Delirium is often undetected or misdiagnosed. In one study, nursing staff anticipated delirium onset in only 31% of patients that subsequently manifested it [23]. Other studies confirmed these difficulties in making a timely diagnosis of delirium [24, 25]. These difficulties are likely due to the limited experience and lack of specific skills of the healthcare professionals to diagnose this syndrome and to make a differential diagnosis from other neuropsychiatric conditions. For this reason, we tried to identify a priori relevant clinical factors which can anticipate delirium onset and help the healthcare workers to make a diagnosis of this condition in a timely manner.
Investigating various clinical factors in all enrolled patients, we found that some of them were significantly more frequent in patients who subsequently developed delirium than in those who did not. In particular, 15 factors were significantly related in univariate analyses, i.e., care in hospice, compromised performance status, kidney disease, fever, renal failure, hypoxia, dehydration, drowsiness, poor well-being, breathlessness, “around the clock” treatment with haloperidol and other drugs acting on the CNS, cardiovascular drugs, anticoagulants, gastroprotective drugs, and morphine. Multivariate analyses stressed the role of care in hospice, breathlessness, and administration of CNS active drugs (particularly haloperidol), as relevant “delirium-predisposing factors” in advanced (cancer) patients.
Our data indicate that the risk of developing delirium is higher in patients in hospice than those cared for at home, suggesting that the relevant factor seems to be the hospitalization. This is consistent with previous studies which reported that old patients requiring hospital admission have a prevalence of delirium between 18% and 35% [3, 16, 17, 26]. The sudden departure from their own habitat to a different environment plays an important role in delirium onset, especially in elderly patients with serious health conditions.
As already reported, we also observed that respiratory activity is important in predicting delirium: patients with breathlessness had an approximately twofold risk of developing delirium. Furthermore, we found an increase of over twofold in the risk of delirium onset in patients who used haloperidol and of more than 70% in those administered other CNS-acting drugs as “around the clock” therapy. This is not surprising, since the role of CNS-active drugs in inducing delirium has been often debated in recent years. Anticholinergics, antidopaminergics, sedative/hypnotics, antipsychotics, opioids, and relaxants, in particular, have been considered as drugs that may cause delirium [26]. It should be also noticed that haloperidol has been considered for years as the gold standard treatment in case of agitation conditions, including delirium [27,28,29]. Recently, a randomized clinical trial highlighted that the administration of risperidone or haloperidol among patients with delirium in palliative care resulted in lower control of symptoms, greater extrapyramidal effects, and lower median survival than in those receiving placebo [30].
In our study, no association was found between level of education or marital status and risk of delirium; this suggests that delirium is related to the patients’ severe clinical condition at the end of life—able to trigger delirium pathogenetic mechanisms—rather than the patients’ cultural and socio-familial background. We also found no association with age, although some previous studies suggested an increased risk of delirium with advancing age [3, 31].
Moreover, the role of the primary pathology and concomitant diseases was not relevant for the onset of delirium. However, it should be considered that in this study the population of the patients was quite clinically homogeneous, since 90% of them had a diagnosis of neoplasm.
Although various risk factors for the onset of delirium have previously been investigated [15,16,17, 32], most studies considered retrospectively these factors in patients who already presented an episode of delirium. In this study, we investigated a number of possible risk factors at the time of admission to the PCU, when the delirium episode had not yet happened, allowing us to identify potentially “delirium-predisposing factors”. Recent data have shown the importance of physical activity on the well-being of PC patients [33]. It would be interesting to explore whether this would also affect the appearance of delirium, and this might be a topic for a future research on those difficult and fragile patients.
This study presents some limitations. In particular, we did not achieve the expected sample size calculated at the moment of planning the project. Given the initial difficulties in undertaking the study and the selection of patients according to eligibility criteria, the final number of recruited patients was 503 (about 63% of the expected sample size). We examined a number of risk factors evaluated at baseline visit, but there are likely many other risk factors, which could occur during the course of a patient's admission, and might be considered as precipitants for delirium, and which were not considered in our analysis. Moreover, the incidence of patients with delirium in our study was lower (about 19%) compared with previous study populations [11,12,13]. This is probably because patients enrolled in our study were at a very advanced stage of disease with a short survival time (average 16 days), reflecting the Italian situation where the delay in sending terminally ill patients to PC is very frequent [34]. Furthermore, it may be also due to the criteria for patient selection and, in particular, to the decision to exclude baseline delirium cases, limiting analysis to cases that occurred during follow-up. Consequently, for some clinical factors, the association with occurrence of new cases of delirium did not reach statistical significance, even in the presence of a high HR.