Study to Evaluate Esmolol (Brevibloc) to Manage Cardiac Function in Patients With Subarachnoid Hemorrhage

University of Michigan

Overview

The purpose of this study is to evaluate the clinical effect of esmolol treatment on cardiac function and electrophysiology; to assess the effects of esmolol treatment on serum adrenergic and cardiac biomarkers; to explore the safety of esmolol treatment shortly after subarachnoid hemorrhage (SAH). Patients will be followed for a maximum of 1 month after the index SAH. The primary outcome will be change in systolic function - ejection fraction by Simpson's rule (baseline versus Day 7 +/- 2 after SAH).

Subarachnoid hemorrhage (SAH) remains one of the most devastating forms of stroke. Over 25% of all stroke related potential years of life lost are from SAH. Outcomes are adversely affected by secondary ischemia from cerebral vasospasm, along with cardiac complications. Trials performed in patients with SAH have demonstrated benefit after the administration of beta blockers - reducing mortality nearly in half; but concerns over diminishing cerebral perfusion inhibited the widespread adoption of this therapy. Our specific aims are as follows: 1. To evaluate the clinical effect of esmolol treatment on cardiac systolic and diastolic function, along with cardiac electrophysiology; 2. To assess the effects of esmolol treatment on serum adrenergic and cardiac biomarkers; 3. To explore the safety of esmolol shortly after SAH. The primary outcome will be change in systolic function - ejection fraction by Simpson's rule (baseline versus Day 7 +/- 2 after SAH).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Subarachnoid Hemorrhage

Interventions

EsmololDRUG

The initial esmolol infusion will be 50 mcg/kg/minute IV. This will be increased by 25 mcg/kg/minute every 15 minutes until one of the following situations is reached: 1. Heart rate less than 70 bpm. 2. Systolic blood pressure less than 120 mmHg 3. Maximum dose of esmolol of 200 mcg/kg/minute is reached.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subarachnoid hemorrhage presumed to be the result of ruptured aneurysm * Age 18 years old or greater * Able to enroll within 24 hours of onset of symptoms * Systolic blood pressure over 140 mm Hg OR administration of antihypertensives after presentation Exclusion Criteria: * Withdrawal of life support imminent (within six hours) * Known heart failure or cardiomyopathy AND ejection fraction 35% or below * Prisoner or pregnant female * Ongoing vasopressor administration to maintain SBP, or clinical suspicion of left ventricular failure * Clinically important arrhythmias (history of cardiac arrest or ventricular arrhythmias), conduction abnormalities (Mobitz Type 2, 3rd degree AV block, or symptomatic Mobitz 1 without pacemaker), clinical cardiogenic shock, or overt clinical heart failure * Active bronchospastic disease (ongoing bronchospasm after SAH presentation or current treatment with oral corticosteroids for asthma or obstructive lung disease) * End stage renal disease

Locations (1)

University of Michigan Health System

Ann Arbor, Michigan, United States

Outcomes

Primary Outcomes

Change in high sensitivity troponin

Time frame: Peak to nadir within 7 days

Secondary Outcomes

Mean difference in time weighted average amount of cerebral perfusion pressure below 60 mmHg.

Time frame: Measured for 4 days from index SAH

Proportion experiencing serious adverse event: hypotension requiring vasopressor (excluding during anesthesia), neurological deterioration, serious bronchospasm, and in hospital case fatality.

Time frame: Measured during index hospitalization or first 30 days from index SAH

Disability (30 days +/-7).

Time frame: 30 days from index SAH

Change in serum norepinephrine level from peak to nadir

Time frame: Baseline versus 4th day after index SAH

Change in corrected QT interval

Time frame: First week after presentation for index SAH

Proportion with echocardiographic wall motion abnormalities at baseline and day 7 +- 2

Time frame: First week after presentation.

Proportion with electrocardiographic abnormalities cumulative through day 7

Time frame: Baseline, and at first week after presentation.

Proportion with depressed ejection fraction on initial echocardiogram 36 - 49%

Time frame: Baseline (within 24 hours of presentation for index SAH)

Proportion with life-threatening arrhythmias or cardiac arrest

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.