Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Cognitive Function

Substudy of the NONSEDA Trial (NCT01967680): Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Cognitive Function

Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level in these patients. The NONSEDA trial is an investigator-initiated, randomised, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden, comparing no sedation with sedation and a daily wake-up trial during mechanical ventilation. This is a substudy of the NONSEDA trial, concerning 250 patients included at trialsite Kolding, Denmark. The aim of the substudy is to assess the effects of no sedation on delirium during admission and cognitive function after discharge from ICU.

Our hypothesis is that critically ill patients who are not sedated during mechanical ventilation will have better cognitive function after discharge.

Study Overview

• Status: Completed
• Conditions: Delirium; Cognition Disorders
• Intervention / Treatment: Other: Non-sedation; Other: Control: Sedation

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Kolding, Denmark, 6000
    • Lillebaelt Hospital, Kolding, Intensive Care Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Endotracheally intubated
• Expected time on ventilator > 24 hours
• Age ≥ 18 years
• Informed consent

Exclusion Criteria:

• Severe head trauma where therapeutic coma is indicated
• Therapeutic hypothermia where therapeutic coma is indicated
• Status epilepticus where therapeutic coma is indicated
• Patient has participated in the study before
• Patient is transferred from another ICU with length of stay > 48 hours
• Patient is comatose at admission
• PaO2/FiO2 ≤ 9, if sedation is necessary for oxygenation
• Patient does not speak Danish, swedish or norwegian at a reasonable level

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Non-sedation; Non-sedation supplemented with pain management during mechanical ventilation.	Other: Non-sedation; Patients are awake or have natural sleep during mechanical ventilation. Pain is treated with morphine iv.
ACTIVE_COMPARATOR: Sedation; Current gold standard: Sedation with a daily wake-up trial.	Other: Control: Sedation; Continuous iv-sedation (propofol first 48 hours, from then midazolam) to Ramsey 3-4 with a daily wake up attempt, where sedation is stopped until patient is awake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function	Cognitive t-score, in percentage, difference between the two groups. The t-score for each patient will be diagnosed by the neuropsycologist at a personal interview and use of following tests: Span of numbers; Coding test; Trailmaking A+B; Rey auditory verbal learning test (immediate, recall); Rey-Ostherrieth complex figure test (immediate, recall, recognition); Word finding test (S-word, animals); Stroop test (congruent+incongruent)	3 months after discharge from ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention/concentration	T-score in the two groups for the cognitive domaine attention/concentration	3 months after discharge from ICU
Learning/memory	t-score in the two groups for the cognitive domaine: learning/memory	3 months after discharge from ICU
Executive dysfunction	t-score in the two groups for the cognitive domaine: executive dysfunction	3 months after discharge from ICU
Mental pace	t-score in the two groups for the cognitive domaine: mental pace	3 months after discharge from ICU
Hypoactive delirium	Occurrence of hypoactive delirium (RASS ≤ 0, CAM-ICU positive) in each group related to cognitive function at follow up	3 months after discharge from ICU
Agitated delirium	Occurrence of agitated delirium (RASS ≥ +2, CAM-ICU positive) in each group related to cognitive function at follow up	3 months after discharge from ICU

Collaborators and Investigators

• Sponsor: Palle Toft
• Collaborators: University of Southern Denmark; Kolding Sygehus; The Danish Council for Strategic Research
• Investigators: Principal Investigator: Helene Joergensen, MD, Lillebaelt Hospital, Kolding

Publications and helpful links

General Publications

• Nedergaard HK, Jensen HI, Stylsvig M, Lauridsen JT, Toft P. 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. Trials. 2016 Jun 1;17(1):269. doi: 10.1186/s13063-016-1390-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2014
• Primary Completion (ACTUAL): June 1, 2017
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (ESTIMATE): January 14, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2019
• Last Update Submitted That Met QC Criteria: March 14, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Respiration, artificial; Critcal care
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders
• Other Study ID Numbers: S-20130025c