Browse Subject Areas

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients: A Systematic Overview. The SENATOR project ONTOP Series

  • Iosief Abraha ,

    Affiliation Geriatrics and Geriatric Emergency Care, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy

  • Fabiana Trotta,

    Affiliation Geriatrics and Geriatric Emergency Care, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy

  • Joseph M. Rimland,

    Affiliation Scientific Direction, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy

  • Alfonso Cruz-Jentoft,

    Affiliation Servicio de Geriatría, Hospital Universitario Ramón y Cajal, Madrid, Spain

  • Isabel Lozano-Montoya,

    Affiliation Servicio de Geriatría, Hospital Universitario Ramón y Cajal, Madrid, Spain

  • Roy L. Soiza,

    Affiliation Department of Medicine for the Elderly, Woodend Hospital, Aberdeen, United Kingdom

  • Valentina Pierini,

    Affiliation Clinica di Medicina Interna e Geriatria, Politecnica University of the Marche Region, Ancona, Italy

  • Paolo Dessì Fulgheri,

    Affiliation Clinica di Medicina Interna e Geriatria, Politecnica University of the Marche Region, Ancona, Italy

  • Fabrizia Lattanzio,

    Affiliation Scientific Direction, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy

  • Denis O’Mahony,

    Affiliation Department of Medicine, University College Cork, Cork, Ireland

  • Antonio Cherubini

    Affiliation Geriatrics and Geriatric Emergency Care, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy

Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients: A Systematic Overview. The SENATOR project ONTOP Series

  • Iosief Abraha, 
  • Fabiana Trotta, 
  • Joseph M. Rimland, 
  • Alfonso Cruz-Jentoft, 
  • Isabel Lozano-Montoya, 
  • Roy L. Soiza, 
  • Valentina Pierini, 
  • Paolo Dessì Fulgheri, 
  • Fabrizia Lattanzio, 
  • Denis O’Mahony



Non-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.

Methods and Findings

We performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I2=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I2=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.


In older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.


The healthcare system is increasingly demanding rapid access to current research to ensure evidence-based informed decision making and practice. Previously, guideline developers and decision makers were overwhelmed by the number of primary studies; they currently contend with an excess of reviews [1]. The number and variety of systematic reviews (SRs) is rapidly growing. Various sources report that for a single topic several systematic reviews can often be identified [2,3]. Furthermore, there is a tendency to perform systematic reviews of reviews in order to provide clinical decision makers with the evidence they need.

There are several reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients[47]. Delirium is the most common complication of hospital admission in older patients with an incidence rate that varies between 11% and 42% among patients in medical wards[8] and is as high as 80% in some surgical conditions in the post-operative phase[9]. Delirium is associated with increased morbidity, mortality and length of hospital stay as well as increased use of healthcare services and costs[10,11]. Since there is no evidence that pharmacological prevention or treatment of delirium is effective, a great deal of attention has been devoted to non-pharmacological interventions[1219].

The non-pharmacological interventions to prevent or treat delirium are quite diverse, ranging from simple single component interventions (e.g., music therapy) to complex multicomponent interventions.

This paper describes the methods used to identify all published systematic reviews concerning non-pharmacological interventions for delirium; identifies and critically appraises the primary studies included in the SRs; lists the elements that compose the multicomponent interventions and, based on the components shared among the studies, presents the meta-analyses, critically summarizes the evidence, discusses the limitations and proposes research priorities for future studies.


This work is part of the ONTOP (Optimal Evidence-Based Non-drug Therapies in Older People) project, a workpackage of a European Union funded FP 7 research named SENATOR (Software ENgine for the Assessment & Optimization of drug and non-drug Therapy in Older peRsons). The ONTOP aim is to undertake a literature search of systematic reviews concerning evidence-based non pharmacological treatments of 15 prevalent medical conditions affecting older people, including delirium[20].

To gather the evidence about non-pharmacological intervention to prevent or treat delirium, the ONTOP Evidence Group was established and took responsibility for defining the clinical questions. To define appropriate clinical question the Group identified a list of outcomes and a list of non-pharmacological interventions deemed relevant independent from the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) [21]. After three rounds of consultations, important and critical outcomes were identified. For delirium prevention the outcome delirium incidence was considered critical whereas for delirium treatment the outcomes delirium improvement (intended as either a delirium resolution and a reduction in its severity) and functional status (intended as the degree of functional autonomy of the patient) were considered critical. In the present paper only the results of the critical outcomes will be presented. For details see S1 Box, S1 and S2 Tables. For results of secondary outcome see S1 File.

Search Strategy and Inclusion Criteria for Systematic Reviews

The search sources included Cochrane Database of Systematic Reviews, PubMed, PsychINFO, EMBASE and CINAHL (S2 Box).

Two criteria were considered for further evaluation of an abstract: a) a paper defined as a review or meta-analysis, b) the mention of any non-pharmacological intervention for delirium.

Subsequently, full-texts of relevant abstracts were obtained and screened to identify SRs of interest based on:

  1. the use of at least one medical literature database;
  2. the inclusion of at least one primary study; and
  3. the use of at least one non-pharmacological intervention for delirium prevention or treatment for patients of 60+ years of age.

Only studies written in English, Italian or Spanish were considered.

We assessed the methodological quality of each systematic review using the AMSTAR (A Measurement Tool to Assess Reviews) instrument that contains 11-items to appraise the quality[22]. Two reviewers independently assessed the quality of the SRs and disagreement was resolved by consensus.

Inclusion Criteria for Primary Studies

From the included SRs we identified any experimental comparative study, either randomized or nonrandomized, that investigated any non-pharmacological intervention to prevent or treat delirium in older patients. Primary studies were excluded if they were observational studies or before-after studies with historical controls.

Data extraction and management

Extracted data were transferred onto data extraction forms. Information collected included trial characteristics, patients characteristics, intervention and comparator characteristics, and outcome measures.

Pairs of reviewers independently screened titles, abstracts and full-texts of articles. Disagreement was resolved by discussion.

Itemizing the elements of the multicomponent intervention

To better understand the characteristics of the multicomponent interventions, we itemized each element of the multicomponent intervention. This process helped to decide whether or not it was appropriate to perform a formal meta-analysis of different studies.

Risk of bias assessment

Assessment of risk of bias for the included primary studies was carried out using criteria from the Cochrane Collaboration[23]. The domains considered were random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other potential biases (e.g., balance in baseline characteristics). We assigned a risk of bias to one of three categories: low risk, high risk and unclear risk. Two reviewers independently assessed the risk of bias of individual studies and any differences in quality assessment results between raters was resolved through consensus.

Grading the quality of evidence

The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology by a panel of reviewers with experience in geriatrics, internal medicine and methodology.

GRADE assessment took into consideration the risk of bias[24], consistency of results across the available studies[25], precision of the results[26], directness[26], and likelihood of publication bias[27]. Randomized trials were privileged for the GRADE evaluation. Where evidence is without randomized trials the GRADE evaluation is performed for other study designs (e.g., controlled clinical trials). The quality of the evidence was categorized as high, moderate, low, or very low based on the judgments for the primary outcome (delirium incidence for prevention; delirium improvement and functional status for treatment). Summary tables were constructed using GRADEpro version 3.6.

Data Synthesis and Analysis

Where a meta-analysis was possible with at least two studies, DerSimonian and Laird random-effects models were used to pool risk ratios of delirium incidence (Review Manager software version 5.3). We used the Chi2 test and I2 statistic to assess heterogeneity[23]. We considered heterogeneity to be statistically significant if the P value is less than 0.1. Publication bias was assessed by visual judgment of a funnel plot and by Egger’s regression method.


Systematic reviews

Our search identified 3329 abstracts after excluding 295 duplicates. Among the 80 potentially relevant publications, 26 were considered relevant for inclusion and 54 were excluded (see Fig 1 for study screening process and S3 Table for list of excluded reviews with reasons). The publication year ranged from 1996 to 2014 and 5 reviews were published in 2014.

While all articles used PubMed to search for primary studies, 13 papers also employed CINAHL[57,2837], 11articles also used the Cochrane Library[7,30,31,34,36,3843], 10 studies also accessed Embase [7,32,34,36,38,41,4346], and 3 studies also searched PsychINFO[5,32,36].

None of the SRs was sponsored by a company. Six studies were funded by a governmental institution[7,38,41] or a non-profit organization[5,43,47].

The reviews were heterogeneous. Some reviews, in addition to examining interventions to treat or prevent delirium, also evaluated the pathogenesis of delirium[47], examined the role of sitters[48], or studied approaches to diagnose delirium[28,39,49]. Only two reviews assessed single component interventions (music therapy[33] and earplugs[50]). The remaining SRs appraised multicomponent interventions.

Three SRs ranked as being of high quality (scoring 8–11), 12 of medium quality (scoring 4–7), and 11 of low quality (scoring 0–3) (S4 Table).

Table 1 summarizes the basic characteristics of the SRs.

Primary studies

Overall the 26 SRs yielded 78 primary studies of which 31 satisfied our inclusion criteria. (see Fig 1 and S5 Table for excluded primary studies).

The identified primary studies are described based on the type of the intervention (single or multicomponent), the aim of the intervention (prevention or treatment), the setting (e.g., surgical), and the study design [randomized controlled trial (RCTs), Controlled Clinical Trials (CCT), and Before After (BA) study].

Evidence of multicomponent, non-pharmacological interventions to prevent delirium in surgical setting.

Nine studies evaluated the efficacy of multicomponent non-pharmacological interventions to prevent delirium in surgical wards. Two studies were randomized trials[62,63], one was a CCT[64] and six were BA studies[6570]. Except for Chen et al.[66] all studies assessed patients with hip fractures. The study characteristics are described in Table 2. All studies considered the incidence of delirium as primary outcome except Chen et al,[66] who investigated functional and cognitive function as the primary outcomes.

Table 2. Characteristics of Primary Studies.

Non-Pharmacological Interventions for Delirium Prevention in Surgical Setting.

The components of the non-pharmacological intervention that were common among the studies are shown in Table 3.

Table 3. Elements of the multicomponent non-pharmacological interventions across primary studies.

Methodological issues.

Given the nature of the intervention, all the comparative studies suffered from performance bias because blinding of patients and personnel could not be carried out. However, all the three trials were immune from detection bias[6264]. Of the two RCTs, only Lundstrom et al.[62] explicitly reported the method of allocation concealment. The non-randomized studies (CCTs and BA studies) were, by their nature, at risk of selection bias. In two of the four BA studies, the outcome assessor could not be blinded, thus raising the possibility of detection bias. Fig 2 summarizes the risk of bias in each study.

Fig 2. Risk of Bias of Primary Studies of Multicomponent Non-Pharmacological Interventions for Prevention and Treatment of Delirium.

✔low risk of bias? unclear risk of bias X high risk of bias; RCT, Randomized Controlled Trial; CCT, Controlled Clinical Trial; BAS before-after studies (*) post-acute skilled nursing facilities.


Incidence of delirium.

Two RCTs presented data that could be combined, given the similarity between the population samples and the items of the non-pharmacological interventions [62,63]. In fact these two trials had the following interventions in common: comprehensive geriatric assessment, management and rehabilitation, prevention, early detection and treatment of major postoperative complications, oxygen therapy, regulation of bowel/bladder function, nutrition and hydration (Table 3).

The study by Marcantonio et al.[63] reported the cumulative incidence of delirium during hospitalization and used the Delirium Symptom Interview (DSI), the Memorial Delirium Assessment Scale (MDAS), and the Confusion Assessment Method (CAM)[73] to assess delirium. Lundstrom et al.[62]measured delirium based on nurses’ interviews and the modified Organic Brain Syndrome Scale, which was applied at 3–5 days after hospital admission. The pooled results showed that the multicomponent intervention significantly reduced the incidence of delirium by 29% [RR 0.71 (95% CI, 0.59 to 0.86); I20%]. The overall GRADE quality of evidence was judged to be moderate (Table 4).

Table 4. GRADE quality of evidence summary table for the comparisons of multicomponent non-pharmacological interventions with usual care for delirium prevention or treatment.

Combining the former results with the single CCT[64], which had similar characteristics, yielded pooled results which remained statistically significant with no change in heterogeneity [RR 0.71 (95%CI, 0.60 to 0.84)] (Fig 3).

Fig 3. Forest plot of risk ratios comparing multicomponent non-pharmacological interventions vs usual care for delirium prevention in older patients in surgical setting.

In three of the 5 BA studies the CAM was employed to assess delirium, while a clinical evaluation was used by Williams et al.[70]and SPMSQ and OBS scale was used by Bjorkelund[65]. Moreover, the assessment time points varied considerably; Wong et al.[69] measured the incidence of delirium every month, Williams et al.[70]measured it within 5 postoperative days, while the remaining studies did not provide the time frame. However, an attempt to pool the data across the studies with patients that received orthopedic surgery, in a meta-analysis, yielded a statistically significant result in favor of the multicomponent interventions [RR 0.57 (95% CI 0.39 to 0.85): I2 27%, P = 0.25][6770].

Evidence of multicomponent, non-pharmacological interventions to prevent delirium in medical setting.

Seven studies evaluated the efficacy of multicomponent interventions to prevent delirium in older patients hospitalized in medical departments. Two studies were RCTs [74,75], three were CCTs[76,77,82] and two were BA studies[83,84](Table 5).

Table 5. Characteristics of Primary Studies—Non-Pharmacological Interventions for Delirium Prevention in Medical Setting.

Yoo et al. evaluated, in a CCT, the efficacy of interdisciplinary intervention by non-geriatricians to prevent delirium. The components of the non-pharmacological intervention in the remaining studies are shown in Table 3. Delirium incidence was a primary outcome in every study except in Asplund et al.[75].

Methodological issues.

Of the two RCTs, Asplund et al.[75] did not report the exact method of random sequence generation and the personnel could have been aware of the group allocation with block randomization, therefore the study was judged to be at high risk of selection bias. In addition, Asplund et al.[75] was at high risk of attrition bias, because the data were analyzed per protocol.

In the remaining non-randomized studies despite selection bias is a threat to these studies, the baseline characteristics of the population were well balanced. Fig 2 describes the risk of bias table.


Randomized trials.

The two RCTs differed substantially in the patient population evaluated. In Asplund et al.[75] where delirium was not a primary outcome and patients were at low risk of developing delirium, non-pharmacological interventions were not able to prevent delirium [RR 1.75 (95% CI 0.50 to 6.10), GRADE quality of evidence was very low]. Conversely, in Martinez et al.[74] patients were at high risk of delirium (age >70 years, a documented cognitive impairment, alcoholism and metabolic imbalances) and the multicomponent intervention, which was performed by family members, was able to reduce the incidence of delirium (evaluated daily with the CAM) by 58% [RR 0.42 (95% CI 0.19 to 0.92)GRADE quality of evidence was low][74].

Controlled clinical trials.

Two of CCTs investigated very similar patient populations (patients at intermediate/high risk of delirium), and type of multicomponent interventions (Table 3), targeting the same risk factors[76,77]. In both studies, delirium was evaluated daily. The meta-analysis demonstrated a significant risk reduction of 35% of delirium incidence [RR 0.65 (95% CI 0.49 to 0.86); I2 0%] (Fig 4). The overall GRADE quality of evidence was judged to be moderate.

Fig 4. Forest plot of risk ratios comparing multicomponent non-pharmacological interventions vs usual care for delirium prevention in older patients in medical setting.

The third CCT evaluated an intervention carried out by non-geriatricians which was not effective in preventing delirium[82].

Before-after studies

The two BA studies were different in the patient populations, settings and interventions[84,85] (Table 5) and the interventions in the two studies were not effective in preventing delirium.

Evidence of multiple-component, non-pharmacological interventions to treat delirium in hospitalized patients.

Four RCTs evaluated the efficacy of non-pharmacological interventions to treat delirium in older patients hospitalized with acute illness in a medical ward trials[7881] and their characteristics are described in Table 6.

Table 6. Characteristics of Included Primary Studies—Non-Pharmacological Interventions for Delirium Treatment.

The components of the non-pharmacological interventions differed between the studies, with only the individual care planning being a common element to all four studies (Table 3). Three studies[7981] measured the mortality rate as a primary outcome, while Cole et al.[78] assessed cognitive improvement as a single primary outcome. The length of hospital stay was evaluated as a primary outcome in two studies[79,81].

Methodological issues.

Two of the RCTs had an adequate method of randomization[78,80]. In the study by Lundstrom et al.[81], the randomization method was unclear, in addition to having a high risk of bias in the allocation concealment (their allocation method depended on the availability of a free bed). The allocation concealment in the study by Cole et al.[79] was unclear. In terms of detection bias three studies displayed low risk of bias and one study [80] had an unclear risk (Fig 2).


Delirium Improvement.

The differences in the components of the interventions and the methods used to assess the outcomes precluded a meta-analysis. In the study by Lundstrom et al.[81], delirium was assessed at day 1, 3 and 7 of hospitalization. Complete remission rate at day 7 was significantly higher in patients that received the non-pharmacological intervention [RR 1.58 (95%CI 1.15 to 2.17)]. Pitkala et al.[80] assessed delirium severity using the MDAS scale. Despite the significant statistical difference in favor of the experimental group, the number of incident cases of patients who improved was not reported. Cole et al.[79] used the CAM to assess delirium, but not to determine delirium improvement. In a subsequent publication in 2002[78], the authors assessed the time and rate of improvement of Delirium Index Score, without finding a significant effect of the intervention. The overall GRADE quality of evidence was judged to be very low (Table 4).

Functional status.

Only two studies evaluated the functional status using the Barthel Index score and results were not statistically significant [78,80].

Evidence of multicomponent, non-pharmacological interventions to treat delirium in post-acute care facilities.

A cluster RCT evaluated the efficacy of a nurse-led delirium abatement program for post-acute care (PAC) in skilled nursing facilities[86]. The primary outcome was the delirium persistence at 2 weeks and 1 month after post-acute care unit admission.

Methodological limitations of the trial are synthesized in Fig 2.

The intervention allowed a better identification of delirium but was ineffective at reducing delirium[86].

Evidence of single-component, non-pharmacological interventions to prevent delirium.

Nine studies evaluated the efficacy of single-component non-pharmacological interventions to prevent delirium in acute medical wards (Table 7).

Table 7. Characteristics of Included Primary Studies—Single-Component Based Non-Pharmacological Intervention for Delirium Prevention.

The risk of bias is summarized in Fig 5.

Fig 5. Risk of Bias of Primary Studies of Single Non-Pharmacological Interventions for Prevention of Delirium.

✔low risk of bias? unclear risk of bias X high risk of bias; RCT, Randomized Controlled Trial; CCT, Controlled Clinical Trial; BAS before-after studies; (*) Geriatric Risk Assessment MedGuide software.

Two RCTs evaluated the efficacy of Bright Light Therapy in an intensive care unit[87,88]. The intervention reduced the incidence of delirium but without statistically significance[RR 0.29 (95% CI, 0.07 to 1.25)].

Van Rompaey’s randomized trial studied the efficacy of using Ear Plugs to prevent delirium and found a hazard ratio of documenting any benefit for delirium prevention [RR 1.05 (95%CI 0.53 to 2.06)][89].

In a large cluster-RCT Lapane et al.[90] a Geriatric Risk Assessment MedGuide software was used to identify resident-specific medications that may contribute to delirium. The intervention significantly reduced the incidence of delirium in newly admitted residents in the intervention homes than those in usual care homes (hazard ratio 0.42, 95%CI 0.35 to 0.52).

In a cluster RCT, Culp et al.[95] evaluated the efficacy of Hydration management in 98 residents of 7 care homes without documenting any efficacy (RR 0.85, 95% CI 0.18 to 4.00).

McCaffrey et al. studied Music Therapy in three RCTs but results of delirium incidence were not clearly reported[9193].

In a CCT, Tabet et al.[94]evaluated the efficacy of Staff Education to prevent delirium in a medical ward. The incidence of delirium was significantly lower on the intervention ward despite a wide confidence interval [RR 0.50 (95%CI 0.26 to 0.96)][94].

In a controlled BA study, Colombo et al.[96] evaluated the efficacy of a Reorientation protocol in 314 critically-ill patients admitted to an ICU. Delirium occurrence was significantly lower in the experimental group [RR 0.63 (95%CI 0.44 to 0.91)].

Table 8 displays the summary of finding with GRADE evidence profile for each single component.

Table 8. GRADE quality of evidence summary table for the comparisons of single component non-pharmacological interventions with usual care for delirium prevention.


This systematic review was aimed at identifying systematic reviews and meta-analyses of non-pharmacological interventions used to prevent or treat delirium in patients aged 60 years or older to provide a summary for decision makers and guideline developers.

From 26 SRs or meta-analyses meeting our inclusion criteria, we analyzed data from 31 primary studies published in the last 20 years.

We found evidence of moderate quality supporting the efficacy of multicomponent non-pharmacological interventions to prevent delirium in older patients acutely admitted to a surgical or a medical ward. It must be emphasized, however, that these interventions are effective when administered to patient at intermediate/high-risk of developing delirium. When single component interventions were considered staff-education, reorientation protocol and the Geriatric Risk Assessment MedGuide software were the only interventions that produced significant reduction in delirium prevention albeit a wide confidence interval, likely due to the fact that only one study has been performed for each of them. However, staff-education, reorientation protocol and drug review were present in trials where the multicomponent interventions resulted effective in reducing the delirium incidence.

On the contrary, evidence was insufficient to determine the benefit of multicomponent interventions in the prevention of delirium in other care settings (i.e., nursing homes). Finally, conflicting but mainly negative evidence was found concerning the utility of multicomponent non-pharmacological interventions to treat delirium in older medical patients.

Strengths and weaknesses of the study

This is the first systematic review to gather evidence from different SRs and meta-analyses concerning non-pharmacological treatments for delirium.

Firstly, most of the reviews included in our analysis had different aims and, consequently, the primary studies were distributed among the different reviews requiring the interested reader to consult all of them. For example, the review of Mak et al.[34], focused on prevention of delirium in patients with hip fracture[34]. Skingleyet al.[33] were interested in music as a single component intervention to prevent delirium[33]; Holroyd-Leduc et al.[38]considered both pharmacological and non-pharmacological interventions without examining the single component intervention[38];the review by Hempenius et al.[98] was limited only to delirium prevention[30] (S6 Table shows how the primary studies were distributed among the reviews). Thus, our systematic overview provides a unique tool that synthesizes the evidence on non-pharmacological intervention.

Secondly, unlike previously published reviews, we carefully examined the multicomponent intervention in order to identify the components that were common among different studies and used this information to decide whether it was feasible to perform a meta-analysis. In fact, in the assessment of non-pharmacological interventions for delirium prevention in older surgical patients, we were able to combine 2 RCTs [62,63] together with the recently published CCT [64] and from this combination of studies, we obtained a more precise estimate of the efficacy of the interventions. Similarly, in the setting of acute medical wards, we meta-analyzed Inouye and Vidan’s CCTs[76,77] based on the fact that they had at least seven components in common.

Third, we categorized the studies based on study design, the provision of intervention (for prevention or treatment), and the setting in which the intervention was provided as well as the risk of bias for each study. We believe that this classification approach will facilitate the formulation of clinical questions to assist clinicians to make decisions and to help guideline developers produce recommendations.

Fourth, the strength of evidence is evaluated according to the GRADE items of risk of bias, inconsistency, indirectness, imprecision, and publication bias.

We acknowledge that two studies were recently published that compares to our analysis. The first, was a meta-analysis that considered the efficacy of multicomponent interventions on, among other outcomes, delirium prevention[99]. The study pooled the results of 11 studies including randomized, controlled clinical trials and non-randomized studies and found an OR 0.47 (95% CI, 0.38 to 0.58) in favor of non-pharmacological intervention. The second article is a practice statement from the American Geriatrics Society[100] and it deals with the risk factors, diagnosis, and management of delirium including the use of non-pharmacological intervention for prevention and treatment of postoperative delirium. The authors identified 11 studies including randomized and non-randomized studies and state that the incidence of delirium was reduced but did not perform a meta-analysis. The conclusions of the two paper about multicomponent interventions to prevent delirium are similar to ours although our approach to meta-analyze data considered the setting in which the intervention is provided, the elements that composed the multicomponent interventions and the study design. In addition, we applied the GRADE approach and provide a summary of findings table that can provide the reader a complete account of the confidence of the evidence for the recommendation of multicomponent interventions.

We acknowledge that our review has some limitation. Firstly, the arbitrary age cut-off that may limit the applicability of the evidence from the present overview to patients with less than 60 years of age. Secondly, the lack of assessment of cost-effectiveness reviews does not allow us to reach any conclusions regarding this topic. Thirdly, the studies examined were heterogeneous in terms of intervention, study design, population, outcome and instrument assessment. To address this issue we adopted the best available methodology, i.e. GRADE, to evaluate and synthesize the available evidence.

Implications for healthcare professionals

Delirium is a geriatric syndrome and as such, it is expected to have a multifactorial etiology in the majority of patients[70,86]. This implies that multicomponent interventions are those with the best chance of being effective. We did find that multicomponent interventions were able to prevent delirium in hospitalized older patients. However, the multicomponent interventions adopted in different studies were quite heterogeneous and therefore difficult to compare. We were able to identify some common elements among different interventions, but no evidence is available to allow either the identification of which multicomponent program is more effective than others, or the relative contribution of each constituent intervention to the positive results in each individual patient. [101].

Unanswered questions and future research

The process of de-itemizing the multicomponent interventions used to provide the rational to pool meta-analyses may have another implication. For example, in delirium prevention in surgical setting, early mobilization, nutrition and hydration, regulation of bowel/bladder function, and early prevention of complications were the items that randomized studies had in common; in medical setting, in addition to early mobilization, nutrition and hydration, the interventions that the two controlled trials had in common were staff education, orientation protocol, avoidance of sensory deprivation. It is conceivable that these items may have more weight in determining the efficacy. Future studies may consider to design different multicomponent modalities in order to understand which items provide the most important contribution to the efficacy of the multicomponent intervention, how they are interrelated and the resources needed to implement the intervention.

Another point worthy of comment is the fact that the multicomponent interventions work well to prevent delirium, but their efficacy to treat delirium is at best controversial, with more negative than positive results from the studies evaluated. There is no simple explanation for these findings. One possibility is that while the risk factors for delirium are well characterized[70] and their management can effectively reduce the incidence of new episodes of this geriatric syndrome, the pathophysiology underlying the onset, development and persistence of confusion is not well understood. Several theories have been proposed, including impairment of cerebral metabolism (metabolic encephalopathy), intoxication by drugs, especially those with anticholinergic effects, inflammation, hypercortisolism, and a combination of the former, but no hypothesis has a strong experimental evidence in support of its validity[102].

Therefore, multicomponent interventions investigated in delirium treatment studies are quite similar to those developed for delirium prevention, but they are applied in a very different clinical scenarios. Further research concerning the pathophysiology of delirium is clearly needed to provide the data to support the development of more effective interventions to treat older patients suffering from delirium.


In older patients at intermediate/high risk of delirium multi-component non-pharmacological interventions as well as some single-components intervention (staff education, reorientation and drug review) reduce the incidence of delirium. Evidence for the role of non-pharmacological interventions in the treatment of delirium is inconclusive.

Supporting Information

S1 Box. List of non-pharmacological interventions to prevent or treat delirium.


S1 Table. List of non-pharmacological interventions.


S2 Table. Ranking of possible important outcomes when making decisions on delirium prevention.


S3 Table. List of excluded reviews with reasons.


S4 Table. Methodological quality assessment of the included studies systematic reviews (AMSTAR).


S5 Table. Excluded primary studies with reasons.


S6 Table. Distribution of Primary Studies (column) across Systematic Reviews (row).



We thank the following panel members that participated in the Delphi process to identify relevant outcomes and non-pharmacological interventions: Hubert Blain, Karen Andersen Ranberg, Regina Roller-Wirnsberger, Fabio Salvi, Andrea Corsonello, Adalsteinn Gudmundsson, Akner Gunnar, MirkoPetrovic.

Author Contributions

Conceived and designed the experiments: IA AC ACJ RLS DO. Performed the experiments: IA JMR FT ILM VP. Analyzed the data: IA JMR FT AC ACJ PDF VP ILM. Contributed reagents/materials/analysis tools: IA AC JMR AC PDF FT RLS DO FL. Wrote the paper: IA FT JMR AC ACJ ILM RLS VP PDF FL DO.


  1. 1. Bastian H, Glasziou P, Chalmers I (2010) Seventy-five trials and eleven systematic reviews a day: how will we ever keep up? PLoS Med 7: e1000326. pmid:20877712
  2. 2. Smith V, Devane D, Begley CM, Clarke M (2011) Methodology in conducting a systematic review of systematic reviews of healthcare interventions. BMC Med Res Methodol 11: 15. pmid:21291558
  3. 3. Smith V, Devane D, Begley CM, Clarke M, Higgins S (2009) A systematic review and quality assessment of systematic reviews of randomised trials of interventions for preventing and treating preterm birth. Eur J Obstet Gynecol Reprod Biol 142: 3–11. pmid:18996637
  4. 4. Fick DM, Agostini JV, Inouye SK (2002) Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc 50: 1723–1732. pmid:12366629
  5. 5. Greer N, Rossom R, Anderson P, MacDonald R, Tacklind J, Rutks I, et al. (2011) Delirium: Screening, Prevention, and Diagnosis—A Systematic Review of the Evidence. Washington DC.
  6. 6. Cole MG, Primeau F, McCusker J (1996) Effectiveness of interventions to prevent delirium in hospitalized patients: a systematic review (Structured abstract). Canadian Medical Association Journal. pp. 1263–1268. pmid:8911292
  7. 7. Fox MT, Persaud M, Maimets I, O'Brien K, Brooks D, Tregunno D, et al. (2012) Effectiveness of acute geriatric unit care using acute care for elders components: a systematic review and meta-analysis. J Am Geriatr Soc 60: 2237–2245. pmid:23176020
  8. 8. Siddiqi N, House AO, Holmes JD (2006) Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing 35: 350–364. pmid:16648149
  9. 9. Dautzenberg PL, Mulder LJ, Olde Rikkert MG, Wouters CJ, Loonen AJ (2004) Delirium in elderly hospitalised patients: protective effects of chronic rivastigmine usage. Int J Geriatr Psychiatry 19: 641–644. pmid:15254920
  10. 10. Inouye SK (1999) Predisposing and precipitating factors for delirium in hospitalized older patients. Dement Geriatr Cogn Disord 10: 393–400. pmid:10473946
  11. 11. Inouye SK, Schlesinger MJ, Lydon TJ (1999) Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med 106: 565–573. pmid:10335730
  12. 12. Gamberini M, Bolliger D, Lurati Buse GA, Burkhart CS, Grapow M, Gagneux A, et al. (2009) Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial. Crit Care Med 37: 1762–1768. pmid:19325490
  13. 13. Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, et al. (2010) Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 38: 428–437. pmid:20095068
  14. 14. Hakim SM, Othman AI, Naoum DO (2012) Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial. Anesthesiology 116: 987–997. pmid:22436797
  15. 15. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, et al. (2005) Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 53: 1658–1666. pmid:16181163
  16. 16. Larsen KA, Kelly SE, Stern TA, Bode RH Jr., Price LL, Hunter DJ, et al. (2010) Administration of olanzapine to prevent postoperative delirium in elderly joint-replacement patients: a randomized, controlled trial. Psychosomatics 51: 409–418. pmid:20833940
  17. 17. Liptzin B, Laki A, Garb JL, Fingeroth R, Krushell R (2005) Donepezil in the prevention and treatment of post-surgical delirium. Am J Geriatr Psychiatry 13: 1100–1106. pmid:16319303
  18. 18. Prakanrattana U, Prapaitrakool S (2007) Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care 35: 714–719. pmid:17933157
  19. 19. Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, et al. (2012) Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med 40: 731–739. pmid:22067628
  20. 20. Abraha IA, Cruz-Jentoft A, Soiza RL, O’Mahony D, Cherubini A (2015) Evidence of and Recommendations for Non-Pharmacological Interventions for common geriatric conditions. The SENATOR-ONTOP Systematic Review Protocol. BMJ Open: (in press).
  21. 21. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. (2011) GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 64: 395–400. pmid:21194891
  22. 22. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. (2007) Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 7: 10. pmid:17302989
  23. 23. Higgins JPT, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 510 (updated March 2011) The Cochrane Collaboration.
  24. 24. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. (2011) GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). J Clin Epidemiol 64: 407–415. pmid:21247734
  25. 25. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. (2011) GRADE guidelines: 7. Rating the quality of evidence--inconsistency. J Clin Epidemiol 64: 1294–1302. pmid:21803546
  26. 26. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. (2011) GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol 64: 1283–1293. pmid:21839614
  27. 27. Guyatt GH, Oxman AD, Montori V, Vist G, Kunz R, Brozek J, et al. (2011) GRADE guidelines: 5. Rating the quality of evidence--publication bias. J Clin Epidemiol 64: 1277–1282. pmid:21802904
  28. 28. Cole MG (1999) Delirium: effectiveness of systematic interventions. Dement Geriatr Cogn Disord 10: 406–411. pmid:10473948
  29. 29. Cole MG, Primeau FJ, Elie LM (1998) Delirium: prevention, treatment, and outcome studies. Journal of Geriatric Psychiatry and Neurology. pp. 126–137. pmid:9894731
  30. 30. Hempenius L, Van Leeuwen BL, Van Asselt DZB, Hoekstra HJ, Wiggers T, Slaets JPJ, et al. (2011) Structured analyses of interventions to prevent delirium. International Journal of Geriatric Psychiatry 26: 441–450. pmid:20848577
  31. 31. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ, et al. (2008) What is "quality of evidence" and why is it important to clinicians? BMJ 336: 995–998. pmid:18456631
  32. 32. Siddiqi N, Stockdale R, Britton AM, Holmes J (2007) Interventions for preventing delirium in hospitalised patients. Cochrane Database Syst Rev: CD005563. pmid:17443600
  33. 33. Skingley A, Vella-Burrows T (2010) Therapeutic effects of music and singing for older people. Nurs Stand 24: 35–41.
  34. 34. Mak JC, Cameron ID, March LM (2010) Evidence-based guidelines for the management of hip fractures in older persons: an update. Med J Aust 192: 37–41. pmid:20047547
  35. 35. Milisen K, Abraham IL, Broos PL (1998) Postoperative variation in neurocognitive and functional status in elderly hip fracture patients. J Adv Nursing 27(1):59–67. pmid:9515609
  36. 36. Koizumi J, Shiraishi H, Ofuku K, Suzuki T (1988) Duration of delirium shortened by the correction of electrolyte imbalance. Jpn J Psychiatry Neurol. 1988 Mar;42(1):81–8. pmid:3398358
  37. 37. Mouchoux C, Rippert P, Duclos A, Fassier T, Bonnefoy M, Comte B, et al. (2011) Impact of a multifaceted program to prevent postoperative delirium in the elderly: the CONFUCIUS stepped wedge protocol. BMC Geriatr 11: 25. pmid:21592324
  38. 38. Holroyd-Leduc JM, Khandwala F, Sink KM (2010) How can delirium best be prevented and managed in older patients in hospital? CMAJ 182: 465–470. pmid:19687107
  39. 39. Weber JB, Coverdale JH, Kunik ME (2004) Delirium: current trends in prevention and treatment. Internal Medicine Journal. pp. 115–121. pmid:15030459
  40. 40. Nagley SJ Predicting and preventing confusion in your patients. pmid:3633943
  41. 41. Naughton BJ, Saltzman S, Ramadan F, Chadha N, Priore R, Mylotte JM (2005) A multifactorial intervention to reduce prevalence of delirium and shorten hospital length of stay. J Am Geriatr Soc. 2005 Jan;53(1):18–23. pmid:15667371
  42. 42. Needham DM, Korupolu R, Zanni JM, Pradhan P, Colantuoni E, Palmer JB, et al. (2010) Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil 91: 536–542. pmid:20382284
  43. 43. Inouye SK, Bogardus St Jr, Williams CS, Leo-Summers L, Agostini JV (2003) The role of adherence on the effectiveness of nonpharmacologic interventions: evidence from the delirium prevention trial. Arch Intern Med. 2003 Apr 28;163(8):958–64. pmid:12719206
  44. 44. Marik PE (2006) Management of the critically ill geriatric patient. Crit Care Med 34: S176–182. pmid:16917421
  45. 45. Girard TD, Kress JP, Fuchs BD, Thomason JWW, Schweickert WD, Pun BT, et al. (2008) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. The Lancet 371: 126–134.
  46. 46. Gonzalez-Montalvo JI, Alarcon T, Mauleon JL, Gil-Garay E, Gotor P, Martin-Vega A (2010) The orthogeriatric unit for acute patients: a new model of care that improves efficiency in the management of patients with hip fracture. Hip Int 20: 229–235. pmid:20544649
  47. 47. Bitsch M, Foss N, Kristensen B, Kehlet H (2004) Pathogenesis of and management strategies for postoperative delirium after hip fracture: a review. Acta Orthop Scand 75: 378–389. pmid:15370579
  48. 48. Flaherty JH, Little MO Matching the environment to patients with delirium: lessons learned from the delirium room, a restraint-free environment for older hospitalized adults with delirium. pmid:22091576
  49. 49. Conn DK, Lieff S (2001) Diagnosing and managing delirium in the elderly. Can Fam Physician 47: 101–108. pmid:11212421
  50. 50. Egbert AM, Parks LH, Short LM, Burnett ML (1990) Randomized trial of postoperative patient-controlled analgesia vs intramuscular narcotics in frail elderly men. Arch Intern Med. 1990 Sep;150(9):1897–903. pmid:1975490
  51. 51. Alway A, Halm MA, Shilhanek M, St Pierre J (2013) Do earplugs and eye masks affect sleep and delirium outcomes in the critically ill? Am J Crit Care 22: 357–360. pmid:23817826
  52. 52. Carr FM (2013) The role of sitters in delirium: an update. Can Geriatr J 16: 22–36. pmid:23440038
  53. 53. Clegg A, Siddiqi N, Heaven A, Young J, Holt R (2014) Interventions for preventing delirium in older people in institutional long-term care. Cochrane Database Syst Rev 1: CD009537. pmid:24488526
  54. 54. Gonzalez M, de Pablo J, Valdes M (2003) [Delirium: the clinical confusion]. Rev Med Chil 131: 1051–1060. pmid:14635594
  55. 55. Grigoryan KV, Javedan H, Rudolph JL (2014) Orthogeriatric care models and outcomes in hip fracture patients: a systematic review and meta-analysis. J Orthop Trauma 28: e49–55. pmid:23912859
  56. 56. Inouye SK, Westendorp RG, Saczynski JS (2014) Delirium in elderly people. Lancet 383: 911–922. pmid:23992774
  57. 57. Milisen K, Lemiengre J, Braes T, Foreman MD (2005) Multicomponent intervention strategies for managing delirium in hospitalized older people: systematic review (Structured abstract). Journal of Advanced Nursing. pp. 79–90. pmid:16149984
  58. 58. Morrison RS, Chassin MR, Siu AL (1998) The medical consultant's role in caring for patients with hip fracture. Ann Intern Med 128: 1010–1020. pmid:9625664
  59. 59. Moyce Z, Rodseth RN, Biccard BM (2014) The efficacy of peri-operative interventions to decrease postoperative delirium in non-cardiac surgery: a systematic review and meta-analysis. Anaesthesia 69: 259–269. pmid:24382294
  60. 60. Reston JT, Schoelles KM (2013) In-facility delirium prevention programs as a patient safety strategy: a systematic review. Ann Intern Med 158: 375–380. pmid:23460093
  61. 61. Zhang H, Lu Y, Liu M, Zou Z, Wang L, Xu FY, et al. (2013) Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials. Crit Care 17: R47. pmid:23506796
  62. 62. Lundstrom M, Olofsson B, Stenvall M, Karlsson S, Nyberg L, Englund U, et al. (2007) Postoperative delirium in old patients with femoral neck fracture: a randomized intervention study. Aging Clin Exp Res 19: 178–186. pmid:17607084
  63. 63. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM (2001) Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 49: 516–522. pmid:11380742
  64. 64. Deschodt M, Braes T, Flamaing J, Detroyer E, Broos P, Haentjens P, et al. (2012) Preventing delirium in older adults with recent hip fracture through multidisciplinary geriatric consultation. J Am Geriatr Soc 60: 733–739. pmid:22429099
  65. 65. Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, et al. (2012) Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 308(19):1985–1992. pmid:23180503
  66. 66. Chen CC, Lin MT, Tien YW, Yen CJ, Huang GH, Inouye SK (2011) Modified hospital elder life program: effects on abdominal surgery patients. J Am Coll Surg 213: 245–252. pmid:21641835
  67. 67. Harari D, Hopper A, Dhesi J, Babic-Illman G, Lockwood L, Martin F (2007) Proactive care of older people undergoing surgery ('POPS'): designing, embedding, evaluating and funding a comprehensive geriatric assessment service for older elective surgical patients. Age Ageing 36: 190–196. pmid:17259638
  68. 68. Milisen K, Foreman MD, Abraham IL, De Geest S, Godderis J, Vandermeulen E, et al. (2001) A nurse-led interdisciplinary intervention program for delirium in elderly hip-fracture patients. J Am Geriatr Soc 49: 523–532. pmid:11380743
  69. 69. Wong D, Bruce J, GB B (2005) Innovations in Aged Care. Delirium prevention after hip fracture Quality project to prevent delirium after hip fracture. Australasian Journal on Ageing 24: 174–177.
  70. 70. Inouye SK, Charpentier PA (1996) Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 275: 852–857. pmid:8596223
  71. 71. Bjorkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D (2010) Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand 54: 678–688. pmid:20236093
  72. 72. Williams MA, Campbell EB, Raynor WJ, Mlynarczyk SM, Ward SE (1985) Reducing acute confusional states in elderly patients with hip fractures. Res Nurs Health 8: 329–337. pmid:3853245
  73. 73. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI (1990) Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 113: 941–948. pmid:2240918
  74. 74. Martinez FT, Tobar C, Beddings CI, Vallejo G, Fuentes P (2012) Preventing delirium in an acute hospital using a non-pharmacological intervention. Age Ageing 41: 629–634. pmid:22589080
  75. 75. Asplund K, Gustafson Y, Jacobsson C, Bucht G, Wahlin A, Peterson J, et al. (2000) Geriatric-based versus general wards for older acute medical patients: a randomized comparison of outcomes and use of resources. J Am Geriatr Soc 48: 1381–1388. pmid:11083312
  76. 76. Inouye SK, Bogardus ST Jr., Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. (1999) A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 340: 669–676. pmid:10053175
  77. 77. Vidan MT, Sanchez E, Alonso M, Montero B, Ortiz J, Serra JA (2009) An intervention integrated into daily clinical practice reduces the incidence of delirium during hospitalization in elderly patients. J Am Geriatr Soc 57: 2029–2036. pmid:19754498
  78. 78. Cole MG, McCusker J, Bellavance F, Primeau FJ, Bailey RF, Bonnycastle MJ, et al. (2002) Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial. CMAJ 167: 753–759. pmid:12389836
  79. 79. Cole MG, Primeau FJ, Bailey RF, Bonnycastle MJ, Masciarelli F, Engelsmann F, et al. (1994) Systematic intervention for elderly inpatients with delirium: a randomized trial. CMAJ 151: 965–970. pmid:7922932
  80. 80. Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS (2006) Multicomponent geriatric intervention for elderly inpatients with delirium: a randomized, controlled trial. J Gerontol A Biol Sci Med Sci 61: 176–181. pmid:16510862
  81. 81. Lundstrom M, Edlund A, Karlsson S, Brannstrom B, Bucht G, Gustafson Y (2005) A multifactorial intervention program reduces the duration of delirium, length of hospitalization, and mortality in delirious patients. J Am Geriatr Soc 53: 622–628. pmid:15817008
  82. 82. Yoo JW, Nakagawa S, Kim S (2013) Delirium and transition to a nursing home of hospitalized older adults: a controlled trial of assessing the interdisciplinary team-based "geriatric" care and care coordination by non-geriatrics specialist physicians. pmid:22762723
  83. 83. Caplan GA, Harper EL (2007) Recruitment of volunteers to improve vitality in the elderly: the REVIVE study. Intern Med J 37: 95–100. pmid:17229251
  84. 84. Skrobik Y, Ahern S, Leblanc M, Marquis F, Awissi DK, Kavanagh BP (2010) Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates. Anesth Analg 111: 451–463. pmid:20375300
  85. 85. Caplan GA, Coconis J, Board N, Sayers A, Woods J (2006) Does home treatment affect delirium? A randomised controlled trial of rehabilitation of elderly and care at home or usual treatment (The REACH-OUT trial). Age Ageing 35: 53–60. pmid:16239239
  86. 86. Inouye SK (1994) The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med 97: 278–288. pmid:8092177
  87. 87. Ono H, Taguchi T, Kido Y, Fujino Y, Doki Y (2011) The usefulness of bright light therapy for patients after oesophagectomy. Intensive Crit Care Nurs 27: 158–166. pmid:21511473
  88. 88. Taguchi T, Yano M, Kido Y (2007) Influence of bright light therapy on postoperative patients: a pilot study. Intensive Crit Care Nurs 23: 289–297. pmid:17692522
  89. 89. Van Rompaey B, Elseviers MM, Van Drom W, Fromont V, Jorens PG (2012) The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit Care 16: R73. pmid:22559080
  90. 90. Lapane KL, Hughes CM, Daiello LA, Cameron KA, Feinberg J (2011) Effect of a pharmacist-led multicomponent intervention focusing on the medication monitoring phase to prevent potential adverse drug events in nursing homes. pmid:21649623
  91. 91. McCaffrey R, Locsin R (2004) The effect of music listening on acute confusion and delirium in elders undergoing elective hip and knee surgery. Journal of Clinical Nursing 13: 91–96. pmid:15724823
  92. 92. McCaffrey R, Locsin R (2006) The effect of music on pain and acute confusion in older adults undergoing hip and knee surgery. Holist Nurs Pract 20: 218–224; quiz 225–216. pmid:16974175
  93. 93. McCaffrey R (2009) The effect of music on acute confusion in older adults after hip or knee surgery. Appl Nurs Res 22: 107–112. pmid:19427572
  94. 94. Tabet N, Hudson S, Sweeney V, Sauer J, Bryant C, Macdonald A, et al. (2005) An educational intervention can prevent delirium on acute medical wards. Age Ageing 34: 152–156. pmid:15713859
  95. 95. Stenvall M, Olofsson B, Nyberg L, Lundstrom M, Gustafson Y (2007) Improved performance in activities of daily living and mobility after a multidisciplinary postoperative rehabilitation in older people with femoral neck fracture: a randomized controlled trial with 1-year follow-up. J Rehabil Med 39: 232–238. pmid:17468792
  96. 96. Ushida T, Yokoyama T, Kishida Y, Hosokawa M, Taniguchi S, Inoue S, et al. Incidence and risk factors of postoperative delirium in cervical spine surgery. pmid:19927098
  97. 97. Robinson S, Rich C, Weitzel T, Vollmer C, Eden B (2008) Delirium Prevention for Cognitive, Sensory, and Mobility Impairments. Research and Theory for Nursing Practice 22: 103–113. pmid:18578220
  98. 98. Hempenius L, van Leeuwen BL, van Asselt DZ, Hoekstra HJ, Wiggers T, Slaets JP, et al. (2011) Structured analyses of interventions to prevent delirium. Int J Geriatr Psychiatry 26: 441–450. pmid:20848577
  99. 99. Hshieh TT, Yue J, Oh E, et al. (2015) Effectiveness of multicomponent nonpharmacological delirium interventions: A meta-analysis. JAMA Internal Medicine.
  100. 100. (2015) Postoperative Delirium in Older Adults: Best Practice Statement from the American Geriatrics Society. Journal of the American College of Surgeons 220: 136–148.e131. pmid:25535170
  101. 101. Burns R (1994) Beyond the black box of comprehensive geriatric assessment. J Am Geriatr Soc 42: 1130. pmid:7930342
  102. 102. Hughes CG, Patel MB, Pandharipande PP (2012) Pathophysiology of acute brain dysfunction: what's the cause of all this confusion? Curr Opin Crit Care 18: 518–526. pmid:22941208