Format

Send to

Choose Destination
N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19.

Early Sedation with Dexmedetomidine in Critically Ill Patients.

Collaborators (427)

Mashonganyika C, McKee H, Tonks A, Donnelly A, Hemmings N, O'Kane S, Blakemore A, Butler M, Cowdrey K, Dalton J, Gilder E, Long S, McCarthy L, McGuinness S, Parke R, Chen Y, McArthur C, McConnochie R, Newby L, Bellomo R, Eastwood G, Peck L, Young H, Boschert C, Edington J, Fletcher J, Smith J, Nand K, Raza A, Sara T, Bennett-Britton J, Bewley J, Bodenham V, Cole L, Driver K, Grimmer L, Howie L, Searles C, Sweet K, Webster D, van Berkel A, Connor H, Dennett J, van Der Graaff M, Henderson S, Mehrtens J, Miller K, Minto E, Morris A, Noble S, Parker K, Bulfin L, Hart N, Shepherd K, Vij S, Dickson S, Elloway E, Ferguson C, Jackson R, MacNaughton P, Marner M, Squire R, Waddy S, Wafer P, Welbourne J, Ashcroft P, Chambler D, Dukes S, Harris A, Horton S, Sharpe S, Williams P, Williams S, Bailey M, Blazquez E, France D, Hutchison R, O'Connor A, Comadira G, Gough M, Tallott M, Bastick M, Cameron R, Donovan S, Ellis K, Gaur A, Gregory R, Naumoff J, Turner E, White M, Au KFJ, Fratzia J, Treloar S, Tan AP, Tang CL, Yong CY, Akaltan M, Berger S, Blaser D, Fazlija L, Jong ML, Lensch M, Ludwig R, Merz T, Nettelbeck K, Roth M, Schafer M, Takala J, Wehr A, Zacharias D, Amran R, Ashraf HN, Azmi N, Basri N, Burhanuddin H, Hadinata Y, Hamdan A, Kadiman Sabran S, Sulaiman S, Zabidi IN, Al-Dawood A, Aljuaid M, Al Anizi H, AlSaeedi A, Arabi Y, Dbsawy M, Deeb A, Hegazy M, Ibrahim M, Clarey E, Corcoran E, Finney C, Harris C, Hopkins P, Noble H, Thompson L, Williams T, Dumlao LA, Bassam R, Hassan MA, Naseem N, Al-Kurdi MH, Al-Harthy AM, Bernard S, Sebafundi L, Serban C, Lim SK, Mazidah N, Saidin N, Sjamsuddin N, Tan ITA, Zabidi N, Brain M, Mineall S, Kanhere M, Soar N, Abd Kadir N, Abdullah NH, Awang R, Emperan Z, Husin NS, Ismail NI, Ismail SZ, Mohd Khadzali FNA, Norddin MF, Aguila J, Bold C, Clatworthy B, Dias A, Hogan C, Kazemi A, Lai V, Song R, Williams A, Bhatia D, Elliot S, Galt P, Lavrans K, Ritchie P, Wang A, Gresham R, Lowrey J, Masters K, Palejs P, Seppelt I, Symonds F, Weisbrodt L, Whitehead C, Babio-Galan M, Calder V, Clement I, Harrison A, McCullagh I, Scott C, Bevan R, Caniba S, Hacking D, Maher L, Azzolini ML, Beccaria P, Colombo S, Landoni G, Leggieri C, Luca C, Mamo D, Moizo E, Monti G, Mucci M, Zangrillo A, Albania M, Arora S, Shi Y, Abudayah A, Almekhlafi G, Al Amodi E, Al Samarrai S, Badawi M, Cubio Caba R, Elffaki O, Mandourah Y, Valerio J, Joyce C, Meyer J, Saylor E, Venkatesh B, Venz E, Walsham J, Wetzig K, Khoo TM, Liew JES, Sakthi AN, Zulkurnain A, Bamford A, Bergin C, Carrera R, Cooper L, Despy L, Harkett S, Mee L, Reeves E, Snelson C, Spruce E, Cooper G, Hodgson R, Pearson D, Rosbergen M, Ali MN, Bahar NI, Ismail A, Ismail WNW, Samat NM, Piah NSM, Abd Rahman R, Duroux M, Ratcliffe M, Warhurst T, Buehner U, Williams E, Jacques N, Keating L, Macgill S, Tamang KL, Tolan N, Walden A, Bower R, Cranshaw J, Molloy K, Pitts S, Butler J, Dunlop R, Fourie C, Jarrett P, Lassig-Smith M, Livermore A, O'Donoghue S, Reade M, Starr T, Stuart J, Campbell L, Phillips M, Stephens D, Thomas J, Cooper D, McAllister R, Andrew G, Barclay L, Dawson H, Griffith DM, Hope D, Wojcik G, McCulloch C, Paterson R, Ascough L, Paisley C, Patrick-Heselton J, Shaw D, Waugh V, Williams K, Welters I, Barge D, Jordan A, MacIsaac C, Rechnitzer T, Bass F, Gatward J, Hammond N, Janin P, Stedman W, Yarad E, Razak NA, Dzulkipli N, Jong SL, Asen K, Voon WL, Liew S, Ball J, Barnes V, Dalton C, Farnell-Ward S, Farrah H, Maher K, Mellinghoff J, Ryan C, Shirley P, Conlon L, Glover A, Martin-Loeches I, O'Toole E, Ewan J, Ferrier J, Litton E, Webb SA, Berry W, Blanco Alonso U, Bociek A, Campos S, Jawara S, Hanks F, Kelly A, Lei K, McKenzie C, Ostermann M, Wan R, Al-Soufi S, Leow S, McCann K, Reynolds C, Brickell K, Fahey C, Hays L, Hyde N, Nichol A, Ryan D, Brailsford J, Buckley A, Forbes L, Maguire T, Moore J, Murray L, Ghosh A, Park M, Said S, Visser A, Abidin HZ, Ali S, Hassan MH, Omar SC, Shukeri WFW, Brealey D, Bercades G, Blackburn E, Macallum N, Macklin A, Ryu JH, Tam K, Smyth D, Arif A, Bassford C, Morgan C, Swann C, Ward G, Wild L, Bone A, Elderkin T, Green D, Sach D, Salerno T, Simpson N, Brohi F, Clark M, Williams L, Brooks J, Cocks E, Cole J, Curtin J, Davies R, Hill H, Morgan M, Palmer N, Whitton C, Wise M, Baskaran P, Hasan MS, Tham LY, Sol Cruz R, Dinsdale D, Edney S, Firkin C, FitzJohn F, Hill G, Hunt A, Hurford S, Jones G, Judd H, Latimer-Bell C, Lawrence C, Lesona E, Navarra L, Robertson Y, Smellie H, Vucago AM, Young P, Clark P, Kong J, Ho J, Nayyar V, Skelly C.

Author information

1
From the School of Clinical Sciences (Y.S.) and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (B.D.H., R.B., M.B., L.M., S.A.W.), Monash University, Monash Health (Y.S.), the Faculty of Medicine, University of Melbourne (R.B., M.B.), Melbourne, VIC, and Austin Hospital, Heidelberg, VIC (R.B.), the Prince of Wales Clinical School of Medicine, University of New South Wales (Y.S.), Royal North Shore Hospital, the George Institute for Global Health (F.E.B.), the Sydney Medical School-Nepean, University of Sydney, and the Department of Clinical Medicine, Macquarie University (I.M.S.), Sydney, the Faculty of Medicine, University of Queensland, Royal Brisbane and Women's Hospital, Brisbane (M.C.R.), the Joint Health Command, Australian Defence Force, Canberra, ACT (M.C.R.), and St. John of God Subiaco Hospital, Subiaco, WA (S.A.W.) - all in Australia; the College of Medicine, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia (Y.M.A.); the Department of Anesthesiology and Intensive Care, IJN-UTM Cardiovascular Engineering Center, National Heart Institute, Kuala Lumpur, Malaysia (S.B.K.); the Department of Critical Care Medicine, Auckland City Hospital, University of Auckland, Auckland, New Zealand (C.J.M.); Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (J.T.); and Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom (M.P.W.).

Abstract

BACKGROUND:

Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.

METHODS:

In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days.

RESULTS:

We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group.

CONCLUSIONS:

Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

Comment in

PMID:
31112380
DOI:
10.1056/NEJMoa1904710
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center