DANish DELIrium Study On Neurointensive Care Patients
Condition: Acquired Brain Injuries; Delirium; Acute Brain Injury
MeSH terms: Brain Injuries; Delirium; Wounds and Injuries
Study type: Interventional

Summary: 
      Abstract Background Studies have shown that delirium in medical and surgical intensive care
      units (ICUs) increases mortality, length of stay (LOS) as well as the risk of dementia
      symptoms and cerebral atrophy after discharge. Only few studies have investigated delirium in
      the neurointensive care unit (N-ICU). Delirium is most often assessed by one of two
      instruments: Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment
      Method for the ICU (CAM-ICU).

      Aims

        1. To measure the effect of a systematic intervention (sedation, sleep, mobilization and
           pain) on delirium symptoms in patients with acute acquired brain injury in N-ICU.

        2. To validate the ICDSC and CAM-ICU to patients with acute acquired brain injury Method
           The design of the study is a two-phase interventional trial. Based on a power
           calculation, 56 patients will be enrolled both in the baseline and the intervention
           group (n=112).

      Part 1: A baseline investigation will be conducted to establish prevalence, duration and type
      of delirium symptoms in patients with acute acquired brain injury before implementing the
      intervention bundle.

      Part 2: A systematic Intervention protocol will be implemented in the N-ICU. The Intervention
      elements consist of a sedation, sleep, mobilization and pain treatment regimen based on the
      newest available evidence.

      Enrolled patients will be contacted 12 months after discharge for a follow-up including a
      quality of life with (EuroQoL-5D) questionnaire, a cognitive test measuring their cognitive
      end point (Repeatable Battery for Assessment of the Neuropsychological Status) and a short
      test for dementia symptoms (MMSE, Mini Mental State Examination).
    

Detailed description: 
      Background It has been established that in medical and surgical intensive care units (ICUs)
      that delirium increases mortality and length of stay (LOS), as well as the risk of dementia
      and cerebral atrophy after discharge. There is a lack of studies into delirium in the
      neurointensive care unit (N-ICU) population, and no studies have addressed the association
      between delirium, quality of life, dementia symptoms and cerebral atrophy in patients with
      acquired brain injury after discharge from N-ICU. A recent study has demonstrated a
      correlation between delirium symptoms in stroke patients and quality of life, and functional
      levels at 3, 6 and 12 months after N-ICU discharge, suggesting that delirium during the acute
      phase effects the long-term outcome.

      Delirium screening has not been introduced systematically in N-ICUs in Denmark or
      internationally, and validated instruments are lacking in this population. The Confusion
      Assessment Method for ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist
      (ICDSC) are internationally most recommended and best validated delirium screening tools for
      non-psychiatric health care staff. Neither of the two instruments, however, has been fully
      validated in patients with acquired brain injury.

      Several studies and guidelines suggest that delirium is potentially preventable by minimizing
      sedation, and ensuring systematic pain management, early mobilization and adequate sleep. The
      present study therefore aims to investigate if delirium is preventable in an N-ICU setting by
      introducing a multi-modal intervention bundle optimizing management of sedation, pain,
      mobilization and sleep.

      Aim

      The primary aim of the study:

      To measure the effect of the intervention bundle on prevalence, duration and type of delirium
      symptoms using the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion
      Assessment Method for the ICU (CAM-ICU) in N-ICU patients with acute acquired brain injury

      Secondary aim: To validate ICDSC and CAM-ICU for adult N-ICU with acute acquired brain
      injury, and investigate if delirium symptoms are negatively correlated with quality of life,
      cognitive function and dementia symptoms at 12-month follow-up post N-ICU discharge.

      Method Study design: A controlled two-phased before-and-after trial. Phase I: Baseline study
      (4 months), Phase II: Intervention study (4 months). This design was chosen as the most
      appropriate, because a randomized clinical trial would have a large spill-over effect.

      The primary outcome is duration of delirium symptoms with ICDSC and CAM-ICU in the N-ICU
      based on a hypothesis that it is possible to decrease time with delirium in the N-ICU 20% or
      more. Power calculation: 56 patients will be enrolled during a 4-month period, in the
      baseline and the intervention group respectively, yielding a total of 112 patients (20%
      drop-out rate, 5% significance, 80% power).

      Inclusion criteria All Danish speaking adults (18 years or above) with an expected N-ICU
      length of stay (LOS) more than 48 hours and admitted with acute brain injury from spontaneous
      or traumatic bleeding, such as subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH)
      or traumatic brain injury (TBI).

      Exclusion criteria Patients not expected to survive 48 hours, or continues Richmond
      Agitation-Sedation Score (RASS) of -4 or -5 during the stay in the N-ICU.

      Data collection Demographics: age, gender, primary diagnosis, marital status and living
      situation, education, BMI, and alcohol consumption. Clinical data include: Glasgow Coma Score
      (GCS), Richmond Agitation and Sedation Scale (RASS), ICDSC, CAM-ICU, Acute Physiology and
      Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score (SAPS II),
      intubation status, sedation agent and dose, type of mobilization and pain status. Follow-up
      includes EuroQoL-5D (EQ-5D), Repeatable Battery for Assessment for the Neuropsychological
      Status (RBANS) and Mini Mental State Examination (MMSE) questionnaire at 12 months after
      discharge.

      Phase I Baseline study (4 months). A baseline investigation will be conducted to establish
      the prevalence, duration and type of delirium symptoms in patients with acute acquired brain
      injury. Usual care will be provided at this time. For validation a psychiatric team will rate
      included patients usingThe Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition (DSM-V) and The International Classification of Diseases (ICD-10) as the gold
      standard. The psychiatric team assesses patients the first and second day after the patient
      has a RASS -2 or above for 24 hours.

      Phase II Intervention study (4 months). After full implementation of the intervention bundle,
      the study will be conducted to establish the prevalence, duration and type of delirium
      symptoms in patients with acute acquired brain injury. The psychiatric team assesses patients
      the first and second day after the patient has a RASS -2 or above for 24 hours.

      Implementation of intervention An all day workshop introducing the multi-modal intervention
      bundle will be held for all nurses in the unit. The study nurses will be specially trained to
      maintain study protocol. Physicians will be informed and trained on a weekly morning meeting
      during phase II, and some will participate in the all day workshop. Journal audits will be
      used as monitoring the implementation. The Intervention bundle consist of a sedation, sleep,
      mobilization and pain treatment regimen based on the newest available evidence in the four
      areas.

      Sedation: Sedatives will be kept to a minimum by daily orders for target RASS sedation level
      and titration of sedatives by primary nurse. Dose and agent will be recorded.

      Sleep: Sleep will be optimized by systematic use of earplugs at night, dim lighting,
      visitation restrictions, and midday rest periods. Procedures (e.g. blood samples) will be
      carried out in the day time instead of night time. Hours of activity/rest will be assessed by
      an actiwatch (actigraph).

      Pain: A strategy of multi-modal pain management combining pharmacological and
      non-pharmacological interventions will be implemented. Pain will be assessed by Critical-Care
      Pain Observation Tool (CPOT) for unresponsive patients and Numeric Rating Scale (NRS) for
      patient-reported pain.

      Mobilization: Systematic early mobilization will be implemented by daily orders for
      mobilization level and a mobilization guideline.

      Follow-up: Follow-up will be conducted on all possible patients in the two study groups at
      twelve months post N-ICU discharge. Patients will come to the hospital for the EQ-5D for
      self-rated health, RBANS for cognitive function and the MMSE questionnaire for dementia
      symptoms.

      Ethical considerations The study includes an observational and an interventional part
      introducing optimized treatment and care according to current best international evidence.
      The intervention items will be implemented in the entire unit as standard care for all
      patients. Most patients will be unable to give initial consent to the study due to their
      cerebral status. Relatives and general practitioner will be contacted and informed verbally
      and in writing to provide consent by proxy. The study is approved by the Regional and
      national ethics committees and the Danish Data Protection Agency.

      Data analysis Prevalence, type and duration of delirium symptoms in the baseline group will
      be compared to the intervention group. Furthermore the two groups will be compared on LOS and
      mortality. Patients ICDSC score are compared with EQ-5D, RBANS and MMSE in order to
      investigate possible associations between delirium and self-rated health, cognitive function
      and dementia.

      All data will be coded and plotted in Excel and SPSS for the statistical data analysis.
      Hardware and worksheets are handled and stored as prescribed by the Danish Data Protection
      Agency. There will be used descriptive and analytical statistics. Categorical variables will
      be described as frequency and percent. Continuous variables will be described as mean and
      standard deviation (SD). The two groups will be compared by correlation analysis, univariate
      and multivariate regression analyzes and questionnaires are analyzed by a paired t-test to
      compare the two groups' average score.
    

Intervention name(s): intervention bundle (sedation, pain, mobilization and sleep)
Intervention type(s): Other
Intervention description(s): Sedation: Sedation after target RASS Pain: Implementing a pain guideline and CPOT for pain assessment. Mobilization: Implementing a guideline on early mobilization and a daily prescribed mobilization level.
Sleep: Implementing a daily quite time and changing procedures to minimize noise during the night
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Delirium; intensive care nursing; Acute acquired brain injury; neurointensive care; Intensive care delirium screening checklist; Confusion Assessment Method for the ICU