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ofer.sadan@gmail.com

OS contributed to the design, acquisition, analysis, and interpretation of the data.

KS contributed to the design, analysis, and interpretation of the data.

JK contributed to the acquisition and analysis of the data.

JMP contributed to the acquisition and analysis of the data.

AG contributed to the acquisition and analysis of the data.

PK contributed to the design, acquisition, and analysis of the data.

CP contributed to the design, acquisition, and analysis of the data.

CLH contributed to the acquisition and analysis of the data.

AP contributed to the acquisition and analysis of the data.

WA contributed to the design, analysis, and interpretation of the data.

JH contributed to the design, analysis, and interpretation of the data.

OS contributed to the design, acquisition, analysis, and interpretation of the data.

All authors read and approved the final manuscript.

The authors appreciate Dr. Michael Connor’s contribution to the review of the final version of the manuscript.

The authors declare that they have no competing interests.

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Research Funding:

The study is funded in part by PHS grant UL1TR000454 from the Clinical and Translational Science Award program, National Institutes of Health, and the National Center for Advancing Translational Sciences.

Keywords:

  • Cerebral edema
  • Subarachnoid hemorrhage
  • Hyperosmolar therapy
  • Hyperchloremia
  • Acute kidney injury
  • Neurocritical care

Low-chloride- versus high-chloride-containing hypertonic solution for the treatment of subarachnoid hemorrhage–related complications: The ACETatE (A low ChloriE hyperTonic solution for brain Edema) randomized trial

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Journal Title:

JOURNAL OF INTENSIVE CARE MEDICINE

Volume:

Volume 8

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Type of Work:

Article | Final Publisher PDF

Abstract:

Background Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl− ≥ 109 mmol/L) and required hyperosmolar treatment. Results We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl− load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Conclusions Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl− load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results.

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© The Author(s) 2020

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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