Guidelines for the Assessment and Management of Delirium in the Last Hours and Days of Life

Transcription

1 D Monnery, 1 K Gaunt, 2 P Shepherd, 2 G Holland, 3 K Nolan, 4 R Telfer, 4 F Ahmad, 5 C Finnegan 6 (Guideline Development Lead) 1 University Hospital Aintree NHS Foundation Trust; 2 Woodlands Hospice, Aintree; 3 Liverpool Heart and Chest Hospital NHS Foundation Trust; 4t St Helens and Knowsley Teaching Hospitals NHS Trust, 5 Wirral Hospice St. John s, 6 West Lancs, Southport & Formby Specialist Palliative Care Service. Summary of Main Recommendations Definition and Prevalence Delirium is defined as an acute confusional state which results from diffuse organic brain dysfunction. 1 It is commonly characterised by disturbed consciousness, impaired cognitive function or perception. Delirium has an acute onset and a fluctuating course. 7 In terminal cancer patients, the prevalence of delirium may be as high as 85%. 4 Assessment and Reversibility Delirium is a clinical diagnosis. The DSM V outlines the criteria necessary for the diagnosis of delirium. 38 [Level 1] If a diagnosis of delirium is suspected due to the clinical features, the Confusion Assessment Method (CAM) diagnostic algorithm may be a helpful screening tool. 40 [Level 3] Patients diagnosed with delirium should be assessed for reversible causes, and these addressed if clinically appropriate. 7 [Level 4] Symptom Control The management of delirium is complex and often involves non-pharmacological and pharmacological approaches [Level 4] Where possible, non-pharmacological interventions should be optimised prior to commencing a pharmacological treatment. 45 [Level 1] Pharmacological options used in the treatment of delirium may cause adverse side effects. These include: drowsiness, decline in cognition, extra-pyramidal symptoms and the small risk of neuroleptic malignant syndrome. 45 [Level 1] Antipsychotic drugs should be the first line pharmacological management. They should be used at the lowest effective dose for the shortest possible duration. 47 [Level 3] Side effects are more common and severe with prolonged drug use. 48 [Level 3] Haloperidol or olanzapine should be the antipsychotic drugs used first line in the management of delirium. 49 [Level 1] Communication If possible the diagnosis of delirium and the proposed management plan should be discussed with the patient. Discussions should also take place with those important to the patient. The discussion or the reasons for non-discussion should be documented. 37 [Level 4] 1 P a g e

2 Section 1: Introduction Delirium is defined as: an acute confusional state which results from diffuse organic brain dysfunction. 1 Delirium is one of the most difficult clinical syndromes to diagnose and treat in patients with terminal disease. 2 It has a severe adverse effect on the quality of life of patients and those important to them, including at the end of life. 3 In patients with cancer in the last hours or days of life, the prevalence of delirium may be as high as 85%, 4 with prevalence during inpatient stays in hospice or hospital estimated at between 28-88%. 5-6 Delirium is characterised by disturbed consciousness, impaired cognitive function or perception, an acute onset and a fluctuating course. 7 The physical manifestations of delirium such as agitation, may result in unnecessary medical intervention, distress to family / caregivers and potentially avoidable admission to a hospice or hospital Delirium can also impair the recognition and treatment of other physical and psychological symptoms such as pain Delirium may be reversible in up to 50% of cases Thorough assessment, appropriate investigation and reaching an accurate diagnosis is essential prior to initiation of pharmacological therapy. Diagnosis is often more complicated in patients who are thought to be in the last hours or days of life. Contributing factors which may lead to a missed or late diagnosis of delirium include: inconsistent use of diagnostic classifications; confusion regarding terminology; complex and often subjective symptoms, which can overlap with the symptoms of underlying disease, and lack of staff training Due to the difficulties in making a diagnosis of delirium, several screening tools have been evaluated The Confusion Assessment Method (CAM) has the most evidence to support use in clinical practice. 24 However successful use isdependent on the skill and experience of the clinician in applying the tool As a result the applicability in daily practice has been questioned. 24,26 The identification of a practical and accurate screening tool for delirium in patients in the last hours or days of life would greatly improve the detection of delirium. The management of delirium is complex and may involve non-pharmacological and pharmacological strategies. The majority of research into the management of delirium using neuroleptic medications has taken place in the elderly care setting with relatively little research focusing on patients with advanced cancer. 31,32 In general delirium is under-treated with suboptimal doses of neuroleptic medications. 33 The NICE Quality Standard 63; Delirium in Adults describes nonpharmacological de-escalation techniques and a recommendation that pharmacological management should follow local antipsychotic guidelines. 7 The guidance aims to improve and standardise practice in the assessment, diagnosis and management of delirium in adults, but does not specifically focus on the palliative care population. 2 P a g e

3 Section 2: Scope and Purpose The following guideline aims to inform practice in the assessment, diagnosis and management of delirium in patients in the last hours and days of life. This focus was chosen because this patient population was not covered by the recent NICE guidance for delirium. 7 The guideline is aimed at specialist palliative care professionals (including doctors, nurses, pharmacists and allied health professionals) and generalists involved in providing palliative care e.g. general practitioners, district nurses, hospital doctors and nurses). This guideline is an update of Guidelines for the Management of Delirium in Advanced Cancer, Due to differences in approach and treatment, agitation is not covered in this guideline. There is alternative regional guidance for the management of agitation in palliative care. 35 The guideline aims to answer the following questions: 1. What is the best method to assess patients for the presence of delirium in the last hours and days of life? 2. What methods of management are recommended in patients diagnosed with delirium in the last hours and days of life? Table 1 summarises the scope and purpose of this guideline. Table 1 Scope of Guideline Population Populations not covered Healthcare setting Topics Topics not covered People aged over 18 years with delirium who are felt to be in the last hours and days of life People under 18 years People not in the last hours and days of life Community care Secondary care Tertiary care Hospice care Diagnosis and screening for delirium in the last hours and days of life Management of delirium in the last hours and days of life General agitation Terminal agitation 3 P a g e

4 Section 3: Methods This guideline is based on the AGREE II criteria, which can be found in detail in the Cheshire and Merseyside Palliative and End of Life Care Network Audit Group Guideline Development Manual Clinical Questions and Interventions Clinical questions were derived from the previous guidelines developed in 2008 and updated in These were refined by the Guideline Development Group which has authored this guideline. The clinical questions used to guide the literature review in PICO (Patient, Intervention, Control, Outcome) format are: 1. In patients in the last hours and days of life (P), is one method of assessment (I) superior to other methods or no formal method (C) in diagnosing delirium? (O). 2. In patients diagnosed with delirium in the last hours and days of life (P), what treatments (pharmacological and non-pharmacological) (I) compared to no treatment or other methods (C) are superior in managing delirium? (O) 3.2 Outcomes To maximise patient comfort by ensuring the best assessment and treatment methods for patients with delirium in the last hours and days of life through: improved knowledge of the definition, assessment and reversible causes of delirium improved knowledge of the non-pharmacological and pharmacological interventions available and the associated risks and benefits promotion of education and training for all staff involved in caring for patients with delirium in the last days and hours of life 3.3 Literature Search Systematic electronic database searches were undertaken to find potentially relevant articles. MEDLINE, Embase, CINAHL and Cochrane databases were searched in August A full outline of the search strategy, results and appraisal of evidence can be found in Appendix 1. The grading of the level of evidence and recommendations follows the Cheshire and Merseyside Palliative and End of Life Care Network Audit Group Guideline Development Manual and uses SIGN criteria. 36 Section 4: Guideline Recommendations 4.1 Assessment and Diagnosis of Delirium There are a number of associated clinical features which should alert health care providers to the possibility of delirium. These are outlined in Table 2. 7 [Level 1] The different sub-types of delirium are described below. They can each present with different clinical features. 7 [Level 1] Hyperactive delirium Characterised by heightened arousal. Patients can be restless, agitated or aggressive. 4 P a g e

5 Hypoactive delirium Characterised by withdrawal. Patients can be quiet or sleepy. Mixed delirium Features of both hyperactive and hypoactive delirium may be present. Hypoactive delirium may be the most common sub-type within the palliative care population. In one prevalence study, approximately two-thirds of all delirium cases were felt to be of the hypoactive subtype. 2 [Level 3] Close attention should be paid to the clinical features which are highlighted in Table 2. Within the palliative care population the recognition of hypoactive delirium is significantly lower than for the other sub-types. 2 [Level 3] Features of altered perception e.g. hallucinations, may pre-date other clinical symptoms and signs of delirium. 37 [Level 4] Delirium is a clinical diagnosis. The Diagnostic and Statistical Manual of Mental Disorders V (DSM V) details the diagnostic criteria for delirium. 38 [Level 1]. See Table 3 for details Table 2 Clinical Features of Delirium 7 [Level 1] Note. Features suggestive of hypoactive delirium are marked with an * Changes in cognitive function: e.g. worsened concentration,* slow responses,* confusion Changes in perception e.g. visual or auditory hallucinations Changes in physical function e.g. reduced mobility,* reduced movement,* restlessness, agitation, changes in appetite,* sleep disturbance Changes in social behaviour e.g. lack of cooperation with reasonable requests, withdrawal,* or alterations in communication, mood and / or attitude 5 P a g e

6 Table 3 DSM V Criteria for the Diagnosis of Delirium 38 [Level 1] A B C D E Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) The disturbance develops over a short period (usually hours to days), represents an acute change from baseline attention and awareness, and tends to fluctuate during the course of the day Change in cognition (e.g., memory deficit, disorientation, language disturbance, perceptual disturbance) The disturbances in Criteria A and C are not better explained by a preexisting, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal such as coma There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e. due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple aetiologies. There is poor recognition of delirium when subjective nursing assessment alone is used. 39 [Level 3] Several tools have been developed to facilitate the reliable detection of delirium in clinical practice. The Confusion Assessment Method (CAM) diagnostic algorithm has been developed from the DSM V criteria. 40 [Level 3] The CAM has been validated for use in the palliative care population with a sensitivity of 0.88 ( ) and a specificity of 1.0 ( ). 27 [Level 3] The performance of the CAM was found to be dependent upon the skill of the operator with training required before use. 27 [Level 3] If the diagnosis of delirium is suspected due to the presence of clinical features listed in Table 2, the CAM screening tool may be helpful. 40,41 A summary of the key features used in the tool can be seen in Figure [Level 3] Any healthcare provider, trained in the use of the CAM tool and confident in assessing for delirium. may be considered competent to make the diagnosis of delirium. 37 [Level 4] 6 P a g e

7 Figure 1 Key Features used in the CAM Screening Tool 40,41,42 [Level 3] Acute onset and fluctuating course And Inattention And Either Or Disorganised thinking Altered level of consciousness 4.2 The Mental Capacity Act, 2005 Where a patient is shown to lack capacity to consent to treatment, the Mental Capacity Act, 2005 must be followed. If the patient lacks capacity to make decisions about their treatment, the known views of the patient should be explored, and the reasoning behind best interest decision-making documented. The known views of the patient may be sought through the family, a nominated spokesperson or an advance statement. 43 [Level 4] Lasting Power of Attorney for Health and Welfare, Advance Decisions to Refuse Treatment, Independent Mental Capacity Advocates and Deprivation of Liberty Safeguards should be utilised where appropriate. 43 [Level 4] 4.3 Reversible Causes of Delirium Patients diagnosed with delirium should be assessed for reversible causes, and these addressed if clinically appropriate. 7 [Level 4] The decision to look for potentially reversible causes with invasive investigations should be made in the context of the overall clinical picture. Invasive investigations may not be appropriate in patients thought to be in the last days and hours of life. 37 [Level 4] There is evidence that psychoactive medications, such as opioids, and dehydration are two of the most common reversible causes of delirium. 17 [Level 2+] 7 P a g e

8 Reversibility may decline with repeated episodes of delirium. 17 [Level 2+] Table 4 lists some of the potentially reversible causes of delirium. 3,17, 44 [Level 4] Table 4 Reversible causes of delirium 3,17,44 [Level 4] Alcohol Biochemical abnormalities e.g. hypercalcaemia, uraemia Cardiovascular causes Cerebral pathology Constipation Dehydration Infections Medications e.g. opioids Nutritional deficiencies Withdrawal from alcohol / nicotine Withdrawal from drugs e.g. antipsychotics, benzodiazepines, opioids Haematological causes 4.4 Non-Pharmacological Management Non-pharmacological measures should be tailored to the individual patient in the context of their clinical situation. For example, it may not be in the patient s best interests to keep them in a ward to help orientate them, if they are also felt to be in the last hours or days of life. 37 [Level 4] Table 5 outlines non-pharmacological options for the management of delirium. 7 [Level 4] Table 5 Non-pharmacological options for the management of delirium 7 [Level 4] Adequate lighting Cognitively stimulating activities Effective communication Familiar environment Familiar healthcare team Involvement of family and those important to the patient Mobility aids Re-orientation Reassurance Sensory impairment aids Verbal / non-verbal techniques to manage distress Visible clock and calendar Maintenance of good sleep hygiene 8 P a g e

9 There is a risk of adverse side effects from medications used in the treatment of delirium. Potential side effects include: drowsiness, decline in cognition, extrapyramidal symptoms and the small risk of neuroleptic malignant syndrome. Where possible, non-pharmacological interventions should be optimised prior to commencing pharmacological treatment. 45 [Level 1] 4.5 Pharmacological Management Reversible causes and non-pharmacological management should be considered before starting pharmacological intervention. 37 [Level 4] The decision to use pharmacological intervention should be based on a thorough assessment of the risks and benefits and should be used as a last resort. 37 [Level 4] Pharmacological intervention aims to treat symptoms and minimise distress in the last hours and days of life. Patients with the hypoactive subtype of delirium are less likely to be overtly symptomatic and distressed. There is a limited role for pharmacological management in patients experiencing hypoactive delirium. 37 [Level 4] Evidence suggests that routine opioid rotation or clinically assisted hydration produces no benefit for patients with delirium unless these factors are contributing to the clinical condition. 46 [Level 2] Neuroleptic medications should be prescribed at the lowest effective dose for the shortest time possible. 47 [Level1] Side effects are more common and severe with prolonged drug use. 48 [Level 3]. Patients managed in an inpatient setting should be reviewed by a healthcare professional every 24 hours. 37 [Level 4]. Review should include an assessment for any side effects of medication. Over-sedation may be an indication to switch to an alternative medication. 37 [Level 4] There is no evidence for the preferential use of one particular antipsychotic. There is equal evidence for the efficacy of haloperidol vs. olanzapine. 49 [Level 1] There is equal evidence for the efficacy of haloperidol vs. chlorpromazine. 45 [Level 1] There is more data for the use of haloperidol because of the widespread use of the drug. 49 There are also reports of risperidone and quetiapine being used for delirium, although efficacy data is not available. 1 [Level 4 Chlorpromazine should be used with caution. There is evidence that it is effective in treating delirium when haloperidol has failed. 50 [Level 4] There is higher level evidence that it may worsen confusion and other side effects after 48 hours when compared to haloperidol. 45 [Level 1] 9 P a g e

10 The dose of antipsychotic medication should be titrated according to the use of breakthrough doses and tolerability. The dose of haloperidol required to reach therapeutic benefit ranges from 500micrograms-8mg (median 2.1mg) per 24 hours. Low starting doses are preferable, with additional doses prescribed for use as required. There should be daily review of the prescribed dose. 48 [Level 3] For patients in the last hours or days of life, use of the oral route may be limited thus influencing the choice of neuroleptic medication. Table 6 summarises a range of pharmacological options for the management of delirium including the options for administration route. Benzodiazepines can be used for managing symptoms of agitation in delirium without increasing the risk of treatment failure when given concurrently with antipsychotic medications. 50 [Level 4] However, benzodiazepines should not be used as monotherapy as they are not as effective as antipsychotics in managing delirium. 45 [Level 1] If agitation is the predominant symptom warranting use of benzodiazepines, please refer to local guidelines for the pharmacological management of agitation for advice on appropriate medication and drug doses. 35 If generalists are managing patients in the last hours or days of life and the delirium is not responding to initial interventions, referral to, or discussion with the local specialist palliative care team is recommended. 37 [Level 4] If a patient is deemed not to be imminently dying and when long term (>months) antipsychotic use is anticipated, consider usual range of side effects i.e. drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation. 51 [Level 4] If a patient is deemed not to be imminently dying and when long term (>months) use of antipsychotics is anticipated, consider usual monitoring i.e. FBC, U&E, LFTs at start of therapy and annually thereafter. Blood lipids and weight should be checked at the start of treatment, at 3 months, and then yearly. Fasting blood glucose should be checked at baseline, at 4-6months, and then yearly. Blood pressure monitoring is advised before starting therapy and frequently during dose titration. It is advisable to monitor prolactin concentrations at the start of therapy, at 6 months, and then yearly. ECG monitoring is advised when haloperidol is prescribed as it can cause potentially fatal prolongation of the QT interval. 51 [Level 4] 4.6 Communication and Information When a diagnosis of delirium is made there should be discussion with the patient where possible, and those important to the patient. The discussion should include an explanation of the diagnosis and the potential for reversibility. 37 [Level 4] The provision of written information to those important to the patient may help improve their understanding and confidence in making decisions. Information should include details of potential causes of the delirium and management options. 52 [Level 2-] 10 P a g e

11 If the patient recovers from an episode of delirium he / she may not fully recollect details of the event. 37 It is important to offer information about what happened and the treatment decisions which were made. 37 [Level 4] Section 5: Standards 1. The diagnosis of delirium should meet with the DSM V diagnostic criteria. 38 [Grade D] 2. Patients with delirium should be assessed and treated for reversible causes if clinically appropriate. 7, 37 [Grade D] 3. Non-pharmacological management strategies should be optimised as part of the overall management of delirium. 7, 45 [Grade A] 4. Anti-psychotic medications should be used as the first-line pharmacological intervention for delirium. 45, 48, 49 [Grade A] 5. Haloperidol or olanzapine should be the antipsychotics drugs of choice in the management of delirium. 49 [Grade A] 6. The diagnosis of delirium and the proposed management plan should be discussed with the patient where possible. The discussion or the reasons for non-discussion should be documented in the case records. 37 [Grade D] 7. The diagnosis of delirium and the proposed management plan should be discussed with those important to the patient. The discussion or the reasons for non-discussion should be documented in the case records. 37 [Grade D] 11 P a g e

12 51, 53, 54 Table 6 Pharmacological Options for the Management of Delirium in the Last Days and Hours of Life Haloperidol [Level 1] Olanzapine [Level 1] Chlorpromazine [Level 1] Levomepromazine [Level 4] Quetiapine [Level 4] Risperidone [Level 4] Starting dose and titration advice Dosing in renal impairment Side effects Contraindications Notes Oral 500micogram-1.5mg po stat, possibly combined with a benzodiazepine, and 2 hourly prn. If necessary, increase the dose. Maximum 8mg/24h. Consider regular dosing schedule if 2 or more prn doses are used in 24 hours. For SC administration Stats: equivalent dosing to oral can be used. Syringe pump range: 1.5mg- 8mg/24h via CSCI. GFR < 10mL/min: Start with a low dose and increase dosing interval. Risk of accumulation with repeated dosage. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation, blood disorders, altered LFTs. QT prolongation, bradycardia, Parkinson s Disease and Parkinsonism. Dilute with water for injection Delirium- unlicensed indication. Oral 2.5mg po stat, 2hourly prn, and nocte. If necessary increase to 5mg- 10mg nocte. For SC administration [Level 4] Equivalent dosing to oral can be used. Syringe pump range: 2.5mg- 10mg/24h via CSCI If GFR <50mL/min, maximum dose is 5mg in 24 hours. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation Incidence of above suggested to be less with second-generation antipsychotics. Also weight gain, dry mouth, constipation, orthostatic hypotension, nervousness, dizziness, peripheral oedema. Acute MI; unstable angina, severe hypotension, bradycardia, sick sinus syndrome, recent heart surgery. Use with caution in Parkinsonism Some experience of administering via CSCI diluted with water for injection. Delirium- unlicensed indication. Oral 25mg po tds or 75mg po nocte. Titrate according to response. Usual maintenance dose 75mg- 300mg daily but up to 1g may be required in psychoses. Higher doses should be divided For SC administration- Not applicable If GFR > 10mL/min, dose as in normal renal function. If GFR < 10mL/min start with a low dose and titrate according to response. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation. Oral 12.5mg-25mg po as required. For SC administration 12.5mg-25mg sc stat and 1 hourly prn (12.5mg in the elderly). Titrate according to response. Maintain with 25mg-200mg/24h via CSCI. Note: Lower starting doses may be effective If GFR > 10mL/min, dose as in normal renal function. If GFR < 10mL/min, start with a low dose and titrate according to response. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation Oral 12.5mg po bd. If necessary, increase in 12.5mg- 25mg increments. Mean effective dose 40mg- 100mg/24h. For SC administration- Not applicable Dose as in normal renal function, according to response. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation. Also dyspnoea, dyslipidaemia, peripheral oedema, increased appetite, sleep disorders, irritability. Hypothyroidism, Parkinsonism Parkinsonism Nil specific. Preferred medication in patients with Parkinsons disease Not often used in palliative care Delirium-unlicensed indication. Protect CSCI from direct sunlight. Delirium-unlicensed indication. Can switch from IR to MR tablets at the equivalent daily dose. Delirium-unlicensed indication. 1mg po nocte and prn. If necessary, increase by 1mg every other day. Usual maximum 4mg/24h. Median maintenance dose is 1mg/24h. SC administration-not applicable If GFR < 50ml/min, initially use 50% of dose. Increases should also be 50% less and at a slower rate. Use with caution. Drowsiness, extrapyramidal side effects, hyperprolactinaemia, sexual dysfunction, QT-interval prolongation, hyperglycaemia, hypotension, neuroleptic malignant syndrome, sedation Also hypertension, respiratory disorders, epistaxis, appetite changes, sleep disorders, anxiety, depression, malaise, urinary disorders, arthralgia, myalgia, toothache, oedema. Parkinsonism Delirium is an unlicensed indication. 12 P a g e

13 Section 7 Applications and Implications This guideline will form the basis of a training programme on the diagnosis and management of delirium in patients felt to be in the last hours and days of life. The programme will be developed in 2017/2018 and will be made available for local delivery across the Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network. The aim is to re-audit practice once change has been implemented. This guideline will also form the basis of an abstract submission to the European Association for Palliative Care 2017, in order to share the work and lessons from it to an international audience. Section 8 Authors Acknowledgments and Declarations of Interest Dr Dan Monnery, Specialty Registrar in Palliative Medicine, University Hospital Aintree NHS Foundation Trust, Liverpool. Dr Kathryn Gaunt, Specialty Registrar in Palliative Medicine, Woodlands Hospice, Aintree, Liverpool. Dr Penny Shepherd, Specialty Registrar in Palliative Medicine, Woodlands Hospice, Aintree, Liverpool. Graham Holland, Clinical Pharmacist specialising in Palliative Care and Medicines Information, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool. Ms Kate Nolan, Clinical Nurse Specialist in Palliative Care, St Helens and Knowsley Teaching Hospitals NHS Trust, Merseyside. Ms R Telfer, Clinical Nurse Specialist in Palliative Care, St Helens and Knowsley Teaching Hospitals NHS Trust, Merseyside. Dr Fawad Ahmad, Consultant in Palliative Medicine, Wirral Hospice St Johns, Wirral Merseyside. Dr Clare Finnegan, Consultant in Palliative Medicine, West Lancs Southport and Formby Specialist Palliative Care Service (Guideline Development Lead). 13 P a g e

14 Contributors The Guideline Development Group gratefully acknowledges the work of the following people in supporting the development of this guideline: Dr Andrew Thorns, Medical Director, Pilgrims Hospices, East Kent, and Consultant in Palliative Medicine, East Kent Hospitals University NHS Foundation Trust for his external review of this guideline Dr Fraser Gordon, Consultant in Geriatric Medicine, Southport Hospital for his expert input to development of this guideline. Sandra Smith, for her contribution as patient, carer and public representative. Members of the Cheshire and Merseyside Palliative and End of Life Care Network Audit and Clinical Guideline Group who submitted data for the regional audit on the management of delirium and contributed to guideline development through expert opinion. Dr Clare Finnegan, Dr Fawad Ahmad, Dr Kate Marley, Dr Cathy Lewis Jones, Dr Averil Fountain, and Dr L Beddows who authored the 2008 guideline. Development of the guideline was funded through the use of supporting professional activity time facilitated by the employing organisations of the authors. The authors and reviewers declare no conflicting interests. The authors contributed as follows: Literature review: DM, GH, KG, PS Audit tools: DM, GH, PS, KG, CF, KN, RT, FA Updated guidance and grading recommendations: DM, GH, PS, KG, CF, KN, RT, FA Standards: DM, GH, PS, KG, CF, KN, RT, FA Final writing of manuscript of guidelines: DM, GH, PS, KG, CF, KN, RT, FA Section 9 Review Date The guideline will be reviewed three years after publication as outlined in the Cheshire and Merseyside Palliative and End of Life Care Network Audit Group Guideline Development Manual P a g e

15 Section 10 References 1. Casarett DJ, Inouye SK. Diagnosis and management of delirium near the end of life. Ann Intern Med, 2001; 135: Fang CK, Chen HW, Liu SI, Lin CJ, Tsai LY, Lai YL. Prevalence, Detection and Treatment of Delirium in Terminal Cancer Inpatients: A Prospective Survey. Jpn J Clin Oncol, [Internet] 2008;[cited 2017 August 14th] 38(1): Available from: 3. Centeno C, Sanz A, Bruera E. Delirium in advanced cancer patients. Palliat Med, 2004; 18: Massie MJ, Holland J, Glass E. Delirium in terminally cancer patients. Am J Psychiatry, 1983; 140(8): Minagawa H, Uchitomi Y, Yamawaki S, Ishitani K. Psychiatric morbidity in terminally ill cancer patients. A prospective study. Cancer, [Internet] 1996; [cited 2017 August 14 th ] 78: Available from: 6. Michaud L, Burnand B, Stiefel F. Taking care of the terminally ill cancer patient: delirium as a symptom of terminal disease. Ann Oncol, [Internet] 2004; [cited 2017 August 14 th ] 15 (suppl 4): Available from: =pdf 7. National Institute for Health and Clinical Excellence (NICE) 2010 Delirium: Prevention, diagnosis and management. Clinical Guideline (CG103):.[Internet] London NICE [cited 2017 August 14 th ].Available from: 8. Bruera E, Miller L, McCallion J, Macmillan K, Krefting L, Hanson J. Cognitive failure in patients with terminal cancer: A prospective study. J Pain Symptom Manage, 1992; 7(4): Namba M, Morita T, Imura C, Kiyohara E, Ishikawa S, Hirai K. Terminal delirium: Families experience. Palliat Med, 2007; 21(7): Morita T, Akechi T, Ikenaga M, Inoue S, Kohara H, Matsubara T, et al. Terminal delirium: Recommendations from bereaved families experiences. J Pain Symptom Manage, 2007; 34(6): Bruera E, Bush SH, Willey J, Paraskevopoulos T, Li Z, Palmer JL, et al. Impact of delirium and recall on the level of distress in patients with advanced cancer and their family caregivers. Cancer, [Internet] 2009;[cited 2017 August 14 th ] 115(9): Available from: Cohen MZ, Pace EA, Kaur G, Bruera E. Delirium in advanced cancer leading to distress in patients and family caregivers. J Palliat Care, 2009; 25(3): Breitbart W, Gibson C, Tremblay A. The delirium experience: Delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics, 2002; 43(3): P a g e

16 14. Bruera E, Fainsinger RL, Miller MJ, Kuehn N. The assessment of pain intensity in patients with cognitive failure: a preliminary report. J Pain Symptom Manage, 1992; 7(5): Fainsinger R, Miller MJ, Bruera E, Hanson J, Maceachern T. Symptom control during the last week of life on a palliative care unit. J Palliat Care, 1991; 7(1): Coyle N, Breitbart W, Weaver S, Portenoy R. Delirium as a contributing factor to crescendo pain: Three case reports. J Pain Symptom Manage, 1994; 9(1): Lawlor PG, Gagnon P, Mancini IL, Pereira JL, Hanson J, Suarez-Almazor ME, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer a prospective study. Arch Intern Med, 2000; 160(6): Gagnon P, Allard P, Masse B, DeSerres M. Delirium in terminal cancer: a prospective study using daily screening, early diagnosis, and continuous monitoring. J Pain Symptom Manage, [Internet] 2000; [cited 2017 August 14 th ] 19(6): Available from: McDaniel JS, Brown FW, Cole SA. Assessment of depression and grief reactions in the medically ill. In: Stoudemire A, Fogel BS, Greenberg DB (eds): Psychiatric Care of the Medical Patient New York: Oxford University Press, pp Inouye SK. The dilemma of delirium: Clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med, 1994; 97(3): Adamis D, Sharma N, Whelan PJP, Macdonald AJD. Delirium scales: a review of current evidence. Aging Ment Health, 2010; 14(5): Hjermstad MJ, Loge JH, Kaasa S. Methods for assessment of cognitive failure and delirium in palliative care patients: implications for practice and research. Palliat Med, 2004; 18(6): Leonard M, Agar M, Mason C, Lawlor P. Delirium issues in palliative care settings. J Psychosom Res, 2008; 65(3): Detroyer E, Clement PM, Baeten N, Pennemans M, Decruyenaere M, Vandenberghe J, et al. Detection of delirium in palliative care unit patients: A prospective descriptive study of the Delirium Observation Screening Scale administered by bedside nurses. Palliat Med, 2014; 28(1): Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium? Value of bedside instruments. JAMA, 2010; 304(7): Lemiengre J, Nelis T, Joosten E, Braes T, Foreman M, Gastmans C. et al. Detection of delirium by bedside nurses using the confusion assessment method. J Am Geriatr Soc, 2006; 54(4): Ryan K, Leonard M, Guerin S, Donnelly S, Conroy M, Meagher D. Validation of the confusion assessment method in the palliative care setting. Palliat Med, 2009; 23(1): Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database of Systematic Reviews 2007 [Internet] Issue 2. Art. No.: CD DOI: / CD pub2.[cited 2017 August 14 th ] Available from: 16 P a g e

17 29. Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother, 2006; 40(11): Inouye SK. Delirium in older persons. N Engl J Med, 2006; 354(11): Akechi T, Uchitomi Y, Okamura H, Fukue M, Kagava A, Niskida A. et al. Usage of haloperidol for delirium in cancer patients. Support Care Cancer, 1996; 4(5): Olofsson SM, Weitzner MA, Valentine AD, Baile WF, Meyers CA. A retrospective study of the psychiatric management and outcome of delirium in the cancer patient. Support Care Cancer, 1996; 4(5): Breibart W, Cochinow HM, Passik SD. Psychiatric symptoms in palliative medicine. In: Doyle D, Hanks G, Cherny NI, Calman K, Eds. Oxford Textbook of Palliative Medicine, 3 rd Ed New York: Oxford University Press: Merseyside and Cheshire Palliative Care Network Audit Group. Standards and Guidelines. 4th Edition Liverpool: Merseyside and Cheshire Palliative Care Network Audit Group; Cheshire and Merseyside Palliative and End of Life Care Network Audit Group. Guidelines for the management of agitation in advanced cancer. [Internet] [cited 2017 August 14 th ] Available from: Y=PDF 36. Cheshire and Merseyside Palliative and End of Life Care Network Audit Group. Guideline Development Manual. [Internet] [2014 (amended 2016) [cited 2017 August 14 th ] Liverpool. Available from: opment_manual_mar14amended16_approved_8nov16_nice.pdf?pdfpathway= PDF 37. Expert opinion based on group consensus at the Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network Group Meeting on 19/5/ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th ed. Washington, DC: American Psychiatric Association; Oligario G, Buch C, Piscotty R. Nurses Assessment of Delirium with underlying Dementia in End of Life Care. J Hosp Palliat Nurs. 2015; 17(1): Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying Confusion: the confusion assessment method. A new method for detecting delirium. Ann Internal Med. 1990; 113(12): Confusion Assessment Method. 1988, 2003, Hospital Elder Life Program. All rights reserved. Adapted from: Inouye SK et al. Ann Intern Med. 1990; 113: Hospital Elder Life Program. Confusion Assessment Method. [Internet] [cited 2017 July 31st] Department of Constitutional Affairs. Mental Capacity Act 2005 Code of Practice. London [Internet][ 2007.[cited 2017 August 14 th ] Available from: 17 P a g e

18 3/Mental-capacity-act-code-of-practice.pdf 44. Inouye SK, Bogardus ST, Charpentier PA, Lee-Summers L, Acampore D. et al. A multicomponent intervention to prevent delirium in hospitalised older patients. N Engl J Med. [Internet] 1999; [cited 2017 August 14 th ] 340(9): Available from: Candy B, Jackson KC, Jones L, Leurent B, Tookman A, King M. Drug therapy for delirium in terminally ill adult patients. Cochrane Database of Systematic Reviews [Internet] 2012, [cited 2017 August 14 th ] Issue 11. Art. No.: CD DOI: / CD pub2. Available from: Morita T, Tei Y, Inoue S. Agitated Terminal Delirium and Association with Partial Opioid Substitution and Hydration. J Palliat Med. 2003; 6(4): Leadership Alliance for the Care of Dying People. One chance to get it right: Improving people s experience of care in the last few days and hours of life. [Internet] [cited 2017 August 14 th ]. Available from: 8/One_chance_to_get_it_right.pdf 48. Crawford GB, Agar M, Quinn SJ, Phillips J, Litster C, Michael N, et al. Pharmacovigilance in Hospice/Palliative Care: Net Effect of Haloperidol for Delirium. J Palliat Med. 2013; 16(11): Lin CJ, Sun FJ, Fang CK, Chen HW, Lai YL. An Open Trial Comparing Haloperidol with Olanzapine for the Treatment of Delirium in Palliative and Hospice Center Cancer Patients. J Intern Med Taiwan. 2008; 19(4): Shin SH, Hui D, Chisholm G, Kang JH, Allo J, Williams J, et al. Frequency and Outcome of Neuroleptic Rotation in the Management of Delirium in Patients with Advanced Cancer. Cancer Res Treat. 2015; 47(3): Pharmaceutical Press and BMJ Group, British National Formulary 70. London, Pharmaceutical Press. 52. Gagnon P, Charbonneau C, Allard P, Stoulard C, Dumont S, Fillon C. Delirium in advanced cancer: a psychoeducational intervention for family caregivers. J Palliat Care. 2002; 18(4): Twycross R, Wilcock A, Howard P. (eds.). (2014). Palliative Care Formulary: 5 th Edition. Chapter 4.2.1: Antipsychotics: Nottingham: Palliative drugs.com 54. UK Renal Pharmacy Group. The Renal Drug Database. London, CRC Press [Internet] 2016; [cited 2017 August 14 th ] Available from: 18 P a g e

19 ELIGIBILITY IDENTIFICATION Appendix 1: Systematic Review Summary Form Guideline Title: Assessment and Management of Delirium in Patients in the Last Hours and Days of Life. Reviewers Finnegan C, Monnery D, Gaunt K, Shepherd P, Holland G, Nolan K, Telfer R What are the best methods of assessing and treating delirium in patients in the last hours and days of life? Delirium AND (palliative OR end of life OR dying) AND (treatment OR diagnosis OR screening OR assessment) E Records identified Medline (n = 68) Records identified EMBASE (n = 205) Records identified Cochane (n =1 ) Records identified CINAHL (n =94 ) INCLUDED SCREENING Records screened (n =368 ) Records after duplicates removed (n =318 ) Records remaining after title screening (unrelated to clinical question) (n = 44) Records remaining after full text review (n=16) Case Report = 1 Unrelated to clinical Question = 5 Target population inappropriate = 1 Not fully published = 1 Records remaining after abstract screening (n =24) Review article = 5 Unrelated to clinical Question =6 Duplicate record = 9 Case Report = 1 Articles included in final Guideline Development (n = 16) 19 P a g e