Abstract
BackgroundDelirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis.MethodsA systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others.ResultsThe 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting.ConclusionThere is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness.
Highlights
Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer
Our aim was to identify biomarkers associated with delirium and with specific clinical situations in advanced cancer; and to evaluate the nature and extent of overlap of the findings
A further 72 were excluded as they did not report a biomarker studied in delirium and advanced cancer
Summary
Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. There has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are common in advanced cancer syndromes such as pain and fatigue. Delirium is a very common cause of acute cognitive change in people with advanced cancer [1] and is associated with increased morbidity and mortality [2, 3]. The prevalence of delirium in patients with advanced cancer in oncology and palliative care settings is higher than that in most other settings, including geriatrics [1, 6,7,8,9]. A systematic review of palliative care patients (with 98.9% of participants with advanced cancer), reported delirium incidence rates between 3% and 45%. Delirium prevalence increased up to 88% in the hours to days before death [1]
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