Characteristics of patients who die in an acute palliative care unit

doi:10.21203/rs.3.rs-5273676/v1

Aim: To evaluate the characteristics of patients with advanced cancer who die in an acute palliative care unit (APCU). The second outcome was to evaluate the risk factors for death in APCU.

Methods: Consecutive patients with advanced cancer admitted to the APCU in a period of 13 months were prospectively assessed. At APCU admission epidemiologic data, characteristics of admission, cachexia, being on-off anticancer treatment, and Edmonton Symptom Assessment System (ESAS) were assessed. Patients who died in APCU were extrapolated from the entire sample. A similar random sample of patients who were discharged alive in the same study period, matched for age and gender, was selected for comparison.

Results: Fifty-four patients (12%) died in APCU. Statistical differences between died and discharged patients atadmission were found in MDAS (p=<0.0005), home palliative care referral (p<0.0005), cachexia (p=0.018), being off-therapy (p=<0.0005), cognitive/clinical decline (p=<0.0005), and symptom burden (P=0.002). At the multivariate analysis, independent factors associated with dying in APCU were MDAS (p=0.006), referral from home care (p=0.025), being off-therapy (p=0.002), pain (<0.05), and dyspnea intensity (p=0.038), and total ESAS (p=0.025).

Conclusion: Mortality risk in APCU is associated with home palliative care referral, high symptom burden, cognitive failure, and general worsening of the clinical condition, as well being off-therapy. More proactive and timely end-of-life care is needed for these patients.

advanced cancer

palliative care

mortality

acute palliative care unit

Patients with advanced cancer often suffer from severe physical and psychosocial distress that requires intensive interdisciplinary palliative care (1, 2). Acute palliative care unit (APCU) in a comprehensive cancer center provides aggressive symptom management and assists with the transition to palliative care (2–6). The APCU has a determining role among the settings of palliative care: it allows rapid pain and symptom control with specialised personnel at any stage of disease even in patients receiving anticancer therapy, provides the possibility of reassessment, using hospital facilities and consultations for transition of care with experts communicating with family. When anticancer treatments are no longer adviced, patients can be referred to other palliative care services, including outpatient clinic, home palliative care, or inpatient hospice (7). In some cases patients are admitted to an APCU before receiving any anticancer treatment, due to symptom burden or very advanced disease (8). During this short and intense hospitalization, patients and clinicians are faced with the challenge of making different treatment and discharge planning decisions, which are dependent on the expected patient survival.

Mortality rate in APCU has been reported to be largely variable, possibly reflecting the attitudes to admit patients in an early stage of disease or in a very advanced stage of disease. This often depends on availability of local resources rather than on a precise choice to select patients to be admitted to APCU (9). In our unit a limited number of patients has been reported to die during admission (7), possibly because most patients were seen during the oncologic treatment for symptom management and re-assessment. (10). The identification of relevant prognostic factors for the unique population of APCU patients is of paramount importance for a timely end-of-life care approach.

The aim of this study was to evaluate the characteristics of patients with advanced cancer who die in the APCU. The second outcome was to evaluate the risk factors for death in APCU.

APCU is a 12-bed unit in a comprehensive cancer center and is connected with a 10 beds hospice in same floor, with an available home palliative care service. In addition to serving the APCU, the supportive/palliative care team also provides services through a consultation-based service and the outpatient clinic. Sources of admission are various and include transfer from the medical oncology ward, outpatient oncology clinic, other department units, home palliative care, other hospitals, either as planned admission or as an emergency (7).

Procedures

All consecutive patients with advanced cancer admitted to the APCU between April 2023 and April 2024 were prospectively assessed. Informed consent was obtained. The study conducted in accordance with the Declaration of Helsinki, and was approved by the local ethical committee of Palermo 1, Azienda ospedaliera universitaria.

At APCU admission (T0) age, gender, primary tumor, and Karnofsky status were recorded, as well characteristics of admission (readmission, planned, emergency, and transfer), the presence of cachexia, being on-off anticancer treatment, and MDAS (Memorial Delirium Assessment Scale). This tool is routinely used in APCU and has been used in previous studies to quantify the changes in cognitive function in advanced cancer patients (7). Cachexia was defined according to common diagnostic criterion for cachexia. (11). Patients were considered off-therapy (no longer candidate for anticancer treatments), on-therapy (when oncologists considered the patient to be a candidate for further treatments), or uncertain (when oncologists were uncertain on the next step). The Edmonton Symptom Assessment System (ESAS) was assessed. ESAS is a validated tool widely used to measure the severity of physical and psychological symptoms, including pain, weakness, nausea, depression, anxiety, drowsiness, dyspnea, poor appetite, poor sleep, and poor feeling of well-being on a numeric rating scale ranging from 0 to 10. (12). A screening test for history of alcohol dependence (CAGE: cut down, annoy, guilt, eye-opener), was performed. CAGE is considered to be positive by “yes” answer to at least two of questions for men, and at least one for women (13).

From this consecutive sample of patients, patients who died in APCU were extrapolated. This group was compared with a similar random sample of patients who were discharged alive.

Statistical analysis

Differences between groups were assessed using the chi-square test or Fisher's exact test, as appropriate for categorical variables, and the independent Student's t-test for continuous parameters. The univariate analysis of variance (ANOVA) was performed for parametric variables with multiple comparisons. Variables significantly related to patient groups were analysed using a multivariate logistic regression model to examine the correlation between patient characteristics (independent variables) and patient groups (dependent variable). Effect sizes were used to express the mean score differences between patient subgroups in relation to the standard deviations. Data were analysed using IBM SPSS Statistics, version 22 (IBM Corp., Armonk, NY, USA). All p-values were two-sided, and a p-value of less than 0.05 was considered statistically.

Of 449 patients who were admitted to APCU in the study period, 54 patients (12%) died in the unit. The mean age was 69.6 ± 9.4 years (range, 30–92 years). Twenty-nine patients were males (53.7%). The most common primary cancer types were lung and gastrointestinal (35.2% and 29.6%, respectively). A random sample of 54 patients who were discharged alive in the same study period, matched for age and gender, was selected for comparison. Baseline characteristics of these 108 patients are summarized in Table 1.

Table 1. Characteristics of patients

	Died in the APCU	Discharged	P
N°	54	54
Age	69.6± 9.4	68.6 ± 12.6	0.641
Gender (M/F)	29 / 25	29 / 25	1.0
Karnofsky	36.9 ± 10.6	37.8 ± 11.2	0.661
MDAS	5.8±2.6	1.9±2.4	<0.0005
REFERRAL
home palliative care oncology other hospitals surgery	17 29 2 6	4 49 1 0	<0.0005
CAGE positive	2	0	0.118
CACHEXIA
no si nv	26 27 1	39 15 0	0.018
ON OFF NAIVE
on off naive	17 18 19	54 0 0	<0.0005
Primary tumor
urogenital lung gastrointestinal breast colon head e neck	6 19 16 3 9 1	6 28 16 3 0 1	0.046
PRINCIPAL REASON FOR ADMISSION (MULTIPLE CHOICE)
pain clinical/cognitive decline pulmonary problems gastrointestinal symptoms	11 20 9 14	44 5 2 3	<0.0005
TYPE OF ADMISSION
planned emergency transfer	26 25 3	27 20 7	0.310

Statistical differences were found in MDAS (p = < 0.0005), referral from home palliative care (p < 0.0005), cachexia (p = 0.018), being off-therapy (p = < 0.0005), and cognitive/clinical decline (p = < 0.0005),

Patients who died in the APCU showed higher symptom distress upon APCU admission compared with patients who were discharged from the APCU alive. These patients had higher mean ESAS scores for pain (p = < 0.0005), dyspnea (p = < 0.0005), depression (p = < 0.0005), drowsiness (p = 0.002), nausea (p = < 0.0005), poor appetite (p = < 0.0005), and poor well-being(p = 0.028). Total ESAS was also significantly higher in patients who died in the APCU (P = 0.002) (see Table 2).

Table 2

Symptom intensity (mean ± SD) at admission to the APCU Reference : Discharged
Symptoms	All patients	Died in the APCU	Discharged	P
Pain	3.6 ± 2.5	6.0 ± 2.1	2.8 ± 2.1	< 0.0005
Dyspnea	2.9 ± 3.1	4.7 ± 3.1	1.5 ± 2.1	< 0.0005
Depression	2.7 ± 3.1	4.2 ± 3.2	1.3 ± 2.3	< 0.0005
Anxiety	2.2 ± 2.7	2.6 ± 2.9	1.9 ± 2.6	0.240
Drowsiness	3.5 ± 3.0	4.6 ± 3.4	2.6 ± 2.4	0.002
Poor sleep	3.7 ± 3.2	3.2 ± 3.2	4.1 ± 3.2	0.233
Weakness	5.2 ± 3.1	4.3 ± 3.6	6.0 ± 2.5	0.010
Nausea	2.0 ± 2.6	3.7 ± 2.7	0.6 ± 1.6	< 0.0005
Poor appetite	2.6 ± 3.4	1.1 ± 2.4	3.9 ± 3.7	< 0.0005
Poor well being	5.8 ± 2.6	6.5 ± 2.9	5.3 ± 2.2	0.028
ESAS TOT	33.0 ± 13.6	41.8 ± 16.2	30.1 ± 11.5	0.002

At the univariate analysis the following factors were associated with dying in APCU: higher MDAS (p < 0.0005), referral from home palliative care in comparison with oncology ward (p < 0.0005), diagnosis of colon cancer (p = 0.046), less awareness (p = 0.001), cachexia (p = 0.018), being off-therapy (p < 0.0005), admission for clinical/cognitive decline, pulmonary and gastrointestinal symptoms in comparison with pain (p < 0.0005).

At the multivariate analysis, independent factors associated with dying in APCU were MDAS (p = 0.006), referral from home care (p = 0.025), being off-therapy (p = 0.002), pain (< 0.05), dyspnea (p = 0.038) and total ESAS (p = 0.025) (see Table 3).

Table 3. Univariate and multivariate analysis of factors associated with death of patients

Symptoms	Crude OR (95%CI)	P	Adj OR (95%CI)	P
MDAS	1.646(1.36-1.99)	<0.0005	2.095(1.24-3.54)	0.006
Referral	0.142(0.04-0.46)	0.001	0.096(0.01-0.74)	0.025
Type of tumour	1.510(1.05-2.17)	0.027	1.462(0.65-3.28)	0.356
Awareness	2.663(1.48-4.78)	0.001	3.160(0.56-17.67)	0.190
Cachessia	2.820(1.29-6.17)	0.009	0.750(0.05-11.76)	0.838
Off - therapy	58.334(7.56-450.06)	<0.0005	32.122(3.70-278.95)	0.002
Causes of admission	3.467(2.04-5.89)	<0.0005	2.516(0.94-6.73)	0.066

Reference : Discharged

Symptoms	Crude OR (95%CI)	P	Adj OR (95%CI)	P
Pain	2.258(1.44-3.55)	<0.0005	2.170(1.01-4.79)	0.05
Dyspnea	1.523(1.26-1.84)	<0.0005	1.850(1.04-3.30)	0.038
Anxiety	1.096(0.94-1.28)	0.238	0.764(0.42-1.40)	0.384
Depression	1.411(1.19-1.67)	<0.0005	1.636(0.94-2.86)	0.085
Poor sleep	0.923(0.81-1.05)	0.230	0.861(0.55-1.36)	0.521
Drowsiness	1.257(1.08-1.46)	0.003	0.922(0.59-1.44)	0.721
Nausea	1.794(1.41-2.28)	<0.0005	1.411(0.62-3.22)	0.413
Poor appetite	0.733(0.62-0.87)	<0.0005	0.624(0.37-1.07)	0.085
Weakness	0.836(0.73-0.96)	0.012	0.964(0.49-1.90)	0.915
Poor well being	1.213(1.02-1.45)	0.032	1.010(0.50-2.02)	0.978
ESAS TOT	1.069(1.02-1.12)	0.006	1.080(1.01-1.15)	0.025

Reference : Discharged

The findings of this study provided interesting information. The mortality rate was quite low, compared to the data of other APCUs (9), although relatively higher compared to our previous data (7). One possible reason is the change of patients’ pattern admitted to APCU, from patients with uncontrolled pain, which was one the principal indications for admission, to patients with worsening of the general conditions, also generated from a larger bed availability. Moreover, discharging home may be problematic, as well transfer to hospice, due to unavailability of hospice beds. Indeed, mortality risk was independently associated with home palliative care referral for patients with cognitive failure and general worsening of the clinical condition, as well being off-therapy. Thus, this profile is the identikit of the patient who will possibly die in APCU. In general, however, mortality rate remains quite low, confirming that most patients are admitted early along the course of disease for many different reasons. Pain and dyspnea, as well the symptom burden represented by total ESAS recorded at admission, were also found to be independently associated with death. This is consistent with the observation of a Korean study (14), in which patients who died in the APCU while waiting transfer to hospice were more likely to have significantly higher symptom burden such as drowsiness and dyspnea, and to be male. Of interest, the mortality rate was 33%, possibly due to less hospice bed availability. An increased symptom burden in the last days of life is expected when assessing the trajectory of symptom burden in the last seven days (15). Such symptom burden was also observed in the present study as an independent factor associated to death. The high symptom burden is likely because patients admitted to APCUs are typically admitted for their level of distress and refractory symptoms (16, 17).

In a retrospectiv Japanese study a greater risk of dying was independently correlated with a high level of baseline symptoms such as dyspnea, drowsiness, low level of baseline anxiety and transfer from emergency center (18). A retrospective study aimed to assess factors associated with increased likelihood of mortality in APCU. Of 500 patients admitted to the APCU, 25% of them died. Factors that were associated with death in APCU were younger age, admission from another oncology floor, some laboratory findings, such as hypo/hypernatremia, high blood ureanitrogen, and some clinical features, including high heart rate, high respiration rate, and the use supplemental oxygen use (19). Signs of imminent death (heart rate, respiatory rate, use of oxygen) are likely to appear in the last days of life, suggesting that in thsi retrsopective stucy ( 19), patients were admitted when they were close to death. In another retropective study, independent factors predicting 72-h mortality after transfer to APCU were no prior palliative care consult, no advance care directive, lower performance status, lower self-care index, and lower blood albumin level (20). Of interest, 20% of transferred patients died within 72 h of arrival on the APCU. In the present prospective study we did not used blood tests, as our intention was to distinguish patients according to process (referral) or charge of symptoms, rather than laboratory findings, which are potentially reversible after proper treatments. Differences in Health Care system and setting of referral may explain the different findings, Indeed, in this study most patients who died were referred from home palliative care, possibly because the clinical conditions, for example cognitive failure, pain or dyspnea, were difficult to manage at home.

The principal limitations of this study lie on the single center experience compared to the large variability in APCU models. A further limitation is based on the lack of examination of other specific data, for example heart rate or renal failure, or extrapolating a prediction model. Such clinical signs, however, develop in the last days of life, not necessarily at admission to APCU, which may last several days. However, the prospective design and the findings provided a typical identikit of patients with higher probabilities to die after admission in APCU in a Health system where home palliative care is particularly developed.

In conclusion mortality risk in APCU is associated with home palliative care referral, high symptom burden, cognitive failure, and general worsening of the clinical condition, as well being off-therapy. More proactive and timely end-of-life care is needed for these patients.

SM: preparation, interpretation, writing

ALC: data manager

AC: statistics

Author Contribution

SM: preparation, interpretation, writingALC: data managerAC: statistics

No conflict of interest

No funding

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No competing interests reported.

Characteristics of patients who die in an acute palliative care unit

Status:

Version 1

Abstract

INTRODUCTION

METHODS

Procedures

Statistical analysis

RESULTS

DISCUSSION

Abbreviations

Declarations

Author Contribution

References

Additional Declarations

Status:

Version 1