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

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. Trial registration clinicaltrials.gov # NCT03204955, registered on 6/28/2017

Acute kidney injury after aneurysmal subarachnoid hemorrhage: is chloride really responsible?

“…Intracranial hypertension, osmotic therapy, and vasopressor therapy are known to be risk factors of AKI after subarachnoid hemorrhage [2]. But in Sadan et al's study [1], we do not know how many patients received vasopressor therapy before and after randomization in each group. Likewise, before randomization, did the patients receive the same amount of hypertonic solution, and was intravenous chloride load similar in each group?…”

“…We were interested in the article written by Sadan et al [ 1 ]. After aneurysmal subarachnoid hemorrhage, the authors found an increase in acute kidney injury (AKI) for patients receiving high-chloride versus low-chloride containing a hypertonic solution.…”

The authors’ response

“…We appreciate the interest in our manuscript [1], and the opportunity to respond to the comments. There is no doubt that our study suffers from several shortcomings.…”

A nomogram based on serum cystatin C for predicting acute kidney injury in patients with traumatic brain injury

“…AKI after TBI has been reported developing in 7.6% to 23% patients and is correlated with mortality, functional outcome and length of hospital stay in TBI patients [4][5][6][7]. Mechanisms involved in development of AKI after TBI are diversified, which included systemic inflammation response, neuroendocrine hormone release, hypoperfusion and iatrogenic factors such as blood transfusion, drugs reducing intracranial pressure and usage of nephrotoxic antibiotics [8][9][10][11]. In view of the unfavorable outcome caused by AKI, exploring novel and available biomarkers to predict the possible occurrence of AKI in early stage and consequently avoid medical treatments adverse to normal renal function is beneficial for outcome and recovery of TBI patients.…”