Onset Acute or sub-acute Insidious. Fluctuating, usually resolves over Progressive

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1 Guideline Name: Delirium Delirium is an acute confusional state characterised by a global disturbance in cerebral function affecting consciousness, attention, cognition and perception with a course that may fluctuate over a period of hours. It is a common cause of disturbed behaviour in medically ill patients and studies have shown that it is extremely common in palliative care patients. Studies have shown that 29-42% of patients have delirium on admission to a palliative care unit; 88% of patients in the last few days of life 1, 2. The symptoms of delirium are distressing for the patient, their relatives and care givers and expose the sufferer to the risk of further harm e.g. falls. Clinical Features Delirium may develop over hours to days and the symptoms and their severity can fluctuate over relatively short periods of time. The symptoms and signs include 3 : Cognitive impairment which can include problems with orientation, memory, visual spatial abilities, calculation, writing and reading. These features can be picked up by formal testing Altered levels of consciousness with changes in the level of awakeness (or arousal) on a spectrum of hyperalert (hyperactive delirium) to hypoalert (hypoactive delirium) and possible fluctuations between the two extremes over relatively short periods of time Disorders of the sleep-wake cycle Impaired attention Mood changes Hallucinations (false perceptions) and illusions (misperceptions) Delusions (abnormal thoughts) which are usually persecutory and can be the basis for aggressive behaviour Delirium is probably under-diagnosed in palliative care inpatients because the majority of cases (78%) fall into the hypoactive subtype where patients have slowed psychomotor function, lethargy, confusion, sedation, reduced awareness of their surroundings and impaired ability to sustain attention 2. The main differential diagnosis is that of dementia 4 and often delirium is superimposed on a pre-existing dementia. Table 1: Differences between delirium & dementia Delirium Dementia Onset Acute or sub-acute Insidious Course Fluctuating, usually resolves over Progressive days to weeks Conscious Level Often impaired, can fluctuate Clear until later stages rapidly Cognitive Defects Poor short term memory, poor attention span Poor short term memory, attention less affected until severe Hallucinations Common, especially visual Often absent Delusions Fleeting, non-systematised Often absent Psychomotor activity Increased, reduced or unpredictable Can be normal Page 1 of 10

2 Aetiology The pathophysiology of delirium is not fully understood. The reticular formation of the brainstem which regulates normal wakefulness and sleep is thought to be important. There are many neurotransmitters and receptors which are important for controlling wakefulness and consciousness and their modification (e.g. with drugs) can cause delirium. Acetylcholine is thought to be the most important which may explain why patients with dementia are at higher risk of developing delirium because of their already impaired cholinergic system 3. Delirium has a large number of possible causes. Common causes Medications e.g. Opioid toxicity, anti-cholinergics, hypnotics Drug withdrawal e.g. alcohol, illicit drugs Hypoxia Metabolic abnormalities e.g. renal or hepatic impairment, hypercalcaemia, dehydration Nutritional deficiency e.g. thiamine, folic acid, vitamin B12 Infections Cerebral metastases Assessment There are various screening tools available for the detection of delirium: Mini-Mental Test (see appendix 1) a 10 part test - screens memory and concentration - it is not specific for delirium and does not assess all components of cognition Mini-Mental State Examination (MMSE) a 30 part test sensitive to changes in cognition and also consciousness and attention it is not specific for delirium and will not differentiate delirium from dementia Confusion Assessment Method (see appendix 2) a diagnostic algorithm which is sensitive and specific but can only be applied by people with training 6 Nursing Delirium Screening Scale (see appendix 3) a new tool with reasonable sensitivity and specificity 7 Management Investigations should be aimed at eliminating common causes in order to improve symptom control especially considering that up to half of all cases of delirium in palliative care patients may be reversible 1, 5. The onset of delirium may not indicate imminent death but patients with irreversible delirium may have a shorter prognosis than those with a reversible cause. A shorter prognosis may also be related to increasing age, severity of cognitive impairment and evidence of organ failure 5. There are five main aspects to managing delirium: Ensure the patient s safety. A risk assessment will need to be performed. If necessary, the patient will require constant supervision. This can be provided by a relative or healthcare professional. If a patient is not responding to treatment or is a danger to themselves or others then the team leader caring for the patient should discuss the case further with the senior nurse and consultant to consider further options for care. Provide a safe and non-stimulating environment. A safe environment is one which limits the risk of harm to the patient i.e. removing objects which could be harmful, consider a mattress on the floor. The environment should also reduce the demands on the patient s impaired cognition i.e. adequate lighting, consistent staff, correction of sensory impairments, use of clocks and calendars and familiar objects. Page 2 of 10

3 Provide psychological support for the patient and family. Families need to be educated about delirium and the measures being used to combat it. They also need to be supported through a traumatic and difficult stage in their loved ones illness. Identify and treat the underlying cause. A full physical examination should be carried out looking for infection, dehydration, hypoxia and organ failure. Routine investigations should include FBC, U&Es, LFTs, TFTs, Ca 2+ and glucose Further investigations including CT or MRI imaging of the brain may also need to be considered. Drug charts should be scrutinised and possible offending medications reduced or stopped if appropriate. Opioids should be reduced or switched depending on results of renal function tests and the patient s symptoms. Prescribe drugs aimed at managing symptoms. Antipsychotic drugs: The side effect profile of each individual drug needs to be taken into account when prescribing anti-psychotics and weighed against the patients individual situation. It is especially important to note history of seizures, Parkinson s Disease, Lewy Body Dementia prostatic symptoms or hypotension. These drugs and their continued use needs to be reviewed on a daily basis, particularly if the underlying cause can be reviewed. 10 Main side effects of anti-psychotics Extra-pyramidal side effects (EPSEs): o Dystonic reactions o Pseudoparkinsonism o Akathisia o Tardive dyskinesia Reduced seizure threshold Postural hypotension Anticholinergic side effects (see appendix 4) Neuroleptic malignant syndrome Others hyperprolactinaemia, weight gain, cardiac side effects, sedation o Haloperidol 0.5-1mg PO/SC q 1 h p.r.n and at bedtime; if necessary titrate the dose gradually. Haloperidol should be kept at the lowest dose possible for the shortest amount of time. <60yrs doses could go up to the range 2.5-5mg but >60yrs doses should be kept lower in the range 0.5-1mg if possible. The maintenance dose is based on the initial cumulative dose needed to settle the patient. First line for management of delirium in palliative care as extensive experience in its use and ability to be given subcutaneously. Cochrane review has found efficacy of low dose haloperidol to be similar to newer atypical antipsychotics. At higher doses (>4.5mg/24 hours) there is increased risk EPSEs 9. Effect can be seen within hours to days. It is less sedating than chlorpromazine and has relatively few side effects. The major problem encountered is that of EPSEs, leading to Parkinson-like symptoms and a tendency to fall. It is metabolised by the liver and should be avoided in hepatic failure. Haloperidol is the drug of choice in hypoactive delirium. o Levomepromazine mg PO/SC stat, and at bedtime, may be used instead if a period of sedation is required in an agitated delirious patient. Excessive sedation and hypotension are limitations of this drug but it can be very useful in terminal agitation (not recommended by NICE) o Olanzapine <60yrs 5mg and >60yrs 2.5mg PO/SC stat, p.r.n. and at bedtime. If necessary, increase to 5-10mg at bedtime. Found to be as effective as low dose antipsychotics 9 and may be worth considering if high dose haloperidol required but causing side effects. Can be sedative and cause postural hypotension. Depending on response daily dose is around mg. Page 3 of 10

4 Benzodiazepines Not generally recommended for the management of delirium unless it is related to alcohol withdrawal as benzodiazepines can worsen the symptoms of delirium. If delirium is felt to be irreversible and is causing symptoms of agitation and restlessness that cannot be managed in any other way then it may be appropriate to use benzodiazepines for symptom control. This may be in addition to antipsychotic medication. o o o o Diazepam 2-5mg orally up to tds Lorazepam 0.5-2mg sublingually PRN (up to 4 hourly) Midazolam via continuous subcutaneous infusion starting at 5-10mg/24hrs and titrating to response Midazolam mg subcutaneously PRN Regular clinical review and follow up. This needs to be done on a daily basis and short term use of less than one week for medications should be considered. Advice regarding the newer antipsychotics and new dementia drugs can be sought from the local psychiatric team. 24hrs Single Point of Access for support for mental health problems Terminal Agitation Symptoms of agitation and restlessness at the end of life may be due to a delirium that is irreversible or it may be inappropriate to investigate them. Under these circumstances palliative sedation therapy may be required. Sedatives should be used proportionately and titrated to response. Midazolam - typical starting dose 10mg/24hrs (range up to 100mg) Levomepromazine - typical starting dose 25mg/24hrs (range up to 100mg) Phenobarbitone - typical starting dose 200mg/24hrs (range up to 600mg) Palliative sedation therapy (PST) is the use of specific sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness. The symptoms most commonly requiring PST are delirium, dyspnoea, pain and nausea or vomiting. The aim of PST is to relieve such symptoms by means of appropriate sedative drugs carefully titrated to the cessation of symptoms. Usually, symptom relief can be achieved with levels of sedation that do not prevent the patient from being able to communicate. It is unusual for a patient to require deep sedation from the initiation of PST. PST can be continuous or intermittent. Related guidelines and policies Guidelines for the Use of Sedation Guidelines for the Management of Psychosis References 1. Lawlor PG et al. Occurrence, causes and outcome of delirium in patients with advanced cancer. Arch Intern Med 2000;160: Spiller JA. Hypoactive delirium: assessing the extent of the problem for inpatient specialist palliative care. Palliative Medicine 2006; 20: Caraceni A, Simonetti F. Palliating delirium in patients with cancer (review). Lancet oncology 2009; 10: Brown TM and Boyle MF. ABC of psychological medicine: Delirium BMJ 2002: 325; Leonard M et al. Reversibility of delirium in terminally ill patients and predictors of mortality. Palliative Medicine 2008; 22: Page 4 of 10

5 6. Wei L, Fearing M, Sternberg E, Inouye SK. The Confusion Assessment Method: a systematic review of current usage. J Am Geriatr Soc 2008; 56: Gaudreau J, Gagnon P, Harel F, Tremblay A, Roy M, Fast, systematic and continuous delirium assessment in hospitalised patients: the Nursing Delirium Screening Scale. J Pain Symptom Manage 2005; 29: Gagnon PR. Treatment of delirium in supportive and palliative care. Current Opinion in Supportive and Palliative Care 2008; 2: Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev NICE; NCGC Delirium, diagnosis, prevention and treatment; Clinical Guideline 103, July 2010; Date Originated: December 2006 Original Author: Date of last review: November 2011 Date of this review: November 2014 Reviewed By: Dr Bruno Capone Next Review Due: October 2018 Issuing Authority: Dr Helen McGee, Consultant Page 5 of 10

6 Appendix 1 Mini-Mental test Score one point for each question answered correctly and give score out of 10. Question - Patient s age - Time (to nearest hour) - Address given for recall at end of test (42 West Street) - Name of hospital (or town if at home) - Current Year - Patient s date of birth - Current month - Years of the first world war - Name of the monarch - Count backwards from 20 to 1 (no errors allowed but may correct self) Page 6 of 10

7 Appendix 2 Confusion Assessment Method (CAM) Shortened Version Worksheet If all items in Box 1 are checked and at least one item in Box 2 is checked a diagnosis of delirium is suggested. Page 7 of 10

8 Appendix 3 The Nursing Delirium Screening Scale (Nu-DESC) Features and descriptions Symptoms Rating (0-2) Symptom Time Period Midnight 8 AM 8 AM 4 PM 4 PM Midnight I. Disorientation Verbal or behavioural manifestation of not being oriented to time or place or misperceiving persons in the environment. II. Inappropriate behaviour Behaviour inappropriate to place and/or time for the person; e.g. pulling at tubes or dressings, attempting to get out of bed when that is contraindicated, and the like. III. Inappropriate communication Communication inappropriate to place and/or for the person; e.g. incoherence, non-communicativeness, nonsensical or unintelligible speech. IV. Illusions/Hallucinations Seeing or hearing things that are not there; distortions of visual objects. V. Psychomotor retardation Delayed responsiveness, few or no spontaneous actions/words; e.g. when the patient is prodded, reaction is deferred and/or the patient is unrousable. Total Score Symptoms are rated from 0 to 2 based on the presence and intensity of each symptom and individual ratings are added to obtain a total score per shift. The patient is considered positive on screening if presenting a score of 2 or more. Page 8 of 10

9 Generic Name Alverine Alprazolam Atenolol Bupropion Captopril Chlorthalidone Cimetidine Clorazepate Codeine Colchicine Diazepam Digoxin Dipyridamole Disopyramide Fentanyl Furosemide Fluvoxamine Haloperidol Hydralazine Hydrocortisone Isosorbide Loperamide Metoprolol Morphine Nifedipine Prednisone Quinidine Ranitidine Risperidone Theophylline Trazodone Triamterene Warfarin Complete References: Drugs with Possible Anticholinergic Effects Brand Name Spasmonal Xanax Tenormin Wellbutrin, Zyban Capoten Diuril, Hygroton Tagamet Tranxene Contin Colcrys Valium Lanoxin Persantine Norpace Duragesic, Actiq Lasix Luvox Haldol Apresoline Cortef, Cortaid Isordil, Ismo Imodium, others Lopressor, Toprol MS Contin, Avinza, Roxanol Procardia, Adalat, Nifedical Deltasone, Sterapred Quinaglute Zantac Risperdal Theodur, Uniphyl Desyrel Dyrenium Coumadin 1. Boustari MA, Campbell NL. Munger S, Maidment I, Fox C=GC,. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008: 4(3): Campbell N, Boustari M, Limbil T, Ott C, et al. The cognitive impact of anticholinergics: a clinical review. Clinical Intervention in Aging. 2009:4(1): /27/12 Do not reproduce without permission contact acb@agingbraincare.org Appendix 4 ANTICHOLINERGIC COGNITIVE BURDEN SCALE Developed by the Aging Brain Program of the IU Center for Aging Research Generic Name Amantadine Amitriptyline Amoxapine Atropine Benztropine Brompheniramine Carbamazepine Carbinoxamine Chlorpheniramine Chlorpromazine Clemastine Clomipramine Clozapine Cyclobenzaprine Darifenacin Desipramine Dicyclomine Dimenhydrinate Diphenhydramine Doxepin Flavoxate Hydroxyzine Hyoscyamine Imipramine Meclizine Meperidine Methocarbamol Nortriptyline Olanzapine Orphenadrine Oxcarbazepine Oxybutynin Paroxetine Perphenazine Promethazine Propantheline Quetiapine Scopolamine Thioridazine Tolterodine Trifluoperazine Trihexyphenidyl Trimipramine Drugs with Definite Anticholinergic Effects Brand Name Symmetrel Elavil Asendin Sal-Tropine Cogentin Dimetapp, Lodrane Tegretol Histex, Carbihist Chlor-Trimeton, Chlorphen Thorazine Tavist Anafranil Clozaril Flexeril Enablex Norpramin Bentyl Dramamine, others Benadryl, others Sinequan, Zonalon Urispas Atarax, Vistaril Anaspaz, Cystospaz, Levsin Tofranil Antivert, Bonine Demerol Robaxin Pamelor Zyprexa Norflex Trileptal Ditropan Paxil Trilafon Phenergan Pro-Banthine Seroquel Scopace, Transderm Scop Mellaril Page 9 of 10 Detrol Stelazine Artane Surmontil

10 The following represents a list of alternative medications developed by an interdisciplinary group of specialists within the Aging Brain Program at Indiana University. These suggestions do not supersede clinical judgment, and are intended to assist clinicians in practicing in acute health care settings who provide care for patients with cognitive impairment such as dementia, mild cognitive impairment or delirium. Recommended alternatives to medications with Definite Anticholinergic Properties Class ACB Drugs Alternatives Brompheniramine Carbinoxamine Allergies or itching: Chlorpheniramine Loratadine or Cetirizine orally First-Generation Clemastine Antihistamines Diphenhydramine Insomnia: Dimenhydrinate Trazadone orally Hydroxyzine Recommended alternatives to medications with Definite Anticholinergic Properties Class ACB Drugs Alternatives Bladder Antispasmodics Darifenacin Flavoxate Oxybutynin Propantheline Tolterodine Hold during acute care stay consider scheduling toileting Antidepressants Amitriptyline Amoxapine Clomipramine Desipramine Doxepin Imipramine Nortriptyline Paroxetine Trimipramine (Clinical judgment to consider if taper warranted) Depression: Sertraline or Citalopram orally Neuropathic pain: Gabapentin orally Insomnia: Trazadone orally GI Antispasmodics Antiemetics Atropine Dicyclomine Hyoscyamine Propantheline Hydroxyzine Meclizine Promethazine Scopolamine Reflux disorders: Esomeprazole orally Painful abdominal cramps: Morphine orally or IV Consider ondansetron IV or PO, or Metoclopramide PO Antipsychotics Chlorpromazine Clozapine Olanzapine Perphenazine Quetiapine Thioridazine Trifluoperazine (Recommendation does not apply to chronic use for psychiatric diagnosis) Acute care environment: Haloperidol orally or IM for 72 hours only Skeletal Muscle Relaxants Cyclobenzaprine Methocarbamol Acetaminophen or oxycodone/ acetaminophen Analgesics Meperidine Morphine sulfate orally or IV Central Anticholinergics Amantadine Benztropine Trihexyphenidyl Orphenadrine Movement disorders: Dopamine agonists or levodopa Antiepileptics Carbamazepine Oxcarbazepine Seizures: Consult neurology for alternative Neuropathic pain: Gabapentin or levetiracetam orally Mood disorders: Consult psychiatry for alternative 6/27/12 Do not reproduce without permission contact acb@agingbraincare.org For more information or permission to duplicate, please contact: Noll Campbell, PharmD or Malaz A. Boustani, MD, MPH Regenstrief Institute, Inc./IU Center for Aging Research 410 West 10 th Street, Suite 2000 Indianapolis, IN Phone: (317) Fax: (317) acb@agingbraincare.org Page 10 of 10