Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

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.).

Non-sedation-Does it improve health-related quality of life after critical illness? A 3-month follow-up sub-study of the NONSEDA trial.

BACKGROUND: Critical illness is associated with severely impaired health-related quality of life (HRQoL) for years following discharge. The NONSEDA trial was a multicenter randomized trial on non-sedation versus sedation with a daily wake-up trial in critically ill, mechanically ventilated patients in Scandinavia. The aim of this sub-study was to assess the effect of non-sedation on HRQoL and degree of independence in activities in daily living (ADL) 3 months post-ICU. METHODS: All survivors were asked to complete the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) and the Barthel Index 3 months post-ICU. To limit missing data, reminders were sent. If unsuccessful, telephone interviews could be used. Outcomes were the level of HRQoL and ADL-function in each group. All outcomes were assessed blinded. RESULTS: Of the 700 patients included 412 survived to follow-up. A total of 344 survivors participated (82%). Baseline data were equal between the two groups. Mean SF-36 scores for the non-sedated vs sedated patients were as follows: Physical Function 45 vs 40, P = .69, Bodily Pain: 61 vs 52, P = .81, General Health: 50 vs 50, P = .84, Vitality: 42 vs 44, P = .85, Social Function: 75 vs 63, P = .85, Role Emotional: 58 vs 50, P = .82, Mental Health: 70 vs 70, P = .89, Role Physical: 25 vs 28, P = .32, Physical Component Score: 38 vs 37, P = .81, Mental Component Score: 48 vs 46, P = .94, Barthel Index: 20 vs 20, P = .74. CONCLUSION: Randomization to non-sedation neither improved nor impaired health-related quality of life or degree of independence in activities in daily living 3 months post-ICU discharge.

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.

Failure of non-sedation strategy in critically ill, mechanically ventilated patients - a retrospective, post-hoc analysis of the NONSEDA trial.

PURPOSE: There is a growing awareness on minimizing sedation in ICUs. In the NONSEDA trial 700 critically ill patients were randomized to light sedation or non-sedation during mechanical ventilation. Approximately 40% of patients randomized to non-sedation needed sedation. The aim of this study is to obtain knowledge on patients, who experienced failure of non-sedation. MATERIALS AND METHODS: This study is a retrospective post-hoc analysis of the NONSEDA trial. Patients, who were randomized to non-sedation are sub-divided into those who did not require sedation during mechanical ventilation ("non-sedation success"), and those who needed continuous sedation at least once ("non-sedation failure"). RESULTS: 348 patients were randomized to non-sedation, 199 experienced non-sedation success, whereas 149 experienced non-sedation failure. Patients in the two groups were comparable with regards to age, BMI, disease severity scores and admission diagnoses. Patients with non-sedation failure were more often male. Propofol was mainly used as rescue sedation. Patients with non-sedation failure had less days alive without sedation, coma, delirium, organ support, mechanical ventilation, ICU- and hospital admission. Mortality and long-term outcomes did not differ between groups. CONCLUSION: Patients with non-sedation success had better in-hospital outcomes, but mortality and long-term outcomes were not affected by success or failure of non-sedation.