DÄ internationalArchive11/2022Structured Delirium Management in the Hospital

Original article

Structured Delirium Management in the Hospital

A randomized controlled trial

Dtsch Arztebl Int 2022; 119: 188-94. DOI: 10.3238/arztebl.m2022.0131

Krämer, J; Nolte, K; Zupanc, L; Schnitker, S; Roos, A; Göpel, C; Cid, J S; Eichler, K; Hooven, T v d; Hempel, G; Pavenstädt, H; Klaas, C; Gosheger, G; Raschke, M J; Wiendl, H; Duning, T

Background: Delirium is a common and serious complication of inpatient hospital care in older patients. The current approaches to prevention and treatment followed in German hospitals are inconsistent. The aim of this study was to test the effectiveness of a standardized multiprofessional approach to the management of delirium in inpatients.

Methods: The patients included in the study were all >65  years old, were treated for at least 3  days on an internal medicine, trauma surgery, or orthopedic ward at Münster University Hospital between January 2016 and December 2017, and showed cognitive deficits on standardized screening at the time of admission (a score of ≤=25 on the Montreal Cognitive Assessment [MoCA] test). Patients in the intervention group received standardized delirium prevention and treatment measures; those in the control group did not. The primary outcomes measured were the incidence and duration of delirium during the hospital stay; the secondary outcomes measured were cognitive deficits relevant to daily living at 12  months after discharge (MoCA and Instrumental Activities of Daily Living [I-ADL]).

Results: The data of 772 patients were analyzed. Both the rate and the duration of delirium were lower in the intervention group than in the control group (6.8% versus 20.5%, odds ratio 0.28, 95% confidence interval [0.18; 0.45]; 3  days [interquartile range, IQR 2–4] versus 6  days [IQR 4–8]). A year after discharge, the patients with delirium in the intervention group showed fewer cognitive deficits relevant to daily living than those in the control group (I-ADL score 2.5 [IQR 2–4] versus 1 [IQR 1–2], P  = 0.02).

Conclusion: Structured multiprofessional management reduces the incidence and duration of delirium and lowers the number of lasting cognitive deficits relevant to daily living after hospital discharge.

LNSLNS

In patients aged over 65, the commonest complication of inpatient treatment is delirium (1, 2, 3): in this population its prevalence is between 40% and 80%. Apart from age (> 65 years), the greatest risk factor for the occurrence of delirium is a preexisting cognitive deficit (4, 5, 6).

Delirium has serious consequences. Not only does it prolong the hospital stay, it also leads to increased mortality (adjusted hazard ratio 1.95; mean follow-up 22.7 ± 15.5 months), worsens functional and cognitive outcome, and increases the risk that patients will go on to need long-term care (7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). Delirium leads to persistent cognitive deficits of dementia-like severity that are relevant to daily living, and these may occur even in the absence of preexisting dementia-like symptoms (21). In addition to this, longer hospital stays, increased nursing requirements, and the resulting consumption of resources are a financial burden on the treating hospital (3, 22, 23, 24).

Although delirium in hospital is of pressing relevance for both patients and and those treating them, it is rare in German hospitals to find any standardized approach to its prevention and treatment – despite the fact that the population is aging and cases of delirium may be expected to rise. One reason for this is that in the current hospital landscape delirium does not fall clearly within one particular specialty or profession, because its symptoms vary widely and its pathophysiology is multifactorial. Against this background, in 2015 the concept of a “dementia-sensitive hospital” was introduced at Münster University Hospital (Universitätsklinikum Münster, UKM) (Box). Through the use of a standardized approach based on this concept, and a multiprofessional delirium prevention and treatment team, it is hoped that the frequency, severity, and duration of delirium during a hospital stay will be reduced. The efficacy of this approach has been tested in a randomized controlled trial. The aim was to achieve a significant reduction in delirium rates and durations and to prevent permanent cognitive deficits relevant to everyday living resulting from the stay in hospital. The study was approved by the ethics committee of the Westphalia–Lippe Medical Association and the University of Münster (December 2015, 2015–531-f-S). It was subsequently registered in the German Register of Clinical Trials (DRKS) on 10 January 2019 (registration number DRKS 00016352).

The concept of the “dementia-sensitive hospital” at Münster University Hospital
Box
The concept of the “dementia-sensitive hospital” at Münster University Hospital

Patients and methods

Study participants

The study included older patients (>65 years of age) who received treatment as an inpatient for at least 3 days in one of the surgical or medical pilot wards (Departments of Orthopedics, Nephrology, and Trauma Surgery) between January 2016 and December 2017 and who scored ≤25 points (at least mild cognitive deficits) on the Montreal Cognitive Assessment (MoCA) (25), adjusted for education, that was administered on admission. Alcohol withdrawal delirium was an exclusion criterion. Further details are given in the eMethods.

Study design

Patients were assigned to the intervention or the control group (Figure 1). Details of the randomization procedure are given in the eMethods section.

Flow diagram of the study design
Figure 1
Flow diagram of the study design

The intervention group received delirium prevention measures and – if required – standardized treatment for delirium (26) (eFigure) from the multiprofessional team in accordance with the concept of the “dementia-sensitive hospital” (Box). The control group received standard therapy without specific delirium prevention or treatment.

Flow chart for pharmacological and nonpharmaceutical treatment of delirium
eFigure
Flow chart for pharmacological and nonpharmaceutical treatment of delirium

Patients in both the intervention and the control group were assessed for symptoms of delirium on the first 3 postoperative days or days in hospital using the Confusion Assessment Method (CAM) (27). In both groups the CAM was always carried out at a fixed time in the afternoon. The testers were trained in its use. The CAM is regarded as a time-efficient and valid screening tool for the detection of delirium and is recommended in the relevant guidelines (27, 28, 29, 30). All patients (intervention and control groups) underwent a second MoCA 1–2 days before discharge. All study participants who developed delirium during their hospital stay were again reassessed by the MoCA 12 months after discharge. In addition, the Instrumental Activities of Daily Living (I-ADL) scale (31) was administered to patients or relatives to quantify the extent of limitations relevant to daily living. Those who administered the CAM, MoCA, and I-ADL tests were blinded as to treatment group (intervention versus control).

Endpoints

The primary endpoints of the study were:

  • Incidence of delirium, objectified using the CAM;
  • Duration of delirium, objectified using the CAM.

The secondary endpoints of the study were:

  • Cognitive deficits at discharge (MoCA score);
  • Cognitive deficits relevant to daily living 12 months after discharge (MoCA and I-ADL test results).

Statistical analysis

All statistical analyses were performed using IBM SPSS software, version 27.0 (IBM Corp., Armonk, NY, USA) and R, version 4.0.3 (R Foundation, Vienna, Austria). A significance level of 5% was set. For details of the analysis, see eMethods.

Results

A total of 1472 patients > 65 years of age were assessed on admission to the pilot wards using the MoCA. Of these, 64% showed at least mild cognitive deficits on admission (≤= 25 points [n = 936]), and of these patients, 785 were included and randomized (Figure 1).

Data from a total of 772 patients (55.4% female) were analyzed. Details are shown in Table 1.

Patient characteristics, MoCA scores, and incidence and duration of delirium
Table 1
Patient characteristics, MoCA scores, and incidence and duration of delirium
Results of the hierarchical linear model
eTable 1
Results of the hierarchical linear model

Primary endpoints

During their hospital stay, 27 of 397 patients (6.8%) in the intervention group developed delirium, compared with 77 of 375 patients (20.5%) in the control group (odds ratio: 0.28; 95% confidence interval: [0.18; 0.45]; P < 0.001; relative risk: 0.33). Delirium in patients in the intervention group lasted an average of 3 days (interquartile range [IQR]: 2–4) and in patients in the control group an average of 6 days (IQR: 4–8) (p < 0.001).

Secondary endpoints

Cognitive deficits at discharge and after 12 months

In 69% of the study participants (273 patients in the intervention group and 256 patients in the control group), repeat cognitive testing (MoCA) was successfully performed at the time of discharge (Figure 1). At this timepoint the median MoCA score had changed in the intervention group (P < 0.001) but not in the control group (P = 0.45). Using a hierarchical linear model, in the next step it was shown that the MoCA score rose over time in patients from the intervention group, while in patients from the control group it fell (P < 0.001), so long as the patients had not developed delirium. In both groups, developing delirium meant a drop in MoCA score by 5.3 points (P < 0.001) (eMethods).

Regarding mortality rate, after 12 months there was no difference between the two groups (59 patients in the intervention group versus 64 patients in the control group; P = 0.40), and no difference between patients with delirium in the intervention group (n = 10) and those with delirium in the control group (n = 22) (P = 0.41).

In a subgroup of 45 of the 104 patients (Figure 1) who developed delirium during their hospital stay, it was possible to carry out a repeat MoCA approximately 12 months after discharge (15 patients in the intervention group, 31 patients in the control group).

While the median MoCA score changed for patients with delirium in the intervention group compared to the score at admission (P = 0.04), this was not the case for patients with delirium in the control group (P = 0.14); using the hierarchical linear model, in the next step it was shown that the cognitive deficits of patients with delirium who were cared for in line with the specific dementia-sensitive approach and by the team (the intervention group) were not permanent (rise in MoCA by 2.85 points during the study) (P = 0.01), whereas cognitive impairments in patients with delirium who were not treated in line with the dementia-sensitive approach during their hospital stay persisted even at 12 months after discharge (fall in MoCA by 1.62 points) (eMethods).

Deficits relevant to everyday living at 12 months after discharge

Out of a total of 772 patients, 525 patients or their relatives were successfully contacted for a telephone interview on the I-ADL scale. The other 247 patients were not reached or had died during the study period (Figure 1).

Patients with delirium in the intervention group (group G2), patients with delirium in the control group (group G4), and patients who did not show delirium during their hospital stay (intervention group: group G1; control group: group G3) differed as to their I-ADL scores 12 months after discharge (Figure 2). Differences were shown between groups G1 and G2 (P = 0.04), G1 and G4 (P < 0.001), G2 and G4 (P = 0.02), and G3 and G4 (P < 0.001) (Table 2). Patients without delirium (G1 and G3, median 5 points) in the hospital showed higher I-ADL scores than patients with delirium (G2 and G4), and also patients with delirium in the intervention group (G2, median 2.5 points) showed higher I-ADL scores than those in the control group (G4, median 1 point) (Figure 2); thus, they had significantly fewer persisent impairments relevant to daily living (I-ADL score = 0: “completely dependent on the support of others”; I-ADL score = 8: “independent, able to carry out necessary activities of daily living”). Persistent cognitive deficits relevant to everyday living were more frequent and more pronounced after delirium in the hospital without the specific dementia-sensitive treatment approach (intervention group) than with this concept (I-ADL 1 point in the control group versus I-ADL 2.5 points in the intervention group) (Figure 2).

I-ADL values from patients without and those with delirium in the intervention group
Figure 2
I-ADL values from patients without and those with delirium in the intervention group
I-ADL values of patients with and those without delirium in the intervention and control groups
Table 2
I-ADL values of patients with and those without delirium in the intervention and control groups
Results of the hierarchical linear model
eTable 2
Results of the hierarchical linear model

Discussion

The results of the study show that structured delirium management in hospital can significantly reduce the incidence and duration of delirium in elderly patients and also likely prevent permanent cognitive deficits.

Implementing this kind of concept of delirium management in a German hospital requires preliminary work in setting up a multiprofessional team to develop and put in place a procedural approach adapted to that hospital without having other tasks to attend to. For the approach described here to become accepted, and for it to succeed in medical and economic terms, it is important that strategies are developed both for delirium prevention and for a standardized treatment for delirium – because not every instance of delirium in a hospital is preventable. Achieving this requires a multidisciplinary approach, i.e., collaboration between different professional groups (e.g., neurologists, psychogeriatricians, nursing staff and nurse scientists, clinical pharmacists).

Approaches to preventing delirium in older patients in hospital have already been published. Although evidence supporting them has been demonstrated in numerous studies (32, 33, 34, 35), to date the implementation of standardized delirium management in German hospitals has not been consistent enough. One reason for this is no doubt the low impact of delirium during a hospital stay on the billing of care. In addition, most studies were conducted in countries with differing health care systems and models of inpatient care, so that it is difficult to simply extrapolate the results to German hospitals with a heterogeneous patient population. For example, the Hospital Elder Life Program (HELP) put forward by S. K. Inouye in 1999 (https://help.agscocare.org/) (22, 36) is now being applied in quite a uniform way in more than 200 hospitals in 32 states in the USA and in 11 other countries, with both economic and medical success. In German hospitals, there has been little experimentation, and that mostly with modified models (37).

Comparison with the data presented here is therefore difficult. However, compared with, for example, existing geriatric-based approaches, the approach to managing delirium presented here is clearly more specifically aimed at preventing and treating delirium. Symptoms of delirium have a multifactorial etiology. Today, the assumption that delirium merely reveals a preexisting dementia that was undiagnosed until the patient was admitted to hospital needs to be revised. People with preexisting neurodegenerative diseases are, it is true, at significantly increased risk of developing delirium, but recent study results show that delirium is an independent risk factor for permanent cognitive deficits, irrespective of the etiology of the delirium or other comorbidities (21).

Despite all the limitations, the results of this study support these observations. Regardless, older patients are fundamentally at higher risk of developing delirium (38). Therefore, to ensure that a management approach can be effectively implemented in practical terms, it seems sensible to focus on older at-risk patients in hospital. In the present study, screening for less obvious cognitive deficits in older patients for the purpose of delirium prevention proved to be effective and feasible, and the etiology of the impairments was deliberately not included. Since implementing this approach was cost-neutral, as calculated by the control department of UKM (chiefly because the hospital stay was shorter), it has since been expanded: currently, all specialties at UKM are taking part.

The “dementia-sensitive hospital” approach is deliberately designed to be practical. Necessary specific treatments, most of which are not focused on cognitive symptoms or symptoms of dementia or delirium (and this is the case on both surgical and medical wards), are accompanied by an interdisciplinary team of delirium specialists using established approaches to delirium prevention and treatment. Given the incidence of delirium and its intensely negative consequences for the patient, the patient’s family, and the health care system, this seems both reasonable and necessary.

One limitation of the study that must be mentioned is a high drop-out rate. Twelve months after hospital discharge, a repeat MoCA was possible in only 43% of all patients who had developed delirium during their hospital stay. Moreover, the repeat measurement of cognitive deficits was limited to patients who had developed delirium while they were in hospital. This restricted use of resources can be justified by the body of recent research, which shows delirium as the greatest single risk factor for persistent deficits in the patient population studied (21). Nevertheless, it cannot be ruled out that other illnesses during the intervening period account for some of the deficits found at follow-up. Because of the small case numbers at follow-up, the results must be considered as only indicative, not representative. The rise in MoCA score in patients in the intervention group is plausible. It is known and to be expected that, because of their limited cognitive reserve, even healthy aged patients in the acute situation of hospital admission will achieve a low MoCA score which is not seen at follow-up after 12 months.

Although mortality is a competing event for long-term outcome, the lack of difference between mortality rates in the control group and the intervention group in the 12 months after discharge makes it highly unlikely that it affected the results.

Another limitation was the structural impossibility of blinding the staff on the wards where the approach was implemented. The raters for the CAM, MoCA, and I-ADL assessments were blinded, but this was not possible for all team members. However, this confounding factor tends to lead to more delirium-preventive treatment for patients in the control group as well, meaning that if anything significant results would be underestimated.

I-ADL score was determined in patients 12 months after discharge but not on admission. Most patients were not admitted electively. For this reason, it is not possible to conclude whether impairments shown in I-ADL scores were delirium-related or were preexisting.

Patients who unexpectedly remained in hospital for less than 3 days were not included. Whether the established approach to delirium management can also prevent delirium in short-stay patients must be investigated in further studies.

To summarize, it was possible to achieve effective delirium reduction with a standardized approach adapted to the hospital. We recommend that a multiprofessional approach to the prevention and also treatment of delirium in hospital should be implemented rigorously and in a coordinated way, so that it can be sufficiently effective and so become permanently accepted. In future, it will certainly make sense and also be economically efficient to reimburse costs for preventive approaches of this kind for patients who have to undergo hospital treatment despite having cognitive impairments.

On this latter point, various initial steps have been taken – for example, the service categories determined by the Joint Federal Committee that are suitable for quality contracts to be signed between hospitals and health insurance companies, and health policy strategies (for example, point 3.3 of the German government’s National Dementia Strategy) – although these need wider implementation. Certainly improvement is needed here at present. However, with the approach shown, the many existing concepts could be developed into a uniform, practical, and effective strategy for German hospitals, which in medical terms already appears worthwhile.

Acknowledgment

We thank Eric Rost of IU International University of Applied Sciences for his assistance in the statistical analysis calculations..

Conflict of interest statement

Laura Zupanc has received fees from Schlütersche Verlagsgesellschaft GmbH & Co. KG.

Prof. Hempel and Dr. Nolte have received lecture fees from the Westphalia–Lippe Chamber of Pharmacists.

The other authors declare that no conflict of interest exists.

Manuscript received on 4 March 2021, revised version accepted on
1 February 2022

Translated from the original German by Kersti Wagstaff, MA.

Corresponding author:
Prof. Dr. med. Thomas Duning
Klinik für Neurologie
Klinikum Bremen-Ost
Züricher Str. 40
28325 Bremen, Germany
Thomas.duning@gesundheitnord.de

Cite this as:
Krämer J, Nolte K, Zupanc L, Schnitker S, Roos A, Göpel C, Santos Cid J, Eichler K, van den Hooven T, Hempel G, Pavenstädt HJ, Klaas C, Gosheger G, Raschke MJ, Wiendl H, Duning T: Structured delirium management in the hospital—a randomized controlled trial.
Dtsch Arztebl Int 2022; 119: 188–94. DOI: 10.3238/arztebl.m2022.0131

Supplementary material:

eMethods, eTables, eFigure:
www.aerzteblatt-international.de/m2022.0131

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Department of Neurology and Institute of Translational Neuroscience, Münster University Medical Center (UKM): PD Dr. med. Julia Krämer
For affiliations of the other authors please see the end of the article.
Affiliations
Department of Neurology and Institute of Translational Neuroscience, Münster University Medical Center (UKM): Dr. rer. nat. Katharina Nolte, Dr. med. Anna Roos, Christopher Göpel, Janina Santos Cid, Kirsten Eichler, Prof. Dr. med. Prof. h. c. Heinz Wiendl, Prof. Dr. med. Thomas Duning
Pharmacy, Münster University Medical Center (UKM): Dr. rer. nat. Katharina Nolte, Dr. rer. nat. Christoph Klaas
Financial Controlling Section, Münster University Medical Center (UKM): Laura Zupanc, Stefan Schnitker
Department of Nursing Science, Münster University Medical Center (UKM): Thomas van den Hooven
Institute of Pharmaceutical and Medicinal Chemistry, Westfälische Wilhelms-Universität Münster: Prof. Dr. rer. nat. Georg Hempel
Department of Medicine D – Internal Medicine, Emergency Medicine, Nephrology and Rheumatology, Münster University Medical Center (UKM): Prof. Dr. med. Hermann-Joseph Pavenstädt
Department of General Orthopaedics and Tumororthopaedics, Münster University Medical Center (UKM): Dr. med. Georg Gosheger
Department of Trauma, Hand and Reconstructive Surgery, Münster University Medical Center (UKM): Prof. Dr. med. Michael J. Raschke
Department of Neurology, Klinikum Bremen-Ost: Prof. Dr. med. Thomas Duning
The concept of the “dementia-sensitive hospital” at Münster University Hospital
Box
The concept of the “dementia-sensitive hospital” at Münster University Hospital
Flow diagram of the study design
Figure 1
Flow diagram of the study design
I-ADL values from patients without and those with delirium in the intervention group
Figure 2
I-ADL values from patients without and those with delirium in the intervention group
Patient characteristics, MoCA scores, and incidence and duration of delirium
Table 1
Patient characteristics, MoCA scores, and incidence and duration of delirium
I-ADL values of patients with and those without delirium in the intervention and control groups
Table 2
I-ADL values of patients with and those without delirium in the intervention and control groups
Flow chart for pharmacological and nonpharmaceutical treatment of delirium
eFigure
Flow chart for pharmacological and nonpharmaceutical treatment of delirium
Results of the hierarchical linear model
eTable 1
Results of the hierarchical linear model
Results of the hierarchical linear model
eTable 2
Results of the hierarchical linear model
1.Fong TG, Tulebaev SR, Inouye SK: Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol 2009; 5: 210–20 CrossRef MEDLINE PubMed Central
2.Inouye SK: Delirium in hospitalized older patients: recognition and risk factors. J Geriatr Psychiatry Neurol 1998; 11: 118–25; discussion 57–8 CrossRef MEDLINE
3.Inouye SK, Westendorp RG, Saczynski JS: Delirium in elderly people. Lancet 2014; 383: 911–22 CrossRef
4.Singler K, Fruhwald T: [Delirium]. Internist (Berl) 2014; 55: 775–81 CrossRef MEDLINE
5.Bickel H, Hendlmeier I, Hessler JB, et al.: The prevalence of dementia and cognitive impairment in hospitals. Dtsch Arztebl Int 2018; 115: 733–40 CrossRef MEDLINE PubMed Central
6.Feinkohl I, Winterer G, Spies CD, Pischon T: Cognitive reserve and the risk of postoperative cognitive dysfunction. Dtsch Arztebl Int 2017; 114: 110–7 CrossRef
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