Flumazenil for Hypoactive Delirium Secondary to Benzodiazepine Exposure
Condition: Hypoactive Delirium
MeSH terms: Delirium; Hypokinesia
Intervention: Flumazenil; Placebo
Intervention description: 0.9% normal saline
Intervention MeSH terms: Flumazenil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: delirium; flumazenil; hypoactive delirium; benzodiazepine; benzodiazepine antagonist; critical care

Summary:

      Delirium within the intensive care unit (ICU) is associated with poor outcomes such as
      increased mortality, ICU and hospital length of stay (LOS), and time on mechanical
      ventilation. Benzodiazepine (BZD) exposure is an independent risk factor for development of
      delirium. Reversal of hypoactive delirium represents a potential opportunity for reducing
      duration of delirium and subsequent complications.

      This is a single-center randomized, double-blind, placebo-controlled study of critically ill
      adult patients with benzodiazepine-associated hypoactive delirium. The hypothesis is that
      flumazenil continuous infusion may reverse hypoactive delirium associated with BZD exposure
      and thereby reduce duration of delirium and ICU LOS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  critically ill adults

          -  RASS score of -3 to 0 after receiving benzodiazepine therapy

          -  CAM-ICU positive

          -  no benzodiazepine therapy within the previous 12 hours

        Exclusion Criteria:

          1. contraindications to flumazenil including hypersensitivity

          2. receipt of benzodiazepines for control of potentially life-threatening conditions
             (e.g., control of intracranial pressure or status epilepticus)

          3. active seizure disorder or on current anti-convulsant therapy for history of seizure
             disorder. Seizures secondary to alcohol withdrawal will NOT be excluded.

          4. history of traumatic brain injury complicated by seizures

          5. acute episode (within prior 30 days) of severe traumatic brain injury

          6. history of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident,
             intra-parenchymal hemorrhage) complicated by seizures

          7. acute episode (within prior 14 days) of structural lesion (e.g. subarachnoid
             hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage)

          8. brain tumor complicated by seizure

          9. history of anoxic brain injury

         10. third-degree burn with total body surface area (TBSA) burn greater than 20%

         11. chronic benzodiazepine (clonazepam:lorazepam:diazepam approximately 4:8:40 mg per day)
             for 7 consecutive days with no taper

         12. chronic delirium that is attributable to other causes

         13. anticipated to transfer to lower level of care within 24 hours

         14. admitted for polysubstance overdose as determined by initial drug toxicity screening

         15. recent exposure (prior 7 days) to pro-convulsant medications (identified via
             medication list, medication reconciliation performed by PI/pharmacy medication
             reconciliation team, or urine drug screening)

         16. children, incarcerated individuals, and pregnant women

         17. unable to provide consent and the legally authorized representative is unable to
             provide consent