Risk factors for incident delirium in acute medical in-patients. A systematic review

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1 Risk factors for incident delirium in acute medical in-patients. A systematic review Reviewers Emily Cull RN, BN(Hons) 1 Bridie Kent PhD, BSc(Hons), RN 2 Dr Nicole M. Phillips DipAppSc(Nsg), BN, GDipAdvNsg(Educ), MNS, PhD, RN 3 Renata Mistarz RN 4 1. The Deakin Centre for Quality and Risk Management in Health: An Affiliate Centre of the Joanna Briggs Institute, ejcull@deakin.edu.au 2. Professor of Nursing - Eastern Health-Deakin University, bridie.kent@deakin.edu.au 3. Senior Lecturer, The Deakin Centre for Quality and Risk Management in Health: An Affiliate Centre of the Joanna Briggs Institute, nikki.phillips@deakin.edu.au 4. Eastern Health, Deakin University Renata.Mistarz@easternhealth.org.au Review question/objective What risk factors are associated with incident delirium in adult patients during an acute medical hospitalisation? More specifically, the objectives are to: Identify and synthesise the best available evidence on the factors which are associated with delirium in adult patients admitted to acute medical facilities. Background Delirium is a complex syndrome that often occurs in elderly hospitalised patients. It is a syndrome that is characterised by symptoms of fluctuating cognition, poor ability to establish and maintain attention, memory impairment and psychomotor disturbances 1. The syndrome has been recognised by physicians for around 2,500 years 2, with a number of reports describing the common symptoms seen today. Delirium has been referred to under a number of different terms, the most common being acute confusion or an acute confusional state 3. Delirium is the name used to describe this syndrome in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and experts have suggested that it remain the term of choice, in order to assist with consistency during practice and research 4. The current definition of delirium from the DSM IV is as follows delirium is a disturbance of consciousness that is accompanied by a change that cannot be better accounted for by a pre-existing or evolving dementia 5. Page 1

2 The syndrome of delirium can also be identified as having three major subtypes: hypoactive, hyperactive and mixed 6. Each subtype is characterised by different symptoms. As the name suggests the hyperactive subtype is characterised by psychomotor hyperactivity, aggression, confusion and restlessness, whereas the hypoactive subtype presents as decreased motivation, withdrawn, confusion and reduced alertness 1. The mixed subtype presents with symptoms of both conditions 5. Delirium prevalence and incidence varies across a range of hospital settings 7. A systematic review that looked closely at occurrence of delirium in acute medical in-patients found that incidence of new delirium can range between 3-29% 8. A discrepancy also exists between actual medically diagnosed cases of delirium and cases in which researchers identify as suspected cases. This can result in a significant under reporting of delirium and its potential impact on patients who have experienced the syndrome 9. A major problem with the development of delirium during hospitalisation is that the condition is often misdiagnosed or under-recognised by health professionals 10. This is a significant problem as delirium can often be the only symptom of a life threatening condition 1. Delirium has been associated with a number of poor outcomes including increased mortality, higher falls rates, increased length of stay in hospital, increased risk of institutionalisation, and increased risk of developing long term cognitive impairment or dementia 1. The specific pathophysiology of delirium is somewhat illusive. Many theories have been suggested that provide some explanation as to how delirium may develop in patients. These theories are somewhat complimentary and offer no competing explanations 11. In fact, it is believed that delirium may be the final common result of a number of conditions and medical illnesses 11. Despite the poor understanding regarding the patho-physical function of delirium there is a significant amount of research on the risk factors, or factors that are strongly related to the development of delirium. Delirium may be the result of a number of factors contributing to the development of the syndrome. Understanding the factors that may interact to cause delirium can also enhance our understanding of delirium pathophysiology and the implementation of appropriate treatment strategies 12. It is also important to know these risk factors so delirium prevention interventions can be targeted to reduce the likelihood that the patient is exposed to some of the modifiable risk factors 13. A systematic review published in 1998, aimed to identify the risk factors associated with the development of delirium in the hospitalised older patient 14. The review included studies published until December 1995, that were prospective in design, included patients who were greater than 50 years of age, investigated at least one risk factor of delirium and used an appropriate definition of delirium. This review was not specific to one particular hospital setting and included studies from medical, surgical and psychiatric patients. The authors offered suggestions for further research stating that there is a need for researchers to differentiate between prevalent and incident delirium. That is, to look closely at incident delirium which involves patients who are not delirious on admission, but develop delirium during hospitalisation. A number of the studies included in the review had not made this differentiation. The significant limitations of the systematic review were that the authors only searched one database, Medline, for appropriate articles and used only delirium as a search term, despite the common use of acute confusion in the literature. The authors suggested that future risk factor research should only be examined by service,. Page 2

3 for example, only medical patients, as there can be significant differences in the risk factors for patients in different settings. A more recent systematic review has been conducted investigating the evidence concerning risk factors for the critically ill patient in the intensive care unit (ICU) 15. The most significant results were that medications administered in the ICU, such as benzodiazepines, were highly associated with delirium. Age was also a common risk factor as well as some biomarkers such as an elevated C-reactive protein. This review has helped to synthesise evidence for delirium risk factors in the intensive care unit. Yet, a systematic review looking specifically at medical in-patients risk factors for delirium has not been conducted. This review will therefore contribute to knowledge regarding which factors are most likely to be associated with delirium specifically in the acute medical in-patient. It will add to the body of knowledge regarding delirium risk factors and inform further research into the possibility of modifying these factors to prevent the development of delirium. The review will look at studies published from January 1996 in order to find relevant quantitative studies that were published after the Elie et al systematic review. 14 Internationally, a number of risk prediction models have also been developed for use in the population with delirium 16. However, the development of these risk prediction models has been based on the results from the cohort in which the study was conducted 17. This systematic review will add evidence supporting the development of risk prediction models specific to the medical population and their ability to be implemented outside the test population and in a number of medial in-patient settings. This review will also provide evidence that will inform the use of risk prediction models in Australia as well as elsewhere in the western world. Keywords Incident delirium, acute care, medical patients, risk factors Inclusion criteria Types of participants This review will consider studies that include adults (defined as 18 years and above) who were admitted to an acute medical setting (e.g. general medical units, stroke units, short stay units and neuromedical units) who were not delirious on admission (in order to differentiate incident delirium) but who developed incident delirium during hospitalisation The review will exclude patients who were: - critically ill and admitted to specialist unit e.g. ICU or CCU - admitted for any type of surgery - admitted for alcohol related reasons - admitted to psychiatric facility These patients will be excluded in order to determine factors that may be exclusive to the medical in patient setting. Page 3

4 Types of intervention(s)/phenomena of interest This review will consider studies that evaluate any risk factors that may contribute to the development of delirium during in-patient hospitalisation. The review will look at factors present on admission (predisposing) and also factors that may occur during hospitalisation (precipitating) that contribute to incident delirium. Types of outcomes This review will consider studies that include the following outcome measures: the incidence of delirium as related to individual risk factors. Types of studies This review will consider both experimental and epidemiological study designs including randomised controlled trials, non-randomised controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion. Search strategy The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilised in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published from January 1996 until current (July 2012) will be considered for inclusion in this review. The review will look at studies published from January 1996 in order to find relevant quantitative studies that were published after the Elie et al systematic review. 14 The databases to be searched include: - Medline - CINAHL - PsycInfo - Cochrane Library - JBI - Informit Health collection - Proquest Health and Medical - Embase - Scopus. Page 4

5 The search for unpublished studies will include: - Proquest Dissertation and Thesis - Mednar JBI Library of Systematic Reviews and the Cochrane Library will be searched for similar systematic reviews that may be potential sources of primary studies. Initial keywords to be used will be: - Risk factor OR risk factors - predisposing factors - precipitating factors - Dementia or Cognitive Impairment - urinary tract infection - pneumonia - sepsis - Delirium - acute confusion - acute confusional state - Confusion - Medical - hospital in-patient - medical in-patient - medical admission - hospitalisation or hospitalization Assessment of methodological quality Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Data collection Data will be extracted from papers included in the review using the standardised data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific Page 5

6 objectives. Data synthesis Quantitative data will, where possible be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio, risk ratio or rate ratio and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. Conflicts of interest Nil conflicts of interest Acknowledgements Thanks to Rachel West, Deakin university librarian for her assistance with developing search strategy. This review will form part of Emily s Doctoral degree.. Page 6

7 References [1] Inouye, SK. Delirium in Older Persons. The New England Journal of Medicine. 2006; 354(11): [2] Lipowski, ZJ. Delirium: Acute Confusional States. Oxford University Press.1990 [3] Andersson, EM, Hallberg, IR, Norberg, A & Edberg, A-K. The meaning of acute confusional state from the perspective of elderly patients. International Journal of Geriatric Psychiatry. 2002; 17(7): [4] Lipowski, ZJ. Delirium (Acute Confusional States). JAMA: The Journal of the American Medical Association.1987; 258(13): [5] American Psychiatric Association. Diagnostic and Statistical manual of Mental disorders. Fourth ed. Washington DC: American Psychiatric Association; [6] Boettger, S & Breitbart, W. Phenomenology of the subtypes of delirium: phenomenological differences between hyperactive and hypoactive delirium. Palliative & Supportive Care. 2011; 9(2): [7] Flaherty, JH. Delirium. Principles and Practice of Geriatric Medicine. 2006; [8] Siddiqi, N, House, AO & Holmes, JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age and Ageing. 2006; 35(4): [9] Flaherty, JH, Rudolph, J, Shay, K, Kamholz, B, Boockvar, KS, Shaughnessy, M, Shapiro, R, Stein, J, Weir, C & Edes, T. Delirium is a serious and under-recognised problem. Why assessment of mental status should be the 6th vital sign. Journal of the American Medical Directors Association. 2007; 8(5): [10] Schuurmans, MJ, Duursma, SA & Shortridge-Baggett, LM. Early recognition of delirium: review of the literature'. Journal of Clinical Nursing. 2001; 10(6): [11] Maldonado, JR. Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Critical care clinics. 2008; 24(4): [12] Rudberg, MA, Pompei, P, Foreman, MD, Ross, RE & Cassel, CK. The natural history of delirium in older hospitalized patients: a syndrome of heterogeneity. Age and Ageing.1997; 26(3): [13] Inouye, SK, Bogardus, ST, Jr., Charpentier, PA, Leo-Summers, L, Acampora, D, Holford, TR & Cooney, LM, Jr. A multicomponent intervention to prevent delirium in hospitalized older patients. The New England Journal of Medicine.1999; 340(9): [14] Elie, M, Cole, MG, Primeau, FJ & Bellavance, F. Delirium risk factors in elderly hospitalized patients. Journal Of General Internal Medicine.1998; 13(3): [15] Mattar, I, Chan, MF & Childs, C. Factors causing acute delirium in critically ill adult patients: a systematic review. JBI Library of Systematic Review.2012; 10(3): [16] Inouye, SK, Viscoli, CM, Horwitz, RI, Hurst, LD & Tinetti, ME. A Predictive Model for Delirium in Hospitalized Elderly Medical Patients Based on Admission Characteristics. Annals of Internal Page 7

8 Medicine.1993; 119(6): [17] Srinonprasert, V, Pakdeewongse, S, Assanasen, J, Eiamjinnasuwat, W, Sirisuwat, A, Limmathuroskul, D & Praditsuwan, R. Risk Factors for Developing Delirium in Older Patients Admitted to General Medical Wards. Journal of the Medical Association of Thailand. 2011; 94(2): 99.. Page 8

9 Appendix I: Appraisal instruments MAStARI Appraisal instrument this is a test message Insert page break Page 9

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11 Appendix II: Data extraction instruments MAStARI data extraction instrument Insert page break Page 11

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