Flumazenil for Hypoactive Delirium Secondary to Benzodiazepine Toxicity
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/1/2018 |
| Start Date: | March 2016 |
| End Date: | May 2019 |
| Contact: | Kendra J Schomer, PharmD |
| Email: | kjschomer@ucdavis.edu |
| Phone: | 916-734-2243 |
Effect of Flumazenil on Hypoactive Delirium Secondary to Benzodiazepine Toxicity in the ICU
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 reverses hypoactive delirium associated with BZD toxicity and
thereby reduces duration of delirium and ICU LOS.
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 reverses hypoactive delirium associated with BZD toxicity and
thereby reduces duration of delirium and ICU LOS.
Benzodiazepines are commonly used for discomfort, anxiety, agitation, and alcohol withdrawal
syndrome (AWS) in the ICU. End organ dysfunction and extended exposure can increase the risk
of complications associated with BZDs, which include increased ICU LOS, time on mechanical
ventilation, and mortality.
Flumazenil as a 1, 4-imidazobenzodiazepine is a competitive antagonist for the benzodiazepine
binding site with weak intrinsic or partial agonistic activity on the GABA receptor. Multiple
studies have confirmed the safety and effectiveness of flumazenil for the reversal of
sedation. Pilot studies have demonstrated safe reversal of over-sedation and statistically
significant improvements in patient cooperation and time to extubation. The current standard
for suspected BZD-associated hypoactive delirium is cessation of benzodiazepine
administration and supportive care.
The role of continuous infusion flumazenil for rapid and sustained reversal of hypoactive
delirium in the ICU has not been evaluated prospectively and therefore remains poorly
defined.
syndrome (AWS) in the ICU. End organ dysfunction and extended exposure can increase the risk
of complications associated with BZDs, which include increased ICU LOS, time on mechanical
ventilation, and mortality.
Flumazenil as a 1, 4-imidazobenzodiazepine is a competitive antagonist for the benzodiazepine
binding site with weak intrinsic or partial agonistic activity on the GABA receptor. Multiple
studies have confirmed the safety and effectiveness of flumazenil for the reversal of
sedation. Pilot studies have demonstrated safe reversal of over-sedation and statistically
significant improvements in patient cooperation and time to extubation. The current standard
for suspected BZD-associated hypoactive delirium is cessation of benzodiazepine
administration and supportive care.
The role of continuous infusion flumazenil for rapid and sustained reversal of hypoactive
delirium in the ICU has not been evaluated prospectively and therefore remains poorly
defined.
Inclusion Criteria:
- critically ill adults
- RASS score of -3 to +1
- CAM-ICU positive
- no benzodiazepine therapy within the previous 12 hours
Exclusion Criteria:
- Contraindications to flumazenil including hypersensitivity and receipt of
benzodiazepines for control of potentially life-threatening conditions (eg, control of
intracranial pressure or status epilepticus)
- active seizure disorder or on current anti-convulsant therapy for history of seizure
disorder. Seizures secondary to alcohol withdrawal will NOT be excluded
- history of traumatic brain injury complicated by seizures
- acute episode (within prior 30 days) of severe traumatic brain injury
- history of structural lesion (e.g. subarachnoid hemorrhage, cerebrovascular accident,
intra-parenchymal hemorrhage) complicated by seizures
- acute episode (within prior 14 days) of structural lesion (e.g. subarachnoid
hemorrhage, cerebrovascular accident, intra-parenchymal hemorrhage)
- brain tumor complicated by seizure
- history of anoxic brain injury
- third-degree burn with total body surface area (TBSA) burn greater than 20%
- chronic benzodiazepine (clonazepam:lorazepam:diazepam approximately 4:8:40 mg per day)
for 7 consecutive days with no taper
- history of chronic delirium that is attributable to other causes
- anticipated to transfer to lower level of care within 24 hours
- admitted for polysubstance overdose (as determined by initial drug toxicity screening)
- recent exposure (prior 7 days) to pro-convulsant medications (identified via
medication history or available urine drug screening) i.e. tricyclic antidepressants,
bupropion
- children, incarcerated individuals, and pregnant women
- unable to provide consent and the legally authorized representative is unable to
provide consent
We found this trial at
1
site
Sacramento, California 95814
Principal Investigator: Kendra Schomer, PharmD
Phone: 916-734-2243
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