Skip to main content

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

A Commentary to this article was published on 26 September 2020

The Original Article was published on 04 May 2020


Sadan et al. find an association between acute kidney injury and high chloride containing a hypertonic solution. Recent large prospective non-randomized studies bring conflicting results on the relationship between chloride and acute kidney injury. We discuss Sadan et al.’s results according to the recent literature.

Dear Sir,

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 concluded that NaCl/Na-acetate may modify the risk of AKI by reducing chloride load. Concerning intracranial pressure decreasing, both product’s effect was similar.

We do not fully agree with their conclusions.

First, the authors planned to randomize 60 patients (30 patients per group); however, only 32 were analyzed.

Then, the results seem to show that groups are not strictly similar despite randomization. In fact, cerebral edema in Na-acetate group could be less serious because they required a lower number of hypertonic solution doses. Moreover, the rate of AKI was lower in the NaCl/Na-acetate group as compared with the NaCl group, while the delta of creatinine post randomization was similar between groups. We only observe two patients who developed AKI after randomization, including one on the sixth day. It is probably too late to blame chloride load.

Third, some confounding factors are not indicated in the study. 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? In fact, in this study, delta intravenous chloride load and treatment with NaCl/Na-acetate appear as factors influencing renal prognosis.

Finally, in figure 3B, we observe seven patients of the 23.4% NaCl group who developed AKI. However, 53.3% of the 15 patients correspond to 8 patients.

Sadan et al. performed an interesting study, but several biases limit the author’s conclusions. Notably, AKI mainly occurred before randomization. It seems difficult to incriminate the type of solute and chloride load in AKI. On the other side, the responsibility of chloride in AKI is still discussed in large non-randomized controlled trials (RCT) performed in ICU [3], in operating room [4], and in RCT realized in high-risk surgical patients like kidney transplantation [5]. Large RCTs are needed to definitively conclude about the role of saline and chloride load in AKI [6].



Randomized controlled trials


Acute kidney injury


  1. Sadan O, Singbartl K, Kraft J, Plancher JM, Greven ACM, Kandiah P, Pimentel C, Hall CL, Papangelou A, Asbury WH, Hanfelt JJ, Samuels O. 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. J Intensive Care. 2020;8:32.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tujjar O, Belloni I, Hougardy JM, Scolletta S, Vincent JL, Creteur J, Taccone FS. Acute kidney injury after subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2017;29:140–9.

    Article  PubMed  Google Scholar 

  3. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW, Investigators S, the Pragmatic Critical Care Research G. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829–39.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Maheshwari K, Turan A, Makarova N, Ma C, Esa WAS, Ruetzler K, Barsoum S, Kuhel AG, Ritchey MR, Higuera-Rueda C, Kopyeva T, Stocchi L, Essber H, Cohen B, Suleiman I, Bajracharya GR, Chelnick D, Mascha EJ, Kurz A, Sessler DI. Saline versus lactated Ringer’s solution: the Saline or Lactated Ringer’s (SOLAR) Trial. Anesthesiology. 2020;132:614–24.

    Article  CAS  PubMed  Google Scholar 

  5. Potura E, Lindner G, Biesenbach P, Funk GC, Reiterer C, Kabon B, Schwarz C, Druml W, Fleischmann E. An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial. Anesth Analg. 2015;120:123–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wanderer JP, Rathmell JP. The great fluid debate: normal saline versus balanced crystalloid. Anesthesiology. 2020;132:A19.

    CAS  PubMed  Google Scholar 

Download references


Not applicable

Author information

Authors and Affiliations



Gildas Gueret wrote the text. Pierre Lefebvre, Pascale Le Maguet, and Renaud Fabre corrected the text. All authors have approved the manuscript.

Corresponding author

Correspondence to Gildas Gueret.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

The content of the letter was not published elsewhere.

Competing interests

The authors have no conflict of interest. None of the authors has any potential competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gueret, G., Lefebvre, P., Le Maguet, P. et al. Acute kidney injury after aneurysmal subarachnoid hemorrhage: is chloride really responsible?. j intensive care 8, 73 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: