Low-chloride versus high-chloride hypertonic solution for the treatment of subarachnoid hemorrhage-related complications (The ACETatE trial): study protocol for a pilot randomized controlled trial

Ofer Sadan, Owen Samuels, William H Asbury, John J Hanfelt, Kai Singbartl, Ofer Sadan, Owen Samuels, William H Asbury, John J Hanfelt, Kai Singbartl

Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI.

Methods: A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl- concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl- concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia.

Discussion: In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl- content on serum Cl- concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl- concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia.

Trial registration: Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017.

Keywords: Acute kidney injury; Hyperchloremia; Hypertonic NaCl; Osmotherapy; Subarachnoid hemorrhage.

Conflict of interest statement

Ethics approval and consent to participate

The latter of Approval from Emory Univerist IRB was submitted to the journal Editor.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Distribution of maximal chloride serum measurements between acute kidney injury (AKI) and non-AKI as a percent of patients in a retrospective cohort of SAH patients
Fig. 2
Fig. 2
ACETatE study flowchart. AVM arteriovenous malformation, ESRD end-stage renal disease, HT hypertonic, HTS hypertonic sailne, ICU intensive care unit, SAH subarachnoid hemorrhage
Fig. 3
Fig. 3
Schedule of enrollment, interventions, and assessments. ICU intensive care unit

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