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. 2020 May 4:8:32.
doi: 10.1186/s40560-020-00449-0. eCollection 2020.

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

Ofer Sadan  1 , Kai Singbartl  2 , Jacqueline Kraft  1 , Joao McONeil Plancher  1 , Alexander C M Greven  3 , Prem Kandiah  1 , Cederic Pimentel  1 , C L Hall  1 , Alexander Papangelou  4 , William H Asbury  5 , John J Hanfelt  6 , Owen Samuels  1
Affiliations

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

Ofer Sadan et al. J Intensive Care. .

Erratum in

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.

Keywords: Acute kidney injury; Cerebral edema; Hyperchloremia; Hyperosmolar therapy; Neurocritical care; Subarachnoid hemorrhage.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient allocation scheme. aAs per the protocol, consent was obtained within 48 h of admission, when symptoms began within a day of admission. In cases where the symptom onset was unclear, patients were excluded. bDuring the study there was national shortage of Na-acetate solution, which led to a temporary delay in recruitment. LAR, legally authorized representative
Fig. 2
Fig. 2
The effect of hypertonic solution content on serum electrolytes. a ∆ Chloride between time of randomization and the highest recorded value post randomization during the ICU stay was marginally lower in the NaCl/Na-acetate group, yet not statistically significant. b ∆ Sodium between time of randomization and the highest value post randomization during ICU stay was marginally higher in the NaCl/Na-acetate group, yet not in a statistically significant manner. c ∆ creatinine was similar between the groups. d ∆ Bicarbonate (HCO3) was higher in the NaCl/Na-acetate group in a statistically significant manner. e Change in sodium pre- and post-dose was higher in the NaCl/Na-acetate group. f Reduction in ICP was similar between the groups at 20 and 60 min post-administration. *p < 0.05
Fig. 3
Fig. 3
The effect of hypertonic solution on renal function and ICP reduction. a The rate of AKI was lower in the NaCl/Na-acetate group as compared with the NaCl group in an intention to treat analysis. b Comparison of Na+/Cl− loads with the study intervention doses, post-randomization. c Histogram of AKI frequency by group of treatment and hospitalization day. *p < 0.05. AKI, acute kidney injury; KDIGO, Kidney Disease: Improving Global Outcomes grading for AKI
Fig. 4
Fig. 4
Change in urine AKI biomarkers along the first 10 days of admission. a–d Change in biomarker concentration between the different treatment groups (non-randomized, randomized to receive NaCl 23.4% and randomized to receive NaCl/Na-acetate 16.4%). The first time point is days 2–3, which was the day of consent, which was either admission day 2 or 3. *p < 0.05 between the groups. AKI, acute kidney injury
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References

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