Early Induced Hypernatremia for the Prevention and Management of Brain Edema (EHIBE)

Early Induced Hypernatremia for the Prevention and Management of Brain Edema in Patients With Severe Traumatic Brain Injury in a University Hospital

The purpose of this study is to estimate the effect of an early induced hypernatremia protocol (150-155 milliequivalent/L) versus normonatremia plus mannitol (135 - 145 milliequivalent/L) in terms of neurologic outcome in patients with severe traumatic brain injury managed at critical care unit.

Study Overview

• Status: Withdrawn
• Conditions: Head Trauma
• Intervention / Treatment: Other: Hypernatremia

Detailed Description

Severe traumatic brain injury is one of the main causes of death in young people. Additionally, it is considered a public health problem because of the high prevalence of motor and cognitive dysfunction in those who survive.

One of the cornerstones of management is the control of both intracranial pressure and brain edema. It is indicated to use osmotic active solutions to modulate the transit of fluids from the interstitial to the intracellular space. Not only mannitol but also hypertonic saline acts at this point. Currently there is no evidence in favor or against one of them.

Mannitol has been usually recommended for intracranial pressure control in patients with brain trauma. However, others recommend hypertonic saline to achieve a serum sodium level of 160 milliequivalent/L to modulate brain edema. It is not clear if these therapies have an impact on the neurologic prognosis and how frequently adverse effects occur.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jorge H Donado, MD, MSc; Phone Number: 9897 574- 4459000; Email: jdonado@hptu.org.co
• Study Contact Backup: Name: Gisela De La Rosa, MD; Phone Number: 9597 574- 4459000; Email: giseladlr@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient greater than 14 years old, who suffered severe non-penetrating Brain Trauma (Glasgow Coma Scale (GCS) equal or less than 8) and a motor GCS equal or less than 5.
2. Criteria time: admitted to the Hospital in the first 24 hours of the Brain Trauma (BT) and admitted to ICU in the first 48 hours of brain trauma.
3. Tomographic evidence of brain edema (one of the following criteria: deviation from the midline, obliteration of perimesencephalic cistern or altered cortico-subcortical differentiation).

Exclusion Criteria:

1. Patient with GCS 3 and bilateral mydriatic pupils and unreactive to light, in the presence of hemodynamic stability (systolic blood pressure equal or greater than 90 mmHg).
2. Patient with insipid diabetes at the ICU admission.
3. Patient with limitation of therapeutic effort.
4. Non-neurological Abbreviated Injury Score greater than 3.
5. Patient past medical history of kidney failure, liver disease or heart failure.
6. Serum sodium less than 135 or greater than 150 milliequivalent/L.
7. Pregnancy.
8. Terminal disease.
9. No authorization to be enrolled in the trial by the patient's caregiver

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypernatremia; Serum sodium between 150 - 155 milliequivalent/L. 7,5% sodium chloride (2 ml/kg every 4 hours), with controls of serum sodium every 4 hours, to achieve a goal of serum sodium between 150 - 155 milliequivalent/L. If after 4 doses of 7.5% sodium chloride the serum sodium is below the target, a bolus of 1 ml/kg of 12% sodium chloride will be used every 4 hours. The goal of serum sodium will be maintained for 48 hours.	Other: Hypernatremia; Serum Sodium goal: 150 - 155 milliequivalent/L.
No Intervention: Normonatremia; Serum sodium between 135 - 145 milliequivalent/L. Mannitol 100 ml every 4 hours for the first three days; 80 ml every 4 hours the fourth day; 60 ml every 4 hours the fifth day and 40 ml every 4 hours the sixth day and then stopping. The mannitol protocol will be interrupted at any moment if serum sodium is below 135, the systolic blood pressure is below 90 mmHg or the patient has signs of hypovolemia. In this case, 2 ml/kg of 3% sodium chloride every 4 hours will be used until the target of serum sodium is achieved and both, normovolemic state and blood pressure are restored. In addition, the mannitol protocol will be suspended when serum osmolality is above 320.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Outcome Scale Extended	The Extended Glasgow Outcome Scale (GOSE) is a global scale for functional outcome that rates patients into eight categories. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. The scale will be used to evaluate the patient through a phone interview at 6 months of the trauma occurred. The structured interview contains nineteen specific questions which determine upper or lower levels of disability.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Mortality by any cause	28 - day AND 180 - day mortality
Ventilator - Free Days	Days free of mechanical ventilation at 30 days	30 days
Fluid balance.	Net fluid balance (input minus output) (ml) at day 1,2,3,4 y 5.	5 days
Acute kidney injury	Acute kidney injury (KDIGO criteria). The criteria for acute kidney injury(AKI) are based on changes in serum creatinine (SCr) and urine output. Stage I : Increase in SCr more than 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days OR increase in SCr more than 0.3 mg/dL within 48 hours OR urine output <0.5 ml/kg/h for 6-12h. Stage II : Increase in SCr between 2.0 - 2.9 times baseline, which is known or presumed to have occurred within the prior 7 days OR urine output <0.5 ml/kg/h for more than 12 hours. Stage III : Increase more than 3.0 times baseline, which is known or presumed to have occurred within the prior 7 days OR Increase in serum creatinine to 4.0 mg/dL OR Initiation of renal-replacement therapy OR urine output <0.3 ml/kg/h for more than 24 hours OR Anuria for more than 12 hours.	7 days
Intracranial pressure (ICP) measurement	Intracranial pressure measurement (mmHg) during the first 5 days at the ICU. Estimate the effect of therapies to control intracranial pressure. An intraparenchymal catheter will used to measure the ICP. Intracranial pressure (ICP) will be measured every hour. Intracranial hypertension will be defined as ICP > 20 mm Hg lasting longer than 5 minutes.	5 days
Need of second line therapies for brain edema	Secondary decompressive craniectomy or barbituric coma for control of brain edema.	7 days
All-cause mortality according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.	Estimate the effects of therapies on mortality according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).	28 - day AND 180 - day mortality
Glasgow Outcome Scale Extended (GOSE) according to subgroups of monitoring: guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring.	Estimate the effects of therapies on the GOSE according to subgroups of treatment (guided by neurologic examination and serial CT imaging or guided by intracranial pressure monitoring).	6 Months

Collaborators and Investigators

• Sponsor: Hospital Pablo Tobón Uribe
• Collaborators: CES University
• Investigators: Principal Investigator: Juan C Lopez de Mesa, MD, Hospital Pablo Tobon Uribe

Study record dates

Study Major Dates

• Study Start (Estimated): January 18, 2017
• Primary Completion (Estimated): January 18, 2017
• Study Completion (Estimated): January 18, 2018

Study Registration Dates

• First Submitted: May 21, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimated): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Mortality; Hypernatremia; Hypertonic saline; Intracranial pressure; Cerebral edema; Mannitol; Extended Glasgow Outcome Scale
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Water-Electrolyte Imbalance; Craniocerebral Trauma; Hypernatremia; Brain Edema
• Other Study ID Numbers: U1111-1183-0891; HPTU (Registry Identifier: 2016.049)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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