A Low ChloridE hyperTonic Solution for Brain Edema

Study Overview
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Brief Summary
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This pilot study will compare the two hypertonic solutions currently used for subarachnoid hemorrhage (SAH) - related complications and to determine if the reduction of chloride load is safer, and as efficacious as the classic hypertonic solution.

Detailed Description
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This pilot study aimed to collect high-quality randomized and prospective information to help plan a future, larger multicenter trial. The study will compare the two hypertonic solutions currently used for subarachnoid hemorrhage (SAH) - related complications and to determine if the reduction of chloride load by using a sodium acetate and sodium chloride mixture can lead to a relative reduction of serum chloride, reduce kidney injury, and as efficacious as the classic hypertonic solution. Hyperosmolar therapy is one of the mainstay treatments for SAH-related cerebral edema and vasospasm, in order to reduce delayed cerebral ischemia. Recent evidence from the literature correlates high chloride load when applying IV fluids with worse outcome in a variety of critically-ill patients. Hypertonic saline, with which most hyperosmolar treatment is done, contains a supra-physiologic chloride load. It is possible that by changing the hypertonic solution to a chloride-lean one, the study team would be able to reduce the side effects of hypertonic sodium-chloride without losing its efficacy in treating SAH-related complications.

Official Title
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Low-chloride Versus High-chloride Containing Hypertonic Solution for the Treatment of Subarachnoid Hemorrhage-Related Complications

Conditions
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Subarachnoid Hemorrhage, Acute Kidney Injury

Intervention / Treatment
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* Drug: Sodium chloride /sodium acetate (16.4%)
* Drug: Sodium chloride (23.4%)
* Drug: PlasmaLyte


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spontaneous SAH with an identified aneurysmal source as identified on neuroimaging obtained at admission to Emory University Hospital or with imaging at an outside hospital Age ≥ 18 years Exclusion Criteria: SAH related to non-aneurysmal vascular anomaly SAH thought due to trauma SAH occurring in relation to another medical procedure (cardiac catheterization, LVAD placement, etc.) SAH with a negative workup for cause (angio-negative) Patients who arrive in a brain-death state or in a devastating clinical status that will be presumed to lead to brain death or early withdrawal of treatment Patient who suffer from end-stage renal disease at baseline and who are routinely treated with dialysis Known pregnancy

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Once consented to the study, patients' serum chloride will be followed daily. Patients who will have a chloride concentration of 109mg/dL or above will be randomized to receive the blinded hypertonic solutions.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium chloride /sodium acetate (16.4%)<br>50cc doses of sodium-chloride/sodium-acetate (16.4%) along with 30cc bag of dummy solution (PlasmaLyte). | Drug: Sodium chloride /sodium acetate (16.4%)<br>* Sodium Acetate is a sterile, nonpyrogenic solution of Sodium Acetate intended as an alternative to sodium chloride to provide sodium ion in parenteral (IV) fluid therapy. Sodium Chloride is sterile, nonpyrogenic hypertonic saline (concentrated sodium-chloride) solution for parenteral (IV) fluid therapy.<br>Drug: PlasmaLyte<br>* PlasmaLyte is an isotonic IV solution that mimics human physiological plasma electrolyte concentrations, osmolality and pH.<br>* Other names: Placebo solution;|
| Active Comparator: Sodium chloride (23.4%)<br>30cc per dose of sodium chloride (23.4%) along with 50cc dummy solution bag (PlasmaLyte) | Drug: Sodium chloride (23.4%)<br>* Sodium Chloride is sterile, nonpyrogenic hypertonic saline (concentrated sodium-chloride) solution for parenteral (IV) fluid therapy.<br>Drug: PlasmaLyte<br>* PlasmaLyte is an isotonic IV solution that mimics human physiological plasma electrolyte concentrations, osmolality and pH.<br>* Other names: Placebo solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between serum chloride level on randomization day and the peak afterwards | Serum chloride levels will be measured as part of standard of care. Difference between serum chloride level on randomization day and the peak afterwards will be calculated. | Baseline, up to once daily during a patient's stay in the ICU, and up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with acute kidney injury (AKI) | AKI diagnosis will be done on the basis of clinical parameters (serum creatinine ≥ 1.5 times baseline or ≥0.3 mg/dl and urine output (<0.5 ml/kg/h for 6 hours) according to Kidney Disease Improving Global Outcomes (KDIGO). Number of patients with acute kidney injury (AKI) will be recorded. | Patients' stay in the ICU, and up to 90 days | 
| All causes of in-hospital mortality. | All causes of in-hospital mortality, including withdrawal of treatment or discharge to a hospice facility, will be recorded. | Patients' stay in the ICU, and up to 90 days | 
| All causes of 90 day mortality. | All causes of mortality, 90 days post admission day, including withdrawal of treatment or discharge to a hospice facility, will be recorded. | Up to 90 days | 
| Change in intracerebral pressure (ICP) measured by ICP monitor following hypertonic treatment. | Change in intracerebral pressure (ICP) following the administration of the hypertonic solution will be recorded. | Continuous measurement as long as the patient has an indication for an ICP monitor, and up to 90 days | 
| Change in serum sodium level following the administration of the hypertonic solution. | Serum sodium levels will be measured as part of standard of care. Difference between serum sodium level on randomization day and the peak afterwards will be calculated. | Baseline, and daily during a patient's stay in the ICU, and up to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osmolar therapy, Acetate