Delirium in adult cancer patients: ESMO Clinical Practice Guidelines
Authors: S.H. Bush, P.G. Lawlor, K. Ryan, C. Centeno, M. Lucchesi, S. Kanji, N. Siddiqi, A. Morandi, D.H.J. Davis, M. Laurent, N. Schofield, E. Barallat, C.I. Ripamonti
Journal: Annals of Oncology (2018)

Delirium is a neurocognitive syndrome that commonly occurs in older populations and people with cancer, particularly in those with advanced disease and in the last hours or days of life. While an underlying malignancy and its complications predispose a person to develop delirium, many of the treatments used in the management of cancer also increase the risk of delirium [1.Lawlor P.G. Bush S.H. Delirium in patients with cancer: assessment, impact, mechanisms and management.Nat Rev Clin Oncol. 2015; 12: 77-92Crossref PubMed Scopus (45) Google Scholar]. In addition to being associated with an increased risk of mortality and causing significant physical morbidity, delirium is often a severely distressing experience, not only for patients, but also for families and professional caregivers [1.Lawlor P.G. Bush S.H. Delirium in patients with cancer: assessment, impact, mechanisms and management.Nat Rev Clin Oncol. 2015; 12: 77-92Crossref PubMed Scopus (45) Google Scholar]. The target population for this European Society for Medical Oncology (ESMO) Clinical Practice Guideline (CPG) is adults with cancer who are at risk of delirium or have been diagnosed with delirium. The intended users for this CPG are healthcare professionals working in the field of oncology, in order to inform both clinical decisions and standards of care. The incidence of delirium in advanced cancer patients has been reported as varying greatly [2.Kang J.H. Shin S.H. Bruera E. Comprehensive approaches to managing delirium in patients with advanced cancer.Cancer Treat Rev. 2013; 39: 105-112Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], with up to 88% of patients developing delirium in the last weeks to hours of life [3.Hosie A. Davidson P.M. Agar M. et al.Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review.Palliat Med. 2013; 27: 486-498Crossref PubMed Scopus (136) Google Scholar]. This variation depends on the study population, the delirium definition and method of assessment used and staff training, as well as delirium subtype and methods used for subtype classification. In clinical settings, physicians and nurse specialists continue to underdiagnose delirium [4.de la Cruz M. Fan J. Yennu S. et al.The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center.Support Care Cancer. 2015; 23: 2427-2433Crossref PubMed Scopus (64) Google Scholar, 5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar, 6.Boyle D.A. Delirium in older adults with cancer: implications for practice and research.Oncol Nurs Forum. 2006; 33: 61-78Crossref PubMed Google Scholar, 7.Hosie A. Agar M. Lobb E. et al.Palliative care nurses' recognition and assessment of patients with delirium symptoms: a qualitative study using critical incident technique.Int J Nurs Stud. 2014; 51: 1353-1365Crossref PubMed Scopus (0) Google Scholar, 8.Elsayem A.F. Bruera E. Valentine A.D. et al.Delirium frequency among advanced cancer patients presenting to an emergency department: a prospective, randomized, observational study.Cancer. 2016; 122: 2918-2924Crossref PubMed Scopus (0) Google Scholar]. The hypoactive subtype is not only the most frequent delirium clinical subtype in patients with cancer [9.Fang C.K. Chen H.W. Liu S.I. et al.Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey.Jpn J Clin Oncol. 2008; 38: 56-63Crossref PubMed Scopus (89) Google Scholar, 10.Uchida M. Okuyama T. Ito Y. et al.Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study.Jpn J Clin Oncol. 2015; 45: 934-940Crossref PubMed Scopus (0) Google Scholar, 11.Spiller J.A. Keen J.C. Hypoactive delirium: assessing the extent of the problem for inpatient specialist palliative care.Palliat Med. 2006; 20: 17-23Crossref PubMed Scopus (0) Google Scholar] but is also commonly missed by the oncology team [4.de la Cruz M. Fan J. Yennu S. et al.The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center.Support Care Cancer. 2015; 23: 2427-2433Crossref PubMed Scopus (64) Google Scholar]. Combining the assessments of palliative care physicians and nurses has been shown to improve the detection of delirium in terminal cancer patients [9.Fang C.K. Chen H.W. Liu S.I. et al.Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey.Jpn J Clin Oncol. 2008; 38: 56-63Crossref PubMed Scopus (89) Google Scholar]. The majority of studies in oncological populations examine delirium in advanced cancer patients admitted to palliative care units (PCUs) or inpatient palliative care consultation services [4.de la Cruz M. Fan J. Yennu S. et al.The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center.Support Care Cancer. 2015; 23: 2427-2433Crossref PubMed Scopus (64) Google Scholar, 9.Fang C.K. Chen H.W. Liu S.I. et al.Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey.Jpn J Clin Oncol. 2008; 38: 56-63Crossref PubMed Scopus (89) Google Scholar, 12.Lawlor P.G. Gagnon B. Mancini I.L. et al.Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.Arch Intern Med. 2000; 160: 786-794Crossref PubMed Google Scholar, 13.Gagnon P. Allard P. Mâsse B. DeSerres M. Delirium in terminal cancer: a prospective study using daily screening, early diagnosis and continuous monitoring.J Pain Symptom Manage. 2000; 19: 412-426Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 14.Şenel G. Uysal N. Oguz G. et al.Delirium frequency and risk factors among patients with cancer in palliative care unit.Am J Hosp Palliat Care. 2017; 34: 282-286Crossref PubMed Scopus (0) Google Scholar, 15.Mercadante S. Adile C. Ferrera P. et al.Delirium assessed by Memorial Delirium Assessment Scale in advanced cancer patients admitted to an acute palliative/supportive care unit.Curr Med Res Opin. 2017; 33: 1303-1308Crossref PubMed Scopus (9) Google Scholar, 16.Hosie A. Lobb E. Agar M. et al.Measuring delirium point-prevalence in two Australian palliative care inpatient units.Int J Palliat Nurs. 2016; 22: 13-21Crossref PubMed Scopus (0) Google Scholar, 17.de la Cruz M. Ransing V. Yennu S. et al.The frequency, characteristics, and outcomes among cancer patients with delirium admitted to an acute palliative care unit.Oncologist. 2015; 20: 1425-1431Crossref PubMed Scopus (37) Google Scholar] and do not include cancer survivors (see Supplementary Table S1, available at Annals of Oncology online). There is limited published information regarding the frequency of delirium in outpatients with advanced cancer [2.Kang J.H. Shin S.H. Bruera E. Comprehensive approaches to managing delirium in patients with advanced cancer.Cancer Treat Rev. 2013; 39: 105-112Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. The authors' literature review found one study in an outpatient setting [18.Bond S.M. Dietrich M.S. Shuster Jr, J.L. Murphy B.A. Delirium in patients with head and neck cancer in the outpatient treatment setting.Support Care Cancer. 2012; 20: 1023-1030Crossref PubMed Scopus (0) Google Scholar]: six out of the 69 (8.6%) patients (aged 33–70 years) with head and neck cancer and receiving outpatient treatment developed delirium, based on assessment with the Confusion Assessment Method (CAM). However, ∼45% of their caregivers reported delirium retrospectively as part of a subsequent mixed-methods study. The literature review found one study of 243 patients presenting to an emergency department [10.Uchida M. Okuyama T. Ito Y. et al.Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study.Jpn J Clin Oncol. 2015; 45: 934-940Crossref PubMed Scopus (0) Google Scholar]. The reported prevalence of delirium is dependent on the patient setting: ∼10% of advanced cancer patients presenting to an emergency department [8.Elsayem A.F. Bruera E. Valentine A.D. et al.Delirium frequency among advanced cancer patients presenting to an emergency department: a prospective, randomized, observational study.Cancer. 2016; 122: 2918-2924Crossref PubMed Scopus (0) Google Scholar], 43% on admission to a general medical ward [10.Uchida M. Okuyama T. Ito Y. et al.Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study.Jpn J Clin Oncol. 2015; 45: 934-940Crossref PubMed Scopus (0) Google Scholar] and up to 42% on admission to a PCU [12.Lawlor P.G. Gagnon B. Mancini I.L. et al.Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.Arch Intern Med. 2000; 160: 786-794Crossref PubMed Google Scholar, 17.de la Cruz M. Ransing V. Yennu S. et al.The frequency, characteristics, and outcomes among cancer patients with delirium admitted to an acute palliative care unit.Oncologist. 2015; 20: 1425-1431Crossref PubMed Scopus (37) Google Scholar]. During hospitalisation, 16.5% [19.Gaudreau J.D. Gagnon P. Harel F. et al.Psychoactive medications and risk of delirium in hospitalized cancer patients.J Clin Oncol. 2005; 23: 6712-6718Crossref PubMed Scopus (126) Google Scholar] to 18% [20.Ljubisavljevic V. Kelly B. Risk factors for development of delirium among oncology patients.Gen Hosp Psychiatry. 2003; 25: 345-352Crossref PubMed Scopus (88) Google Scholar] of patients with cancer or a haematological malignancy admitted to oncology or internal medicine units developed delirium and 26%–47% developed it after admission to an acute PCU (APCU) [9.Fang C.K. Chen H.W. Liu S.I. et al.Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey.Jpn J Clin Oncol. 2008; 38: 56-63Crossref PubMed Scopus (89) Google Scholar, 12.Lawlor P.G. Gagnon B. Mancini I.L. et al.Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.Arch Intern Med. 2000; 160: 786-794Crossref PubMed Google Scholar, 13.Gagnon P. Allard P. Mâsse B. DeSerres M. Delirium in terminal cancer: a prospective study using daily screening, early diagnosis and continuous monitoring.J Pain Symptom Manage. 2000; 19: 412-426Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 15.Mercadante S. Adile C. Ferrera P. et al.Delirium assessed by Memorial Delirium Assessment Scale in advanced cancer patients admitted to an acute palliative/supportive care unit.Curr Med Res Opin. 2017; 33: 1303-1308Crossref PubMed Scopus (9) Google Scholar, 17.de la Cruz M. Ransing V. Yennu S. et al.The frequency, characteristics, and outcomes among cancer patients with delirium admitted to an acute palliative care unit.Oncologist. 2015; 20: 1425-1431Crossref PubMed Scopus (37) Google Scholar]. Most studies confirm that the frequency of delirium increases with age [5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar, 9.Fang C.K. Chen H.W. Liu S.I. et al.Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey.Jpn J Clin Oncol. 2008; 38: 56-63Crossref PubMed Scopus (89) Google Scholar, 20.Ljubisavljevic V. Kelly B. Risk factors for development of delirium among oncology patients.Gen Hosp Psychiatry. 2003; 25: 345-352Crossref PubMed Scopus (88) Google Scholar]. At the end of life, ∼90% of patients who died in an APCU had delirium [12.Lawlor P.G. Gagnon B. Mancini I.L. et al.Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.Arch Intern Med. 2000; 160: 786-794Crossref PubMed Google Scholar] (Supplementary Table S1, available at Annals of Oncology online, provides more detailed information on the prevalence and incidence of delirium in admitted patients with cancer, and frequency of different delirium subtypes when reported). Outcomes of delirium in the general hospital population have been examined in systematic reviews; delirium is associated with increased post-discharge mortality [hazard ratio 2.0; 95% confidence interval (CI): 1.5–2.5] and institutionalisation [odds ratio (OR) 2.4; 95% CI: 1.8–3.3] [21.Witlox J. Eurelings L.S. de Jonghe J.F. et al.Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis.JAMA. 2010; 304: 443-451Crossref PubMed Scopus (979) Google Scholar]. Estimates in oncological populations vary widely because samples are drawn from a range of clinical contexts and settings [22.Lawlor P.G. Davis D.H.J. Ansari M. 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; 48: 159-175Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar]. Nonetheless, associations between delirium and adverse outcomes are evident in patients with cancer to an even greater extent. A number of studies report the association of delirium with mortality (see Supplementary Table S2, available at Annals of Oncology online). Mainly conducted in APCUs, all studies except two [23.Elsayem A. Mori M. Parsons H.A. et al.Predictors of inpatient mortality in an acute palliative care unit at a comprehensive cancer center.Support Care Cancer. 2010; 18: 67-76Crossref PubMed Scopus (0) Google Scholar, 24.Mori M. Parsons H.A. De la Cruz M. et al.Changes in symptoms and inpatient mortality: a study in advanced cancer patients admitted to an acute palliative care unit in a comprehensive cancer center.J Palliat Med. 2011; 14: 1034-1041Crossref PubMed Scopus (0) Google Scholar] reported associations between delirium and increased mortality rates of at least twofold. The highest estimate was in a sample undergoing bone marrow transplant (OR 14) [25.Beglinger L.J. Duff K. Van Der Heiden S. et al.Incidence of delirium and associated mortality in hematopoietic stem cell transplantation patients.Biol Blood Marrow Transplant. 2006; 12: 928-935Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar]. The association is consistent when considering both inpatient and post-discharge mortality. The delirium-mortality association was still observed where crude estimates were adjusted for covariates including age, sex and cancer type. In cancer patients in the last months of life, shorter survival is associated with the hypoactive and mixed delirium subtypes [26.Kim S.Y. Kim S.W. Kim J.M. et al.Differential associations between delirium and mortality according to delirium subtype and age: a prospective cohort study.Psychosom Med. 2015; 77: 903-910Crossref PubMed Scopus (6) Google Scholar]. Prognostic tools for predicting survival in terminally ill cancer patients, such as the Palliative Prognostic Index (PPI) and In-hospital Mortality Prediction in Advanced Cancer Patients (IMPACT) model, include delirium as a variable [27.Morita T. Tsunoda J. Inoue S. Chihara S. The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients.Support Care Cancer. 1999; 7: 128-133Crossref PubMed Scopus (406) Google Scholar, 28.Hui D. Kilgore K. Fellman B. et al.Development and cross-validation of the in-hospital mortality prediction in advanced cancer patients score: a preliminary study.J Palliat Med. 2012; 15: 902-909Crossref PubMed Scopus (25) Google Scholar]. The Palliative Prognostic (PaP) score was recently updated with the incorporation of delirium (D-PaP score) as a significant variable in predicting survival [29.Scarpi E. Maltoni M. Miceli R. et al.Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium.Oncologist. 2011; 16: 1793-1799Crossref PubMed Scopus (64) Google Scholar]. There are wider effects on general health as a consequence of delirium, though this has not been studied systematically in oncology populations. Extrapolating from older people (aged ≥ 65 years) admitted to a hospital rehabilitation unit, delirium increases rehabilitation needs [30.Morandi A. Davis D. Fick D.M. et al.Delirium superimposed on dementia strongly predicts worse outcomes in older rehabilitation inpatients.J Am Med Dir Assoc. 2014; 15: 349-354Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar] and may be complicated by pressure sores and aspiration pneumonia [31.Fong T.G. Davis D. Growdon M.E. et al.The interface between delirium and dementia in elderly adults.Lancet Neurol. 2015; 14: 823-832Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar] and significantly higher rates of residential or nursing home placement in the 2 years following admission [32.Eeles E.M. Hubbard R.E. White S.V. et al.Hospital use, institutionalisation and mortality associated with delirium.Age Ageing. 2010; 39: 470-475Crossref PubMed Scopus (72) Google Scholar]. Other studies have shown that functional decline is more common following delirium [33.Buurman B.M. Hoogerduijn J.G. de Haan R.J. et al.Geriatric conditions in acutely hospitalized older patients: prevalence and one-year survival and functional decline.PLoS One. 2011; 6: e26951Crossref PubMed Scopus (193) Google Scholar, 34.Davis D.H.J. Muniz Terrera G. Keage H. et al.Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study.Brain. 2012; 135: 2809-2816Crossref PubMed Scopus (282) Google Scholar, 35.Marcantonio E.R. Simon S.E. Bergmann M.A. et al.Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery.J Am Geriatr Soc. 2003; 51: 4-9Crossref PubMed Scopus (174) Google Scholar], along with higher rates of readmission [36.Marcantonio E.R. Kiely D.K. Simon S.E. et al.Outcomes of older people admitted to postacute facilities with delirium.J Am Geriatr Soc. 2005; 53: 963-969Crossref PubMed Scopus (197) Google Scholar]. Overall, these associations are more pronounced in patients with underlying dementia [37.Fong T.G. Jones R.N. Marcantonio E.R. et al.Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease.Ann Intern Med. 2012; 156: 848-856Crossref PubMed Google Scholar]. In patients admitted to an APCU, more severe delirium is associated with lower performance status, greater symptom burden and longer length of stay [15.Mercadante S. Adile C. Ferrera P. et al.Delirium assessed by Memorial Delirium Assessment Scale in advanced cancer patients admitted to an acute palliative/supportive care unit.Curr Med Res Opin. 2017; 33: 1303-1308Crossref PubMed Scopus (9) Google Scholar]. Delirium also causes significant psychological distress for patients, their families and healthcare providers [1.Lawlor P.G. Bush S.H. Delirium in patients with cancer: assessment, impact, mechanisms and management.Nat Rev Clin Oncol. 2015; 12: 77-92Crossref PubMed Scopus (45) Google Scholar]. (See also the section on the 'Experiential impact of delirium' for further discussion of this topic.) Risk factors for delirium are often described as 'predisposing' or 'precipitating'. 'Predisposing' factors refers to those conditions that already exist in a person at baseline, and increase the person's susceptibility to develop delirium, whereas 'precipitating' factors are those that are responsible for activating a specific delirium episode. Direct and indirect risk factors and other predisposing comorbidities for delirium in the cancer patient are summarised in Table 1. As delirium is ubiquitous, it is possible that cancer survivors with no active disease but who have developed cognitive impairment due to the effects of cancer and/or its treatment may also be at risk for developing delirium. None of the papers that were reviewed for the epidemiology section (see Supplementary Table S1, available at Annals of Oncology online) reported on cancer survivors.Table 1Risk factors and predisposing comorbidities implicated in the onset of delirium in adult patients with cancerDirect risk factors for deliriumCancer related-factors [20.Ljubisavljevic V. Kelly B. Risk factors for development of delirium among oncology patients.Gen Hosp Psychiatry. 2003; 25: 345-352Crossref PubMed Scopus (88) Google Scholar]Primary CNS tumoursSecondary CNS tumours–Brain metastases–Meningeal metastasesPara-neoplastic neurological syndromesToxicities from anticancer treatments [20.Ljubisavljevic V. Kelly B. Risk factors for development of delirium among oncology patients.Gen Hosp Psychiatry. 2003; 25: 345-352Crossref PubMed Scopus (88) Google Scholar, 39.Neefjes E.C.W. van der Vorst M.J.D.L. Verdegaal B.A.T.T. et al.Identification of patients with cancer with a high risk to develop delirium.Cancer Med. 2017; 6: 1861-1870Crossref PubMed Scopus (5) Google Scholar, 48.Matsuoka H. Yoshiuchi K. Koyama A. et al.Chemotherapeutic drugs that penetrate the blood–brain barrier affect the development of hyperactive delirium in cancer patients.Pall Supp Care. 2015; 13: 859-864Crossref PubMed Scopus (0) Google Scholar]Radiation to brain: acute or delayed encephalopathyChemotherapy: methotrexate, cisplatin, vincristine, procarbazine, asparaginase, cytarabine (cytosine arabinoside), 5-fluorouracil, ifosfamide, tamoxifen (rare), etoposide (high-dose), nitrosourea compounds, alkylating agents (high-dose or arterial route)Indirect risk factors for deliriumPhysical complications in cancer patients [40.Jeejeebhoy N.K. Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia: overlap of clinical features.Curr Opin Clin Nutr Metab Care. 2012; 15: 213-219Crossref PubMed Scopus (108) Google Scholar, 41.Laird B.J. McMillan D.C. Fayers P. et al.The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer.Oncologist. 2013; 18: 1050-1055Crossref PubMed Scopus (74) Google Scholar]Metabolic encephalopathy due to hepatic, renal or pulmonary failureElectrolyte abnormalities, including SIADHGlucose abnormalitiesInfections, sepsis—at any site, including intravenous linesHaematological abnormalitiesNutritional deficiency–Thiamine (vitamin B1)–Folic acid (vitamin B9)–Cobalamin (vitamin B12)DehydrationPost-seizure; nonconvulsive status epilepticusVasculitisMedications [5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar, 45.Caraceni A. Drug-associated delirium in cancer patients.EJC Suppl. 2013; 11: 233-240Crossref PubMed Scopus (0) Google Scholar]Anxiolytics, hypnoticsOpioidsCorticosteroidsNSAIDsAnticonvulsantsAnticholinergics–Scopolamine (hyoscine hydrobromide)–Atropine–Belladonna alkaloids–Drugs with established anticholinergic activity, e.g. tricyclic antidepressants, diphenhydramine, promethazine, trihexyphenidyl, hyoscine butylbromideOther psychoactive: antipsychotics, antidepressants, levodopa, lithiumAnti-infectives: ciprofloxacin, acyclovir, ganciclovirHistamine H2 blockersOmeprazoleImmunomodulators: interferon, interleukins, ciclosporinMedication polypharmacyOther status or predisposing comorbidities [5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar, 39.Neefjes E.C.W. van der Vorst M.J.D.L. Verdegaal B.A.T.T. et al.Identification of patients with cancer with a high risk to develop delirium.Cancer Med. 2017; 6: 1861-1870Crossref PubMed Scopus (5) Google Scholar]Age > 70 yearsPre-existing cognitive impairment, e.g. dementiaHistory of deliriumHearing impairmentOther status or predisposing comorbidities [5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar, 39.Neefjes E.C.W. van der Vorst M.J.D.L. Verdegaal B.A.T.T. et al.Identification of patients with cancer with a high risk to develop delirium.Cancer Med. 2017; 6: 1861-1870Crossref PubMed Scopus (5) Google Scholar]Visual impairmentUrinary retention or use of urinary catheterConstipationAlcohol or drug abuse, or withdrawal (including nicotine)CNS diseases or trauma; history of stroke or transient ischaemiaLiver failureRenal failureEnd-stage cardiac diseaseEnd-stage lung diseaseEndocrinopathyCNS, central nervous system; NSAID, non-steroidal anti-inflammatory drug; SIADH, syndrome of inappropriate antidiuretic hormone secretion. Open table in a new tab CNS, central nervous system; NSAID, non-steroidal anti-inflammatory drug; SIADH, syndrome of inappropriate antidiuretic hormone secretion. Studies in oncology settings have not documented specific socio-demographic and disease-related predictive factors for delirium. In addition, most studies in cancer patients have explored a range of psychiatric diagnoses rather than addressing factors specific to delirium. As a consequence, the number of patients with delirium in these studies has often been insufficient to precisely determine associated risk factors. A multifactorial model for hospitalised patients aged ≥ 70 years has been proposed [5.Inouye S.K. Westendorp R.G. Saczynski J.S. Delirium in elderly people.Lancet. 2014; 383: 911-922Abstract Full Text Full Text PDF PubMed Scopus (1380) Google Scholar]. The model involves the interaction between 'baseline vulnerability' and 'precipitating factors or insults'. Predisposing factors that are specifically demonstrated to be contributory to the baseline vulnerability in older patients include visual impairment, severity of illness, pre-existing cognitive impairment and dehydration (demonstrated by an elevated blood urea nitrogen/creatinine ratio of ≥ 18). Patients who have high baseline vulnerability may develop delirium with any precipitating factor, whereas those with low baseline vulnerability will be more resistant to the development of delirium, even with noxious insults. Accordingly, in less advanced cancer, relatively minor intercurrent illness can result in delirium in older, frail persons [38.Quinlan N. Marcantonio E.R. Inouye S.K. et al.Vulnerability: the crossroads of frailty and delirium.J Am Geriatr Soc. 2011; 59: S262-S268Crossref PubMed Scopus (86) Google Scholar], whereas more severe acute illness might be necessary to produce delirium in younger individuals. In a prospective observational study over a 10-week period, 113 patients (145 hospital admissions) with haematological malignancies or cancer were admitted to an acute oncology unit. The majority of patients (57%) had a haematological malignancy, most commonly lymphoma (n = 47). For patients with cancer, the stage was not reported. The five factors associated with the occurrence of delirium on multivariate analysis were found to be: advanced age, cognitive impairment on admission, hypoalbuminaemia, presence of bone metastases (independent of serum calcium level) and the diagnosis of a haematological malignancy [20.Ljubisavljevic V. Kelly B. Risk factors for development of delirium among oncology patients.Gen Hosp Psychiatry. 2003; 25: 345-352Crossref PubMed Scopus (88) Google Scholar]. From a retrospective study of 574 patients with solid malignancies and 1733 admissions to a medical oncology ward, Neefjes et al. recently developed a delirium prediction algorithm [39]. They identified that patients admitted as an emergency in combination with a metabolic disturbance had a one in three delirium risk. Cancer stage was not recorded, except for the presence of intracranial disease (as primary tumour or metastasis) in 36 patients (6%). Study limitations include a low overall incidence of delirium (3.5 per 100 admissions) and retrospective design. Other delirium risk factors have been implicated in other studies, including age, dementia, depression, alcohol abuse, poor functional status, organ dysfunction and abnormal levels of serum sodium, potassium or glucose, among others [40.Jeejeebhoy N.K. Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia: overlap of clinical features.Curr Opin Clin Nutr Metab Care. 2012; 15: 213-219Crossref PubMed Scopus (108) Google Scholar, 41.Laird B.J. McMillan D.C. Fayers P. et al.The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer.Oncologist. 2013; 18: 1050-1055Crossref PubMed Scopus (74) Google Scholar, 42.Marcantonio E.R. Goldman L. Mangione C.M. et al.A clinical prediction rule for delirium after elective noncardiac surgery.JAMA. 1994; 271: 134-139Crossref PubMed Google Scholar, 43.MacDonald N. Terminology in cancer cachexia: importance and status.Curr Opin Clin Nutr Metab Care. 2012; 15: 220-225Crossref PubMed Scopus (34) Google Scholar, 44.Fearon K. Arends J. Baracos V. Understanding the mechanisms and treatment options in cancer cachexia.Nat Rev Clin Oncol. 2013; 10: 90-99Crossref PubMed Scopus (457) Google Scholar]. Moreover, many medications are implicated as risk factors for delirium, in particular opioids, benzodiazepines, corticosteroids and antipsychotics [45.Caraceni A. Drug-associated delirium in cancer patients.EJC Suppl. 2013; 11: 233-240Crossref PubMed Scopus (0) Google Scholar] (Table 1). In a study of 140 hospitalised, confused adult cancer patients, 31% had a single determinant factor for their delirium, whereas 69% had multiple factors, with a median of three probable causes [46.Tuma R. DeAngelis L.M. Altered mental status in patients with cancer.Arch Neurol. 2000; 57: 1727-1731Crossref PubMed Google Scholar]. One-hundred and two patients (73%) were known to have metastatic cancer, with brain or leptomeningeal metastase