Acute urinary retention and delirium in end-of-life cancer patients.

Acute urinary retention and delirium in end-of-life cancer patients. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Acute urinary retention and delirium in end-of-life cancer patients. Miguel Borregón, Javier-David Benítez-Fuentes, Alejandro Moya-Martínez, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4447011/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Symptom management at end-of-life (EOL) is crucial for nurses, oncologists, and palliative care providers. Acute urinary retention (AUR) is a common issue at EOL, often influenced by various factors including medications and underlying disease. Despite its significance, literature on AUR in EOL cancer patients remains limited, especially regarding its association with delirium. Methods: We included patients at EOL admitted to the Palliative Care Unit (PCU) of Hospital Virgen de la Salud de Toledo, Spain, between January and February 2018. EOL was defined as patients presenting with conditions ultimately leading to their demise during the hospital admission. AUR was confirmed based on clinical assessment from electronic medical records, defined as the inability to voluntarily urinate, or AUR concordant physical examination, and the need for bladder catheterization to urinate. We evaluated delirium clinically, considering altered consciousness, cognition, and perception. We used descriptive statistics to summarize demographic characteristics and clinical features. We employed a logistic regression analysis to identify predictors of AUR and AUR-associated delirium. Results: Among 51 new admissions, 39 (76.4%) were EOL patients, with 13 (33.3%) experiencing AUR. Patients with AUR were older (mean age 78.8 years) compared to those without AUR (mean age 71.5 years). AUR was associated with butylscopolamine use, advanced age, lung cancer, and distant metastases. Physical examination revealed palpable distended bladders in most AUR cases, with a mean urine volume of 536 cc at catheterization. Delirium was present in over 50% of AUR cases, resolving after catheterization in the majority. Conclusion: Improving recognition of AUR symptoms and causes in the EOL setting could improve patient relief and comfort. End-of-life acute urinary retention delirium palliative care cancer. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction At the end of life (EOL), achieving optimal symptom control stands as a key goal for nurses, oncologists, and palliative care specialists [ 1 ]. This phase often presents a complex array of symptoms, rendering identification of underlying causes challenging. These symptoms not only contribute to physical discomfort but also significantly impact the patient’s overall quality of life. Among these challenges, acute urinary retention (AUR) emerges as a prevalent concern, influenced by different factors, including individual patient characteristics, cancer physiopathology, and medication profiles [ 2 , 3 ]. Drugs commonly prescribed for EOL management, such as opioids, benzodiazepines, anticholinergics, and antidepressants, are recognized for their potential to disrupt bladder function, predisposing patients to AUR [ 4 ]. AUR not only induces discomfort but may also be associated with delirium, further complicating the patient’s EOL clinical course [ 5 ]. Despite its clinical significance, literature addressing AUR in this context remains scarce, with limited studies exploring this phenomenon. Recognizing the substantial burden of illness associated with AUR in EOL cancer patients, we studied its epidemiology and its relationship with delirium. Through our investigation, we studied the prevalence and clinical behaviour of AUR in EOL cancer patients, while also exploring its correlation with delirium, a critical aspect of symptom management in palliative care. By analyzing these complexities, our study seeks to provide valuable insights that could inform evidence-based practice and enhance the delivery of care to this vulnerable patient population. Methods We conducted a retrospective study of patients admitted to the cancer Palliative Care Unit (PCU) of Hospital Virgen de la Salud de Toledo, Spain, who presented EOL stage, between January and February 2018 (60 days). AUR epidemiology, clinical features and relationship with delirium were evaluated. EOL was defined as patients presenting with conditions ultimately leading to their demise during the hospital admission. Patients who did not meet this condition were excluded from the study. AUR diagnosis was confirmed based on clinical assessment derived from electronic medical records and defined as the inability to voluntarily urinate, or AUR concordant physical examination findings, coupled with the need for bladder catheterization to facilitate urination. The diagnosis of delirium was extracted from electronic medical records with consideration given to alterations in consciousness, cognition, and perception. Descriptive statistics were employed to summarize demographic characteristics and clinical features. Between AUR patients, the Mann Whitney U test was used or the comparison of medians. Fisher’s test or the Chi-square test were used for the comparison of qualitative variables depending on its suitability. Logistic regression analysis was utilized to identify predictors associated with the development of AUR and AUR-associated delirium. Data analysis was performed using R statistical software, with significance levels set at p ˂ 0.05. The study protocol was approved by the ethics committee of Hospital Virgen de la Salud de Toledo. All procedures performed in this study were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki and its subsequent amendments. Informed consent was waived due to the retrospective nature of the study, and patient data were anonymized to maintain confidentiality and privacy. This analysis and study have needed long time to see the light due to coronavirus pandemic logistic side effects. During the last years most of health resources in our hospital were focused on clinical activity instead of researching activity. Results Demographic, tumor, clinical and statistical models are presented in Figs. 1 – 4 . During the period of data collection there were 51 new admissions in the PCU. These admissions accounted for a total of 48 unique patients, observing 3 instances of readmission, constituting 5.9% of the admissions. Most of patients, 39 (76.4%), had conditions ultimately leading to their demise during the hospital admission and were those included in the study. Among the EOL patients, 13 individuals (33.3%) experienced acute urinary retention (AUR), with a notable preponderance of male patients, 9 (69.2%). The mean age of patients presenting with AUR was 78.8 years, indicating an advanced age within this subgroup. The mean duration from admission to death was comparable between patients with AUR (10.2 days) and those without (10.3 days). Tumor-related data revealed a diverse spectrum of cancer types among patients experiencing AUR, with lung cancer being the most prevalent, 6 (46.1%), followed by kidney cancer, 2 (15.4%) patients, and colorectal cancer, 2 (15.4%) patients. Physical examination findings among patients with AUR revealed diverse degrees of bladder distention, with 8 (61.5%) patients presenting with a palpable distended bladder. Among these patients, the mean urine volume at the time of bladder catheterization was 536 cc. The mean survival duration from bladder catheterization to death was 3.1 days. Regarding risk factors associated with AUR development, all patients who experienced AUR were being treated with butylscopolamine for secretions relief. Notably, a higher prevalence of AUR was observed among patients with lung cancer, 6 (46.1%), and distant metastases, 12 (92.3%). Delirium emerged as a prevalent complication among patients with AUR, with 7 (53.8%) patients experiencing it at the time of AUR diagnosis. To note, a significant proportion, 5 (71.4%), of these patients demonstrated resolution of delirium following bladder catheterization. Data about delirium development were not collected for patients who did not experience AUR, highlighting a potential area for further investigation and comprehensive assessment in future studies. Significant differences between the comparison of patients experiencing AUR versus those without were not found. Regarding the logistic regression model, we introduced the sociodemographic variables and clinical variables. It was found that the variable age categorised by age under or equal to 73 years and over 73 years was a predictor for AUR development. The variable metastases was also included, as it behaves as a confounder in our model. The multivariate model explains that patients who are older than 73 years present 5.30 times more risk for AUR than patients with less than or equal to 73 years (p-value = 0.036), with the influence of the variable metastases. Similarly, we can say that patients presenting metastases have a 6.79 times higher risk for belonging to the AUR group than patients without metastases (p-value = 0.112), adjusted for the variable age. Although not significant, the variable metastases behaves as a confounding factor because it alters the age risk from 4.25 to 5.30. Discussion The findings of this retrospective study seed light on the epidemiology and clinical characteristics of AUR in cancer patients presenting EOL, as well as its association with delirium. The observed prevalence of AUR (33.3%) among EOL cancer patients in our cohort is consistent with previous reports, indicating the significant burden of this condition in palliative care settings. The predominance of male patients experiencing AUR aligns with existing literature [ 1 ] and the advanced mean age of patients presenting with AUR underscores the vulnerability of elderly cancer patients to urinary dysfunction at the EOL stage [ 6 ]. Tumor-related data revealed a diverse distribution of cancer types among patients experiencing AUR, with lung cancer emerging as the most prevalent, along with a very high prevalence of distant metastases in AUR patients. The clinical assessment of AUR through physical examination identified palpable distended bladder in most patients, suggesting that this finding may serve as an important indicator necessitating prompt evaluation. Among patients presenting palpable distended bladder, mean volume of urine was more than 500 cc. Survival after bladder catheterisation was limited, indicating that AUR could be an early sign of short survival in this setting. The prevalence of bladder catheterization in PCU patients was first described by Fainsinger et al. with a 72% incidence rate [ 6 ]. Gutmanis et al. described an incidence rate of 57.5% and found that 69% patients presented with a poor performance status when bladder catheterization was performed. They also described the reasons for this catheterization, finding that the indication was AUR in 81% patients, energy preservation in 7.1%, and urinary tract infection in 4.8%. They describe a mean volume of urine at the time of catheter insertion was 561.7 cc for males and 657.4 cc for females [ 7 ]. In our study, the risk factors for the development of AUR were advanced age, butylscopolamine prescription, previous AUR episodes, lung cancer and presence of distant metastases. Some studies have addressed the relation between polypharmacy and AUR. Currow et al. described that the average number of prescribed medications in the days preceding death in PCU patients was seven [ 8 ]. Sera et al. described that among cancer patients admitted to hospice, almost all patients received an opioid analgesic, and the majority received anticholinergics, benzodiazepines and antidopaminergics [ 9 ]. A retrospective case-control study carried in a PCU in Ontario, Canada, focuses on the medication prescription associated with AUR [ 10 ]. This study did not find the addition of different classes of AUR related medications increasing the risk for its development. Antidopaminergic medication was the only to show statistically significant differences between patients who were catheterized for AUR and those who were not catheterized (85.3% versus 61.3%). Authors suggest that AUR might be a physiological phenomenon that is inherent to EOL setting for some people, especially those with poor performance status. Agar et al. described the side effects of anticholinergic load in the palliative care setting [ 11 ]. They found that anticholinergic load rises close to EOL, related to the need of symptom relief. Symptoms significantly associated to EOL were dry mouth, hard concentrating and decreasing performance status. In our study, delirium rates in AUR patients were high, with over 50% of AUR patients experiencing delirium. In most cases, delirium was resolved after bladder catheterization. Delirium is characterised by a disturbance of consciousness, cognition, and perception, with sudden start and fluctuating course. Its consequences are distressing for the patient and family, as well as frustrating and challenging for the medical team. Sometimes it is possible to find a relation between delirium episodes and drugs prescription, metabolic disturbances, or the cancer itself. Almost 50% of delirium episodes are reversible. Delirium is under-treated and poorly identified in many EOL cancer patients; however, it is possible to improve its recognition if strict clinical assessment is performed. AUR is an important condition to assess bedside at the onset of delirium [ 12 , 13 ]. No other published studies have, to our knowledge, described and compared the relationship between AUR and delirium in cancer patients at the EOL. The strength of the study lies in its clinical relevance and comprehensive approach investigating AUR in cancer patients at the EOL, a crucial aspect of symptom management in palliative care settings. By examining both the epidemiology of AUR and its association with delirium, the study offers a strong understanding of these issues, providing educational insights into the complex nature of symptom burden in this patient population. Despite the valuable insights provided by our study, several limitations warrant consideration. The retrospective nature of the study introduces inherent biases and limitations associated with data collection from electronic medical records. Additionally, the small sample size and single-center design restricts the generalizability of findings to other palliative care settings. Other limitations of the study include the examination of butylscopolamine as the only class of retention-causing medications. There was also a lack of data regarding delirium development in patients not suffering AUR. Conclusion This study describes AUR epidemiology, clinical features, and association with delirium in oncology patients at EOL. AUR is found to be a common problem at EOL, and its routine screening among patients suffering delirium in the PCU setting is warranted. AUR identification by physical examination is feasible, and its treatment is relatively simple. Training and improving recognition of symptoms and its causes in the palliative care setting by nurses and physicians may help improve symptom relief and comfort, the main goals in EOL care. Declarations 10. Disclosures. The authors of this article declare that there is no conflict of interest with respect to its publication. All the authors have participated in the study and have read and approved the manuscript. Likewise, we assume all the responsibility about it contents. 11. Funding. The authors of this article declare there was no funding involved in this study. 12. Acknowledgements. The authors of this manuscript express their gratitude to all the patients and their families at the Palliative Care Unit of Hospital General Universitario de Toledo. Author Contribution Conceived and designed the analysis: Miguel Borregón, Javier David Benítez Fuentes.Collected the data: Miguel Borregón, María Victoria Baeza, Inmaculada Raja, Elia Martínez. Contributed data or analysis tools: Miguel Borregón, Javier David Benítez Fuentes, Alejandro Moya-Martínez.Performed the analysis: Miguel Borregón, Javier David Benítez Fuentes.Wrote the paper: Miguel Borregón, Javier David Benítez Fuentes. Data Availability The study protocol was approved by the ethics committee of Hospital Virgen de la Salud de Toledo. All procedures performed in this study were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki and its subsequent amendments. Informed consent was waived due to the retrospective nature of the study, and patient data were anonymized to maintain confidentiality and privacy. References Singer PA, Martin DK, Kelner M. Quality end-of-life care: patients' perspectives. JAMA. 1999;281(2):163-168. doi:10.1001/jama.281.2.163. Lichter I, Hunt E. The last 48 hours of life. J Palliat Care. 1990;6(4):7-15. Hui D, dos Santos R, Chisholm GB, Bruera E. Symptom Expression in the Last Seven Days of Life Among Cancer Patients Admitted to Acute Palliative Care Units. J Pain Symptom Manage. 2015;50(4):488-494. doi:10.1016/j.jpainsymman.2014.09.003. Verhamme KM, Sturkenboom MC, Stricker BH, Bosch R. Drug-induced urinary retention: incidence, management and prevention. Drug Saf. 2008;31(5):373-388. doi:10.2165/00002018-200831050-00002. Kim S, Haider A, Reddy A, Bruera E. Management challenges at end-of-life in a patient with agitated delirium and benzodiazepine withdrawal at comprehensive cancer care center. Ann Palliat Med . 2021;10(6):6979-6983. doi:10.21037/apm-20-495 Fainsinger RL, MacEachern T, Hanson J, Bruera E. The use of urinary catheters in terminally ill cancer patients. J Pain Symptom Manage. 1992;7(6):333-338. doi:10.1016/0885-3924(92)90085-v. Gutmanis I, Shadd J, Woolmore-Goodwin S, Whitfield P, Byrne J, Faulds C. Prevalence and indications for bladder catheterization on a palliative care unit: a prospective, observational study. Palliat Med. 2014;28(10):1239-1240. doi:10.1177/0269216314536090. Currow DC, Stevenson JP, Abernethy AP, Plummer J, Shelby-James TM. Prescribing in palliative care as death approaches. J Am Geriatr Soc. 2007;55(4):590-595. doi:10.1111/j.1532-5415.2007.01124.x. Sera L, McPherson ML, Holmes HM. Commonly prescribed medications in a population of hospice patients. Am J Hosp Palliat Care. 2014;31(2):126-131. doi:10.1177/1049909113476132. Bergstra TG, Gutmanis I, Byrne J, et al. Urinary Retention and Medication Utilization on a Palliative Care Unit: A Retrospective Observational Study. J Pain Palliat Care Pharmacother. 2017;31(3-4):212-217. doi:10.1080/15360288.2017.1417951. Agar M, Currow D, Plummer J, Seidel R, Carnahan R, Abernethy AP. Changes in anticholinergic load from regular prescribed medications in palliative care as death approaches. Palliat Med. 2009;23(3):257-265. doi:10.1177/0269216309102528. Cobb JL, Glantz MJ, Nicholas PK, et al. Delirium in patients with cancer at the end of life. Cancer Pract. 2000;8(4):172-177. doi:10.1046/j.1523-5394.2000.84006.x. Centeno C, Vara F, Pérez P, Sanz A, Bruera E. Presentación clínica e identificación del delirium en el cáncer avanzado. Med Pal 2003; Vol. 10, pp. 24-35. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4447011","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":305243897,"identity":"340bc96b-217a-4934-af5d-d516b5c87775","order_by":0,"name":"Miguel Borregón","email":"data:image/png;base64,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","orcid":"","institution":"Hospital General Universitario de Elche","correspondingAuthor":true,"prefix":"","firstName":"Miguel","middleName":"","lastName":"Borregón","suffix":""},{"id":305243898,"identity":"60449240-d2bf-4b0a-b074-d654feea455d","order_by":1,"name":"Javier-David Benítez-Fuentes","email":"","orcid":"","institution":"Hospital General Universitario de Elche","correspondingAuthor":false,"prefix":"","firstName":"Javier-David","middleName":"","lastName":"Benítez-Fuentes","suffix":""},{"id":305243899,"identity":"5d46c6ee-2d12-4502-ab01-e76d52bc8cee","order_by":2,"name":"Alejandro Moya-Martínez","email":"","orcid":"","institution":"FISABIO. Hospital General Universitario de Elche","correspondingAuthor":false,"prefix":"","firstName":"Alejandro","middleName":"","lastName":"Moya-Martínez","suffix":""},{"id":305243901,"identity":"c5b60f95-3d2e-4c53-98bd-67f3bc626aea","order_by":3,"name":"María Victoria Baeza","email":"","orcid":"","institution":"Palliative Care service. Hospital General Universitario de Toledo","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"Victoria","lastName":"Baeza","suffix":""},{"id":305243904,"identity":"20cb8eed-9932-467b-9c40-4d8f8009575a","order_by":4,"name":"Inmaculada Raja","email":"","orcid":"","institution":"Palliative Care service. Hospital General Universitario de Toledo","correspondingAuthor":false,"prefix":"","firstName":"Inmaculada","middleName":"","lastName":"Raja","suffix":""},{"id":305243908,"identity":"ec47b8cf-b5fb-402a-bfc6-a9cd52b3483f","order_by":5,"name":"Elia Martínez","email":"","orcid":"","institution":"Medical oncology service. Hospital Universitario de Fuenlabrada","correspondingAuthor":false,"prefix":"","firstName":"Elia","middleName":"","lastName":"Martínez","suffix":""}],"badges":[],"createdAt":"2024-05-20 06:27:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4447011/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4447011/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57943197,"identity":"dd24b4e3-0052-420e-a686-d2c2045610d7","added_by":"auto","created_at":"2024-06-07 19:03:21","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103629,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDemographic characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAUR: acute urinary retention.\u003c/p\u003e\n\u003cp\u003eEOL: end-of-life.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4447011/v1/4af251d1cac71bdd7d8cfd65.jpg"},{"id":57943198,"identity":"9cc5ebea-37fc-4c97-a46a-cdf2aec12422","added_by":"auto","created_at":"2024-06-07 19:03:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":139250,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTumor characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAUR: acute urinary retention.\u003c/p\u003e\n\u003cp\u003eEOL: end-of-life situation.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4447011/v1/a58b8da598716deb7232086a.jpg"},{"id":57943193,"identity":"caa6fd6a-f70c-4101-8bac-2c3851e7fe97","added_by":"auto","created_at":"2024-06-07 19:03:18","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":81464,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical features.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAUR: acute urinary retention.\u003c/p\u003e\n\u003cp\u003eEOL: end-of-life situation.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4447011/v1/8efbe7bf91ad2c765d2d0c54.jpg"},{"id":57943201,"identity":"b348cfa1-586f-430f-a136-9ac9dbeb5f16","added_by":"auto","created_at":"2024-06-07 19:03:28","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":33180,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLogistic regression models for predicting factors associated with AUR patients.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAUR: acute urinary retention.\u003c/p\u003e\n\u003cp\u003eEOL: end-of-life situation.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4447011/v1/0192e29e3401c6881adb2ca2.jpg"},{"id":58970852,"identity":"5ee7730d-faf0-42f4-a17f-1568c18e4bd7","added_by":"auto","created_at":"2024-06-24 20:37:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":650295,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4447011/v1/09940bb2-a49a-405a-91d5-5d61b780ca17.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute urinary retention and delirium in end-of-life cancer patients.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAt the end of life (EOL), achieving optimal symptom control stands as a key goal for nurses, oncologists, and palliative care specialists [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This phase often presents a complex array of symptoms, rendering identification of underlying causes challenging. These symptoms not only contribute to physical discomfort but also significantly impact the patient’s overall quality of life. Among these challenges, acute urinary retention (AUR) emerges as a prevalent concern, influenced by different factors, including individual patient characteristics, cancer physiopathology, and medication profiles [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Drugs commonly prescribed for EOL management, such as opioids, benzodiazepines, anticholinergics, and antidepressants, are recognized for their potential to disrupt bladder function, predisposing patients to AUR [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAUR not only induces discomfort but may also be associated with delirium, further complicating the patient’s EOL clinical course [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite its clinical significance, literature addressing AUR in this context remains scarce, with limited studies exploring this phenomenon.\u003c/p\u003e \u003cp\u003eRecognizing the substantial burden of illness associated with AUR in EOL cancer patients, we studied its epidemiology and its relationship with delirium. Through our investigation, we studied the prevalence and clinical behaviour of AUR in EOL cancer patients, while also exploring its correlation with delirium, a critical aspect of symptom management in palliative care. By analyzing these complexities, our study seeks to provide valuable insights that could inform evidence-based practice and enhance the delivery of care to this vulnerable patient population.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003e We conducted a retrospective study of patients admitted to the cancer Palliative Care Unit (PCU) of Hospital Virgen de la Salud de Toledo, Spain, who presented EOL stage, between January and February 2018 (60 days). AUR epidemiology, clinical features and relationship with delirium were evaluated. EOL was defined as patients presenting with conditions ultimately leading to their demise during the hospital admission. Patients who did not meet this condition were excluded from the study. AUR diagnosis was confirmed based on clinical assessment derived from electronic medical records and defined as the inability to voluntarily urinate, or AUR concordant physical examination findings, coupled with the need for bladder catheterization to facilitate urination. The diagnosis of delirium was extracted from electronic medical records with consideration given to alterations in consciousness, cognition, and perception.\u003c/p\u003e\u003cp\u003eDescriptive statistics were employed to summarize demographic characteristics and clinical features. Between AUR patients, the Mann Whitney U test was used or the comparison of medians. Fisher’s test or the Chi-square test were used for the comparison of qualitative variables depending on its suitability. Logistic regression analysis was utilized to identify predictors associated with the development of AUR and AUR-associated delirium. Data analysis was performed using R statistical software, with significance levels set at p ˂ 0.05.\u003c/p\u003e\u003cp\u003e The study protocol was approved by the ethics committee of Hospital Virgen de la Salud de Toledo. All procedures performed in this study were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki and its subsequent amendments. Informed consent was waived due to the retrospective nature of the study, and patient data were anonymized to maintain confidentiality and privacy.\u003c/p\u003e\u003cp\u003eThis analysis and study have needed long time to see the light due to coronavirus pandemic logistic side effects. During the last years most of health resources in our hospital were focused on clinical activity instead of researching activity.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic, tumor, clinical and statistical models are presented in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e. During the period of data collection there were 51 new admissions in the PCU. These admissions accounted for a total of 48 unique patients, observing 3 instances of readmission, constituting 5.9% of the admissions. Most of patients, 39 (76.4%), had conditions ultimately leading to their demise during the hospital admission and were those included in the study. Among the EOL patients, 13 individuals (33.3%) experienced acute urinary retention (AUR), with a notable preponderance of male patients, 9 (69.2%). The mean age of patients presenting with AUR was 78.8 years, indicating an advanced age within this subgroup. The mean duration from admission to death was comparable between patients with AUR (10.2 days) and those without (10.3 days).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTumor-related data revealed a diverse spectrum of cancer types among patients experiencing AUR, with lung cancer being the most prevalent, 6 (46.1%), followed by kidney cancer, 2 (15.4%) patients, and colorectal cancer, 2 (15.4%) patients.\u003c/p\u003e \u003cp\u003ePhysical examination findings among patients with AUR revealed diverse degrees of bladder distention, with 8 (61.5%) patients presenting with a palpable distended bladder. Among these patients, the mean urine volume at the time of bladder catheterization was 536 cc. The mean survival duration from bladder catheterization to death was 3.1 days.\u003c/p\u003e \u003cp\u003eRegarding risk factors associated with AUR development, all patients who experienced AUR were being treated with butylscopolamine for secretions relief. Notably, a higher prevalence of AUR was observed among patients with lung cancer, 6 (46.1%), and distant metastases, 12 (92.3%).\u003c/p\u003e \u003cp\u003eDelirium emerged as a prevalent complication among patients with AUR, with 7 (53.8%) patients experiencing it at the time of AUR diagnosis. To note, a significant proportion, 5 (71.4%), of these patients demonstrated resolution of delirium following bladder catheterization. Data about delirium development were not collected for patients who did not experience AUR, highlighting a potential area for further investigation and comprehensive assessment in future studies.\u003c/p\u003e \u003cp\u003eSignificant differences between the comparison of patients experiencing AUR versus those without were not found. Regarding the logistic regression model, we introduced the sociodemographic variables and clinical variables. It was found that the variable age categorised by age under or equal to 73 years and over 73 years was a predictor for AUR development. The variable metastases was also included, as it behaves as a confounder in our model. The multivariate model explains that patients who are older than 73 years present 5.30 times more risk for AUR than patients with less than or equal to 73 years (p-value\u0026thinsp;=\u0026thinsp;0.036), with the influence of the variable metastases. Similarly, we can say that patients presenting metastases have a 6.79 times higher risk for belonging to the AUR group than patients without metastases (p-value\u0026thinsp;=\u0026thinsp;0.112), adjusted for the variable age. Although not significant, the variable metastases behaves as a confounding factor because it alters the age risk from 4.25 to 5.30.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this retrospective study seed light on the epidemiology and clinical characteristics of AUR in cancer patients presenting EOL, as well as its association with delirium. The observed prevalence of AUR (33.3%) among EOL cancer patients in our cohort is consistent with previous reports, indicating the significant burden of this condition in palliative care settings. The predominance of male patients experiencing AUR aligns with existing literature [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and the advanced mean age of patients presenting with AUR underscores the vulnerability of elderly cancer patients to urinary dysfunction at the EOL stage [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTumor-related data revealed a diverse distribution of cancer types among patients experiencing AUR, with lung cancer emerging as the most prevalent, along with a very high prevalence of distant metastases in AUR patients.\u003c/p\u003e \u003cp\u003eThe clinical assessment of AUR through physical examination identified palpable distended bladder in most patients, suggesting that this finding may serve as an important indicator necessitating prompt evaluation. Among patients presenting palpable distended bladder, mean volume of urine was more than 500 cc. Survival after bladder catheterisation was limited, indicating that AUR could be an early sign of short survival in this setting. The prevalence of bladder catheterization in PCU patients was first described by Fainsinger et al. with a 72% incidence rate [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Gutmanis et al. described an incidence rate of 57.5% and found that 69% patients presented with a poor performance status when bladder catheterization was performed. They also described the reasons for this catheterization, finding that the indication was AUR in 81% patients, energy preservation in 7.1%, and urinary tract infection in 4.8%. They describe a mean volume of urine at the time of catheter insertion was 561.7 cc for males and 657.4 cc for females [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the risk factors for the development of AUR were advanced age, butylscopolamine prescription, previous AUR episodes, lung cancer and presence of distant metastases.\u003c/p\u003e \u003cp\u003eSome studies have addressed the relation between polypharmacy and AUR. Currow et al. described that the average number of prescribed medications in the days preceding death in PCU patients was seven [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Sera et al. described that among cancer patients admitted to hospice, almost all patients received an opioid analgesic, and the majority received anticholinergics, benzodiazepines and antidopaminergics [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A retrospective case-control study carried in a PCU in Ontario, Canada, focuses on the medication prescription associated with AUR [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This study did not find the addition of different classes of AUR related medications increasing the risk for its development. Antidopaminergic medication was the only to show statistically significant differences between patients who were catheterized for AUR and those who were not catheterized (85.3% versus 61.3%). Authors suggest that AUR might be a physiological phenomenon that is inherent to EOL setting for some people, especially those with poor performance status. Agar et al. described the side effects of anticholinergic load in the palliative care setting [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. They found that anticholinergic load rises close to EOL, related to the need of symptom relief. Symptoms significantly associated to EOL were dry mouth, hard concentrating and decreasing performance status.\u003c/p\u003e \u003cp\u003eIn our study, delirium rates in AUR patients were high, with over 50% of AUR patients experiencing delirium. In most cases, delirium was resolved after bladder catheterization. Delirium is characterised by a disturbance of consciousness, cognition, and perception, with sudden start and fluctuating course. Its consequences are distressing for the patient and family, as well as frustrating and challenging for the medical team. Sometimes it is possible to find a relation between delirium episodes and drugs prescription, metabolic disturbances, or the cancer itself. Almost 50% of delirium episodes are reversible. Delirium is under-treated and poorly identified in many EOL cancer patients; however, it is possible to improve its recognition if strict clinical assessment is performed. AUR is an important condition to assess bedside at the onset of delirium [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNo other published studies have, to our knowledge, described and compared the relationship between AUR and delirium in cancer patients at the EOL. The strength of the study lies in its clinical relevance and comprehensive approach investigating AUR in cancer patients at the EOL, a crucial aspect of symptom management in palliative care settings. By examining both the epidemiology of AUR and its association with delirium, the study offers a strong understanding of these issues, providing educational insights into the complex nature of symptom burden in this patient population.\u003c/p\u003e \u003cp\u003eDespite the valuable insights provided by our study, several limitations warrant consideration. The retrospective nature of the study introduces inherent biases and limitations associated with data collection from electronic medical records. Additionally, the small sample size and single-center design restricts the generalizability of findings to other palliative care settings. Other limitations of the study include the examination of butylscopolamine as the only class of retention-causing medications. There was also a lack of data regarding delirium development in patients not suffering AUR.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study describes AUR epidemiology, clinical features, and association with delirium in oncology patients at EOL. AUR is found to be a common problem at EOL, and its routine screening among patients suffering delirium in the PCU setting is warranted. AUR identification by physical examination is feasible, and its treatment is relatively simple. Training and improving recognition of symptoms and its causes in the palliative care setting by nurses and physicians may help improve symptom relief and comfort, the main goals in EOL care. \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e10. Disclosures.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors of this article declare that there is no conflict of interest with respect to its publication. All the authors have participated in the study and have read and approved the manuscript. Likewise, we assume all the responsibility about it contents.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e11. Funding.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors of this article declare there was no funding involved in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e12. Acknowledgements.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors of this manuscript express their gratitude to all the patients and their families at the Palliative Care Unit of Hospital General Universitario de Toledo.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceived and designed the analysis: Miguel Borreg\u0026oacute;n, Javier David Ben\u0026iacute;tez Fuentes.Collected the data: Miguel Borreg\u0026oacute;n, Mar\u0026iacute;a Victoria Baeza, Inmaculada Raja, Elia Mart\u0026iacute;nez. Contributed data or analysis tools: Miguel Borreg\u0026oacute;n, Javier David Ben\u0026iacute;tez Fuentes, Alejandro Moya-Mart\u0026iacute;nez.Performed the analysis: Miguel Borreg\u0026oacute;n, Javier David Ben\u0026iacute;tez Fuentes.Wrote the paper: Miguel Borreg\u0026oacute;n, Javier David Ben\u0026iacute;tez Fuentes.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe study protocol was approved by the ethics committee of Hospital Virgen de la Salud de Toledo. All procedures performed in this study were conducted in accordance with the ethical standards outlined in the Declaration of Helsinki and its subsequent amendments. Informed consent was waived due to the retrospective nature of the study, and patient data were anonymized to maintain confidentiality and privacy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSinger PA, Martin DK, Kelner M. Quality end-of-life care: patients\u0026apos; perspectives. JAMA. 1999;281(2):163-168. doi:10.1001/jama.281.2.163. \u003c/li\u003e\n\u003cli\u003eLichter I, Hunt E. The last 48 hours of life. J Palliat Care. 1990;6(4):7-15.\u003c/li\u003e\n\u003cli\u003eHui D, dos Santos R, Chisholm GB, Bruera E. Symptom Expression in the Last Seven Days of Life Among Cancer Patients Admitted to Acute Palliative Care Units. J Pain Symptom Manage. 2015;50(4):488-494. doi:10.1016/j.jpainsymman.2014.09.003.\u003c/li\u003e\n\u003cli\u003eVerhamme KM, Sturkenboom MC, Stricker BH, Bosch R. Drug-induced urinary retention: incidence, management and prevention. Drug Saf. 2008;31(5):373-388. doi:10.2165/00002018-200831050-00002. \u003c/li\u003e\n\u003cli\u003eKim S, Haider A, Reddy A, Bruera E. Management challenges at end-of-life in a patient with agitated delirium and benzodiazepine withdrawal at comprehensive cancer care center. \u003cem\u003eAnn Palliat Med\u003c/em\u003e. 2021;10(6):6979-6983. doi:10.21037/apm-20-495\u003c/li\u003e\n\u003cli\u003eFainsinger RL, MacEachern T, Hanson J, Bruera E. The use of urinary catheters in terminally ill cancer patients. J Pain Symptom Manage. 1992;7(6):333-338. doi:10.1016/0885-3924(92)90085-v.\u003c/li\u003e\n\u003cli\u003eGutmanis I, Shadd J, Woolmore-Goodwin S, Whitfield P, Byrne J, Faulds C. Prevalence and indications for bladder catheterization on a palliative care unit: a prospective, observational study. Palliat Med. 2014;28(10):1239-1240. doi:10.1177/0269216314536090.\u003c/li\u003e\n\u003cli\u003eCurrow DC, Stevenson JP, Abernethy AP, Plummer J, Shelby-James TM. Prescribing in palliative care as death approaches. J Am Geriatr Soc. 2007;55(4):590-595. doi:10.1111/j.1532-5415.2007.01124.x.\u003c/li\u003e\n\u003cli\u003eSera L, McPherson ML, Holmes HM. Commonly prescribed medications in a population of hospice patients. Am J Hosp Palliat Care. 2014;31(2):126-131. doi:10.1177/1049909113476132.\u003c/li\u003e\n\u003cli\u003eBergstra TG, Gutmanis I, Byrne J, et al. Urinary Retention and Medication Utilization on a Palliative Care Unit: A Retrospective Observational Study. J Pain Palliat Care Pharmacother. 2017;31(3-4):212-217. doi:10.1080/15360288.2017.1417951.\u003c/li\u003e\n\u003cli\u003eAgar M, Currow D, Plummer J, Seidel R, Carnahan R, Abernethy AP. Changes in anticholinergic load from regular prescribed medications in palliative care as death approaches. Palliat Med. 2009;23(3):257-265. doi:10.1177/0269216309102528.\u003c/li\u003e\n\u003cli\u003eCobb JL, Glantz MJ, Nicholas PK, et al. Delirium in patients with cancer at the end of life. Cancer Pract. 2000;8(4):172-177. doi:10.1046/j.1523-5394.2000.84006.x.\u003c/li\u003e\n\u003cli\u003eCenteno C, Vara F, P\u0026eacute;rez P, Sanz A, Bruera E. Presentaci\u0026oacute;n cl\u0026iacute;nica e identificaci\u0026oacute;n del delirium en el c\u0026aacute;ncer avanzado. Med Pal 2003; Vol. 10, pp. 24-35.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"End-of-life, acute urinary retention, delirium, palliative care, cancer.","lastPublishedDoi":"10.21203/rs.3.rs-4447011/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4447011/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSymptom management at end-of-life (EOL) is crucial for nurses, oncologists, and palliative care providers. Acute urinary retention (AUR) is a common issue at EOL, often influenced by various factors including medications and underlying disease. Despite its significance, literature on AUR in EOL cancer patients remains limited, especially regarding its association with delirium.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included patients at EOL admitted to the Palliative Care Unit (PCU) of Hospital Virgen de la Salud de Toledo, Spain, between January and February 2018. EOL was defined as patients presenting with conditions ultimately leading to their demise during the hospital admission. AUR was confirmed based on clinical assessment from electronic medical records, defined as the inability to voluntarily urinate, or AUR concordant physical examination, and the need for bladder catheterization to urinate. We evaluated delirium clinically, considering altered consciousness, cognition, and perception. We used descriptive statistics to summarize demographic characteristics and clinical features. We employed a logistic regression analysis to identify predictors of AUR and AUR-associated delirium.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 51 new admissions, 39 (76.4%) were EOL patients, with 13 (33.3%) experiencing AUR. Patients with AUR were older (mean age 78.8 years) compared to those without AUR (mean age 71.5 years). AUR was associated with butylscopolamine use, advanced age, lung cancer, and distant metastases. Physical examination revealed palpable distended bladders in most AUR cases, with a mean urine volume of 536 cc at catheterization. Delirium was present in over 50% of AUR cases, resolving after catheterization in the majority.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eImproving recognition of AUR symptoms and causes in the EOL setting could improve patient relief and comfort.\u003c/p\u003e","manuscriptTitle":"Acute urinary retention and delirium in end-of-life cancer patients.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-07 19:03:05","doi":"10.21203/rs.3.rs-4447011/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e873c25-b71e-4ec4-a9fa-3385a219792c","owner":[],"postedDate":"June 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-24T20:29:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-07 19:03:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4447011","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4447011","identity":"rs-4447011","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}