Controlling Hyperadrenergic Activity in Neurologic Injury

Study Overview
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Brief Summary
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Traumatic brain injury (TBI) is frequently associated with a hyperadrenergic state accompanied by elevated levels of plasma catecholamines. In its more severe presentation, the hyperadrenergic state presents as dysautonomia, which is characterized by paroxysmal alteration in vital signs, including tachycardia. The investigators hypothesize that intravenous (IV) esmolol is as effective at controlling heart rate in hyperadrenergic states as oral propranolol, which is the standard of care. Our primary endpoint is efficacy of IV esmolol vs a PRN regimen of intermittent B-blockade in controlling heart rate below a pre-specified level (< 100 bpm) after Traumatic Brain Injury (TBI) or hemorrhagic neurologic injury. Heart rates will be recorded continuously as well as hourly.

Official Title
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Controlling Hyperadrenergic Activity in Neurologic Injury

Conditions
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Dysautonomia, Traumatic Brain Injury

Intervention / Treatment
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* Drug: Esmolol
* Drug: Propranolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: TBI (Moderate/Severe TBI (GCS 12 or Head AIS>1) or hemorrhagic neurologic injury Hyperadrenergic Activity: At least one paroxysmal episode (lasting at least 15 minutes) of Heart Rate 110 beats per minute during two or more consecutive days plus at least two more of the following that may not be better explained by another disease process (ex: sepsis): Temperature of 38.5C Respiratory Rate 20 breaths per minute Agitation Diaphoresis Dystonia Stimulus responsive (triggering of paroxysm) - Informed Consent obtained Exclusion Criteria: Patients that do not meet criteria for dysautonomia (as stated above) Age <18 years Pregnancy Hypotension - requiring pressor therapy to maintain baseline adequate CPP or mean arterial pressure Cardiac arrhythmia - sinus bradycardia (HR <60), 2nd or 3rd degree AV block Hemodynamic contraindications to intravenous beta-blockade such as a documented history of congestive heart failure (CHF), dependency on cardiac inotropes or documented bronchospastic disease Any patient on chronic beta blockade as an outpatient. Life expectancy < 48 hours or patients with do not resuscitate orders Ongoing seizure activity Informed consent not obtained

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects Receiving Esmolol<br>The Esmolol arm is defined as a 48-hour intravenous infusion of esmolol (Brevibloc 20mg/ml), which will be started on enrollment. | Drug: Esmolol<br>* The Esmolol arm is defined as a 48-hour intravenous infusion of esmolol (Brevibloc 20mg/ml), which will be started on enrollment. The infusion rate will begin at 50 micrograms/kg/min and be adjusted to achieve heart rates between 80 and 100 beats/min with standard dosing regimens used in our Neuro intensive care unit. The infusion will be started at a rate of 0.05 milligrams/kg/min (50 micrograms/kg/min) for 5 minutes. After the 5 minutes of initial infusion, maintenance infusion may be continued at 0.05 mg/kg/min or increased stepwise (e.g. 0.1 mg/kg/min, 0.15 mg/kg/min to a maximum of 0.2 mg/kg/min) with each step being maintained for 4 or more minutes until the target heart rate is achieved.<br>* Other names: Brevibloc;|
| Active Comparator: Subjects receiving Propranolol<br>The comparison arm will be comprised of oral propranolol, starting with 20mg PO every 6 hours prn (as needed) to reduce heart rate into target range. If 20mg is ineffective, the dose will be doubled at each dosing interval until an adequate dose is found, not to exceed 120mg four times daily. (ex: 20mg, 40mg, 80mg, 120mg) | Drug: Propranolol<br>* The comparison arm will be comprised of oral propranolol, starting with 20mg PO every 6 hours prn (as needed) to reduce heart rate into target range. If 20mg is ineffective, the dose will be doubled at each dosing interval until an adequate dose is found, not to exceed 120mg four times daily. (ex: 20mg, 40mg, 80mg, 120mg)<br>* Other names: Inderal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Controlling heart rate in traumatic brain injured patients | Once the patient is randomized and start getting the study medication, we monitor heart rate and other vital signs for 72hrs | 72 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic Brain Injury, Dysautonomia, Brain Injury, Sympathetic hyperactivity