Delirium at the end of life Agar, Meera R
Age and ageing,
2020-Apr-27, Letnik:
49, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract
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.
Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns exist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as ...a substitute for non‐pharmacological approaches when identifiable causes are not found or they challenge ward processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large European survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium. Never before, therefore, is there a greater need to examine whether indeed these medications are clinically useful for the treatment of delirium. With this in mind, evidence‐based arguments for and against prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper concludes with a moderation piece to help guide clinical practice.
ObjectivesTo estimate the economic impact of delirium in the Australian population in 2016–2017, including financial costs, and its burden on health.Design, setting and participantsA cost of illness ...study was conducted for the Australian population in the 2016–2017 financial year. The prevalence of delirium in 2016–2017 was calculated to inform cost estimations. The costs estimated in this study also include dementia attributable to delirium.Main outcome measuresThe total and per capita costs were analysed for three categories: health systems costs, other financial costs including productivity losses and informal care and cost associated with loss of well-being (burden of disease). Costs were expressed in 2016–2017 pound sterling (£) and Australian dollars ($A).ResultsThere were an estimated 132 595 occurrences of delirium in 2016–2017, and more than 900 deaths were attributed to delirium in 2016–2017. Delirium causes an estimated 10.6% of dementia in Australia. The total costs of delirium in Australia were estimated to be £4.3 billion ($A8.8 billion) in 2016–2017, ranging between £2.6 billion ($A5.3 billion) and £5.9 billion ($A12.1 billion). The total estimated costs comprised financial costs of £1.7 billion and the value of healthy life lost of £2.5 billion. Dementia attributable to delirium accounted for £2.2 billion of the total cost of delirium.ConclusionsThese findings highlight the substantial burden that delirium imposes on Australian society—both in terms of financial costs associated with health system expenditure and the increased need for residential aged care due to the functional and cognitive decline associated with delirium and dementia. To reduce the substantial well-being costs of delirium, further research should seek to better understand the potential pathways from an episode of delirium to subsequent mortality and reduced cognitive functioning outcomes.
This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on ...appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0-10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).
Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care.
To determine efficacy of risperidone or ...haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care.
A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more.
Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety.
Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival.
Two hundred forty-seven participants (mean SD age, 74.9 9.8 years; 85 women 34.4%; 218 with cancer 88.3%) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14).
In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.
anzctr.org.au Identifier: ACTRN12607000562471.
Background
Ketamine at subanaesthetic dosages (≤0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, ...its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses.
Objective
To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting.
Methods
This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number—ACTRN12618001586202). We recruited adults (≥ 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1–0.4mg/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity.
Results
Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants/month across sites with 50% of treated participants achieving ≥ 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set
a priori
. There were no clinically relevant harms encountered.
Conclusions
A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.
Older adults with cancer are at risk of overtreatment or undertreatment when decision-making is based solely on chronological age. Although a geriatric assessment is recommended to inform care, the ...time and expertise required limit its feasibility for all patients. Screening tools offer the potential to identify those who will benefit most from a geriatric assessment. Consensus about the optimal tool to use is lacking.
To appraise the evidence on screening tools used for older adults with cancer and identify an optimal screening tool for older adults with cancer who may benefit from geriatric assessment.
Systematic review of 4 databases (MEDLINE, Embase, CINAHL Cumulative Index to Nursing and Allied Health Literature, and PubMed) with narrative synthesis from January 1, 2000, to March 14, 2019. Studies reporting on the diagnostic accuracy and use of validated screening tools to identify older adults with cancer who need a geriatric assessment were eligible for inclusion. Data were analyzed from March 14, 2019, to March 23, 2020.
Seventeen unique studies were included, reporting on the use of 12 screening tools. Most studies were prospective cohort studies (n = 11) with only 1 randomized clinical trial. Not all studies reported time taken to administer the screening tools. The Geriatric-8 (G8) (n = 12) and the Vulnerable Elders Survey-13 (VES-13) (n = 9) were the most frequently evaluated screening tools. The G8 scored better in sensitivity and the VES-13 in specificity. Other screening tools evaluated include the Groningen Frailty Index, abbreviated comprehensive geriatric assessment, and Physical Performance Test in 2 studies each. All other screening tools were evaluated in 1 study each.
To date, the G8 and VES-13 have the most evidence to recommend their use to inform the need for geriatric assessment. When choosing a screening tool, clinicians will need to weigh the tradeoffs between sensitivity and specificity. Future research needs to further validate or improve current screening tools and explore other factors that can influence their use, such as ease of use and resourcing.
Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated.
...Does oxycodone reduce chronic breathlessness compared with placebo?
A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0–100 mm visual analogue scale) comparing arms Days 5–7. Secondary end points were average and worst breathlessness, quality of life, function, and harms.
Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001).
There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness.
Delirium is a serious neurocognitive syndrome which is highly prevalent in people approaching the end of life. Existing trials of interventions to prevent or treat delirium in adults receiving ...palliative care report heterogeneous outcomes.
To undertake an international consensus process to develop a core outcome set for trials of interventions, designed to prevent and/or treat delirium, for adults receiving palliative care.
The core outcome set development process included a systematic review, qualitative interviews, modified Delphi method and virtual consensus meetings using nominal group technique (Registration http://www.comet-initiative.org/studies/details/796). Participants included family members, clinicians, and researchers with experience of delirium in palliative care.
Forty outcomes were generated from the systematic review and interviews informing the Delphi Round one survey. The international Delphi panel comprised 92 participants including clinicians (n = 71, 77%), researchers (n = 13, 14%), and family members (n = 8, 9%). Delphi Round two was completed by 77 (84%) participants from Round one. Following the consensus meetings, four outcomes were selected for the core outcome set: 1) delirium occurrence (incidence and prevalence); 2) duration of delirium until resolution defined as either no further delirium in this episode of care or death; 3) overall delirium symptom profile (agitation, delusions or hallucinations, delirium symptoms and delirium severity); 4) distress due to delirium (person with delirium, and/or family and/or carers including healthcare professionals).
Using a rigorous consensus process, we developed a core outcome set comprising four delirium-specific outcomes for inclusion in future trials of interventions to prevent and/or treat delirium in palliative care.
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