Title: Lower serum chloride concentrations are associated with increased risk of mortality in
critically ill cirrhotic patients: an analysis of the MIMIC-III database
Version: 1 Date: 21 Dec 2020
Reviewer's report:
This was retrospective analysis of 1409 cirrhotic patients. I applaud the authors for a large data
set of and a use of novel evaluation of chloride in cirrhotic patients. The demonstrated that
hyponatremia and hypochloremia are significant risk factors for mortality in cirrhotic patients.
I have several significant issues that need to be addressed.
In the Methods: there is no a clear description of the timing of the serum levels. Were all of
these labs taken on admission? During the first 24 hours?
For the definition of hypochloremia, they categorized by hypochloremia and normochloremia.
Did they exclude patients with hyperchloremia? If so it should be stated, otherwise they are
comparing hypochloremia and non-hypochloremia. There is also data in general critically ill
populations that shows that both hypochloremia and hyperchloremia are harmful and that the
mortality vs. level makes a “U”. It would be interesting to see if this remains true in this
population as well.
There are multiple studies also that discuss the change in chloride is predictive of poor outcomes
(AKI, mortality). Was there any consideration for the change of these levels?
For the multivariable logistic regression analysis, was sodium and chloride incorporated into the
same analysis or were they separately run with the same other co-variables? This was unclear
in the methods, it was included in the results, please include in the methods.
Also, it would be nice to see the covariables listed in the methods rather than in the results. Also
how were these variables chosen, a priori? Please state the method.
Given the relationship of AKI and the chloride levels, I would consider adding AKI as covariable
in the regression analyses.
Also in the methods, it would be nice to have the specific sub group analyses spelled out. Please
also include the rationale for why those subgroups were included. If its just for severity of illness
or severity of liver disease then I might consider including those variables in the regression
analyses.
Discussion is appropriate and discusses how this is hypothesis generating. I appreciate the
limitations. One other to consider, was there was no discussion of fluids or diuretics. Since this
is only admission to ICU, fluids/diuretics given prior may have an impact and if they choose to
make edits with multiple time points then this would be a greater consideration.
Minor: multiple grammatical issues. A closer edit is needed. Examples “This result was
remained” and  differences in consistency of spelling of hypchloremia and hypochloraemia.
Title: Lower serum chloride concentrations are associated with increased risk of mortality in
critically ill cirrhotic patients: an analysis of the MIMIC-III database
Version: 1 Date: 21 Dec 2020
Reviewer's report:
This was retrospective analysis of 1409 cirrhotic patients. I applaud the authors for a large data
set of and a use of novel evaluation of chloride in cirrhotic patients. The demonstrated that
hyponatremia and hypochloremia are significant risk factors for mortality in cirrhotic patients.
I have several significant issues that need to be addressed.
In the Methods: there is no a clear description of the timing of the serum levels. Were all of
these labs taken on admission? During the first 24 hours?
For the definition of hypochloremia, they categorized by hypochloremia and normochloremia.
Did they exclude patients with hyperchloremia? If so it should be stated, otherwise they are
comparing hypochloremia and non-hypochloremia. There is also data in general critically ill
populations that shows that both hypochloremia and hyperchloremia are harmful and that the
mortality vs. level makes a “U”. It would be interesting to see if this remains true in this
population as well.
There are multiple studies also that discuss the change in chloride is predictive of poor outcomes
(AKI, mortality). Was there any consideration for the change of these levels?
For the multivariable logistic regression analysis, was sodium and chloride incorporated into the
same analysis or were they separately run with the same other co-variables? This was unclear
in the methods, it was included in the results, please include in the methods.
Also, it would be nice to see the covariables listed in the methods rather than in the results. Also
how were these variables chosen, a priori? Please state the method.
Given the relationship of AKI and the chloride levels, I would consider adding AKI as covariable
in the regression analyses.
Also in the methods, it would be nice to have the specific sub group analyses spelled out. Please
also include the rationale for why those subgroups were included. If its just for severity of illness
or severity of liver disease then I might consider including those variables in the regression
analyses.
Discussion is appropriate and discusses how this is hypothesis generating. I appreciate the
limitations. One other to consider, was there was no discussion of fluids or diuretics. Since this
is only admission to ICU, fluids/diuretics given prior may have an impact and if they choose to
make edits with multiple time points then this would be a greater consideration.
Minor: multiple grammatical issues. A closer edit is needed. Examples “This result was
remained” and  differences in consistency of spelling of hypchloremia and hypochloraemia.
Please review this paper.
user
Title: Lower serum chloride concentrations are associated with increased risk of mortality in
critically ill cirrhotic patients: an analysis of the MIMIC-III database
Version: 1 Date: 21 Dec 2020
Reviewer's report:
This was retrospective analysis of 1409 cirrhotic patients. I applaud the authors for a large data
set of and a use of novel evaluation of chloride in cirrhotic patients. The demonstrated that
hyponatremia and hypochloremia are significant risk factors for mortality in cirrhotic patients.
I have several significant issues that need to be addressed.
In the Methods: there is no a clear description of the timing of the serum levels. Were all of
these labs taken on admission? During the first 24 hours?
For the definition of hypochloremia, they categorized by hypochloremia and normochloremia.
Did they exclude patients with hyperchloremia? If so it should be stated, otherwise they are
comparing hypochloremia and non-hypochloremia. There is also data in general critically ill
populations that shows that both hypochloremia and hyperchloremia are harmful and that the
mortality vs. level makes a “U”. It would be interesting to see if this remains true in this
population as well.
There are multiple studies also that discuss the change in chloride is predictive of poor outcomes
(AKI, mortality). Was there any consideration for the change of these levels?
For the multivariable logistic regression analysis, was sodium and chloride incorporated into the
same analysis or were they separately run with the same other co-variables? This was unclear
in the methods, it was included in the results, please include in the methods.
Also, it would be nice to see the covariables listed in the methods rather than in the results. Also
how were these variables chosen, a priori? Please state the method.
Given the relationship of AKI and the chloride levels, I would consider adding AKI as covariable
in the regression analyses.
Also in the methods, it would be nice to have the specific sub group analyses spelled out. Please
also include the rationale for why those subgroups were included. If its just for severity of illness
or severity of liver disease then I might consider including those variables in the regression
analyses.
Discussion is appropriate and discusses how this is hypothesis generating. I appreciate the
limitations. One other to consider, was there was no discussion of fluids or diuretics. Since this
is only admission to ICU, fluids/diuretics given prior may have an impact and if they choose to
make edits with multiple time points then this would be a greater consideration.
Minor: multiple grammatical issues. A closer edit is needed. Examples “This result was
remained” and  differences in consistency of spelling of hypchloremia and hypochloraemia.
assistant