Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination

Sponsor

Prisma Health-Midlands (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03743805

Collaborator

(none)

Enrollment

Location

Arm

30.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Current standard of care prior to determination of brain death in subjects with suspected anoxic brain injury is to exclude complicating medical conditions that may confound clinical assessment (such as severe electrolyte, acid base, endocrine or circulatory disturbance), achieve normothermia and normal systolic blood pressure over 100 mmHg (with or without vasopressor use), exclude the presence of neuromuscular blocking agents (with the presence of a train of 4 twitches with maximal ulnar nerve stimulation) as well as to exclude the presence of CNS depressant drug effects. At the present time the latter is done by history, drug screen and allowing enough time for paralytic and sedative drugs to be metabolized and cleared from the body. Clearance is calculated by using 5 times the drug's half-life assuming normal hepatic and renal functions. Half-life can also be prolonged in subjects who have been treated with induced hypothermia. Literature search revealed articles with general guidelines and approaches to brain death, but none addressed pharmacological reversal of sedative drugs

Condition or Disease	Intervention/Treatment	Phase
Brain Death Anoxic Brain Injury Cardiac Arrest Sedative Intoxication Narcotic Intoxication	Drug: Flumazenil Drug: Naloxone	Early Phase 1

Detailed Description

Question of proposed study is whether a subject's comatose state is secondary to delayed clearance of a previously administered CNS depressant. By using pharmacologic reversal agents of commonly used benzodiazepines and opioids, the investigators aim to identify participants that may likely improve after complete clearance of the drugs from their system.

Prospective trial with enrollment of 30 subjects in 2 intensive care units at Palmetto Health Richland from January 1st 2019 to June 30th 2020. Research procedures will be performed in the intensive care setting. If participants had undergone targeted temperature management (33-36 degrees Celsius for 24 hours via intravascular or surface control methods, with or without sedation or neuromuscular blockade, followed by rewarming actively or passively at 0.25-0.5 degrees per hour over 8-12 hours to 37 degrees) investigators will wait 24 hours after rewarming prior to testing. End point is to evaluate if pharmacological reversal agents would result in improved GCS scores or return of cerebral or brainstem functions in some comatose subjects, which will be considered a positive test result.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination

Actual Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Jul 20, 2021

Actual Study Completion Date :

Jul 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reversal drugs Flumazenil and naloxone	Drug: Flumazenil 0.2 mg IV push, which may be repeated every 20 minutes for up to a total of 1 mg Other Names: Romazicon Drug: Naloxone 0.4 mg IV push, which may be repeated every 2 minutes for up to a total of 2 mg Other Names: Narcan Evzio

Arm

Intervention/Treatment

Experimental: Reversal drugs

Flumazenil and naloxone

Drug: Flumazenil

0.2 mg IV push, which may be repeated every 20 minutes for up to a total of 1 mg

Other Names:

Romazicon

Drug: Naloxone

0.4 mg IV push, which may be repeated every 2 minutes for up to a total of 2 mg

Other Names:

Narcan

Evzio

Outcome Measures

Primary Outcome Measures

Improved GCS scores or return of cerebral or brainstem functions in comatosed subjects [Within 30 minutes post treatment]
Subjects will be observed closely and tested before and after intervention for any signs of cerebral or brainstem function (1-Response to pain stimulus with earlobe pinching, trapezius squeezing and sternal rub or other brain-originating movements, e.g. seizures, decerebrate or decorticate posturing. 2-Pupillary light reflex with bright light. 3-Corneal reflexes with the use of cotton swab or tissue paper. 4-Gag reflex with a tongue depressor looking for bilateral palatal elevation. 5-Cough with tracheal suctioning at the carinal level) and GCS re-evaluated

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adults with cardiac arrest who may have completed targeted temperature management (hypothermia protocol) and have had no neurological recovery after 24 hours of rewarming will be enrolled. Subjects will have a suspected diagnosis of anoxic brain injury secondary to cardiac arrest, and seizures ruled out with an EEG. All subjects are expected to be unable to consent and consent will be obtained from their legal authorized representative.