Principal Investigator

David
Hui
Awardee Organization

University Of Tx Md Anderson Can Ctr
United States

Fiscal Year
2022
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Strategies for Persistent Agitated Delirium in Palliative Care

Delirium is the most common and distressing neuropsychiatric syndrome in cancer patients. It has a negative effect on symptom assessment, patient-clinician communication, decision making, and survival. Approximately 50% of patients with hyperactive or mixed delirium continue to experience agitation despite low-dose haloperidol, which can be particularly distressing to patients and caregivers. Neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal may provide good control of agitation. However, no delirium trials have ever been completed to directly compare these options; such trials are urgently needed to improve the quality of life of patients with this devastating syndrome. Our long-term goal is to develop evidence-based therapy for the palliation of delirium in cancer patients. The proposed study is a high-impact, 4-arm, multi-center, double-blind, double-dummy, randomized controlled trial to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal in the treatment of persistent agitated delirium in cancer patients admitted to acute palliative care units (APCUs). We hypothesize that benzodiazepine rotation and combination therapy are particularly effective against agitated delirium. The primary specific aim of this study is to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on the change in Richmond Agitation Sedation Scale (RASS) over 24 hours in patients who did not experience a response to low-dose haloperidol. The second aim is to compare the effects of these treatments on (1) rescue medication use, (2) the proportion of patients in the target RASS range, (3) perceived comfort by caregivers and bedside nurses, (4) delirium-related distress in caregivers and nurses, (5) achievement of the proxy comfort goal, (6) symptom expression, (7) delirium severity, (8) adverse effects, and (9) quality of end-of-life care. The third aim is to identify novel predictive markers of response to haloperidol and lorazepam. After obtaining surrogate consent, we will administer the study medications under a titration scheme and monitor the participants closely until discharge. This study is highly innovative because (1) multiple previously untested treatment strategies are studied, (2) the outcome measures (e.g., proxy comfort goals) are novel, (3) biomarkers are included as potential predictors of treatment response, (4) the patient population (i.e., short survival) is unique, and (5) the study setting (i.e., the APCU) is distinctive. Successful completion of this definitive study will identify the optimal strategy to reduce agitation, improve patient comfort, and palliate delirium-related distress; provide timely data to address the ongoing debate regarding the proper use of haloperidol and lorazepam in delirium; inform novel strategies to monitor patients with delirium; and stimulate further studies to identify better strategies to palliate persistent agitation and improve patients' quality of life.

Publications

  • Hui D, Hoge G, Bruera E. Models of supportive care in oncology. Current opinion in oncology. 2021 Jul 1;33(4):259-266. PMID: 33720070
  • Hui D, Hernandez F, Larsson L, Liu D, Kilgore K, Naberhuis J, Virgilio A, Reddy S, Reddy A, Dalal S, Haider A, Driver L, Azhar A, Dev R, Bruera E. Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial. Journal of pain and symptom management. 2019 Oct;58(4):605-613. Epub 2019 Jul 2. PMID: 31276809
  • Chang YK, Kaplan H, Geng Y, Mo L, Philip J, Collins A, Allen LA, McClung JA, Denvir MA, Hui D. Referral Criteria to Palliative Care for Patients With Heart Failure: A Systematic Review. Circulation. Heart failure. 2020 Sep;13(9):e006881. Epub 2020 Sep 9. PMID: 32900233
  • An A, Hui D. Immunotherapy Versus Hospice: Treatment Decision-Making in the Modern Era of Novel Cancer Therapies. Current oncology reports. 2022 Mar;24(3):285-294. Epub 2022 Feb 3. PMID: 35113356
  • Hui D, Paiva CE, Del Fabbro EG, Steer C, Naberhuis J, van de Wetering M, Fernández-Ortega P, Morita T, Suh SY, Bruera E, Mori M. Prognostication in advanced cancer: update and directions for future research. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2019 Jun;27(6):1973-1984. Epub 2019 Mar 13. PMID: 30863893
  • Hui D, Bruera E. Use of short-acting opioids in the management of breathlessness: an evidence-based review. Current opinion in supportive and palliative care. 2020 Sep;14(3):167-176. PMID: 32701856
  • Mo L, Urbauer DL, Bruera E, Hui D. Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer. The oncologist. 2021 Jan;26(1):77-83. Epub 2020 Sep 23. PMID: 32915490
  • Hui D, Casarett D. Controversies in Palliative Care: A New JPSM Series. Journal of pain and symptom management. 2023 Jan;65(1):e79. PMID: 36566050
  • Hui D, Naberhuis J, Dibaj S, Naqvi M, Liu D, Bruera E. Association Between Plasma Brain Natriuretic Peptide and Overall Survival in Patients With Advanced Cancer: Preliminary Findings. Journal of pain and symptom management. 2019 Sep;58(3):465-471. Epub 2019 May 22. PMID: 31128228
  • Hui D, De La Rosa A, Urbauer DL, Nguyen T, Bruera E. Personalized sedation goal for agitated delirium in patients with cancer: Balancing comfort and communication. Cancer. 2021 Dec 15;127(24):4694-4701. Epub 2021 Aug 25. PMID: 34432293
  • Hui D, Agar M, Maeda I. Should Neuroleptics Be Used in Patients With Delirium Seen by Palliative Care? Journal of pain and symptom management. 2023 Jan;65(1):e81-e85. Epub 2022 Oct 8. PMID: 36220457
  • Hui D, De La Rosa A, Wilson A, Nguyen T, Wu J, Delgado-Guay M, Azhar A, Arthur J, Epner D, Haider A, De La Cruz M, Heung Y, Tanco K, Dalal S, Reddy A, Williams J, Amin S, Armstrong TS, Breitbart W, Bruera E. Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial. The Lancet. Oncology. 2020 Jul;21(7):989-998. Epub 2020 May 29. PMID: 32479786
  • Chang YK, Allen LA, McClung JA, Denvir MA, Philip J, Mori M, Perez-Cruz P, Cheng SY, Collins A, Hui D. Criteria for Referral of Patients With Advanced Heart Failure for Specialized Palliative Care. Journal of the American College of Cardiology. 2022 Jul 26;80(4):332-344. PMID: 35863850
  • Hui D, De La Rosa A, Bruera E. State of Integration of Palliative Care at National Cancer Institute-Designated and Nondesignated Cancer Centers. JAMA oncology. 2020 Aug 1;6(8):1292-1295. PMID: 32614444
  • Mori M, Morita T, Bruera E, Hui D. Prognostication of the Last Days of Life. Cancer research and treatment. 2022 Jul;54(3):631-643. Epub 2022 Mar 30. PMID: 35381165
  • Hui D, Paiva CE, Del Fabbro EG, Mori M. Prognostication, palliative care, and patient outcomes (reply to Rossi et al.). Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020 Apr;28(4):1547-1548. Epub 2020 Jan 6. PMID: 31903534
  • Hui D, Maxwell JP, Paiva CE. Dealing with prognostic uncertainty: the role of prognostic models and websites for patients with advanced cancer. Current opinion in supportive and palliative care. 2019 Dec;13(4):360-368. PMID: 31689273
  • Zimmermann C, Buss MK, Rabow MW, Hannon B, Hui D. Should Outpatient Palliative Care Clinics in Cancer Centers be Stand Alone or Embedded? Journal of pain and symptom management. 2023 Feb;65(2):e165-e170. Epub 2022 Nov 25. PMID: 36437178
  • Hui D. Delirium in the palliative care setting: "Sorting" out the confusion. Palliative medicine. 2019 Sep;33(8):863-864. PMID: 31395002
  • Goswami R, Moore J, Bruera E, Hui D. Assessment of the Decision-Making Capacity for Clinical Research Participation in Patients With Advanced Cancer in the Last Weeks of Life. Journal of pain and symptom management. 2020 Aug;60(2):400-406. Epub 2020 Feb 24. PMID: 32105788
  • Hui D, Hernandez F, Urbauer D, Thomas S, Lu Z, Elsayem A, Bruera E. High-Flow Oxygen and High-Flow Air for Dyspnea in Hospitalized Patients with Cancer: A Pilot Crossover Randomized Clinical Trial. The oncologist. 2021 May;26(5):e883-e892. Epub 2020 Dec 15. PMID: 33289276
  • Chang YK, McClung JA, Allen LA, Philip J, Hui D. Reply: Early Integration of Specialist Palliative Care in Advanced Heart Failure: A Multipronged Approach. Journal of the American College of Cardiology. 2022 Nov 29;80(22):e205-e206. PMID: 36423999
  • Hui D, Mahler DA, Larsson L, Wu J, Thomas S, Harrison CA, Hess K, Lopez-Mattei J, Thompson K, Gomez D, Jeter M, Lin S, Basen-Engquist K, Bruera E. High-Flow Nasal Cannula Therapy for Exertional Dyspnea in Patients with Cancer: A Pilot Randomized Clinical Trial. The oncologist. 2021 Aug;26(8):e1470-e1479. Epub 2020 Dec 14. PMID: 33289280
  • Tang M, Chen M, Bruera E, Hui D. Association among rescue neuroleptic use, agitation, and perceived comfort: secondary analysis of a randomized clinical trial on agitated delirium. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2021 Dec;29(12):7887-7894. Epub 2021 Jun 29. PMID: 34184130
  • Mo L, Urbauer DL, Bruera E, Hui D. Recommendations for supportive care and best supportive care in NCCN clinical practice guidelines for treatment of cancer: Differences between solid tumor and hematologic malignancy guidelines. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2021 Dec;29(12):7385-7392. Epub 2021 May 29. PMID: 34052931
  • Hui D, De La Rosa A, Chen J, Delgado Guay M, Heung Y, Dibaj S, Liu D, Bruera E. Palliative care education and research at US cancer centers: A national survey. Cancer. 2021 Jun 15;127(12):2139-2147. Epub 2021 Mar 4. PMID: 33662148
  • Gravier AL, Shamieh O, Paiva CE, Perez-Cruz PE, Muckaden MA, Park M, Bruera E, Hui D. Meaning in life in patients with advanced cancer: a multinational study. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020 Aug;28(8):3927-3934. Epub 2019 Dec 19. PMID: 31858248
  • Patel S, Hoge G, Fellman B, Kaur S, Heung Y, Bruera E, Hui D. Timing of referral to outpatient palliative care for patients with haematologic malignancies. British journal of haematology. 2022 Sep;198(6):974-982. Epub 2022 Jul 21. PMID: 35866185
  • Del Fabbro E. Improving the perception of physician compassion, communication skills, and professionalism in the outpatient clinic. Cancer. 2021 Nov 1;127(21):3924-3925. Epub 2021 Jul 15. PMID: 34264521
  • Humphrey TJ, Cruickshank JG, Cubitt WD. An outbreak of calicivirus associated gastroenteritis in an elderly persons home. A possible zoonosis? The Journal of hygiene. 1984 Oct;93(2):293-9. PMID: 6094667
  • Hui D, Mo L, Paiva CE. The Importance of Prognostication: Impact of Prognostic Predictions, Disclosures, Awareness, and Acceptance on Patient Outcomes. Current treatment options in oncology. 2021 Jan 11;22(2):12. PMID: 33432524
  • Hui D, De La Rosa A, Chen J, Dibaj S, Delgado Guay M, Heung Y, Liu D, Bruera E. State of palliative care services at US cancer centers: An updated national survey. Cancer. 2020 Jan 1;126(9):2013-2023. Epub 2020 Feb 12. PMID: 32049358
  • Hui D, Anderson L, Tang M, Park M, Liu D, Bruera E. Examination of referral criteria for outpatient palliative care among patients with advanced cancer. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020 Jan;28(1):295-301. Epub 2019 May 1. PMID: 31044305
  • Hui D, Abdelghani E, Chen J, Dibaj S, Zhukovsky D, Dev R, Tanco K, Haider A, Azhar A, Reddy A, Epner D, Arthur J, Dalal S, Heung Y, Reddy S, De La Cruz M, Liu D, Bruera E. Chronic Non-Malignant Pain in Patients with Cancer Seen at a Timely Outpatient Palliative Care Clinic. Cancers. 2020 Jan 15;12. (1). PMID: 31952220
  • Hui D, Puac V, Shelal Z, Liu D, Maddi R, Kaseb A, Javle M, Overman M, Yennurajalingam S, Gallagher C, Bruera E. Fixed-Dose Netupitant and Palonosetron for Chronic Nausea in Cancer Patients: A Double-Blind, Placebo Run-in Pilot Randomized Clinical Trial. Journal of pain and symptom management. 2021 Aug;62(2):223-232.e1. Epub 2021 Jan 1. PMID: 33388382
  • Lastrapes K, Dang M, Cassel JB, Orr T, Proffitt T, Del Fabbro E. Delirium documentation in hospitalized pediatric patients with cancer. Palliative & supportive care. 2021 Jun;19(3):283-286. PMID: 33641695
  • Hui D. Palliative Cancer Care in the Outpatient Setting: Which Model Works Best? Current treatment options in oncology. 2019 Feb 11;20(2):17. PMID: 30741353
  • Hui D, Nortje N, George M, Wilson K, Urbauer DL, Lenz CA, Wallace SK, Andersen CR, Mendoza T, Haque S, Ahmed S, Delgado-Guay M, Dalal S, Rathi N, Reddy A, McQuade J, Flowers C, Pisters P, Aloia T, Bruera E. Impact of an Interdisciplinary Goals-of-Care Program Among Medical Inpatients at a Comprehensive Cancer Center During the COVID-19 Pandemic: A Propensity Score Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Jan 20;41(3):579-589. Epub 2022 Oct 6. PMID: 36201711
  • Mo L, Geng Y, Chang YK, Philip J, Collins A, Hui D. Referral criteria to specialist palliative care for patients with dementia: A systematic review. Journal of the American Geriatrics Society. 2021 Jun;69(6):1659-1669. Epub 2021 Mar 2. PMID: 33655535
  • Azhar A, Hui D. Management of Physical Symptoms in Patients with Advanced Cancer during the Last Weeks and Days of Life. Cancer research and treatment. 2022 Jul;54(3):661-670. Epub 2022 Jun 30. PMID: 35790195
  • Mo L, Hui D. Reply to comment on: Referral criteria to specialist palliative care for patients with dementia-A systematic review. Journal of the American Geriatrics Society. 2021 Jul;69(7):2038-2039. Epub 2021 May 3. PMID: 33939835
  • Simon ST, Mori M, Ekström M, Pralong A, Yamaguchi T, Hui D. Should Benzodiazepines be Used for Reducing Dyspnea in Patients with Advanced Illnesses? Journal of pain and symptom management. 2023 Mar;65(3):e219-e223. Epub 2022 Nov 29. PMID: 36455801
  • Hui D, Darke AK, Guthrie KA, Subbiah IM, Unger JM, Hershman DL, Krouse RS, Bakitas M, O'Rourke MA. Association Between Health-Related Quality of Life and Progression-Free Survival in Patients With Advanced Cancer: A Secondary Analysis of SWOG Clinical Trials. JCO oncology practice. 2022 Apr;18(4):e442-e451. Epub 2021 Oct 4. PMID: 34606328