Hanne T Olsen1, Helene K Nedergaard1, Thomas Strøm1, Jakob Oxlund1, Karl-Andre Wian1, Lars M Ytrebø1, Bjørn A Kroken1, Michelle Chew1, Serkan Korkmaz1, Jørgen T Lauridsen1, Palle Toft1. 1. From the Departments of Anesthesiology and Intensive Care, Odense University Hospital-Svendborg Hospital, Svendborg (H.T.O.), the Departments of Clinical Research (H.T.O., H.K.N., T.S., J.O., P.T.) and Business and Economics (S.K., J.T.L.), University of Southern Denmark, and the Department of Anesthesiology and Intensive Care, Odense University Hospital (T.S., P.T.), Odense, the Department of Anesthesiology and Intensive Care, Hospital Lillebaelt, Kolding (H.K.N.), and the Department of Anesthesiology and Intensive Care, Esbjerg Hospital, Esbjerg (J.O.) - all in Denmark; the Department of Anesthesiology and Intensive Care, Vestfold Hospital, Tønsberg (K.-A.W.), and the Department of Anesthesiology and Intensive Care, University Hospital of North Norway, Tromsø (L.M.Y., B.A.K.) - both in Norway; and the Department of Anesthesiology and Intensive Care, Linköping University Hospital, Linköping, Sweden (M.C.).
Abstract
BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).
RCT Entities:
BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).
Authors: Fayez Alshamsi; Kallirroi Laiya Carayannopoulos; Anders Granholm; Joshua Piticaru; Kimberley Lewis; Zainab Al Duhailib; Dipayan Chaudhuri; Laura Spatafora; Yuhong Yuan; John Centofanti; Jessica Spence; Bram Rochwerg; Dan Perri; Dale M Needham; Anne Holbrook; John W Devlin; Osamu Nishida; Kimia Honarmand; Begüm Ergan; Eugenia Khorochkov; Pratik Pandharipande; Mohammed Alshahrani; Tim Karachi; Mark Soth; Yahya Shehabi; Morten Hylander Møller; Waleed Alhazzani Journal: Intensive Care Med Date: 2022-06-01 Impact factor: 41.787
Authors: Katarzyna Kotfis; Irene van Diem-Zaal; Shawniqua Williams Roberson; Mark van den Boogaard; Yahya Shehabi; E Wesley Ely; Marek Sietnicki Journal: Crit Care Date: 2022-07-05 Impact factor: 19.334
Authors: John W Devlin; Hollis R O'Neal; Christopher Thomas; Mary Ann Barnes Daly; Joanna L Stollings; David R Janz; E Wesley Ely; John C Lin Journal: Crit Care Explor Date: 2020-06-12
Authors: Matthew S Duprey; Sandra M A Dijkstra-Kersten; Irene J Zaal; Becky A Briesacher; Jane S Saczynski; John L Griffith; John W Devlin; Arjen J C Slooter Journal: Am J Respir Crit Care Med Date: 2021-09-01 Impact factor: 30.528
Authors: Kenneth E Remy; Philip A Verhoef; Jay R Malone; Michael D Ruppe; Timothy B Kaselitz; Frank Lodeserto; Eliotte L Hirshberg; Anthony Slonim; Cameron Dezfulian Journal: Pediatr Crit Care Med Date: 2020-07 Impact factor: 3.624
Authors: Matthew F Mart; Brenda T Pun; Pratik Pandharipande; James C Jackson; E Wesley Ely Journal: Crit Care Med Date: 2021-08-01 Impact factor: 9.296