Using Propranolol in Traumatic Brain Injury to Reduce Sympathetic Storm Phenomenon

Using Propranolol in Traumatic Brain Injury to Reduce Sympathetic Storm Phenomenon: A Prospective Randomized Clinical Trial Injury to Reduce Sympathetic Storm Phenomenon: A Prospective Randomized Clinical Trial

Traumatic Brain Injury (TBI) is one of the leading causes of death. Severe TBT is correlated with an exaggerated stress response due to plasma catecholamine levels known as sympathetic storming. It is also autonomic dysfunction syndrome. This phenomenon is also associated with brain tumors, severe hydrocephalus and subarachnoid hemorrhage. Patients are presented by tachycardia, tachypnea hypertension, diaphoresis, dystonia, hyperthermia, and dilated pupils with elevated levels of plasma catecholamine and blood glucose .

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Propranolol Hydrochloride 1 MG/ML; Other: Normal saline

Detailed Description

The sympathetic storming events can be triggered by suctioning, repositioning, or environmental stimuli. To differentiate sympathetic storming from similar conditions, symptoms and signs have to occur in TBI patients a minimum of 1 cycle per day for 3 consecutive days (body temperature of 38.5 °C or more, heart rate at least 120 beat / min, systolic blood pressure > 140 mmHg, respiratory rate > 20 breaths / min, in presence of dystonia, diaphoresis, agitation and laboratory investigations confirm elevated serum catecholamines. Beta blockers has a cardio protective effect via lowering heart rate, stroke volume and mean arterial blood pressure which limits myocardial O2 consumptions and guards against myocardial infarction. They also have neuron protective effects via reducing cerebral blood flow thus lowering O2 and glucose consumption as cerebral metabolism is reduced. Propranolol a nonselective B receptor antagonists works on β1 receptors in brain, heart, and kidney and β 2 receptors in lungs, liver, skeletal muscles, eye and arterioles.We suppose that using Beta - adrenergic receptor blockers as propranolol blunts the sympathetic storming phenomenon as it is a nonselective β inhibitor and has a lipophilic property which enables it to penetrate blood brain barrier.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients with isolated blunt TBI
• From 18 to 60 years old both sex
• Not in need of mechanical ventilation
• GCS on admission between 9 and 12
• Rotterdam CT score from 2-4.
• Normal Procalcitonin test to exclude infection.

Exclusion criteria:

• Preexisting heart disease
• Myocardial injury
• Craniotomy
• Preexisting cerebral dysfunction
• Spinal cord injury
• Diabetes mellitus
• Severe liver or kidney disease
• Patients with sepsis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intervention; Adminstration of propranolol hydrochloride ( 1 MG /ml) 1 mg every 6 hrs .	Drug: Propranolol Hydrochloride 1 MG/ML; Propranolol 1 mg every 6 hrs in the first 24 hrs after isolated blunt traumatic brain injury
PLACEBO_COMPARATOR: Control; Adminstration of normal saline 1 mg every 6 hrs	Other: Normal saline; Normal Saline 1 ml every 6 hrs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
catecholamine level	Norepinephrine plasma levels in pg./ml	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temperature	Temperature in °C	7 days

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2016
• Primary Completion (ACTUAL): June 10, 2017
• Study Completion (ACTUAL): August 1, 2017

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (ACTUAL): January 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 1345 AUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No