Pilot Study Comparing Treatment With Dexmedetomidine to Midazolam for Symptom Control in Advanced Cancer Patients

Summary

Cancer patients with very difficult to control symptoms at the Abbotsford (AC) and Fraser Valley (FVC) Cancer Centers are referred and admitted to the Tertiary Palliative Care Units at the Abbotsford Regional Hospital and Cancer Center(ARHCC). For symptom management, patients are sometimes given midazolam continuously through a needle placed underneath the skin. While effective in symptom management, midazolam can be sedating, leaving patients unable to interact with loved ones in their last days. This study is a pilot project. Before proceeding to a full-scale study, a "pilot study" or "feasibility study" is often carried out first to test the design of a study, the likelihood of successful recruitment or the acceptability of the intervention to potential subjects. The basic idea is to find out whether it will be practical to proceed to a larger study that will include more subjects. This type of study involves only a small number of subjects and therefore the results can only be used as a guide for further larger studies. The investigators also will determine whether palliative care cancer patients taking a medication called dexmedetomidine would have improved rousability (more easily and fully awakened) and symptom control (pain, shortness of breath, nausea or confusion) compared with those taking standard of care which is receiving the medication midazolam. The use of dexmedetomidine in other clinical situations (in the Operating Room or Intensive Care Unit where the patient can still respond to the doctor) has been shown to be effective in symptom control and to provide a better degree of rousability to patients but has not been well studied in the palliative care environment.

Timeline

Start

2012-11

Primary completion

2014-11

Completion

2014-11

Publications

• Background Abernethy AP. Pain and palliative care pharmacotherapy literature summaries and analyses. J Pain Palliat Care Pharmacother. 2008;22(2):145-51. doi: 10.1080/15360280801992140.
• Background Anger KE, Szumita PM, Baroletti SA, Labreche MJ, Fanikos J. Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center. Crit Pathw Cardiol. 2010 Dec;9(4):221-6. doi: 10.1097/HPC.0b013e3181f4ec4a.
• Background Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg. 2004 Jan;98(1):153-158. doi: 10.1213/01.ANE.0000093225.39866.75.
• Background Brinkkemper T, van Norel AM, Szadek KM, Loer SA, Zuurmond WW, Perez RS. The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: a systematic review. Palliat Med. 2013 Jan;27(1):54-67. doi: 10.1177/0269216311425421. Epub 2011 Nov 1.
• Background Caraceni A, Simonetti F. Palliating delirium in patients with cancer. Lancet Oncol. 2009 Feb;10(2):164-72. doi: 10.1016/S1470-2045(09)70018-X.
• Background Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symptom Assessment Scale. Cancer. 2000 May 1;88(9):2164-71. doi: 10.1002/(sici)1097-0142(20000501)88:93.0.co;2-5.
• Background Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007 Nov;62(11):1132-8. doi: 10.1111/j.1365-2044.2007.05230.x.
• Background Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol. 2008 May;4(5):619-27. doi: 10.1517/17425255.4.5.619.
• Background Clark, S., & Ezra, M. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients. Journal of the Intensive Care Society, 12(3), 244-245, 2011.
• Background Coull JT, Jones ME, Egan TD, Frith CD, Maze M. Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans. Neuroimage. 2004 May;22(1):315-22. doi: 10.1016/j.neuroimage.2003.12.022.
• Background Coyne PJ, Wozencraft CP, Roberts SB, Bobb B, Smith TJ. Dexmedetomidine: exploring its potential role and dosing guideline for its use in intractable pain in the palliative care setting. J Pain Palliat Care Pharmacother. 2010 Dec;24(4):384-6. doi: 10.3109/15360288.2010.518227.
• Background Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, Dagli G. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol. 2010 Jul;27(7):648-52. doi: 10.1097/EJA.0b013e3283347bfe.
• Background Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. doi: 10.1001/jama.289.22.2983.
• Background Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009 Dec;43(12):2064-74. doi: 10.1345/aph.1M310.
• Background Guinter JR, Kristeller JL. Prolonged infusions of dexmedetomidine in critically ill patients. Am J Health Syst Pharm. 2010 Aug;67(15):1246-53. doi: 10.2146/ajhp090300.
• Background Jackson KC 3rd, Wohlt P, Fine PG. Dexmedetomidine: a novel analgesic with palliative medicine potential. J Pain Palliat Care Pharmacother. 2006;20(2):23-7.
• Background Jones GM, Murphy CV, Gerlach AT, Goodman EM, Pell LJ. High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety. Ann Pharmacother. 2011 Jun;45(6):740-7. doi: 10.1345/aph.1P726. Epub 2011 Jun 10.
• Background Kehl KA. Treatment of terminal restlessness: a review of the evidence. J Pain Palliat Care Pharmacother. 2004;18(1):5-30.
• Background Kent CD, Kaufman BS, Lowy J. Dexmedetomidine facilitates the withdrawal of ventilatory support in palliative care. Anesthesiology. 2005 Aug;103(2):439-41. doi: 10.1097/00000542-200508000-00028. No abstract available.
• Background Kunisawa T. Dexmedetomidine hydrochloride as a long-term sedative. Ther Clin Risk Manag. 2011;7:291-9. doi: 10.2147/TCRM.S14581. Epub 2011 Jul 11.
• Background Lum, K. L., & Sanders, H. G. A comparison of midazolam and flunitrazepam in end-of-life care. Progress in Palliative Care, 19(1), 1-6, 2011.
• Background Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009 May-Jun;50(3):206-17. doi: 10.1176/appi.psy.50.3.206.
• Background Maze M, Angst MS. Dexmedetomidine and opioid interactions: defining the role of dexmedetomidine for intensive care unit sedation. Anesthesiology. 2004 Nov;101(5):1059-61. doi: 10.1097/00000542-200411000-00002. No abstract available.
• Background Mercadante S, Intravaia G, Villari P, Ferrera P, David F, Casuccio A. Controlled sedation for refractory symptoms in dying patients. J Pain Symptom Manage. 2009 May;37(5):771-9. doi: 10.1016/j.jpainsymman.2008.04.020. Epub 2008 Nov 28.
• Background Muttu S, Liu EH, Ang SB, Chew PT, Lee TL, Ti LK. Comparison of dexmedetomidine and midazolam sedation for cataract surgery under topical anesthesia. J Cataract Refract Surg. 2005 Sep;31(9):1845-6. doi: 10.1016/j.jcrs.2005.09.019. No abstract available.
• Background Prommer E. Review article: dexmedetomidine: does it have potential in palliative medicine? Am J Hosp Palliat Care. 2011 Jun;28(4):276-83. doi: 10.1177/1049909110389804. Epub 2010 Dec 3.
• Background Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
• Background Roberts SB, Wozencraft CP, Coyne PJ, Smith TJ. Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. J Palliat Med. 2011 Mar;14(3):371-3. doi: 10.1089/jpm.2010.0235. Epub 2011 Jan 17.
• Background Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, Sarapohja T, Bratty JR, Takala J; "Dexmedetomidine for Continuous Sedation" Investigators. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009 Feb;35(2):282-90. doi: 10.1007/s00134-008-1296-0. Epub 2008 Sep 16.
• Background Shehabi, Y., Botha, J. A., Ernest, D., Freebairn, R. C., Reade, M., Roberts, B. L., et al. Clinical application, the use of dexmedetomidine in intensive care sedation. Critical Care and Shock, 13(2), 40-50, 2010.
• Background Soares LG, Naylor C, Martins MA, Peixoto G. Dexmedetomidine: a new option for intractable distress in the dying. J Pain Symptom Manage. 2002 Jul;24(1):6-8. doi: 10.1016/s0885-3924(02)00423-2. No abstract available.
• Background Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010 Jun;36(6):926-39. doi: 10.1007/s00134-010-1877-6. Epub 2010 Apr 8.
• Background Tobias JD. Subcutaneous dexmedetomidine infusions to treat or prevent drug withdrawal in infants and children. J Opioid Manag. 2008 Jul-Aug;4(4):187-91. doi: 10.5055/jom.2008.0024.
• Background Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):229-42. doi: 10.1176/jnp.13.2.229.
• Background Ustun Y, Gunduz M, Erdogan O, Benlidayi ME. Dexmedetomidine versus midazolam in outpatient third molar surgery. J Oral Maxillofac Surg. 2006 Sep;64(9):1353-8. doi: 10.1016/j.joms.2006.05.020.
• Background Wallace S, Mecklenburg B, Hanling S. Profound reduction in sedation and analgesic requirements using extended dexmedetomidine infusions in a patient with an open abdomen. Mil Med. 2009 Nov;174(11):1228-30. doi: 10.7205/milmed-d-00-6009.
• Background Fraser Health Authority (FHA) Hospice Palliative Care Program Symptom Guideline "Refractory Symptoms and Palliative Sedation Therapy Guideline", May 9, 2011. Retrieved from http://www.fraserhealth.ca/media/RefractorySymptomsandPalliativeSedationTherapyRevised_Sept%2009.pdf )
• Background Flanagan E, Gentry J. He's taking how much Dilaudid! Dexmedetomidine: a novel approach to refractory symptom management. Presentation of the American Academy of Hospice and Palliative Medicine & Hospice and Palliative Nurses Association Conference 2011 Feb 16-19; Vancouver, British Columbia
• Background Doyle, D. et al, Oxford Textbook of Palliative Medicine, Third Edition 2004, p. 219.
• Background Storey P, Knight C. Assessment and Treatment of Pain in the Terminally Ill. UNIPAC Three, Hospice/Palliative Care Training for Physicians, A Self-Study Program, American Academy of Hospice and Palliative Medicine, Second Edition, Mary Ann Liebert, Inc., 2003, p. 62.

Drugs

Indications