Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients

Summary

Delirium is common in septic patients, especially those receiving mechanical ventilation in the intensive care unit (ICU). Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Use of dexmedetomidine in mechanically ventilated ICU patients is associated with less delirium and improved outcomes. However, dexmedetomidine infusion produces dose-dependent bradycardia and hypotension; these limited the use of dexmedetomidine in ICU patients. This study is designed to test the hypothesis that low-dose dexmedetomidine infusion can also reduce delirium in mechanically ventilated ICU patients with sepsis.

Timeline

Start

2021-05-28

Primary completion

2024-02-02

Completion

2024-03-02

Outcome

Outcome not reported

Stopped (Enrollment): “The trial was stopped prematurely because of slow recruitment.”

Publications

• Background Guenther U, Radtke FM. Delirium in the postanaesthesia period. Curr Opin Anaesthesiol. 2011 Dec;24(6):670-5. doi: 10.1097/ACO.0b013e32834c7b44.
• Background Roberts B, Rickard CM, Rajbhandari D, Turner G, Clarke J, Hill D, Tauschke C, Chaboyer W, Parsons R. Multicentre study of delirium in ICU patients using a simple screening tool. Aust Crit Care. 2005 Feb;18(1):6, 8-9, 11-4 passim. doi: 10.1016/s1036-7314(05)80019-0.
• Background Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.
• Background Balas MC, Happ MB, Yang W, Chelluri L, Richmond T. Outcomes Associated With Delirium in Older Patients in Surgical ICUs. Chest. 2009 Jan;135(1):18-25. doi: 10.1378/chest.08-1456. Epub 2008 Nov 18.
• Background Ansaloni L, Catena F, Chattat R, Fortuna D, Franceschi C, Mascitti P, Melotti RM. Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg. 2010 Feb;97(2):273-80. doi: 10.1002/bjs.6843.
• Background Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.
• Background Franco K, Litaker D, Locala J, Bronson D. The cost of delirium in the surgical patient. Psychosomatics. 2001 Jan-Feb;42(1):68-73. doi: 10.1176/appi.psy.42.1.68.
• Background Abelha FJ, Luis C, Veiga D, Parente D, Fernandes V, Santos P, Botelho M, Santos A, Santos C. Outcome and quality of life in patients with postoperative delirium during an ICU stay following major surgery. Crit Care. 2013 Oct 29;17(5):R257. doi: 10.1186/cc13084.
• Background Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Elseviers M, Bossaert L. Long term outcome after delirium in the intensive care unit. J Clin Nurs. 2009 Dec;18(23):3349-57. doi: 10.1111/j.1365-2702.2009.02933.x. Epub 2009 Sep 4.
• Background Bickel H, Gradinger R, Kochs E, Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord. 2008;26(1):26-31. doi: 10.1159/000140804. Epub 2008 Jun 24.
• Background Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1092-7. doi: 10.1164/rccm.200904-0537OC. Epub 2009 Sep 10.
• Background Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H; Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) Trial Investigators. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial. JAMA. 2017 Apr 4;317(13):1321-1328. doi: 10.1001/jama.2017.2088.
• Background Wunsch H, Kahn JM, Kramer AA, Wagener G, Li G, Sladen RN, Rubenfeld GD. Dexmedetomidine in the care of critically ill patients from 2001 to 2007: an observational cohort study. Anesthesiology. 2010 Aug;113(2):386-94. doi: 10.1097/ALN.0b013e3181e74116.
• Background van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, Schultz MJ, Nurnberg P, Bonten MJ, Cremer OL, van der Poll T; MARS Consortium. Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. JAMA. 2016 Apr 12;315(14):1469-79. doi: 10.1001/jama.2016.2691.
• Background Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.
• Background Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016 Feb;124(2):362-8. doi: 10.1097/ALN.0000000000000951.
• Background Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.
• Background Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707.
• Background Geloen A, Chapelier K, Cividjian A, Dantony E, Rabilloud M, May CN, Quintin L. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med. 2013 Dec;41(12):e431-8. doi: 10.1097/CCM.0b013e3182986248.
• Background Brummel NE, Jackson JC, Pandharipande PP, Thompson JL, Shintani AK, Dittus RS, Gill TM, Bernard GR, Ely EW, Girard TD. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med. 2014 Feb;42(2):369-77. doi: 10.1097/CCM.0b013e3182a645bd.

Drugs

Indications