug chart, try to minimise exposure to medication associated with delirium. Ensure all doses appropriate (e.g. penicillins reduce dose in renal failure).Prescribe alternative agents where possible to minimise anti-cholinergic activity. Treat pain, hypoxia, constipation, pyrexia. Correct sleep/wake cycle; avoid lights at night ensure light in day. Provide usual glasses, hearing aids, dentures if needed. Review environment: avoid excessive noise, consistency with designated nurse, familiar items from home, access to a clock, involve familiar to maximise feelings of security, optimise room temperature. Communicate clearly to patients: orientate patients to time, remind of day and location.  Chlordiazepoxide as per hospital pathway
Haloperidol 1 to 2.5mg qds iv
Haloperidol 0.5mg tds
 Pabrinex® 2 pairs tds for 72 hours
Haloperidol 2.5 to 5mg qds po
 Consider clonidine or haloperidol if
severe agitation (especially if poses risk to Haloperidol 1 to 2.5mg to max
Olanzepine 5mg nocte
self or others). Note clonidine will not prevent alcohol withdrawal seizures.
Second Line:
Olanzepine 5mg od
 If clear symptoms of nicotine withdrawal consider starting  First choice NRT on critical care are nicotine patches. Consider in addition if severe agitation 25mg patch over 16 hours if smoke over 20 cigarettes per day (especially if poses risk to self or others). 15mg patch over 16 hours for patients who smoke under 20 Clonidine
Patches should be applied at 6am and removed at 10pm  24 hour patches should be avoided where possible due to a Benzodiazepine
Or
Low dose propofol
 Consider clonidine or haloperidol if severe agitation (especially if poses risk to self or others).  All prescriptions for antipsychotics should be endorsed ‘delirium’ to aid review of therapy.  Antipsychotics should be gradually withdrawn over 2 to 3 days when the patient is negative for delirium.  Benzodiazepines are associated with delirium and so should be used as a last resort except in alcohol withdrawal.  Risperidone may be considered third line if haloperidol and olanzepine have been tried unsuccessfully.  Antipsychotics should be discontinued if a patient is fully sedated.  Patients should not be prescribed more than one antipsychotic concomitantly. References
www.emc.medicines.org.uk accessed 01/02/12
Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3.
September 2011. Sheffield Teaching Hospitals NHS Foundation Trust.
Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 Table 1: Drugs commonly associated with delirium7

Medication
Comments
• Review for excess anticholinergic/ dopamine activity • Discuss with neuromedical/ geriatric team acute management and consider benefits of temporarily reducing anticholinergic and • When possible limit benzodiazepine use to cover benzodiazepine or alcohol withdrawal • Review use as night-time sleep aid and consider trazodone/ mirtazapine (see Management of Sleep Disturbances section) Use lowest effective dose and discontinue as soon as clinically Consider withholding digoxin, or alternative medication for heart rate control e.g. β-blocker/ amiodarone • Maintain plasma levels within lowest effective range. • Maintain plasma levels within lowest effective range. •Attempt to optimise pain control with adjunctive opioid sparing agents e.g. paracetamol; gabapentin; local anaesthetics; ketamine (low dose) •Avoid accumulation of neurotoxic metabolites in patients with severe renal failure e.g. (morphine-3-glucuronide; norpethidine) •Tramadol has significant serotonin activity, therefore review appropriateness of continued/ new therapy and consider alternative analgesia/ opioids Maintain plasma levels within the therapeutic range Maintain plasma levels within the therapeutic range (account for albumin and “free drug” concentrations) • Review dose in severe renal dysfunction • Discuss with microbiology if alternative antibiotic appropriate Selective serotonin reuptake inhibitors • Review for other drugs with serotonin activity • Consider withholding depending on clinical circumstances, balancing risk of withdrawal versus toxicity
Table 2: Commonly used medications with moderate to high anticholinergic activity7
Medication
Alternative
Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012
Pharmacological management of sleep disturbances
Background
Sleep disturbances in critical care patients are characterised by sleep fragmentation. Patients are often sleep
deprived, the sleep tends to be fragmented. It is a problem of sleep continuity and results in reduced
quantities of deeper sleep phases, such as slow wave sleep (SWS) and rapid eye movement sleep (REM).
Sleep disturbances may contribute to patient morbidity including adverse consequences on respiratory,
cardiac, neurological and immunological function.6
Causes of sleep disturbances in critical care patients are multi-factorial and include: the environment (e.g.
noise, light), pain, ventilator dys-synchrony, delirium, circadian rhythm disturbances and medication (e.g.
opioids, benzodiazepines).

Treatment of sleep disturbances therefore should not solely rely on pharmacological treatment, but seek to
identify sleep disturbing factors (e.g. pain) and correct them if possible. Sleep hygiene should be encouraged
and targeted drug treatment employed only if necessary.

All new prescriptions for acute treatment should be endorsed “short-term sleep-aid” and reviewed prior to
discharge for critical care.
Sleep hygiene
Sleep hygiene refers to attempts to make conditions suitable for sleep to occur.
 Encourage the patient to be active during the day, e.g. early morning physiotherapy, sitting out
of bed, range of motion exercises. Try to avoid long naps later in the day as these reduce the
normal sleep drive and reduce nocturnal sleep quality.
 Avoid caffeinated drinks (tea/ coffee) after 1800hours.  Try to re-enforce a day-night cycle with bright lights during the day and lights off during the night. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 MANAGEMENT OF SLEEP DISTURBANCE
This guideline is a summary, ful details are available from the SPC www.emc.medicines.org.uk Review all patients who have inadequate sleep (less than 4 hours of continuous sleep or inability to sleep at night and excessive daytime drowsiness). Reinforce sleep hygiene and sleep wake cycle
Control excess noise at night
Bright light in daytime, darkness at night
Encourage regular morning wake up time
Control environmental temperature
Encourage range of motion exercises and activity e.g. patient sitting out
Ensure comfortable position
Avoid caffeine intake by patients in the evening
Review current medication. Reduce/minimise disruptive medication. Consider withdrawal reactions
Review pain control. Optimise non-opioid analgesia
Pharmacological Management
Delirium
Mirtazapine 15mg nocte is an alternative agent if not responding to trazodone If the patient has a disruption in normal circadian rhythm and is falling asleep during the day but is awake at night consider starting Melatonin MR 2mg nocte All prescriptions must be reviewed prior to discharge from critical care. Annotate prescription with ‘short term sleep aid’ References
www.emc.medicines.org.uk accessed 01/02/12
Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care
(Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 References

1. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr., Inouye SK, Bernard GR, Dittus RS: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004, 291:1753-1762. 2. Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, Fang YF, Shieh MH, Kuo HP: The impact of delirium on the survival of mechanically ventilated patients. Critical Care Med 2004, 32:2254-2259. 3. Delirium; diagnosis, prevention and management. Nice CG 103:63-69. July 2010. http://www.nice.org.uk/nicemedia/live/13060/49909/49909.pdf 4. Pandharipande PP, Pun BT, Her DL et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2009; 301: 489-99. 5. Riker RR, Sehabi , Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized controlled trial. JAMA. 2009; 301 : 489-99. 6. Friese R: Sleep and recovery from critical illness and injury: A review of theory, current practice, and future directions. Critical Care Med 2008, 36:697-705. 7. Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 HALOPERIDOL
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk 1. Indication
Haloperidol is a ‘typical’ (butyrophenone) antipsychotic with predominantly dopamine antagonist activity. It is used first line for the treatment of hyperactive delirium and at low dose for the treatment of hypoactive delirium. 2. Presentation
Intravenous Injection 5mg/ml amps Oral 500microgram capsules Nasogastric Oral solution 2mg/ml Hyperactive delirium
1 to 2.5mg qds intravenously
Depending on the severity of symptoms. Prescribe additional PRN doses of 1 to 2.5mg.
Maximum daily dose 30mg.
Intravenous doses above 20mg daily should not routinely be used due to an increase in
side effects and lack of increase in clinical efficacy.
Hypoactive delirium
Start with lower doses such as 0.5mg tds intravenously
4. Common Side Effects
Risk of QT prolongation (especially with intravenous administration or with concurrent medication known to cause QT prolongation e.g. clarithromycin) Ventricular arrhythmias Increase in cerebrovascular events (mechanism unknown) Neuroleptic malignant syndrome. Symptoms include: hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness. This is a medical emergency requiring prompt treatment and withdrawal of the antipsychotic. Extrapyramidal side effects (consider therapy with procyclidine) 5. Contraindications
Parkinson’s disease, known hypersensitivity to haloperidol, comatose states.  Consider lower doses in hepatic impairment and in elderly patients.  The oral bioavailability is 60%, therefore oral and parenteral doses are not equivalent.  ECG monitoring is required when haloperidol is given intravenously. Discontinue  Avoid concomitant use of other antipsychotics 7. References
www.emc.medicines.org.uk accessed 01/02/12 BNF edition 61 March 2011 Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. OLANZAPINE
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk 1. Indication
Second line for treatment of hyperactive and hypoactive delirium. It is an atypical antipsychotic with greater anti serotonin versus dopamine activity. Delirium is an unlicensed indication. 2. Presentation
Orodispersible tablets: 5mg and 10mg which may be administered via NG tube. Tablets: 2.5mg, 5mg, 7.5mg and 10mg Intramuscular injection: 10mg (or subcutaneously, note this route is unlicensed). Oral. Starting dose 5mg to 10mg daily (best given at night time due to sedative effects) Consider using lower doses in older patients and in renal hepatic impairment. Intramuscular/subcutaneous. Starting dose of 10mg Maximum dose 20mg daily by oral/parenteral route. 4. Administration
Intramuscular injection should be reconstituted with 2.1ml water for injection to produce a 5mg/ml solution. 5. Common Side Effects
Risk of QT prolongation (especially with intravenous administration or with concurrent
medication known to cause QT prolongation e.g. clarithromycin). Ventricular arrhythmias.
Hyperglycaemia (sometimes associated with diabetic ketoacidosis). Increase in
cerebrovascular events. Extrapyramidal side effects (consider therapy with procyclidine).
Olanzapine has anticholinergic activity so may be associated with constipation and other
related side effects. Deranged LFTs. Consider dosage reduction is patients with raised
AST or ALT. In the event of hepatocellular injury or cholestatic injury, olanzapine should be
discontinued. Neutropenia (more common when olanzapine given with valproate).
Olanzapine may lower seizure threshold is patients who have previously had seizures.
Hypotension.

Neuroleptic malignant syndrome. Symptoms include: hyperthermia, generalised muscle
rigidity, autonomic instability, altered consciousness. This is a medical emergency
requiring prompt treatment and withdrawal of the antipsychotic.
6. Contraindications
Parkinson’s disease, known hypersensitivity to olanzapine, comatose states.

 Doses over 5mg are associated with a greater incidence of extra pyramidal side Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012  Oral and intramuscular/subcutaneous olanzapine should not be used concomitantly. 8. References
www.emc.medicines.org.uk accessed 08/02/12 BNF edition 61 March 2011 Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 RISPERIDONE
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk 1. Indication
Treatment of hypoactive delirium, this is an unlicensed indication. Risperidone is an atypical antipsychotic. 2. Presentation
500microgram tablets 1mg/ml oral solution. Starting dose in hypoactive delirium 500micrograms bd In severe renal or hepatic impairment reduce dose to 250micrograms bd Doses in the region of 250micrograms to 1.5mg daily in divided doses may be used. 4. Common Side Effects
Risk of QT prolongation (especially with intravenous administration or with concurrent medication known to cause QT prolongation e.g. clarithromycin) Ventricular arrhythmias Hyperglycaemia (sometimes associated with diabetic ketoacidosis). Increase in cerebrovascular events (mechanism unknown), avoid using in patients with risk factors for stroke. Neuroleptic malignant syndrome. Symptoms include: hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness. This is a medical emergency requiring prompt treatment and withdrawal of the antipsychotic. Extrapyramidal side effects (consider therapy with procyclidine). Deranged LFTs. Consider dosage reduction is patients with raised AST or ALT. Jaundice Neutropenia (more common when olanzapine given with valproate). Hypotension, tachycardia. Anemia, thrombocytopenia Dyspnoea, blurred vision, constipation, abdominal discomfort, vomiting. Rash, erythema. 5. Contraindications
Parkinson’s disease
Known hypersensitivity to risperidone
Comatose states
Patients with dementia (high risk of stroke)
 Some trials using risperidone noted a higher mortality in patients also receiving furosemide, no mechanism for this has been found. 7. References
www.emc.medicines.org.uk accessed 08/02/12 BNF edition 61 March 2011 Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 CLONIDINE
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk
1. Indication
Sedation and analgesia in adult patients
Clonidine is a central y acting antihypertensive agent. It is an α2-agonist producing
sedation and analgesia with minimal effect on respiratory function. Clonidine is of value
when opioid or benzodiazepine requirements are increasing. Clonidine may be used to
treat patients withdrawing from drugs or alcohol, note it has no effect on convulsions so
should not be used as sole therapy for alcohol withdrawal.
Continuous infusion of clonidine for sedation is an unlicensed method of administration.

2. Presentation
150 microgram /mL injection

3. Dose
Intermittent infusion
Doses of 50 to 400micrograms TDS or QDS have been used
Continuous Infusion
Doses in the range of 1 to 4microgram/kg/hour have been used. Using ideal body weight.
The normal dose range is 1 to 2 microgram /kg /hour. Doses should normally start at
around
2 microgram /kg/hour for an hour and the rate is titrated to sedative effect.
4. Administration
Route Drug
Concentration
Initial Maximum
Rate*
*Infusion rates are based on a 70kg patient.
Use a lower starting rate if blood pressure is compromised.

5.
Common Side Effects
Hypotension and bradycardia (especially after prolonged administration >7-10 days), may potentiate, or cause sinus bradycardia and AV block. Hyperglycaemia Acute colonic pseudo-obstruction has been reported at high doses Constipation, nausea, vomiting and headache Rash, itching Rarely fluid retention and abnormal LFTs. Dry mucous membranes Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012
6. Contraindications
Known hypersensitivity to the active ingredient or other components of the product
Severe bradyarrhythmia resulting from either sick sinus syndrome or AV block of 2nd or
3rd degree.
Clonidine should only be used with caution in patients with depression, with Raynaud's
disease or other peripheral vascular occlusive disease. As with other antihypertensive
drugs, treatment in patients with heart failure should be carefully monitored.
7. Y
compatibility
Compatible with:
Aminophylline, fentanyl, heparin, midazolam, morphine and potassium chloride.
Amiodarone and dobutamine if clonidine made up with glucose 5%.
8. Notes
Tolerance /tachyphylaxis occurs within 7 days of starting therapy
 Withdrawal of clonidine should be gradual due to risk of rebound hypertension,
tachycardia and agitation. Advise reduce over several days if on infusion over 2 days.  The blood pressure lowering effect of clonidine may be exacerbated by other hypotensive agents including other sedative drugs, diuretics, vasodilators.  t½ 10-20 hours - mean 13 hours (extended to up to 41 hours in severe renal  60% renally excreted as unchanged drug. The remaining 40% is metabolised by oxidation to metabolite, p-hydroxyclonidine, which is pharmacologically inactive.  Clearance is reduced in renal impairment  Should not be administered concomitantly with methylphenidate, cases of severe adverse effects including sudden death have been reported.  Drugs with α2- adrenoceptor antagonist properties such as Mirtazepine may reduce the  High intravenous doses of clonidine may increase the arrhythmogenic effect/QT  Clonidine can aid mild/moderate symptoms of alcohol withdrawal although has no effect on convulsions so should not be used as sole therapy.
9. References
www.ukcpa.org.uk accessed
www.emc.medicines.org.uk accessed 31/10/11
www.medicinescomplete.com accessed 31/10/11
http://medusa.wales.nhs.uk Medusa medicines guide accessed 31/10/11
 Hall, JE et al. Sedative, analgesic and cognitive effects of clonidine infusions in humans.
2001. British Journal of Anaesthesia 86 (1) 5-11. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012  Rubine AS et al. Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study. 2010. Interactive cardiovascular and thoracic surgery.10 58-62.  Kamibayashi T et al. Clinical uses of α2-adrenergic agonists. 2000. Anesthesiology 93  Clonidine guideline for critical care. Guys and St Thomas’ NHS Foundation Trust. 2004. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 ZOPICLONE
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk 1. Indication
Short term treatment of insomnia in delirium negative patients.
All prescriptions should be endorsed ‘short term sleep aid’.

Zopiclone is a non-benzodiazepine GABA-minergic hypnotic agent. It has less disruptive
effects on normal sleep architecture compared to benzodiazepines such as temazepam,
which are not recommended.
2. Presentation
Starting dose 7.5mg nocte Use lower dose 3.75mg nocte in elderly patients and in renal/hepatic impairment. 4. Common Side Effects
5. Contraindications
Myasthenia gravis
Severe hepatic insufficiency
Known hypersensitivity to zopiclone or any other ingredient in the product

 Due to the risk of dependence it is advised that treatment is not continued beyond 4  Rebound insomnia can occur on discontinuation.  Drugs which inhibit cytochrome P450 enzymes such as erythromycin may 7. References
www.emc.medicines.org.uk accessed 13/02/12 BNF edition 61 March 2011 Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012 TRAZODONE
This guideline is a summary, full details are available from the SPC www.emc.medicines.org.uk ZODONE 1. Indication
Short term treatment of insomnia in both delirium positive and delirium negative patients. All prescriptions should be endorsed ‘short term sleep aid’. Trazodone is a non-tricyclycic antidepressant with sedative effects. It has limited antimuscarinic activity and therefore minimal adverse effects on the normal sleep cycle. 2. Presentation
50mg and 100mg capsules 50mg/5ml syrup for nasogasrtic administration Starting dose 50mg nocte Dose may be increased to 100mg nocte if necessary. 4. Common Side Effects
Hypotension, tacchycardia Priapism (discontinue trazodone) Deranged LFTs including jaundice and hepatocellular damage (discontinue trazodone) Blood dyscrasias including thrombocytopenia and agranulocytosis. Rarely QT prolongation Rarley neuroleptic malignant syndrome or serotonin syndrome 5. Contraindications
Hypersensitivity to trazodone or any ingredients  Potent inhibitors of cytochrome P450 enzymes may potentiate the effects of  Concomitant treatment with trazodone may result in elevated levels of digoxin and 7. References
www.emc.medicines.org.uk accessed 13/02/12 BNF edition 61 March 2011 Bourne R. Pharmacological guidelines on the management of delirium and sleep disturbance in critical care patients version 3. September 2011. Sheffield Teaching Hospitals NHS Foundation Trust. Delirium and Sleep Disturbances in Critical Care – Clinical Guideline V1. Principal author:Ms D Hughes (Pharmacist) Dr P Prashast (Consultant Intensivist) Approved by Medicine Clinical Guidance Subcommittee Date: June 2012

Source: http://www.cmccn.nhs.uk/files/1813/7692/7314/Delirium_and_sleep_disturbances_FINAL.pdf