Interventions for preventing delirium in hospitalised patients.

BACKGROUND: Delirium is a common mental disorder with serious adverse outcomes in hospitalised patients. It is associated with increases in mortality, physical morbidity, length of hospital stay, institutionalisation and costs to healthcare providers. A range of risk factors has been implicated in its aetiology, including aspects of the routine care and environment in hospitals. Prevention of delirium is clearly desirable from patients' and carers' perspectives, and to reduce hospital costs. Yet it is currently unclear whether interventions for prevention of delirium are effective, whether they can be successfully delivered in all environments, and whether different interventions are necessary for different groups of patients. OBJECTIVES: Our primary objective was to determine the effectiveness of interventions designed to prevent delirium in hospitalised patients. We also aimed to highlight the quality and quantity of research evidence to prevent delirium in these settings. SEARCH STRATEGY: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 28th September, 2005. As the searches in MEDLINE, EMBASE, CINAHL and PsycINFO for the Specialized Register would not necessarily have picked up all delirium prevention trials, these databases were searched again on 28th October, 2005. We also examined reference lists of retrieved articles, reviews and books. Experts in this field were contacted and the Internet searched for further references and to locate unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating any interventions to prevent delirium in hospitalised patients. DATA COLLECTION AND ANALYSIS: Data collection and quality assessment were performed by three reviewers independently and agreement reached by consensus. MAIN RESULTS: Six studies with a total of 833 participants were identified for inclusion. All were conducted in surgical settings, five in orthopaedic surgery and one in patients undergoing resection for gastric or colon cancer. Only one study of 126 hip fracture patients comparing proactive geriatric consultation with usual care was sufficiently powered to detect a difference in the primary outcome, incident delirium. Total cumulative delirium incidence during admission was reduced in the intervention group (OR 0.48 [95% CI 0.23, 0.98]; RR 0.64 [95% CI 0.37, 0.98]), suggesting a 'number needed to treat' of 5.6 patients to prevent one case. The intervention was particularly effective in preventing severe delirium. In logistic regression analyses adjusting for pre fracture dementia and Activities of Daily Living impairment, there was no reduction in effect size, OR 0.6, but this no longer remained significant [95% CI 0.3,1.3]. There was no effect on the duration of delirium episodes, length of hospital stay, and cognitive status or institutionalisation at discharge. There was also no significant difference in cumulative delirium incidence between treatment and control groups in a sub-group of 50 patients with dementia (RR 0.9 [95% CI 0.59, 1.36]). In another trial of low dose haloperidol prophylaxis, there was no difference in delirium incidence but the severity and duration of a delirium episode, and length of hospital stay were all reduced. We identified no completed studies in hospitalised medical, care of the elderly, general surgery, cancer or intensive care patients. In outcomes, no studies examined for death, use of psychotropic medication, activities of daily living, psychological morbidity, quality of life, carers or staff psychological morbidity, cost of intervention and cost to health care services. Outcomes were only reported up to discharge, with no studies reporting medium or longer-term effects. AUTHORS' CONCLUSIONS: Research evidence on effectiveness of interventions to prevent delirium is sparse. Based on a single study, a programme of proactive geriatric consultation may reduce delirium incidence and severity in patients undergoing surgery for hip fracture. Prophylactic low dose haloperidol may reduce severity and duration of delirium episodes and shorten length of hospital admission in hip surgery. Further studies of delirium prevention are needed.

Antipsychotics for delirium.

BACKGROUND: Delirium occurs in up to 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. Recently published reports have suggested that the standard drug for delirium, haloperidol, a typical antipsychotic that may cause adverse extrapyramidal symptoms among patients, may be replaced by atypical antipsychotics such as risperidone, olanzapine or quetiapine, that are as effective as haloperidol in controlling delirium, but that have a lower incidence of extrapyramidal adverse effects. OBJECTIVES: To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 August 2006 using the search terms:haloperidol or haldol or risperidone or risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole or sertindole or leponex* or zeldox* or ziprasidone. SELECTION CRITERIA: Types of studies included unconfounded, randomised trials with concealed allocation of subjects. For inclusion trials had to have assessed patients pre- and post-treatment. Where cross-over studies are included, only data from the first part of the study were examined. Interrupted time series were excluded. Length of trial and number of measurements did not influence the selection of trials for study. Where indicated, individual patient data were requested for further examination. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from included trials. Data were pooled where possible, and analysed using appropriate statistical methods. Odds ratios of average differences were calculated. Only 'intention to treat' data were included. Analysis included haloperidol treated patients, compared with placebo. MAIN RESULTS: Three studies were found that satisfied selection criteria. These studies compared haloperidol with risperidone, olanzapine, and placebo in the management of delirium and in the incidence of adverse drug reactions. Decrease in delirium scores were not significantly different comparing the effect of low dose haloperidol (< 3.0 mg per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio 0.63 (95% CI 10.29 - 1.38; p = 0.25). Low dose haloperidol did not have a higher incidence of adverse effects than the atypical antipsychotics. High dose haloperidol (> 4.5 mg per day) in one study was associated with an increased incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose haloperidol decreased the severity and duration of delirium in post-operative patients, although not the incidence of delirium, compared to placebo controls in one study. There were no controlled trials comparing quetiapine with haloperidol. AUTHORS' CONCLUSIONS: There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo. These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.

The comparative bioavailability of cimetidine-alginate treatments.

The comparative bioavailability of cimetidine in cimetidine-alginate combinations has been investigated in twelve healthy volunteers in an open crossover study. Each volunteer received a single oral dose of a commercially available alginate-cimetidine combination tablet (Algitec) or cimetidine tablets (Tagamet), co-administered with a commercially available alginate reflux suppressant liquid or tablet (Gaviscon). No significant differences were observed between treatments for Cmax, tmax, AUC0-12 or AUC0- infinity. The study demonstrated equivalent bioavailability of cimetidine when administered separately with alginate products and as a fixed dose combination product.