Effect of Nonsedation on Cognitive Function in Survivors of Critical Illness.

OBJECTIVES: Critical illness can cause severe cognitive impairments. The objective of this trial was to assess the effect of nonsedation versus sedation with a daily wake-up call during mechanical ventilation on cognitive function in adult survivors of critical illness. DESIGN: Single-center substudy of the multicenter, randomized Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation trial. Three months after ICU-discharge participants were tested for cognitive function by a neuropsychologist. SETTING: Mixed 14-bed ICU in teaching hospital. PATIENTS: A total of 205 critically ill, orally intubated, and mechanically ventilated adults. INTERVENTIONS: Patients were randomized within the first 24 hours from intubation to either nonsedation with sufficient analgesia or light sedation with a daily wake-up call during mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: A total of 118 patients survived to follow-up and 89 participated (75%). The participating survivors in the two groups did not differ regarding baseline data or premorbid cognitive impairments. Sedated patients had received more sedatives, whereas doses of morphine and antipsychotics were equal. The primary outcome was that no significant difference was found in the number of patients with mild/moderate cognitive impairments (six nonsedated patients vs four sedated patients) or severe cognitive impairments (16 nonsedated patients vs 17 sedated patients; p = 0.71). Secondary outcomes were cognitive test scores, and no differences were found between the scores in nonsedated and sedated patients. Hypothetical worst case scenarios where all patients, who had not participated in follow-up assessment, were assumed to have severe cognitive impairments were analyzed, but still no difference between the groups was found. We found more patients with delirium in the sedated group (96% vs 69% of patients; p = 0.002) and increased duration of delirium in sedated patients (median 5 vs 1 d; p < 0.001). Delirium subtypes were equally distributed between the groups, with hypoactive delirium most frequent (61%), followed by mixed delirium (39%). CONCLUSIONS: Nonsedation did not affect cognitive function 3 months after ICU-discharge.

Effect of non-sedation on post-traumatic stress and psychological health in survivors of critical illness-A substudy of the NONSEDA randomized trial.

BACKGROUND: Critical illness can cause post-traumatic stress and impaired mental health. The NONSEDA trial was a Scandinavian multicenter RCT, assessing non-sedation versus sedation with a daily wake-up call during mechanical ventilation in critically ill adults. The aim of this substudy was to assess the effect of non-sedation on post-traumatic stress and mental health. METHODS: This substudy is based on all participating patients from a single NONSEDA trial site (Kolding, Denmark). Patients were randomized to sedation or non-sedation within the first 24 hours of mechanical ventilation. Three months after ICU discharge survivors were examined by a neuropsychologist for post-traumatic stress, anxiety and depression, and filled out the SF-36 questionnaire regarding quality of life. RESULTS: The two groups of survivors were similar with regard to baseline characteristics, length of admission and mechanical ventilation. Sedated patients received more propofol and midazolam. Doses of morphine and haloperidole were equal. PRIMARY OUTCOME: the number of patients with post-traumatic stress disorder did not differ between groups (non-sedated: 2 patients vs sedated: 0, P = .23). SECONDARY OUTCOMES: there were no differences between groups in Beck Anxiety Index (median, non-sedated: 0 vs sedated: 0, P = .62), Beck Depression Index (median, non-sedated: 7 vs sedated: 4, P = .24), SF-36 mental component score (mean, non-sedated: 46.7 vs sedated: 47.5, P = .73) or number of patients with symptoms of post-traumatic stress (8 in both groups, P = .89). CONCLUSION: Levels of PTSD, anxiety and depression and quality of life regarding mental health were similar between the non-sedated and sedated group.

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.

BACKGROUND: The 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. METHODS: This 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. DISCUSSION: If non-sedation can improve long-term cognitive function, it could be an approach worth considering for a larger group of critically ill patients. TRIAL REGISTRATION: The study has been approved by the relevant scientific ethics committee and is registered at ClinicalTrials.gov (ID: NCT02035436 , registered on 10 January 2014).

Long-term psychological effects of a no-sedation protocol in critically ill patients.

INTRODUCTION: A protocol of no sedation has been shown to reduce the time patients receive mechanical ventilation and to reduce intensive care and total hospital length of stay. The long-term psychological effects of this strategy have not yet been described. The purpose of the study was to test whether a strategy of no sedation alters long-term psychological outcome compared with a standard strategy with sedation. METHODS: During intensive care stay, 140 patients requiring mechanical ventilation were randomized to either no sedation or sedation with daily interruption of sedation. This study was done as a single-blinded cohort study. After discharge, patients were interviewed by a neuropsychologist assessing quality of life, depression, anxiety, and posttraumatic stress disorder. RESULTS: Two years after randomization, 38 patients were eligible for interview, and 26 patients were interviewed (13 from each group). No difference was found with respect to quality of life (Medical Outcome Study, 36-item short-form health survey). Both mental and physical components were nonsignificant. The Beck depression index was low in both groups (one patient in intervention group versus three patients in the control group were depressed, p = 0.32). Evaluated with the Impact of Events Scale, both groups had low stress scores (one in the intervention group versus two in the control group had scores greater than 32; p = 0.50). State anxiety scores were also low (28 in the control group versus 30 in the intervention group, p = 0.58). CONCLUSIONS: Our data suggest that a protocol of no sedation applied to critically ill patients undergoing mechanical ventilation does not increase the risk of long-term psychological sequelae after intensive care compared with standard treatment with sedation.