Morphine Administration in the Emergency Department for Dyspnea at the End of Life

Morphine Administration in the Emergency Department for Dyspnea at the End of Life | 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 Morphine Administration in the Emergency Department for Dyspnea at the End of Life Asher Taragin, Asher Taragin, Avigail Bar Tikvah, Meir Frankel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8339033/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 Background Dyspnea is a common and distressing symptom at the end of life, particularly among patients with advanced cancer, heart failure, or chronic lung disease. Morphine, an opioid analgesic, is well established as an effective treatment for relieving dyspnea by modulating the central perception of breathlessness and reducing respiratory effort. However, despite strong evidence and clinical guidelines supporting its use, morphine remains underutilized in the Emergency Department (ED). Studies indicate that many terminally ill patients who could benefit from opioid therapy for dyspnea do not receive it, suggesting barriers related to clinician awareness, attitudes, and comfort with end-of-life care. This study investigates the patterns and determinants of morphine administration in the ED for dyspnea at the end of life and evaluates its association with patient outcomes. Methods A retrospective analysis done on a medical records database of dyspniac patients at the end-of-life adult patients admitted to ED at Shaare-Zedek Medical Center, Israel, between 2023–2024. Statistical analysis was performed on demographic and clinical characteristics of the entire cohort. Results 250 patients included in the research, mean age 83.2 ± 11.5 years, 51.2% female. 15.2% received morphine in the ED, while 68% eventually received morphine during hospitalization. Multivariate logistic regression identified lung cancer (OR = 3.413, p = 0.022), DNR status (OR = 3.173, p = 0.010), and pulse rate upon arrival (OR = 1.022, p = 0.008) as significant predictors of morphine administration in the ED. No significant difference in time to death was found between those who received morphine in the ED (mean = 231.95 hours) and those who did not (mean = 242.64 hours, p = 0.165). However, morphine use during hospitalization was associated with a significant extension in survival (mean = 282.20 hours vs. 152.35 hours, p < 0.001). Conclusions Morphine remains significantly underutilized in the emergency setting, with only 15.2% of terminally ill patients receiving this treatment. Factors such as lung cancer, DNR status, and vital signs influence morphine use in the ED. Although morphine in the ED did not impact time to death, its use during hospitalization was associated with a meaningful extension in survival time. Figures Figure 1 Background Dyspnea, or shortness of breath, is defined as “a subjective experience of breathing discomfort,” and is a strong predictor of mortality 1 . Dyspnea may be experienced as air hunger, difficulty in inhalation or exhalation, or a feeling of suffocation. It is highly prevalent in patients with advanced diseases such as cancer, heart failure, and chronic lung diseases-conditions that account for over 50% of all deaths in the United States 2 . Among patients with advanced cancer, dyspnea occurs in 50–70% of cases 2 , and in up to 90% of those with lung cancer. Similarly, 90% of patients with advanced pulmonary disease and 50% of those with heart failure suffer from significant dyspnea 2 . In these three patient groups, dyspnea is a severe and distressing symptom, especially in the final six months of life. Moreover, in the last three days of life, dyspnea occurs in up to 90% of patients 2 . Terminally ill patients are often unable to communicate the severity of their dyspnea, and many do not receive appropriate treatment for this distressing symptom. Opioids, particularly morphine, are effective in treating dyspnea through various mechanisms. Opioids act on opioid receptors in the central nervous system, reducing the responsiveness of the brainstem respiratory center, thereby relieving the sensation of dyspnea 3 . Opioids may also induce mild relaxation of airway smooth muscles and alleviate anxiety, a factor that frequently exacerbates dyspnea. When dyspnea is pain-related, opioids may also alleviate the discomfort by addressing the underlying pain 3 . Opioids, particularly intravenous morphine, are strongly recommended for managing dyspnea in terminal patients. Numerous medical associations-including the American Thoracic Society 1 , the European Respiratory Society 2 , and the National Hospice and Palliative Care Organization 4 -endorse this approach, emphasizing careful dosing to minimize the risk of respiratory depression. The suggested palliative dose is 2.5 mg IV, which may be repeated every 15–30 minutes if symptoms persist and can be doubled if needed 1 . There are no absolute contraindications for opioid use in terminal dyspnea. Despite these recommendations and morphine’s demonstrated effectiveness, it remains underutilized in hospital settings for dying patients. For instance, a 2018 retrospective study in Brazil involving 296 terminal patients (86% with cancer) found that although 77% experienced dyspnea, only 73% of these patients received morphine, with significantly higher use in oncology hospitals (85%) compared to general hospitals (15.5%) 5 . The goal of this study is to retrospectively evaluate the proportion of patients presenting to the Shaare Zedek Medical Center ED with dyspnea at end of life who received morphine during their ED stay, and to assess clinical or demographic factors associated with the decision to administer morphine. Methods Data were extracted from electronic medical records for patients presenting to the emergency department (ED) with dyspnea who subsequently died during the same hospitalization, similar to the cohort selection approach described by Morris and Galicia-Castillo 6 . Collected variables included demographics, comorbidities (e.g., CHF, COPD, lung cancer, metastatic cancer, CKD, pneumonia), clinical characteristics, laboratory values, vital signs on presentation, pain scores, DNR/I status, respiratory support, morphine administration (in the ED and/or during hospitalization), and time from ED arrival to death. Patients under 18 years of age, those without dyspnea as a presenting symptom, and those who survived to hospital discharge were excluded. The primary outcome was the proportion of patients who received morphine in the ED. Secondary outcomes included time to morphine administration, type of respiratory support, and morphine use during hospitalization. Univariate analyses were performed to identify variables associated with ED morphine use; significant predictors were then included in a multivariate logistic regression model, reported as odds ratios (OR) with 95% confidence intervals (CI). Survival outcomes were compared across three exposure groups—no morphine, morphine during hospitalization only, and morphine initiated in both the ED and hospitalization—using Kaplan–Meier analysis and log-rank testing. A Cox proportional hazards regression model was employed to identify independent predictors of mortality. Statistical significance was defined as p < 0.05. Ethical Considerations The study protocol was approved by the Institutional Ethics Committee (IRB) of Shaare Tzedek hospital, and the requirement for informed consent was waived by the committee due to the study's retrospective nature. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki. This work was performed in partial fulfillment of the requirements for the degree of Doctor of Medicine (M.D.) at the Jerusalem Faculty of Medicine. Results Study Population A total of 250 terminally ill patients presenting to the emergency department (ED) with dyspnea were included in the final analysis. The mean age at hospitalization was 83.2 years (SD = 11.5), and 51.2% of patients were female. The majority were of Jewish ethnicity (91.5%) and most arrived via ambulance (89.6%). Prevalent underlying diagnoses included congestive heart failure (CHF, 53.6%), chronic obstructive pulmonary disease (COPD, 19.6%), chronic kidney disease (CKD, 10.8%), and metastatic cancer (22%). Documented Do Not Resuscitate/Intubate (DNR/I) orders were present in 14.8% of cases. Morphine Administration Only 15.2% of patients (n = 38) received morphine during their ED stay, while 68% (n = 170) were administered morphine at some point during their hospitalization. The average time to morphine administration among ED recipients was 5.8 hours (SD = 4.3). Respiratory Support in the ED The vast majority of patients (87.4%) received respiratory support in the ED. Of these, 65.3% were treated with nasal cannula, 51.9% with high-flow nasal cannula (Optiflow), 38.4% with BIPAP, and 5.6% underwent endotracheal intubation. Univariate Analyses of Morphine Administration in the ED Patients with lung cancer were significantly more likely to receive morphine in the ED compared to those without lung cancer (36.4% vs. 13.2%, p = 0.004). A similar association was observed for patients with a DNR/I order, among whom 32.4% received morphine versus only 12.2% in those without a DNR/I (p = 0.002). No statistically significant differences were observed in morphine administration based on the presence of metastatic cancer ( p = 0.563), cancer of any type ( p = 0.166), CHF ( p = 0.058), COPD ( p = 0.805), CKD ( p = 0.234), pneumonia ( p = 0.730), or smoking status ( p = 0.092). Additionally, morphine use in the ED was not significantly associated with gender ( p = 0.610), ethnicity ( p = 0.521), or mode of arrival (ambulance vs. self-transport, p = 0.584). Patients who received morphine in the ED had a significantly higher mean pulse rate upon arrival compared to those who did not (109.8 bpm vs. 95.1 bpm, p = 0.001). No significant differences were found in age, systolic or diastolic blood pressure, temperature, or oxygen saturation. Multivariate Logistic Regression A multivariate logistic regression model was constructed to identify independent predictors of morphine administration in the ED. The model included lung cancer, DNR/I status, CHF, and initial pulse rate. Multivariate logistic regression analysis identified three independent predictors of morphine administration in the emergency department: lung cancer (OR = 3.41, 95% CI: 1.19–9.79, p = 0.022), DNR/I order (OR = 3.17, 95% CI: 1.32–7.64, p = 0.010), and pulse rate upon arrival (OR = 1.022 per beat increase, 95% CI: 1.006–1.039, p = 0.008). Congestive heart failure was not a significant predictor in the multivariable model (p = 0.484). The model demonstrated a Nagelkerke R² of 0.158 with an overall classification accuracy of 85.5%. Outcomes Survival Analysis Survival outcomes were compared between patients who received morphine during hospitalization ( n = 170) and those who did not ( n = 79). Kaplan–Meier survival analysis demonstrated a significant difference between the two groups (Log-Rank χ² = 13.208, df = 1, p < 0.001), as shown in Fig. 1 . Patients who received morphine during hospitalization had a longer mean survival time of 282.2 hours (95% CI: 225.5–338.9) and a median survival time of 159.0 hours (95% CI: 115.3–202.7), compared with a mean survival time of 152.4 hours (95% CI: 114.2–190.5) and a median survival time of 82.0 hours (95% CI: 48.1–115.9) among those who did not receive morphine. A multivariate Cox regression analysis of 237 patients identified five significant predictors of survival time to death. The strongest predictor was respiratory support requirement (HR = 3.67, 95% CI: 2.43–5.54, p < 0.001), indicating patients needing respiratory assistance had nearly four times higher risk of earlier death, Morphine administration during hospitalization was also significantly associated with survival (HR = 1.51, p = 0.005), indicating that patients who did not receive morphine had a higher likelihood of earlier death Additional predictors included age at hospitalization (HR = 1.02 per year, p = 0.004), higher pulse rate on arrival (HR = 1.009 per beat, p = 0.003), and higher diastolic blood pressure on arrival (HR = 0.98, p < 0.001). Discussion This study of 250 terminally ill patients represents the first to specifically examine morphine administration for dyspnea in the emergency department setting, as opposed to general morphine use throughout hospitalization, thereby yielding important insights into this critical acute phase of symptom management. The concerning underutilization of morphine for dyspnea management in the ED setting demonstrated here has significant implications for symptom relief in this vulnerable population. Morphine Underutilization in Emergency Care The main takeaway remains that morphine use is low in acute care settings where care is not primarily palliative. In our cohort, only 15.2% of patients received morphine during their ED stay, compared with 68% during hospitalization, highlighting a significant gap in symptom management in acute settings. This mirrors the findings of Stanzani et al.6, who reported similarly low rates of morphine use (15.5%) in general hospital settings. However, caution is needed when comparing these results, as Stanzani 5 focused on the last 24 hours of life and contrasted specialized palliative care hospitals, where morphine use was high, with general hospitals. Overall, these data suggest that in acute, non-palliative-focused settings, morphine remains underutilized for dyspnea management. 6 The American Thoracic Society emphasizes that dyspnea represents a multifaceted symptom requiring prompt recognition and intervention, particularly in terminally ill patients where symptom relief should be prioritized alongside diagnostic workup.¹ Johnson and Currow's 3 comprehensive review demonstrates that low-dose morphine (2.5-5mg oral equivalent every 4 hours) effectively reduces dyspnea intensity without clinically significant respiratory depression, making it particularly suitable for emergency settings. The significant underutilization found here in the ED, as well as the delayed initiation of morphine therapy (average 5.8 hours in the ED), suggest that emergency clinicians may be hesitant to initiate morphine therapy despite its established efficacy for breathlessness. This may represent missed opportunities for early symptom relief in patients experiencing significant respiratory distress during their initial acute presentation. Clinical Decision-Making Patterns The association between a lung cancer diagnosis and increased morphine administration (36.4% vs. 13.2%, p = 0.004) suggests that emergency physicians may be more comfortable prescribing opioids for patients with a clearly terminal or high-symptom burden diagnosis. This finding partially aligns with Stanzani et al. 5 , who reported frequent morphine use for cancer patients in oncology hospital settings. However, in their study, all patients were treated in oncology hospitals without distinguishing between cancer types, where care may generally be more oriented toward symptom relief and palliative management. In contrast, in our cohort, the increased use of morphine was specific to lung cancer, highlighting potential disparities in symptom management for patients with other life-limiting conditions presenting acutely to the emergency department. The significant association between DNR/I status and morphine administration (32.4% vs. 12.2%, p = 0.002 indicates a potential barrier where effective dyspnea treatment may be delayed or withheld for patients without established end-of-life care plans, despite similar symptom burden. Morphine for dyspnea should be considered primarily based on symptom severity rather than being reserved exclusively for end-of-life contexts. Physiological Markers and Treatment Decisions Patients with higher heart rates on arrival were more likely to receive morphine (109.8 vs. 95.1 bpm, p = 0.001). This makes sense, as tachycardia often reflects severe dyspnea and physiological stress, suggesting that these patients may have an even greater need for symptom relief. 1 Respiratory Support Utilization The high utilization of respiratory support interventions (87.4% of patients) demonstrates appropriate recognition of respiratory distress in this population. However, the physicians’ decisions to treat with mechanistic support alone overlooks the patient experience, and goes against current medical opinion, 5 which emphasize that morphine and respiratory support should be viewed as complementary rather than competing interventions.⁴ The integration of both approaches is optimal for patient comfort and clinical outcomes. Morphine Administration and Time to Death Azoulay et al.'s 7 analysis of hospice patients previously established a lack of significant association between opioid use and shortened survival. Similarly, Kawaguchi et al. 8 demonstrated that morphine therapy for refractory dyspnea, when appropriately administered, does not accelerate the dying process but rather provides necessary symptom relief. The current study expands this finding to a non-palliative setting. Moreover, it suggests that morphine administration during hospitalization may extend survival in patients with dyspnea at end of life. In our study, patients who received morphine during hospitalization had significantly longer survival compared with those who did not, with a mean survival of 282.2 hours versus 152.4 hours and a median survival of 159.0 versus 82.0 hours (Log-Rank χ² = 13.208, p < 0.001). Patients who began receiving morphine in the ED demonstrated intermediate survival outcomes, with no statistically significant difference compared to either the hospitalization-only group (χ² = 2.493, p = 0.114) or the no-morphine group (χ² = 1.948, p = 0.163). This lack of statistical significance may reflect the relatively small number of patients receiving morphine in the emergency setting (n = 38), which limits the power to detect potentially clinically meaningful differences. The multivariate Cox regression analysis showed that morphine administration during hospitalization was independently associated with prolonged survival (HR = 1.51, p = 0.005), even after adjusting for key predictors such as respiratory support, which itself was strongly associated with increased mortality (HR = 3.67, p < 0.001). These findings demonstrate a significant extension of life associated with morphine administration that challenges traditional concerns about opioid use in end-of-life care. More particularly, it contrasts with the lower administration rates in the absence of a DNR/I order in this study, which suggest that such concerns still influence clinical practice. Clinical and Ethical Implications Perhaps most importantly, these findings have profound implications for clinical practice, particularly for physicians who may hesitate to prescribe morphine due to concerns about hastening death. Our results demonstrate that morphine administration in patients at the end of life is associated with prolonged rather than shortened survival, providing reassurance that appropriate symptom management aligns with life-preserving rather than life-limiting care. This distinction is especially significant where religious or cultural considerations, including prohibitions against actions that might shorten life, influence treatment decisions. Physicians can thus approach morphine therapy for dyspnea at the end of life with greater confidence, hopefully bridging the gap of underutilization demonstrated here. Study Limitations and Future Directions The primary limitations of this study are its retrospective design and number of patients. The retrospective design limits our ability to assess symptom severity or patient-reported outcomes, which are crucial for evaluating dyspnea management effectiveness and patient comfort, and would shed light on the relationship between symptom burden and treatment decisions. Additionally, the study population's predominantly elderly, Jewish demographic may limit generalizability. The relatively small number of patients receiving ED morphine (n = 38) significantly limited our ability to detect potential survival benefits in this subgroup, as acknowledged in our statistical analysis, inviting future investigation with a larger cohort. Conclusion This study reveals significant opportunities for improving morphine utilization in emergency dyspnea management for terminally ill patients. While clinical decision-making appropriately considers patient diagnosis and goals of care, the overall low utilization rate suggests that many patients may be experiencing suboptimal symptom relief. Enhanced education, protocol development, and early palliative care integration could improve outcomes for this vulnerable population presenting with one of medicine's most distressing symptoms. References Parshall MB, Schwartzstein RM, Adams L et al (2012) An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 185(4):435–452. 10.1164/rccm.201111-2042ST Baker Rogers J, Modi P, Minteer JF (2024) Dyspnea in Palliative Care Johnson MJ, Currow DC (2020) Opioids for breathlessness: a narrative review. BMJ Support Palliat Care 10(3):287–295. 10.1136/bmjspcare-2020-002314 National Hospice and Palliative Care Organization Dyspnea at End-of-Life. Fast Fact #54. National Hospice and Palliative Care Organization Stanzani LZL, Marques M, Martins M, Vieira W, Amorim F, Carvalho R (2021) Morphine use in the treatment of dyspnea in terminally ill patients. Clinical Problems. European Respiratory Society, p PA3135. doi: 10.1183/13993003.congress-2021.PA3135 Morris D, Galicia-Castillo M (2017) Dying With Dyspnea in the Hospital. Am J Hosp Palliat Care 34(2):132–134. 10.1177/1049909115604140 Azoulay D, Jacobs JM, Cialic R, Mor EE, Stessman J (2011) Opioids, survival, and advanced cancer in the hospice setting. J Am Med Dir Assoc 12(2):129–134. 10.1016/j.jamda.2010.07.012 Kawaguchi J, Hamatani Y, Hirayama A et al (2020) Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients. J Cardiol 75(6):682–688. 10.1016/j.jjcc.2019.12.015 Tables Table 1. Patient Characteristics and Clinical Frequencies (N = 250) Characteristic Category Frequency (n) Valid Percent (%) Gender Female 128 51.2 Male 122 48.8 Ethnicity Not Jewish 20 8.5 Jewish 215 91.5 Way of Arrival Ambulance 224 89.6 Independently 26 10.4 Chronic Heart Failure (CHF) Yes 134 53.6 Chronic Obstructive Pulmonary Disease (COPD) Yes 49 19.6 Chronic Kidney Disease (CKD) Yes 27 10.8 Lung Cancer Yes 22 8.8 Metastatic Cancer Yes 55 22.0 Cancer (Any Type) Yes 75 30.0 Do Not Resuscitate (DNR/I) Yes 37 14.8 Smoking Status Smoker 95 38.6 Table 2. Patient Characteristics by Morphine Administration in the Emergency Department Characteristic No Morphine (n=212) Morphine (n=38) Total (N=250) p-value Age (years), mean ± SD 83.36 ± 11.53 82.11 ± 11.17 83.19 ± 11.47 0.534ᵃ Gender, n (%) 0.608ᵇ • Female 110 (85.9) 18 (14.1) 128 (51.2) • Male 102 (83.6) 20 (16.4) 122 (48.8) Ethnicity, n (%) 0.520ᵇ • Jewish 182 (84.7) 33 (15.3) 215 (91.5) • Not Jewish 18 (90.0) 2 (10.0) 20 (8.5) Way of Arrival, n (%) 0.583ᵇ • Ambulance 189 (84.4) 35 (15.6) 224 (89.6) • Independently 23 (88.5) 3 (11.5) 26 (10.4) Vital Signs on Arrival Systolic BP (mmHg), mean ± SD 116.86 ± 26.72 111.66 ± 28.38 116.10 ± 26.99 0.292ᵃ Diastolic BP (mmHg), mean ± SD 67.37 ± 14.10 71.43 ± 18.31 67.93 ± 14.77 0.134ᵃ Pulse (bpm), mean ± SD 95.08 ± 22.50 109.78 ± 26.50 97.30 ± 23.77 0.001 ᵃ Temperature (°C), mean ± SD 37.27 ± 1.07 37.33 ± 1.55 37.28 ± 1.15 0.808ᵃ Oxygen saturation (%), mean ± SD 90.25 ± 8.49 89.89 ± 6.61 90.19 ± 8.24 0.808ᵃ Comorbidities CHF, n (%) 119 (88.8) 15 (11.2) 134 (53.6) 0.058ᵇ COPD, n (%) 41 (83.7) 8 (16.3) 49 (19.6) 0.806ᵇ CKD, n (%) 25 (92.6) 2 (7.4) 27 (10.8) 0.232ᵇ Cancer Status Any cancer, n (%) 60 (80.0) 15 (20.0) 75 (30.0) 0.166ᵇ Lung cancer, n (%) 14 (63.6) 8 (36.4) 22 (8.8) 0.004 ᵇ Metastatic cancer, n (%) 48 (87.3) 7 (12.7) 55 (22.0) 0.563ᵇ Clinical Status DNR/DNI, n (%) 25 (67.6) 12 (32.4) 37 (14.8) 0.002 ᵇ Smoking, n (%) 0.092ᵇ • Non-smoker 125 (81.7) 28 (18.3) 153 (61.4) • Smoker 86 (89.6) 10 (10.4) 96 (38.6) Pneumonia, n (%) 94 (83.9) 18 (16.1) 112 (44.8) 0.730ᵇ Table 3. Comparison of Survival Outcomes by Morphine Administration Variable Morphine in ER Morphine During Hospitalization No Yes No Yes Mean (hours to death) 242.64 231.95 152.35 282.20 Median (hours to death) 144.00 122.00 82.00 160.00 Standard deviation 332.25 332.52 172.81 377.15 Minimum (hours) 3 6 3 6 Maximum (hours) 2874 1266 739 2874 N (patients) 211 38 79 170 Table 4. Mann–Whitney Test Results for Survival Differences Grouping Variable N (No) N (Yes) Mann–Whitney U Z p-value (2-tailed) Morphine in ER 211 38 3441.000 -1.390 0.165 Morphine During Hospitalization 79 170 4807.500 -3.606 <0.001 Notes Data presented as mean ± SD for continuous variables and n (%) for categorical variables. Percentages for morphine groups represent within-group (row) percentages. ᵃ Independent-samples t-test. ᵇ Pearson chi-square test or Fisher’s exact test as appropriate. DNR/DNI = Do Not Resuscitate / Do Not Intubate; COPD = Chronic Obstructive Pulmonary Disease; BP = Blood Pressure. 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1","display":"","copyAsset":false,"role":"figure","size":19892,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves comparing cumulative survival (hours to death) between patients who received morphine during hospitalization (red line) and those who did not (blue line). Patients treated with morphine demonstrated prolonged survival (\u003cem\u003eLog-Rank χ² = 13.208, p \u0026lt; 0.001\u003c/em\u003e).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8339033/v1/f26498b15666999922fff28f.png"},{"id":99797721,"identity":"9a89b97f-5d60-4aea-947c-84f0f9294f6f","added_by":"auto","created_at":"2026-01-08 13:46:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":998014,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8339033/v1/2165184e-c119-4618-9648-6de56d81a675.pdf"},{"id":98758642,"identity":"9d405cf0-9d03-465f-b18e-44c350f26dfd","added_by":"auto","created_at":"2025-12-22 09:40:33","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":471980,"visible":true,"origin":"","legend":"","description":"","filename":"COIallauthorsformAsher.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8339033/v1/38003e1b41afa9e7fc7a787b.pdf"}],"financialInterests":"","formattedTitle":"Morphine Administration in the Emergency Department for Dyspnea at the End of Life","fulltext":[{"header":"Background","content":"\u003cp\u003eDyspnea, or shortness of breath, is defined as \u0026ldquo;a subjective experience of breathing discomfort,\u0026rdquo; and is a strong predictor of mortality\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Dyspnea may be experienced as air hunger, difficulty in inhalation or exhalation, or a feeling of suffocation. It is highly prevalent in patients with advanced diseases such as cancer, heart failure, and chronic lung diseases-conditions that account for over 50% of all deaths in the United States\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong patients with advanced cancer, dyspnea occurs in 50\u0026ndash;70% of cases\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, and in up to 90% of those with lung cancer. Similarly, 90% of patients with advanced pulmonary disease and 50% of those with heart failure suffer from significant dyspnea\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. In these three patient groups, dyspnea is a severe and distressing symptom, especially in the final six months of life. Moreover, in the last three days of life, dyspnea occurs in up to 90% of patients\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Terminally ill patients are often unable to communicate the severity of their dyspnea, and many do not receive appropriate treatment for this distressing symptom.\u003c/p\u003e \u003cp\u003eOpioids, particularly morphine, are effective in treating dyspnea through various mechanisms. Opioids act on opioid receptors in the central nervous system, reducing the responsiveness of the brainstem respiratory center, thereby relieving the sensation of dyspnea\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Opioids may also induce mild relaxation of airway smooth muscles and alleviate anxiety, a factor that frequently exacerbates dyspnea. When dyspnea is pain-related, opioids may also alleviate the discomfort by addressing the underlying pain\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOpioids, particularly intravenous morphine, are strongly recommended for managing dyspnea in terminal patients. Numerous medical associations-including the American Thoracic Society\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, the European Respiratory Society\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, and the National Hospice and Palliative Care Organization\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e-endorse this approach, emphasizing careful dosing to minimize the risk of respiratory depression. The suggested palliative dose is 2.5 mg IV, which may be repeated every 15\u0026ndash;30 minutes if symptoms persist and can be doubled if needed \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. There are no absolute contraindications for opioid use in terminal dyspnea.\u003c/p\u003e \u003cp\u003eDespite these recommendations and morphine\u0026rsquo;s demonstrated effectiveness, it remains underutilized in hospital settings for dying patients. For instance, a 2018 retrospective study in Brazil involving 296 terminal patients (86% with cancer) found that although 77% experienced dyspnea, only 73% of these patients received morphine, with significantly higher use in oncology hospitals (85%) compared to general hospitals (15.5%)\u003csup\u003e5\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe goal of this study is to retrospectively evaluate the proportion of patients presenting to the Shaare Zedek Medical Center ED with dyspnea at end of life who received morphine during their ED stay, and to assess clinical or demographic factors associated with the decision to administer morphine.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eData were extracted from electronic medical records for patients presenting to the emergency department (ED) with dyspnea who subsequently died during the same hospitalization, similar to the cohort selection approach described by Morris and Galicia-Castillo\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Collected variables included demographics, comorbidities (e.g., CHF, COPD, lung cancer, metastatic cancer, CKD, pneumonia), clinical characteristics, laboratory values, vital signs on presentation, pain scores, DNR/I status, respiratory support, morphine administration (in the ED and/or during hospitalization), and time from ED arrival to death. Patients under 18 years of age, those without dyspnea as a presenting symptom, and those who survived to hospital discharge were excluded.\u003c/p\u003e \u003cp\u003eThe primary outcome was the proportion of patients who received morphine in the ED. Secondary outcomes included time to morphine administration, type of respiratory support, and morphine use during hospitalization. Univariate analyses were performed to identify variables associated with ED morphine use; significant predictors were then included in a multivariate logistic regression model, reported as odds ratios (OR) with 95% confidence intervals (CI). Survival outcomes were compared across three exposure groups\u0026mdash;no morphine, morphine during hospitalization only, and morphine initiated in both the ED and hospitalization\u0026mdash;using Kaplan\u0026ndash;Meier analysis and log-rank testing. A Cox proportional hazards regression model was employed to identify independent predictors of mortality. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthical Considerations\u003c/h2\u003e \u003cp\u003e The study protocol was approved by the Institutional Ethics Committee (IRB) of Shaare Tzedek hospital, and the requirement for informed consent was waived by the committee due to the study's retrospective nature. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eThis work was performed in partial fulfillment of the requirements for the degree of Doctor of Medicine (M.D.) at the Jerusalem Faculty of Medicine.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eA total of 250 terminally ill patients presenting to the emergency department (ED) with dyspnea were included in the final analysis. The mean age at hospitalization was 83.2 years (SD\u0026thinsp;=\u0026thinsp;11.5), and 51.2% of patients were female. The majority were of Jewish ethnicity (91.5%) and most arrived via ambulance (89.6%).\u003c/p\u003e \u003cp\u003ePrevalent underlying diagnoses included congestive heart failure (CHF, 53.6%), chronic obstructive pulmonary disease (COPD, 19.6%), chronic kidney disease (CKD, 10.8%), and metastatic cancer (22%). Documented Do Not Resuscitate/Intubate (DNR/I) orders were present in 14.8% of cases.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMorphine Administration\u003c/h3\u003e\n\u003cp\u003eOnly 15.2% of patients (n\u0026thinsp;=\u0026thinsp;38) received morphine during their ED stay, while 68% (n\u0026thinsp;=\u0026thinsp;170) were administered morphine at some point during their hospitalization. The average time to morphine administration among ED recipients was 5.8 hours (SD\u0026thinsp;=\u0026thinsp;4.3).\u003c/p\u003e\n\u003ch3\u003eRespiratory Support in the ED\u003c/h3\u003e\n\u003cp\u003eThe vast majority of patients (87.4%) received respiratory support in the ED. Of these, 65.3% were treated with nasal cannula, 51.9% with high-flow nasal cannula (Optiflow), 38.4% with BIPAP, and 5.6% underwent endotracheal intubation.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate Analyses of Morphine Administration in the ED\u003c/h2\u003e \u003cp\u003ePatients with lung cancer were significantly more likely to receive morphine in the ED compared to those without lung cancer (36.4% vs. 13.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). A similar association was observed for patients with a DNR/I order, among whom 32.4% received morphine versus only 12.2% in those without a DNR/I (p\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e \u003cp\u003eNo statistically significant differences were observed in morphine administration based on the presence of metastatic cancer (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.563), cancer of any type (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.166), CHF (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.058), COPD (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.805), CKD (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.234), pneumonia (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.730), or smoking status (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.092). Additionally, morphine use in the ED was not significantly associated with gender (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.610), ethnicity (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.521), or mode of arrival (ambulance vs. self-transport, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.584).\u003c/p\u003e \u003cp\u003ePatients who received morphine in the ED had a significantly higher mean pulse rate upon arrival compared to those who did not (109.8 bpm vs. 95.1 bpm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). No significant differences were found in age, systolic or diastolic blood pressure, temperature, or oxygen saturation.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMultivariate Logistic Regression\u003c/h3\u003e\n\u003cp\u003eA multivariate logistic regression model was constructed to identify independent predictors of morphine administration in the ED. The model included lung cancer, DNR/I status, CHF, and initial pulse rate. Multivariate logistic regression analysis identified three independent predictors of morphine administration in the emergency department: lung cancer (OR\u0026thinsp;=\u0026thinsp;3.41, 95% CI: 1.19\u0026ndash;9.79, p\u0026thinsp;=\u0026thinsp;0.022), DNR/I order (OR\u0026thinsp;=\u0026thinsp;3.17, 95% CI: 1.32\u0026ndash;7.64, p\u0026thinsp;=\u0026thinsp;0.010), and pulse rate upon arrival (OR\u0026thinsp;=\u0026thinsp;1.022 per beat increase, 95% CI: 1.006\u0026ndash;1.039, p\u0026thinsp;=\u0026thinsp;0.008). Congestive heart failure was not a significant predictor in the multivariable model (p\u0026thinsp;=\u0026thinsp;0.484). The model demonstrated a Nagelkerke R\u0026sup2; of 0.158 with an overall classification accuracy of 85.5%.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurvival Analysis\u003c/h2\u003e \u003cp\u003eSurvival outcomes were compared between patients who received morphine during hospitalization (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;170) and those who did not (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;79). Kaplan\u0026ndash;Meier survival analysis demonstrated a significant difference between the two groups (Log-Rank χ\u0026sup2; = 13.208, \u003cem\u003edf\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients who received morphine during hospitalization had a longer mean survival time of 282.2 hours (95% CI: 225.5\u0026ndash;338.9) and a median survival time of 159.0 hours (95% CI: 115.3\u0026ndash;202.7), compared with a mean survival time of 152.4 hours (95% CI: 114.2\u0026ndash;190.5) and a median survival time of 82.0 hours (95% CI: 48.1\u0026ndash;115.9) among those who did not receive morphine.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA multivariate Cox regression analysis of 237 patients identified five significant predictors of survival time to death. The strongest predictor was respiratory support requirement (HR\u0026thinsp;=\u0026thinsp;3.67, 95% CI: 2.43\u0026ndash;5.54, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating patients needing respiratory assistance had nearly four times higher risk of earlier death, Morphine administration during hospitalization was also significantly associated with survival (HR\u0026thinsp;=\u0026thinsp;1.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), indicating that patients who did not receive morphine had a higher likelihood of earlier death Additional predictors included age at hospitalization (HR\u0026thinsp;=\u0026thinsp;1.02 per year, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), higher pulse rate on arrival (HR\u0026thinsp;=\u0026thinsp;1.009 per beat, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), and higher diastolic blood pressure on arrival (HR\u0026thinsp;=\u0026thinsp;0.98, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study of 250 terminally ill patients represents the first to specifically examine morphine administration for dyspnea in the emergency department setting, as opposed to general morphine use throughout hospitalization, thereby yielding important insights into this critical acute phase of symptom management. The concerning underutilization of morphine for dyspnea management in the ED setting demonstrated here has significant implications for symptom relief in this vulnerable population.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMorphine Underutilization in Emergency Care\u003c/h2\u003e \u003cp\u003eThe main takeaway remains that morphine use is low in acute care settings where care is not primarily palliative. In our cohort, only 15.2% of patients received morphine during their ED stay, compared with 68% during hospitalization, highlighting a significant gap in symptom management in acute settings. This mirrors the findings of Stanzani et al.6, who reported similarly low rates of morphine use (15.5%) in general hospital settings. However, caution is needed when comparing these results, as Stanzani\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e focused on the last 24 hours of life and contrasted specialized palliative care hospitals, where morphine use was high, with general hospitals. Overall, these data suggest that in acute, non-palliative-focused settings, morphine remains underutilized for dyspnea management.\u003c/p\u003e \u003cp\u003e \u003csup\u003e6\u003c/sup\u003eThe American Thoracic Society emphasizes that dyspnea represents a multifaceted symptom requiring prompt recognition and intervention, particularly in terminally ill patients where symptom relief should be prioritized alongside diagnostic workup.\u0026sup1; Johnson and Currow's\u003csup\u003e3\u003c/sup\u003e comprehensive review demonstrates that low-dose morphine (2.5-5mg oral equivalent every 4 hours) effectively reduces dyspnea intensity without clinically significant respiratory depression, making it particularly suitable for emergency settings. The significant underutilization found here in the ED, as well as the delayed initiation of morphine therapy (average 5.8 hours in the ED), suggest that emergency clinicians may be hesitant to initiate morphine therapy despite its established efficacy for breathlessness. This may represent missed opportunities for early symptom relief in patients experiencing significant respiratory distress during their initial acute presentation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eClinical Decision-Making Patterns\u003c/h2\u003e \u003cp\u003eThe association between a lung cancer diagnosis and increased morphine administration (36.4% vs. 13.2%, p\u0026thinsp;=\u0026thinsp;0.004) suggests that emergency physicians may be more comfortable prescribing opioids for patients with a clearly terminal or high-symptom burden diagnosis. This finding partially aligns with Stanzani et al.\u003csup\u003e5\u003c/sup\u003e, who reported frequent morphine use for cancer patients in oncology hospital settings. However, in their study, all patients were treated in oncology hospitals without distinguishing between cancer types, where care may generally be more oriented toward symptom relief and palliative management. In contrast, in our cohort, the increased use of morphine was specific to lung cancer, highlighting potential disparities in symptom management for patients with other life-limiting conditions presenting acutely to the emergency department.\u003c/p\u003e \u003cp\u003eThe significant association between DNR/I status and morphine administration (32.4% vs. 12.2%, p\u0026thinsp;=\u0026thinsp;0.002 indicates a potential barrier where effective dyspnea treatment may be delayed or withheld for patients without established end-of-life care plans, despite similar symptom burden. Morphine for dyspnea should be considered primarily based on symptom severity rather than being reserved exclusively for end-of-life contexts.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePhysiological Markers and Treatment Decisions\u003c/h2\u003e \u003cp\u003ePatients with higher heart rates on arrival were more likely to receive morphine (109.8 vs. 95.1 bpm, p\u0026thinsp;=\u0026thinsp;0.001). This makes sense, as tachycardia often reflects severe dyspnea and physiological stress, suggesting that these patients may have an even greater need for symptom relief.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRespiratory Support Utilization\u003c/h2\u003e \u003cp\u003eThe high utilization of respiratory support interventions (87.4% of patients) demonstrates appropriate recognition of respiratory distress in this population. However, the physicians\u0026rsquo; decisions to treat with mechanistic support alone overlooks the patient experience, and goes against current medical opinion,\u003csup\u003e5\u003c/sup\u003e which emphasize that morphine and respiratory support should be viewed as complementary rather than competing interventions.⁴ The integration of both approaches is optimal for patient comfort and clinical outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMorphine Administration and Time to Death\u003c/h2\u003e \u003cp\u003eAzoulay et al.'s\u003csup\u003e7\u003c/sup\u003e analysis of hospice patients previously established a lack of significant association between opioid use and shortened survival. Similarly, Kawaguchi \u003cem\u003eet al.\u003c/em\u003e\u003csup\u003e8\u003c/sup\u003e demonstrated that morphine therapy for refractory dyspnea, when appropriately administered, does not accelerate the dying process but rather provides necessary symptom relief. The current study expands this finding to a non-palliative setting. Moreover, it suggests that morphine administration during hospitalization may extend survival in patients with dyspnea at end of life. In our study, patients who received morphine during hospitalization had significantly longer survival compared with those who did not, with a mean survival of 282.2 hours versus 152.4 hours and a median survival of 159.0 versus 82.0 hours (Log-Rank χ\u0026sup2; = 13.208, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients who began receiving morphine in the ED demonstrated intermediate survival outcomes, with no statistically significant difference compared to either the hospitalization-only group (χ\u0026sup2; = 2.493, p\u0026thinsp;=\u0026thinsp;0.114) or the no-morphine group (χ\u0026sup2; = 1.948, p\u0026thinsp;=\u0026thinsp;0.163). This lack of statistical significance may reflect the relatively small number of patients receiving morphine in the emergency setting (n\u0026thinsp;=\u0026thinsp;38), which limits the power to detect potentially clinically meaningful differences.\u003c/p\u003e \u003cp\u003eThe multivariate Cox regression analysis showed that morphine administration during hospitalization was independently associated with prolonged survival (HR\u0026thinsp;=\u0026thinsp;1.51, p\u0026thinsp;=\u0026thinsp;0.005), even after adjusting for key predictors such as respiratory support, which itself was strongly associated with increased mortality (HR\u0026thinsp;=\u0026thinsp;3.67, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These findings demonstrate a significant extension of life associated with morphine administration that challenges traditional concerns about opioid use in end-of-life care. More particularly, it contrasts with the lower administration rates in the absence of a DNR/I order in this study, which suggest that such concerns still influence clinical practice.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Ethical Implications\u003c/h2\u003e \u003cp\u003ePerhaps most importantly, these findings have profound implications for clinical practice, particularly for physicians who may hesitate to prescribe morphine due to concerns about hastening death. Our results demonstrate that morphine administration in patients at the end of life is associated with prolonged rather than shortened survival, providing reassurance that appropriate symptom management aligns with life-preserving rather than life-limiting care. This distinction is especially significant where religious or cultural considerations, including prohibitions against actions that might shorten life, influence treatment decisions. Physicians can thus approach morphine therapy for dyspnea at the end of life with greater confidence, hopefully bridging the gap of underutilization demonstrated here.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitations and Future Directions\u003c/h2\u003e \u003cp\u003eThe primary limitations of this study are its retrospective design and number of patients. The retrospective design limits our ability to assess symptom severity or patient-reported outcomes, which are crucial for evaluating dyspnea management effectiveness and patient comfort, and would shed light on the relationship between symptom burden and treatment decisions. Additionally, the study population's predominantly elderly, Jewish demographic may limit generalizability. The relatively small number of patients receiving ED morphine (n\u0026thinsp;=\u0026thinsp;38) significantly limited our ability to detect potential survival benefits in this subgroup, as acknowledged in our statistical analysis, inviting future investigation with a larger cohort.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study reveals significant opportunities for improving morphine utilization in emergency dyspnea management for terminally ill patients. While clinical decision-making appropriately considers patient diagnosis and goals of care, the overall low utilization rate suggests that many patients may be experiencing suboptimal symptom relief. Enhanced education, protocol development, and early palliative care integration could improve outcomes for this vulnerable population presenting with one of medicine's most distressing symptoms.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eParshall MB, Schwartzstein RM, Adams L et al (2012) An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 185(4):435\u0026ndash;452. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/rccm.201111-2042ST\u003c/span\u003e\u003cspan address=\"10.1164/rccm.201111-2042ST\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker Rogers J, Modi P, Minteer JF (2024) \u003cem\u003eDyspnea in Palliative Care\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson MJ, Currow DC (2020) Opioids for breathlessness: a narrative review. BMJ Support Palliat Care 10(3):287\u0026ndash;295. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjspcare-2020-002314\u003c/span\u003e\u003cspan address=\"10.1136/bmjspcare-2020-002314\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Hospice and Palliative Care Organization Dyspnea at End-of-Life. Fast Fact #54. National Hospice and Palliative Care Organization\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStanzani LZL, Marques M, Martins M, Vieira W, Amorim F, Carvalho R (2021) Morphine use in the treatment of dyspnea in terminally ill patients. Clinical Problems. European Respiratory Society, p PA3135. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1183/13993003.congress-2021.PA3135\u003c/span\u003e\u003cspan address=\"10.1183/13993003.congress-2021.PA3135\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorris D, Galicia-Castillo M (2017) Dying With Dyspnea in the Hospital. Am J Hosp Palliat Care 34(2):132\u0026ndash;134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1049909115604140\u003c/span\u003e\u003cspan address=\"10.1177/1049909115604140\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzoulay D, Jacobs JM, Cialic R, Mor EE, Stessman J (2011) Opioids, survival, and advanced cancer in the hospice setting. J Am Med Dir Assoc 12(2):129\u0026ndash;134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jamda.2010.07.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jamda.2010.07.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawaguchi J, Hamatani Y, Hirayama A et al (2020) Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients. J Cardiol 75(6):682\u0026ndash;688. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jjcc.2019.12.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jjcc.2019.12.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patient Characteristics and Clinical Frequencies (N = 250)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eValid Percent (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e51.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e48.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNot Jewish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eJewish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e91.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWay of Arrival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAmbulance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e89.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIndependently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic Heart Failure (CHF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e53.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic Obstructive Pulmonary Disease (COPD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic Kidney Disease (CKD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLung Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMetastatic Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCancer (Any Type)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDo Not Resuscitate (DNR/I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSmoking Status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSmoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Patient Characteristics by Morphine Administration in the Emergency Department\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Morphine (n=212)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphine (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (N=250)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years), mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e83.36 \u0026plusmn; 11.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e82.11 \u0026plusmn; 11.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e83.19 \u0026plusmn; 11.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.534ᵃ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.608ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e110 (85.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e128 (51.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e102 (83.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e122 (48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.520ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Jewish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e182 (84.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e215 (91.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Not Jewish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWay of Arrival, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.583ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Ambulance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e189 (84.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e224 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (88.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVital Signs on Arrival\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSystolic BP (mmHg), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e116.86 \u0026plusmn; 26.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e111.66 \u0026plusmn; 28.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e116.10 \u0026plusmn; 26.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.292ᵃ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiastolic BP (mmHg), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67.37 \u0026plusmn; 14.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e71.43 \u0026plusmn; 18.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67.93 \u0026plusmn; 14.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.134ᵃ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePulse (bpm), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e95.08 \u0026plusmn; 22.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e109.78 \u0026plusmn; 26.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e97.30 \u0026plusmn; 23.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cstrong\u003eᵃ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTemperature (\u0026deg;C), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.27 \u0026plusmn; 1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.33 \u0026plusmn; 1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.28 \u0026plusmn; 1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.808ᵃ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOxygen saturation (%), mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e90.25 \u0026plusmn; 8.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e89.89 \u0026plusmn; 6.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e90.19 \u0026plusmn; 8.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.808ᵃ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCHF, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e119 (88.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e134 (53.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.058ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCOPD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41 (83.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e49 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.806ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCKD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (92.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.232ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCancer Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAny cancer, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.166ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLung cancer, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14 (63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003cstrong\u003eᵇ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMetastatic cancer, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e48 (87.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55 (22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.563ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDNR/DNI, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003cstrong\u003eᵇ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSmoking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.092ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Non-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e125 (81.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28 (18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e153 (61.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e86 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e96 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePneumonia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e94 (83.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e112 (44.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.730ᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Comparison of Survival Outcomes by Morphine Administration\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphine in ER\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphine During Hospitalization\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (hours to death)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e242.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e231.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e152.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e282.20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (hours to death)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e144.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e122.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e82.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e160.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStandard deviation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e332.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e332.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e172.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e377.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinimum (hours)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum (hours)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2874\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN (patients)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Mann\u0026ndash;Whitney Test Results for Survival Differences\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrouping Variable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN (No)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN (Yes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMann\u0026ndash;Whitney U\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value (2-tailed)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMorphine in ER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3441.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-1.390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMorphine During Hospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4807.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-3.606\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eData presented as mean \u0026plusmn; SD for continuous variables and n (%) for categorical variables.\u003c/li\u003e\n \u003cli\u003ePercentages for morphine groups represent within-group (row) percentages.\u003c/li\u003e\n \u003cli\u003eᵃ\u0026nbsp;Independent-samples t-test.\u003c/li\u003e\n \u003cli\u003eᵇ\u0026nbsp;Pearson chi-square test or Fisher\u0026rsquo;s exact test as appropriate.\u003c/li\u003e\n \u003cli\u003eDNR/DNI = Do Not Resuscitate / Do Not Intubate;\u003cbr\u003e\u0026nbsp;COPD = Chronic Obstructive Pulmonary Disease;\u003cbr\u003e\u0026nbsp;BP = Blood Pressure.\u003c/li\u003e\n\u003c/ul\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":"","lastPublishedDoi":"10.21203/rs.3.rs-8339033/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8339033/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDyspnea is a common and distressing symptom at the end of life, particularly among patients with advanced cancer, heart failure, or chronic lung disease. Morphine, an opioid analgesic, is well established as an effective treatment for relieving dyspnea by modulating the central perception of breathlessness and reducing respiratory effort. However, despite strong evidence and clinical guidelines supporting its use, morphine remains underutilized in the Emergency Department (ED). Studies indicate that many terminally ill patients who could benefit from opioid therapy for dyspnea do not receive it, suggesting barriers related to clinician awareness, attitudes, and comfort with end-of-life care. This study investigates the patterns and determinants of morphine administration in the ED for dyspnea at the end of life and evaluates its association with patient outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective analysis done on a medical records database of dyspniac patients at the end-of-life adult patients admitted to ED at Shaare-Zedek Medical Center, Israel, between 2023\u0026ndash;2024. Statistical analysis was performed on demographic and clinical characteristics of the entire cohort.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e250 patients included in the research, mean age 83.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5 years, 51.2% female. 15.2% received morphine in the ED, while 68% eventually received morphine during hospitalization. Multivariate logistic regression identified lung cancer (OR\u0026thinsp;=\u0026thinsp;3.413, p\u0026thinsp;=\u0026thinsp;0.022), DNR status (OR\u0026thinsp;=\u0026thinsp;3.173, p\u0026thinsp;=\u0026thinsp;0.010), and pulse rate upon arrival (OR\u0026thinsp;=\u0026thinsp;1.022, p\u0026thinsp;=\u0026thinsp;0.008) as significant predictors of morphine administration in the ED. No significant difference in time to death was found between those who received morphine in the ED (mean\u0026thinsp;=\u0026thinsp;231.95 hours) and those who did not (mean\u0026thinsp;=\u0026thinsp;242.64 hours, p\u0026thinsp;=\u0026thinsp;0.165). However, morphine use during hospitalization was associated with a significant extension in survival (mean\u0026thinsp;=\u0026thinsp;282.20 hours vs. 152.35 hours, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMorphine remains significantly underutilized in the emergency setting, with only 15.2% of terminally ill patients receiving this treatment. Factors such as lung cancer, DNR status, and vital signs influence morphine use in the ED. Although morphine in the ED did not impact time to death, its use during hospitalization was associated with a meaningful extension in survival time.\u003c/p\u003e","manuscriptTitle":"Morphine Administration in the Emergency Department for Dyspnea at the End of Life","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 09:39:55","doi":"10.21203/rs.3.rs-8339033/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":"f3905c94-a437-42ae-b826-5a17c7395f05","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T15:27:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 09:39:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8339033","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8339033","identity":"rs-8339033","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}