Most long-term care (LTC) residents are of age >65 years and have multiple chronic health conditions affecting their cognitive and physical functioning. Although some individuals in nursing homes return home after receiving therapy services, most will remain in a LTC facility until their deaths. This article seeks to provide guidance on how to assess and effectively select treatment for delirium, behavioral and psychological symptoms for patients with dementia, and address other common challenges such as advanced care planning, decision-making capacity, and artificial hydration at the end of life. To do so, we draw upon a team of physicians with training in various backgrounds such as geriatrics, palliative medicine, neurology, and psychiatry to shed light on those important topics in the following "Top 10" tips.
OBJECTIVE: To clarify the safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer receiving palliative care.
METHODS: This was a prospective observational study involving consecutive patients with advanced cancer and delirium receiving antipsychotics in inpatient hospices or psycho-oncology settings. Adjusted mean scores of the Delirium Rating Scale Revised-98 (DRS; range: 0-39) were calculated at baseline and Day 3 using generalized estimating equations. Adverse events over 7 days were evaluated.
RESULTS: Data from 756 patients were analyzed (Mage = 72 ± 11 years, 62% male, 48% bedridden). The adjusted mean DRS score significantly decreased after antipsychotics administration (21.5 [95% confidence interval 19.5 to 23.4] to 20.8 [18.9 to 22.8], p = 0.03, effect size [ES] = 0.02). Significant improvement was associated with age of 75 or older (ES = 0.07), better performance status (0.32), longer estimated prognosis (0.25), psycho-oncological consultation settings (0.20), hyperactive (0.14) or mix-motor subtypes (0.24) of delirium, and quetiapine administration (0.19); significant deterioration was observed in patients with "days" prognosis (0.18). Extrapyramidal symptoms (9.8%) and somnolence (8.5%) were the most prevalent adverse events.
CONCLUSIONS: The use of antipsychotics as part of comprehensive delirium management was safe and may provide some symptomatic benefits for patients with terminal illness and delirium. Along with adequate non-pharmacological interventions, judicious use of antipsychotics is still recommended.
Objectives: Patients with terminal illness are at high risk of developing delirium, in particular, those with multiple predisposing and precipitating risk factors. Delirium in palliative care is largely under-researched, and few studies have systematically assessed key aspects of delirium in elderly, palliative-care patients.
Methods: In this prospective, observational cohort study at a tertiary care center, 229 delirious palliative-care patients stratified by age: <65 (N = 105) and =65 years (N = 124), were analyzed with logistic regression models to identify associations with respect to predisposing and precipitating factors.
Results: In 88% of the patients, the underlying diagnosis was cancer. Mortality rate and median time to death did not differ significantly between the two age groups. No inter-group differences were detected with respect to gender, care requirements, length of hospital stay, or medical costs. In patients =65 years, exclusively predisposing factors were relevant for delirium, including hearing impairment [odds ratio (OR) 3.64; confidence interval (CI) 1.90–6.99; P < 0.001], hypertonia (OR 3.57; CI 1.84–6.92; P < 0.001), and chronic kidney disease (OR 4.84; CI 1.19–19.72; P = 0.028). In contrast, in patients <65 years, only precipitating factors were relevant for delirium, including cerebral edema (OR 0.02; CI 0.01–0.43; P = 0.012).
Significance of results: The results of this study demonstrate that death in delirious palliative-care patients occurs irrespective of age. The multifactorial nature and adverse outcomes of delirium across all age in these patients require clinical recognition. Potentially reversible factors should be detected early to prevent or mitigate delirium and its poor survival outcomes.
BACKGROUND: The general in-hospital mortality and interrelationship with delirium are vastly understudied. Therefore, this study aimed to assess the rates of in-hospital mortality and terminal delirium.
METHOD: In this prospective cohort study of 28,860 patients from 37 services including 718 in-hospital deaths, mortality rates and prevalence of terminal delirium were determined with simple logistic regressions and their respective odds ratios (ORs).
RESULTS: Although overall in-hospital mortality was low (2.5%), substantial variance between services became apparent: Across intensive care services the rate was 10.8% with a 5.8-fold increased risk, across medical services rates were 4.4% and 2.4-fold, whereas at the opposite end, across surgical services rates were 0.7% and 87% reduction, respectively. The highest in-hospital mortality rate occurred on the palliative care services (27.3%, OR 19.45). The general prevalence of terminal delirium was 90.7% and ranged from 83.2% to 100%. Only across intensive care services (98.1%, OR 7.48), specifically medical intensive care (98.1%, OR 7.48) and regular medical services (95.8%, OR 4.12) rates of terminal delirium were increased. In contrast, across medical services (86.4%, OR 0.32) and in particular oncology (73.9%, OR 0.25), pulmonology (72%, OR 0.31) and cardiology (63.2%, OR 0.4) rates were decreased. For the remaining services, rates of terminal delirium were the same.
SIGNIFICANCE OF RESULTS: Although in-hospital mortality was low, the interrelationship with delirium was vast: most patients were delirious at the end of life. The implications of terminal delirium merit further studies.
Evidence to support the use of antipsychotic medications for the management of delirium symptoms remains limited. The primary objective of this study was to compare the effect of antipsychotic and non-antipsychotic treatments for delirium symptoms among palliative care inpatients. Secondary outcomes were use of midazolam and overall survival. This involved retrospective analysis of medical records (November 2018 to April 2019) for adult palliative care patients diagnosed with delirium at an Australian tertiary hospital. NuDESC was used to assess symptoms daily from baseline to Day 3. All 65 patients (mean age 73.5 ± 13.7 years, 48% female, 59% with cancer) included received standard care which included management of underlying causes of delirium symptoms, of which 17 received additional treatment using antipsychotic medications. Forty-eight did not receive any antipsychotic medication. An absolute reduction in NuDESC score was observed in the group that did not receive additional treatment using antipsychotics (by 1.37 units, 95% CI 0.79–1.95, p < 0.0001). A significantly higher proportion of midazolam use (n = 9, 53% versus n = 2, 4%, p < 0.001) and shorter median survival (13 days versus 26 days, p = 0.03) was observed in the group of patients that received antipsychotics. The use of antipsychotic medications in addition to standard treatments targeting underlying precipitants did not lead to a significant improvement in delirium symptoms and was associated with a greater midazolam use and lower median duration of survival. Individualized treatment of underlying causes still appears to be essential in the management of delirium in patients receiving palliative care.
Objectives: The objectives of this study are to investigate how many advanced cancer patients became unconscious or non-communicative after pharmacological treatment for delirium, and to explore whether existing delirium assessment tools can successfully evaluate its severity at the end of life.
Methods: This was a secondary analysis of a registry study that examined the efficacy and safety of antipsychotics for advanced cancer patients with delirium. A total of 818 patients were recruited from 39 specialized palliative care services in Japan. The severity of delirium was measured using the Richmond Agitation-Sedation Scale-Palliative care version, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Nursing Delirium Screening Scale (Nu-DESC) on Day 3. Data from 302 patients with motor anxiety with an Agitation Distress Scale score =2 on Day 0 were analyzed for this study. The patients were categorized into four treatment response groups: complete response (CR: no agitation and fully communicative), partial response (PR: no/mild agitation and partially communicative), unconscious/non-communicative (UC), and no change (NC).
Results: On Day 3, 29 (10%; 95% confidence intervals (CI), 7-13) and 2 (1%; 95% CI, 0-2) patients became unconscious and non-communicative, respectively. Forty-four patients were categorized as CR, 97 as PR, 31 as UC, and 96 as NC. The scores of the DRS-R-98 and Nu-DESC in the UC group were rated higher than patients in the NC group were.
Conclusions: A considerable number of cancer patients with delirium became unconscious or non-communicative. Existing delirium assessment tools may be inappropriate for measuring the severity of delirium in end-of-life.
Delirium occurs frequently at end of life. Palliative care clinical nurse specialists (CNSs) are involved in community palliative care provision. Many patients prefer being cared for at home, yet managing delirium in this setting presents unique challenges, potentially resulting in emergency hospital or hospice admission. We examined the experiences and practice of palliative care CNSs managing delirium in the community; 10 interviews were undertaken. Data were analysed using the framework approach. Challenges to delirium management in the community included limited time with patients, reliance on families and access to medications. Assessment tools were not used routinely; time limited visits and inconsistent retesting were perceived barriers. Management approaches differed depending on CNSs' previous delirium education. Strategies to prevent delirium were not used. Community delirium management presents challenges; support surrounding these could be beneficial. Routine assessment tool use and delirium prevention strategies should be included in further education and research.
Background: Delirium is a distressing neurocognitive disorder that is common among terminally ill individuals, although few studies have described its occurrence in the acute care setting among this population.
Aim: To describe the prevalence of delirium in patients admitted to acute care hospitals in Ontario, Canada, in their last year of life and identify factors associated with delirium.
Design: Population-based retrospective cohort study using linked health administrative data. Delirium was identified through diagnosis codes on hospitalization records.
Setting/participants: Ontario decedents (1 January 2014 to 31 December 2016) admitted to an acute care hospital in their last year of life, excluding individuals age of <18 years or >105 years at admission, those not eligible for the provincial health insurance plan between their hospitalization and death dates, and non-Ontario residents.
Results: Delirium was recorded as a diagnosis in 8.2% of hospitalizations. The frequency of delirium-related hospitalizations increased as death approached. Delirium prevalence was higher in patients with dementia (prevalence ratio: 1.43; 95% confidence interval: 1.36–1.50), frailty (prevalence ratio: 1.67; 95% confidence interval: 1.56–1.80), or organ failure–related cause of death (prevalence ratio: 1.23; 95% confidence interval: 1.16–1.31) and an opioid prescription (prevalence ratio: 1.17; 95% confidence interval: 1.12–1.21). Prevalence also varied by age, sex, chronic conditions, antipsychotic use, receipt of long-term care or home care, and hospitalization characteristics.
Conclusion: This study described the occurrence and timing of delirium in acute care hospitals in the last year of life and identified factors associated with delirium. These findings can be used to support delirium prevention and early detection in the hospital setting.
Being given a new diagnosis, living with serious illness, going through the dying process, and grieving all clearly will have a large impact on a patient’s emotional and psychiatric health. For Physician Assistants working in diverse settings, including primary care, oncology, cardiology, and other specialties, fluency in psychiatric issues in the seriously ill or dying patient is a necessity to providing holistic care. The Physician As-sistant has the opportunity to identify psychiatric issues and be proactive about a team-based approach to therapeutic interventions. Many patients appropriate for palliative care can have a psychological overlap in how they face disease, cope with treatments, interact with family, and ultimately view death. In the health care setting, there can be a tendency to separate the physical symptoms of disease and treatments; however, they are intimately intertwined with the mental, psychological,and spiritual aspects of care. Mental health impacts not only the individual patient but also caregivers and families of those with serious illness
Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium.
Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486.
Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [–4·4 to -2·2]), and combination group (n=10, -3·0 [–4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths.
Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group.
Funding: National Institute of Nursing Research.
This issue of Medical Clinics, guest edited by Dr. Eric Widera, is devoted to Palliative Care. Articles in this important issue include: Hospice and palliative care: an overview; Goals of care conversations in palliative care: A practical guide; The art and science of prognostication in palliative care; Recognizing and managing polypharmacy in advanced illness; Pain management in those with serious illness; Management of grief, depression, and suicidal thoughts in those with serious illness; Management of respiratory symptoms in those with serious illness; Management of gastrointestinal symptoms inadvanced illness; Management of urgent medical conditions at the end of life; Delirium at the end of life; Options of last resort: palliative sedation, Physician aid in dying and voluntary cessation of eating and drinking; Cannabis for symptom management; and Self-care of physicians caring for patients with serious illness.
OBJECTIVES: Delirium is common and distressing in palliative care settings. This survey aims to describe current practice regarding delirium identification in specialist palliative care units (SPCU), such as inpatient hospices, in the UK.
METHODS: An 18-item anonymous online survey was distributed by Hospice UK to their network of clinical leads (n=223), and to their research mailing list (n=228). The survey was also sent to the chair of the Hospice UK executive clinical leads forum for direct dissemination to forum representatives (n=20). Clinical leads and forum representatives were asked to distribute the survey to healthcare staff in their SPCUs.
RESULTS: 220 SPCU staff (48% nurses; 31% doctors; 10% healthcare assistants) completed the survey. Approximately half reported using clinical judgement alone to screen (97/204; 48%) and/or diagnose (124/220; 56%) delirium. Over a third used an assessment tool to screen for delirium (76/204; 37%). The majority (150/220; 68%) reported screening in response to clinical symptoms, while few reported routine on-admission (11/220; 5%) or daily-during-admission (12/220; 6%) screening. Most respondents had received some training on delirium (137/220; 62%). However, 130/220 (59%) said their SPCU did not have a training programme for delirium screening and only 79/220 (36%) reported that their SPCU had delirium clinical guidelines. The main barriers to routine screening included: lack of delirium training, lack of guidelines and complexity of patient's conditions.
CONCLUSION: There is variation in practice for delirium screening and diagnosis in SPCUs. Clinical guidelines for delirium, including consensus on which screening tools to use, are needed for this setting.
Background: Delirium is a common debilitating complication of advanced cancer.
Objective: To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial.
Design: Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1–7. Control sites then implemented the intervention (“waitlist sites”).
Setting: Four Australian palliative care units.
Measurements: The primary outcome was adherence, with an a priori endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially.
Rsults: Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites (p = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 (p = 0.6) intervention and 18.7 + 7.8 (p = 0.5) waitlist sites. The intervention caused no adverse events.
Conclusion: The intervention requires modification for optimal adherence in a phase III trial.
Delirium is a prevalent acute neurocognitive condition in patients with progressive life-limiting illness. Delirium remains underdetected; a systematic approach to screening is essential. Delirium at the end of life requires a comprehensive assessment. Consider the potential for reversibility, illness trajectory, patient preference, and goals of care before proceeding with investigations and interventions. Management should be interdisciplinary, and nonpharmacologic therapy is fundamental. For patients with refractory and severe agitation or perceptual disturbance, judicious use of medication may also be required. Carers and family should be seen as partners in care and be involved in shared decision making about care.
Terminal delirium is a common occurrence in patients at the end of life, and its presence is widely accepted as a poor prognostic indicator. The hyperactive subtype is characterized by psychomotor agitation that is distressing to patients, caregivers, and providers. The purpose of this study was to determine whether physical, psychosocial, or spiritual data collected at hospice admission are associated with development of hyperactive terminal delirium. In this retrospective cohort study, 154 patients were assigned to one of two cohorts depending on whether or not they had signs of hyperactive terminal delirium. Hospice admission data from the Hospice Item Set, psychosocial assessment, and spiritual assessment were analyzed using descriptive statistics, inferential statistics, and logistic regression. Although there were no statistically significant relationships among the physical, psychosocial, and spiritual variables and hyperactive terminal delirium, there were some findings that are clinically significant for nurses caring for patients at the end of life. Specifically, this study highlights the importance of ongoing physical, psychosocial, and spiritual assessment throughout the end-of-life trajectory, as well as prompt management of symptoms.
Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and health-care-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyper- and hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when non-pharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.
CONTEXT: Few studies have examined how clinicians assess decision-making capacity for research in the last weeks of life.
OBJECTIVE: We examined the decision-making capacity for participation in a research study and its association with clinician impression and delirium among cancer patients with days to weeks of life expectancy.
METHODS: Patients admitted to our Palliative and Supportive Care Unit (PSCU) were approached for a prospective observational study. We assessed for their decision-making capacity based on clinical impression of physician and nurse, Memorial Delirium Assessment Scale (MDAS) and the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR).
RESULTS: Among the 206 patients, 131 patients (64%) did not require MacCAT-CR assessment because they were overtly delirious or unresponsive; 37 (18%) patients were alert but did not complete the MacCAT-CR assessment for other reasons and 38 patients (18%) completed the MacCAT-CR assessment. Among these 38 patients, 5 (13%) were incapable and had normal albeit significantly higher MDAS scores compared to those who were capable (1.8 vs. 4.2, P=0.002). Compared against MacCAT-CR and MDAS, the overall agreement with capacity assessment with a clinician was 88% (95% CI 82-93%) for physicians and 90% (95% CI 82-94%) for nurses. The area-under the receiver-operating characteristics curve was 0.93 (95% CI 0.88-0.96) for physicians and 0.94 (95% CI 0.89-0.97) for nurses, suggesting high discrimination.
CONCLUSION: A majority of patients in the PSCU lacked decision-making capacity for participation in clinical research. Clinician impression had high accuracy. Few patients with normal MDAS were found to be incapable with MacCAT-CR assessment.
Background: Delirium in the hospitals leads to worse outcomes for patients. There were no previous studies that characterize patients with delirium from multiple hospital locations.
Objective: To describe patient characteristics screening positive for delirium and identify any correlations with hospital location and medication use.
Design, Settings, Patients: Retrospective chart review of 227 hospitalized patients from a large, academic, tertiary referral, 2-campus health system. Patients were =18 years old and had delirium for at least =24 hours. Validated delirium screening tools were utilized.
Measurements: Patients’ demographics, inpatient stay information, delirium episodes characteristics, drugs, and palliative and psychiatry teams’ involvement.
Results: Most patients were older with a mean age of 64.1 years. The most common primary diagnoses were infection, cardiac, and pulmonary. Average length of delirium was 7.2 days (standard deviation [SD] = 8.2), and average length of stay (LOS) was 18.7 days (median = 10.5, SD = 35.1, 95% confidence interval = 14.1-23). Thirty-day readmission rate was 24.8% (65/262 hospitalizations); 12.8% of patients died in the hospital (29/227). Around one-third of hospitalizations had involvement of palliative care, palliative psychiatry, or general psychiatry team. There was a decrease in the number of medications administered 24 hours after the first recording of delirium compared to the immediate preceding 48 hours. Those hospitalizations where delirium first occurred in the intensive care unit (ICU) did have a longer LOS (average = 22.9, SD = 45.7) than those where delirium first occurred outside the ICU (average = 14.8, SD = 20.5). Patients were likely to have received an opioid within 48 hours in 51% of hospitalizations and to have received benzodiazepines in 16% of hospitalizations.
Conclusion: In our study, we found that delirium significantly impacted length of delirium episode, number of episodes of delirium, length of hospital admission, and mortality. The population most sensitive to the impacts of delirium were elderly patients.
BACKGROUND: Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004.
OBJECTIVES: To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries.
SELECTION CRITERIA: We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older).
DATA COLLECTION AND ANALYSIS: We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables.
MAIN RESULTS: We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported.
SECONDARY OUTCOMES: use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE.
AUTHORS' CONCLUSIONS: We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential.
Delirium is highly prevalent in people with advanced life limiting illness(es), and current evidence can inform how we provide best delirium care in this setting. Whilst strategies to prevent and reverse delirium are the cornerstones of optimal care, the care for delirious patients who are approaching the end of life and their families pose specific challenges particularly if delirium is refractory flagging a grave prognosis. These include addressing additional supportive care needs, clinical decision-making about the degree of investigation and intervention, minimising distress from the symptoms of delirium itself and considering other concurrent problems contributing to agitation. A fine balance is needed to address other symptoms such as pain whilst minimizing psychoactive medication load. There is need for regular and clear information and communication about prognosis and goals of care. Witnessing a delirium episode in a loved one in close proximity to death requires consideration of the needs of the family into bereavement care. Palliative care is person and family-centred care provided for a person with an active, progressive, advanced disease; who has little or no prospect of cure and who is expected to die, and for whom the primary treatment goal is to optimise quality of life. It is an approach which can be provided regardless of setting and diagnosis, and by both specialist palliative care teams and other health professionals.