Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial

Toft, Palle; Olsen, Hanne Tanghus; Jørgensen, Helene Korvenius; Strøm, Thomas; Nibro, Helle Lykkeskov; Oxlund, Jacob; Wian, Karl-Andre; Ytrebø, Lars Marius; Kroken, Bjørn A.; Chew, Michelle

doi:10.1186/1745-6215-15-499

Cited by 26 publications

(25 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The strengths of the present study are its design coherent with guidelines, always suggesting an early conscious sedation target [1]. Rather than making it different in the two groups [31, 36], two separate strategies were compared in the achievement of the same shared goal: a calm, conscious, and cooperative critically ill patient. Moreover, the lack of homogeneity among participant centers could render the results generalizable.…”

Section: Discussionmentioning

confidence: 99%

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

et al. 2019

View full text Add to dashboard Cite

BackgroundICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation.MethodsThis was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality.ResultsThere were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1–100), intravenous 94.4% (78–100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71–100) vs 83% (61–100), p < 0.01; and lower total drug costs: 2.39 (0.75–9.78) vs 4.15 (1.20–20.19) €/day with mechanical ventilation (p = 0.01).ConclusionsAlthough enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target.Trial registrationClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2280-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The trial is a substudy in the NONSEDA trial [ 1 ]. The NONSEDA trial is an investigator-initiated, randomized, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.…”

Section: Methodsmentioning

confidence: 99%

“…In this substudy we will investigate how non-sedation versus sedation with a daily wake-up trial affects physical function after ICU discharge. For details about the interventions please see the NONSEDA trial protocol [ 1 ] (Fig. 1 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Non-sedation versus sedation with a daily wake-up trial in critically ill patients recieving mechanical ventilation - effects on long-term cognitive function: Study protocol for a randomized controlled trial, a substudy of the NONSEDA trial

Nedergaard

Jensen

Stylsvig

et al. 2016

Trials

Self Cite

View full text Add to dashboard Cite

BackgroundThe effects of non-sedation on cognitive function in critically ill patients on mechanical ventilation are not yet certain. This trial is a substudy of the NONSEDA trial where critically ill patients are randomized to non-sedation or to sedation with a daily wake-up attempt during mechanical ventilation in the intensive care unit (ICU).The aim of this substudy is to assess the effects of non-sedation versus sedation with a daily wake-up attempt on long-term cognitive function.MethodsThis is an investigator-initiated, randomized, clinical, parallel-group, superiority trial, including 200 patients.Inclusion criteria will be adult patients who are intubated and on mechanical ventilation with an expected duration of more than 24 hours. Exclusion criteria will be patients who are comatose at admission and patients with conditions requiring therapeutic coma (i.e., severe head trauma, status epilepticus, patients treated with therapeutic hypothermia and patients with severe hypoxia).The experimental intervention will be non-sedation supplemented with pain management during mechanical ventilation. The control intervention will be sedation with a daily wake-up attempt.The primary outcome will be cognitive function 3 months after discharge from intensive care.The secondary outcomes will be the results of seven specific cognitive tests, performed 3 months after discharge from intensive care, and the association between hypoactive and agitated delirium during ICU admission and long-term cognitive function.DiscussionIf non-sedation can improve long-term cognitive function, it could be an approach worth considering for a larger group of critically ill patients.Trial registrationThe study has been approved by the relevant scientific ethics committee and is registered at ClinicalTrials.gov (ID: NCT02035436, registered on 10 January 2014).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1390-5) contains supplementary material, which is available to authorized users.

show abstract

“…Investigators, patients or their relatives, and physicians caring for the patients were aware of the trial-group assignments. The protocol and statistical analysis plan have been published previously 7 and are available with the full text of this article at NEJM.org.…”

Section: Patient Selection and Randomizationmentioning

confidence: 99%

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients

2020

View full text Add to dashboard Cite

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.

show abstract

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial

Cited by 26 publications

References 28 publications

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

Non-sedation versus sedation with a daily wake-up trial in critically ill patients recieving mechanical ventilation - effects on long-term cognitive function: Study protocol for a randomized controlled trial, a substudy of the NONSEDA trial

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients

Contact Info

Product

Resources

About