Cancer patients with delirium in the Emergency Department: a frequent and distressing problem that calls for

Transcription

1 Page 1 of 11 1 patients with delirium in the Emergency Department: a frequent and distressing problem that calls for better assessment Running title:, delirium and emergency care Peter G Lawlor MB FRCPI MMedSc Corresponding author: Peter G Lawlor MB FRCPI MMedSc Associate Professor, Division of Palliative Care, Department of Medicine, University of Ottawa; Clinical Investigator, Bruyère and Ottawa Hospital Research Institutes; and Physician, Palliative Care Unit, Bruyère Continuing Care Contact Details: Dr Peter G Lawlor 43 Bruyère Street Ottawa, ON Canada K1N 5C8 Tel: , Ext Fax: plawlor@bruyere.org Pages: 11 Word Count: 2084 References: 20 This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version record. Please cite this article as doi: /cncr

2 Page 2 of 11 2 Precis Delirium is acknowledged as a common complication of cancer that frequently results in a visit to the emergency department, yet it is poorly assessed and the diagnosis missed as a consequence. Given that age is a major risk factor for delirium, and as population demographics change, there is a critical need to develop optimal delirium screening strategies for cancer patients who access this point of care Keywords: delirium, encephalopathy, confusion, cognitive, neuropsychiatric, cancer, palliative, emergency Disclosures: no conflict of interest declared Acknowledgements: PGL wishes to acknowledge research funding support for the SUNDIPS (Studies to Understand Delirium in Palliative Settings) Program of research from the Gillin Family Fund and the Bruyere Foundation

3 Page 3 of 11 3 Delirium is a complex and distressing neurocognitive syndrome that occurs in patients with cancer, especially those with advanced disease, in whom rates as high as 88% are reported before death. (1) However, delirium may occur anywhere along the cancer disease trajectory, arising acutely as a result of the disease or its treatment. (2) It is a recognized complication of often multiple underlying medical problems such as infection, organ failure, metabolic abnormalities or medication effects such as opioids, other psychotropic agents and chemotherapy. (2,3) Reversal of delirium has been reported in 50% of episodes occurring in cancer patients admitted to a hospital palliative care unit. (3) However, reversibility is contingent on the goals of care, prompt identification of relevant precipitants and how amenable they are to treatment. (3) Unlike dementia, delirium has an acute onset (hours to days) and manifests itself as cognitive deficits, hallucinations, paranoia, and other behavioural and psychomotor disturbances, ranging from extreme agitation to profound hypoactivity. (4,5) The diagnosis of delirium is frequently missed due to its fluctuating symptoms and its similarity to dementia and depression. (2,5) Communication with family may be impeded as a result of delirium, and healthcare practitioners assessment of pain and other symptoms may be compromised. (2) Delirium is associated with high levels of mortality, morbidity (including falls), prolonged hospital stay and a major cost burden. (6) Dementia, older age and cancer are recognized risk factors for delirium. (2,5) is predominantly a disease of older age groups and the projected demographic changes in developed countries highlight the need for physicians in general to be knowledgeable regarding the nature of the syndrome, its assessment and its management. (2) This is particularly important in relation to the hospital emergency department (ED), given that delirium is regarded as a manifestation of an acute medical abnormality, and a medical emergency. However, more often the neurobehavioral manifestations of delirium and the consequent distress for the patient and their family triggers an emergency room visit. Some features of delirium warrant special recognition in the ED context. First, the distress that the delirium is causing the patient and family must be recognized and addressed. Although the frenzied environments of most EDs arguably represent the antithesis of what is recommended for the symptomatic management of a patient with delirium, it may be the main access point for care of the delirious patient. Recognizing that ED visits

4 Page 4 of 11 4 may be necessary for many cancer patients with delirium, it seems wise to minimize the duration of the ED visit, especially in the case of those with advanced cancer, whose goals of care may be more focussed on symptom control. The ED visit in itself may result in an environmental exacerbation of delirium for some of these patients. Many EDs will fast track this type of patient. Second, for some patients, delirium may be the sole and sometimes subtle clinical manifestation of underlying problems such as infection or hypercalcemia. Third, the temporal fluctuation in the intensity of delirium symptoms and the relatively narrow window of the patient s exposure to physicians and nurses in the ED may together contribute to the diagnosis being missed, especially if systematic screening assessments are not conducted. Collectively, these issues highlight the importance of a prompt and accurate diagnosis of delirium in cancer patients who attend the ED. In this current issue of, Elsayem et al (7) report a cross sectional study to determine the prevalence of delirium in patients with cancer who attended the hospital emergency department. The investigators screened a total of 1832 patients for study entry, and having excluded patients as ineligible, mostly because of nonadvanced cancer (n=694), they had an eligible sample of 624. From these, 291 were unapproachable for a variety of reasons, leaving 243 who were enrolled into the study. Using the Confusion Assessment Method (CAM), 22/243 (9%) screened positive for delirium, mostly with mild (n=18, 82%) to moderate (n=4, 18%) scores on the Memorial Delirium Assessment Scale (MDAS) for delirium severity. In the absence of comparative data on delirium prevalence in patients with cancer in the ED, the 9% prevalence is consistent with estimates obtained from other recent studies, most of them conducted in elderly patients in the ED, and most reporting a prevalence in the 7-20% range. (5,8-10) However, given the higher prevalence figures for delirium in hospitalized cancer patients, (1) the 9% prevalence seems low. Of the study eligible patients (n=624), 47% (n=291) were noted to be unapproachable for a variety of reasons, including the fact that they were sleeping/tired. Some of these patients may well have been delirious. Furthermore, selection biases may arise as a result of the exclusion of patients with dementia and the restricted 10am to 6pm interval of participant recruitment, thus failing to capture the sundowner patients after 6pm. The generalizability of the study s prevalence finding is therefore limited because of these selection biases. The external validity of a study

5 Page 5 of 11 5 conducted in the setting of an ED housed specifically in a cancer center is also open to question, as many cancer patients with delirium may be seen in general EDs. In the study by Elsayem et al, (7) the research assistant rated both the CAM and the MDAS. Interestingly, the authors report that had they used the MDAS cut off score of 7 for a delirium diagnosis instead of the CAM, they would have identified twice as many delirious patients. Unfortunately, this study did not include a psychiatrist s assessment in addition to the CAM and MDAS. A psychiatrist s assessment might have provided more validity in terms of diagnosis, especially in light of the gap between the 9% CAM based and 18% MDAS based prevalence figures for delirium. As acknowledged by the authors, further studies are clearly needed to determine the correct MDAS cut off score for delirium diagnosis. Elsayem et al also assessed the accuracy of physician diagnosis of delirium in their study and found that the diagnosis was missed in 9 (41%) of participants. (7) Other studies of elderly patients attending the ED reported an even higher frequency of missing the diagnosis of delirium, ranging from 65-84%. (5,8,9) The lower frequency of missed diagnosis found by Elsayem et al could relate to many factors: the delivery of two lectures to their ED physicians on delirium; priming the ED physician in assessing whether the patient could be approached for study recruitment; and exclusion of patients with dementia and those attending between 6pm and 10am. Regardless, missing the diagnosis of delirium in 41% of cases is a serious concern. Of the delirium psychomotor subtypes, the hypoactive form is more likely to be missed, especially if the window of exposure for physician assessment is narrow, as is invariably the case in the ED. (5) Most of the patients with delirium (n=18, 82%) were classified as having the hypoactive psychomotor subtype (albeit based on observations over a relatively narrow temporal window), which may partly explain why delirium was often missed. However, the most likely explanation for physicians missing the diagnosis is a failure to conduct a systematic assessment, an issue that has been reported in many different settings of care. (2,5,8,11) What is the best strategy for assessing delirium in cancer patients who present to the ED? A recent systematic review of screening for delirium in the ED identified the CAM as the only validated tool to screen for delirium in the ED, noting reported sensitivities of 86% and 94% in a higher quality Canadian and lesser quality

6 Page 6 of 11 6 Brazilian validation study, respectively. (9) The optimal timing of when a screening tool is administered in the ED is unclear and warrants further study. (9) Although the MDAS has been validated as a diagnostic and severity rating tool, It is relatively time-consuming to rate and arguably unsuited to the ED environment. Given the frequently rushed environment in most EDs and the time demands on physician and nursing staff, the ideal screening assessment tool for delirium in the ED must be brief. (11) Although the original long version of the CAM with 10 assessment items has broadly acquired gold standard status, its completion time and training requirements weigh against its routine use in the ED. The 4-item short form of the CAM would appear to meet the brevity requirement for the ED, yet it may take 5 minutes to complete with a formal test of cognition. The Brief Confusion Assessment Method (bcam) consists of the 4 short form CAM items in addition to asking the patient to recite the months of the year backwards from December to July, as a test of attention. A validation study of the bcam in the ED setting reported a completion time of less than 2 minutes and a sensitivity of 78% and 84% for a research assistant and physician, respectively. (10) In a secondary analysis, a modification of the bcam by adding a Vigilance A test reported a sensitivity and specificity of 82% and 96.1%, respectively. (12) Notably, the CAM and its adapted forms are meant to be administered along with a formal test of cognition, or at least a test of attention, which is characteristically impaired in delirium. The 3D-CAM, recently validated in hospitalized elderly patients, is a version of the CAM that incorporates brief standardized tests of cognition, especially orientation and attention. (13) It has a median administration time of 3 minutes, and sensitivity and specificity of 95% and 94%, respectively. Although the CAM and its adapted versions have been used for both screening and diagnosis, briefer tools have a strong appeal, especially in the ED, at least for screening purposes. The 4 A s Test was designed a brief (2 minutes) tool to screen for delirium. It has similarities to the short version of the CAM and incorporates 4 items, including a request to recite the months of the year backwards to test attention. It was validated in hospitalized elderly patients and found to have a sensitivity of 89.7% and a specificity of 84.1%. (14) Although there are no reported studies of its use to date in the ED, it would appear to have potential in this setting. The task of reciting the months of the year backwards either in full or for the December to July part has been used as a test of attention with sensitivity results for delirium detection in the region of

7 Page 7 of %. (15,16) The Richmond Agitation Sedation Scale (RASS) is an assessment tool that was originally designed to assess sedation and agitation on a continuous numerical scale (-5 to +4) in intensive care. It can be administered in 10 seconds and is largely observational. When performed by a research assistant in a study of elderly patients attending an academic ED, a RASS score of > 0 or < 0 had a sensitivity of 84% in detecting delirium. (17) Han et al combined the RASS with a request to spell LUNCH backwards (testing attention) in their Delirium Triage Screen (DTS), as a rapid (20 seconds) and sensitive rule out assessment in a study of 406 elderly ED patients. (10) The DTS had a sensitivity of 98% and a negative likelihood ratio of (10) The ideal tool for screening or diagnosis should optimally address the competing needs of brevity, burden and psychometric rigour. The informant or collateral history is an essential but sometimes overlooked component of delirium assessment in the ED. (18) In this regard, the Single Question in Delirium (SQiD) has been tested in one study in a palliative care setting and found to have a moderate sensitivity of 80%. (19) The SQiD involves asking a friend or family member the question, Do you think that (patient s name) has been more confused lately. In this context, it may be viewed as a very brief informant screen. The completion time estimates, sensitivities and specificities of briefer tools with potential for use in the ED are summarized in Table 1. In summary, delirium is a common complication in patients with cancer and often precipitates a visit to the ED. The 9% prevalence of delirium reported by Elsayem in cancer patients attending the ED is likely an underestimate, owing to selection bias. Their reported 41% proportion of missed delirium diagnoses is also likely to be an underestimate and highlights the need for further studies to examine the role of various screening strategies, their optimal scheduling and the association with outcomes, including risk-benefit and costeffectiveness. (20) The ideal package to complement a good informant or collateral history in this context remains to be established. Currently, the tools that incorporate some cognitive testing such as the briefer CAM versions and the 4AT can all be recommended for screening in clinical practice in the ED, but these along with the ultrabrief tests of attention and arousal warrant further evaluation in the ED environment.

8 Page 8 of 11 8 References (1) Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: A systematic review. Palliat Med 2013 Jun;27(6): (2) Lawlor PG, Bush SH. Delirium in patients with cancer: assessment, impact, mechanisms and management. Nat Rev Clin Oncol 2014 Sep 2. (3) Lawlor PG, Gagnon B, Mancini IL, Pereira JL, Hanson J, Suarez-Almazor ME, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med 2000 Mar 27;160(6): (4) American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. Arlington, VA: American Psychiatric Association; (5) Han JH, Zimmerman EE, Cutler N, Schnelle J, Morandi A, Dittus RS, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med 2009 Mar;16(3): (6) Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010 Jul 28;304(4): (7) Elsayem A, Bruera E, Valentine A, Warneke C, Yeung J, Page V, et al. Delirium frequency among advanced cancer patients presenting to an emergency department: a prospective randomized observational study (8) Barron EA, Holmes J. Delirium within the emergency care setting, occurrence and detection: a systematic review. Emergency Medicine Journal 2013 Apr;30(4): (9) LaMantia MA, Messina FC, Hobgood CD, Miller DK. Screening for delirium in the emergency department: a systematic review. Ann Emerg Med 2014 May;63(5): e2.

9 Page 9 of 11 9 (10) Han JH, Wilson A, Vasilevskis EE, Shintani A, Schnelle JF, Dittus RS, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method. Ann Emerg Med 2013 Nov;62(5): (11) Kennelly SP, Morley D, Coughlan T, Collins R, Rochford M, O'Neill D. Knowledge, skills and attitudes of doctors towards assessing cognition in older patients in the emergency department. Postgrad Med J 2013 Mar;89(1049): (12) Han JH, Wilson A, Graves AJ, Shintani A, Schnelle JF, Ely EW. A quick and easy delirium assessment for nonphysician research personnel. Am J Emerg Med 2016 Mar 3. (13) Marcantonio ER, Ngo LH, O'Connor M, Jones RN, Crane PK, Metzger ED, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med 2014 Oct 21;161(8): (14) Belleli G, Morandi A, Davis DHJ, Mazzola P, Turco R, Gentile S et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age and Ageing 2014;43: (15) O'Regan NA, Ryan DJ, Boland E, Connolly W, McGlade C, Leonard M, et al. Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry 2014 Feb 25. (16) Fick DM, Inouye SK, Guess J, Ngo LH, Jones RN, Saczynski JS, et al. Preliminary development of an ultrabrief two-item bedside test for delirium. J Hosp Med 2015 Oct;10(10): (17) Han JH, Vasilevskis EE, Schnelle JF, Shintani A, Dittus RS, Wilson A, et al. The Diagnostic Performance of the Richmond Agitation Sedation Scale for Detecting Delirium in Older Emergency Department Patients. Acad Emerg Med 2015 Jul;22(7): (18) Dyer AH, Nabeel S, Briggs R, O'Neill D, Kennelly SP. Cognitive assessment of older adults at the acute care interface: the informant history. Postgrad Med J 2016 Jan 19.

10 Page 10 of (19) Sands MB, Dantoc BP, Hartshorn A, Ryan CJ, Lujic S. Single Question in Delirium (SQiD): testing its efficacy against psychiatrist interview, the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Palliat Med 2010 Sep;24(6): (20) Lawlor PG, Davis DH, Ansari M, Hosie A, Kanji S, Momoli F, et al. An analytical framework for delirium research in palliative care settings: integrated epidemiologic, clinician-researcher, and knowledge user perspectives. J Pain Symptom Manage 2014 Aug;48(2):

11 Page 11 of 11 Screening Tool Completion time* Sensitivity Specificity 3-Dimensional CAM (3D-CAM) (13) 3 minutes 95% 94% 4 A s Test (4AT) (14) 2 minutes 90% 84% Modified bcam (12) 2 minutes 82-86% 95-96% Brief Confusion Assessment Method (bcam) (10,12) < 2 minutes 78-84% 96-97% Months of the year backwards (MOTYB) (15,16) seconds 83% 69% Delirium Triage Screen (DTS) (10) 20 seconds 98% 55% Richmond Agitation Sedation Scale (RASS) (10,17) 10 seconds 84% 87.6% Single Question in Delirium (SQiD) 19 <10 seconds 80% 71% Table 1 Metrics summary of a selection of delirium screening tools with potential for use in the ED. *Reported estimates unless otherwise specified; completion times may vary depending on the level of impairment. Based on inference from available data and personal opinion.