2 Research recommendations
The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline (see section 5).
In people in hospital who are at high risk of delirium, which medication (atypical antipsychotics, typical antipsychotics, benzodiazepines or acetylcholinesterase inhibitors), compared with placebo or each other, is more clinically and cost effective in preventing the development of delirium?
The serious nature of delirium and its consequences makes it important to establish all methods of prevention. Pharmacological agents may be a simple preventive treatment for delirium, but there is uncertainty about effectiveness and side effects so they should be used with caution. The evidence is limited: three low-quality studies were found, each of which was unrepresentative either of the population or the medication used, but there was some indication of clinical effectiveness. A large randomised trial (with at least 100 people in each arm) should be conducted in people in hospital who are at high risk of delirium to compare atypical antipsychotics, typical antipsychotics, benzodiazepines or acetylcholinesterase inhibitors with placebo, or each other, for preventing delirium. The included populations should be defined in terms of their delirium risk (for example people at high risk could be those with two or more risk factors for delirium). The primary outcome should be the incidence of delirium, measured at least daily using a validated diagnostic tool. The severity and duration of delirium should also be recorded, together with adverse effects of the medication, notably extrapyramidal symptoms and stroke.
In people in hospital who have delirium, which is the most effective medication (atypical antipsychotics, typical antipsychotics or benzodiazepines) compared with placebo or each other for treating delirium?
Pharmacological interventions are currently used in clinical practice to manage the symptoms of delirium but the evidence for this is limited. One moderate-quality study showed that typical and atypical antipsychotics were clinically and cost effective compared with placebo, but there is no evidence for benzodiazepines. Pharmacological agents that alter the course of delirium or control particular symptoms might be useful in treating delirium, but we need to determine whether the medication should be given routinely or for selected symptoms, and what adverse events may occur. A large randomised trial (with at least 100 people in each arm) should be conducted in people in hospital with delirium to compare atypical antipsychotics, typical antipsychotics, or benzodiazepines with placebo, or each other, for the treatment of delirium. The outcomes should be recovery from delirium (complete response), and the duration and severity of delirium, measured using a validated diagnostic tool. Adverse events, notably extrapyramidal symptoms and stroke, should also be recorded.
For people in long-term care, is a multicomponent non-pharmacological intervention more clinically and cost effective than usual care in preventing the development of delirium?
Although there is moderate-quality evidence of clinical and cost effectiveness for multicomponent interventions for the prevention of delirium in people in hospital, there is no evidence in a long-term care setting. It is anticipated that such an intervention would benefit this long-term care population. A large, adequately powered, randomised trial, or a large, adequately powered, cluster randomised trial should be conducted in people in long-term care to compare a multicomponent intervention with usual care. The multicomponent intervention should include assessment by a trained and competent healthcare professional, who would recommend actions tailored to the person's needs. The intervention should include the recommended interventions to prevent delirium, particularly reorientation, medication review, hydration and sleep hygiene. The primary outcome should be the incidence of delirium, measured at least daily using a validated diagnostic tool. The severity and duration of delirium should also be recorded using a validated tool, together with the consequences of delirium, including admission to hospital.
How common is delirium and what are its adverse outcomes in people in long-term care?
Although there is evidence for adverse outcomes consequent to delirium in hospital, there is very little evidence from long-term care. It is important to determine whether people in long-term care, who already have a high risk of death, dementia and other adverse outcomes, have a further increased risk of these outcomes if they develop delirium. The risk of hospital admission as a consequence of delirium is also unknown. A large cohort study should be conducted in people in long-term care to determine:
the prevalence of delirium in this setting, and
if the presence of delirium is a prognostic factor for death, dementia, admission to hospital, falls and other adverse outcomes.
The multivariate analysis conducted in this study should take into consideration the potential significant risk factors and confounding factors identified in the guideline. Such a study would also inform cost-effectiveness analyses for the prevention and treatment of delirium.
Does a staff education programme (compared with an educational leaflet or usual care) reduce the incidence of delirium and improve the recognition and recording of delirium in people in hospital?
There is some evidence from multicomponent prevention studies to suggest that an education programme for healthcare professionals who care for people at risk of delirium reduces the incidence of delirium. However, the quality of this evidence is poor. There is a need to determine whether education has an important preventive effect on the incidence of delirium. There is also a need to find out if an educational programme increases awareness of delirium, so that delirium is recorded accurately, which is not the case in the UK at present. A cluster randomised trial should be carried out, with whole hospitals randomised to the educational interventions (thereby reducing the trial contamination effects of staff vicariously picking up education from colleagues randomised to the education programme arm). The primary outcomes (incidence of delirium and recording of delirium in the person's healthcare record) should be measured at a minimum of three timepoints before and after the intervention.