Title: Incidence and risks of excessive distension absorption in hysteroscopic surgery using 5%
mannitol solution: a retrospective descriptive study.
Version: 4 Date: 26 Aug 2024
Reviewer:  Antonio Bandala-Jacques
Reviewer's report:
Dear authors -
I have received your revised submission, and offer the following comments:
First, I will address my specific comments from a prior revision:
A) There are still some language issues that should be addressed in the
manuscript, for example, in your first paragraph, I don't think the word
"unpleasant" is the one you mean to use. I would omit it all together
Our response:
Thanks for the advice. We have replaced the “unpleasant condition” with “adverse
events” in the revised manuscript.
Reviewer response:  I think this is adequate
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B) I would avoid starting a sentence with a number ".5% mannitol solution..." If
required, I would spell it out
Our response#
Thanks for the advice. Spelling out the number at the beginning of the sentence is a
more stylistic choice for formal academic writing.
This sentence was also detected and advised to edit due to repletion with the formal
description by Reviewer 5. So, we have deleted this repeated description in the third
paragraph.
Reviewer response: thank you for implementing the suggestion
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C) You should end your introduction with a clear objective or hypothesis. It is in
the abstract, but should be explicit in the manuscript too
Our response:
Thanks for the advice. We have made a supplement at the end of the introduction to
explicit the objective of the study as follow:
“We conducted this study to determine the exact incidence of fluid overload in
hysteroscopic surgeries using mannitol, to assess the clinical disturbances associated
with varying blood sodium levels, and to explore patients’ clinical presentation and
manifestation as fluid deficit increases.”
Reviewer response:  This is clear now
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MATERIALS AND METHODS
D) Your inclusions and exclusions would greatly benefit from a flowchart, as the
source population is in one paragraph, and the study population in a different
one.
Our response:
Thanks a lot for the advice. We have included the following flowchart in the Methods
section:
Reviewer response:  The flowchart is clear
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E) I would also be clear with the study design, as "retrospective" can be very
vague
Our response:
Thanks for the advice. We have clearly defined our study design at the beginning of
the Methods section as: “This is a retrospective descriptive study.”. Corresponding
changes have also been made in the study design section of the abstract.
Reviewer response:  I think this is better
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F) The methods needs a statistical analysis section, which should adhere to the
proposed addition of an objective to your introduction
Our response:
Thank you for the advice. A statistical analysis section has been added in the
penultimate paragraph of the Methods section as follows:
“Continuous variables, including age, body weight, and blood pressure were
presented as means ± standard deviations. Categorical variables, such as the incidence
of clinical signs or symptoms, were presented as relative frequencies. The incidence
of excessive distension absorption and clinical disturbance were calculated for each
surgical group. Data was analyzed using SPSS version 25 (IBM, Armonk, NY).”.
Reviewer response:  This is adequate
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RESULTS
G) With a low final sample size, I would use one decimal at most
Our response:
Thank you for the suggestion. We appreciate your guidance. However, we would like
to retain two decimal places to align with the journal's publication standards and
maintain consistency with similar studies [1].
[1] Nakamura, M., Ikeda, K. & Uezono, S. Metabolic acidemia due to saline
absorption during transurethral and transcervical surgery: a report of 2 cases. BMC
Anesthesiol, 24, 62 (2024)
Reviewer response:  This is a valid argument
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H) You should operationalize all of the covariates you mention here in the
methods
Our response:
Thank you for the valuable suggestion. We have provided detailed descriptions of
how each covariate was measured at the end of the first paragraph in the Methods
section as:
“Medical history and physical examination were taken by the residents on the first
day of admission. Age, menstruation cycle and duration, gravida and parity were
recorded. Body weight, blood pressure was measured on the admission day.
Laboratory tests including serum sodium were texted before surgery. Intraoperative
serum sodium was texted by the anesthetists when the fluid overload was detected.
Surgical time and fluid deficit was recorded by the circulating nurse. Clinical
consequences such as coughing, nausea, vomiting, hypotension, hypoxemia,
tachycardia, laryngeal and pulmonary edema were detected and documented in the
patients' medical records by the physicians.”.
Reviewer response:  This is adequate, but I'm confused by the use of the word "texted" as it is
more generally used as a neologism for  'text messaging'. is this what you meant?
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I) The inclusion of new techniques is adequate, as recommended in prior
revisions
Our response:
Thank you for your advice. We do recognize the importance of emerging new
techniques. We have read and cited the publication about new techniques
recommended by Reviewer 1 and Reviewer 3 in the second paragraph of the
discussion section.
Other new techniques such “Hysteroscopic scissor, HEOS, MyoSure, and bipolar
electrosurgical instrument” mentioned in the method section all these instruments
using saline as distension media.
At the outset of this study, we did conduct a brief review of procedures using saline at
our institute. Notably, we did not observe any cases of fluid overload in TCRA
procedures performed with scissors. We have included a comparison of these findings
with TCRA using a monopolar needle in the discussion section.
Due to the differing physical properties of saline and mannitol, the associated clinical
disturbances vary. Specifically, one of the major concerns with 5% mannitol
absorption is hyponatremia, a complication that is absent in cases of saline overload,
and which we have discussed in this manuscript. To maintain focus and avoid
complexity, we chose not to include procedures utilizing saline in this study. And we
wish to explore such hysteroscopic complications using different kind distension
media and emerging techniques in future studies
Reviewer response:  This is a valid response
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J) The discussion needs significant language editing. There are several isolated
ideas and phrases that make some paragraphs difficult to read
Our response:
Thanks for your advice. We have rearranged the discussion section with language
editing in order to make it readable for English speaker and non-English speaker.
Reviewer response:   Your edits of the discussion have improved the manuscript
K) You mention "The risk of excessive distension absorption would be eliminated
through certain procedures, such as endometrial preparation, reducing surgery
time, avoiding unnecessary deep myometrial resection, and improving the
proficiency and safety awareness of the surgeon"This is a strong statement, and
although some of the assertions might be obvious from available literature, I
don't think your study design can make these assertions, as it is subject to issues
such as inverse causality. I would rephrase this in a way that does not overstate
what you can conclude given your study design,
Our response:
Thanks for your advice. Sorry for the overstate impression. This manuscript was a
revised version of our original submission. We have added this statement to the
original discussion section since reviewers recommended to “highlight the clinical
implication”. We have rephrased this statement as follows:
“Given the published literature and our study, we believe the risk of excessive
distension absorption would be decreased through certain procedures, such as
endometrial preparation [13], reducing surgery time [16], avoiding unnecessary deep
myometrial resection [11], and improving the proficiency and safety awareness of the
surgeon.”
Reviewer response:  I believe this an adequate re-statement
I offer additional comments on the revised version, mostly related to style and editing
ADDITIONAL COMMENTS:
1) In "While excessive absorption of 5% mannitol solution which is isotonic, electrolyte-
poor, low-viscosity, could lead to fluid overload along with hyponatremia and hypoosmolality,
potentially developing into pulmonary edema, congestive heart failure and cerebral edema"
I believe this sentence needs to be restructured. The use of "while" implies that the is a
subordinate sentence that is missing. Maybe try re-reading it without the word "while"
2) In "Once hyponatremic encephalopathy developed, mortality and the risk of permanent
cerebral damage increase significantly in the female at reproductive age"
I believe "developed" here should be in the present tense if stating a fact
3) the sentence "Despite extensive knowledge about excessive distension absorption as a
hysteroscopic complication, variability in terminology, definition, multiple choice of distending
media and setting for distension pressure have led to a lack of specific descriptions regarding
the incidence, clinical presentation, management and prognosis of such complication. "
This sentence is hard to follow. May I suggest: "Despite extensive knowledge regarding
excessive distension absorption as a hysteroscopic complication, issues such as variability in
terminology,  multiple choices of distending media, and settings for distension pressure have
led to a lack of  descriptions regarding the incidence, clinical presentation, management and
prognosis of such complication. "
4) In "We only include inpatient hysteroscopic surgical procedures using 5% mannitol as
distension media with a 120mmHg inflow pressure", included should be in the past tense. Later,
in the same parapgraph I would change "have been completed ", to "were performed". Later in
the same paragraph you write "completed in our hospital using a monopolar instrument distended
with 5% mannitol solution.". This implies the instrument was distended
5) In "All these inpatient surgeries were arranged in the operation theatre under general
anesthesia. " I would substitute 'arranged' for 'performed'
6) "Ultimately, we collected 49 cases diagnosed excessive distension absorption", should read
'diagnosed with ...'
7) I would restructure "Hysteroscopic scissor, Hysteroscopic Endo Operative System (HEOS),
MyoSure Hysteroscopic Tissue Removal System and bipolar electrosurgical instrument using
salinehave been introduced since 2017.Those procedures were not included in this study." to
"We excluded X, Y, and Z methods" Also, please mind the lack of a space between 'saline' and
'have'
8) Shouldn't  "This study is by far the largest single-center retrospective study of excessive
distension absorption. The surgical procedures, including distension media selection and
pressure settings, are highly standardized. " go in the strengths area of the discussion?
9) When referring to your own results, I recommend the use of the past tense. "Incidence of the
excessive distention absorption was 0.46%  generally", instead of "is".
Also, I would what do you mean by generally? As in, 'overall'?
10) In table 2, I recommend adding column totals, such as "No. of Procedures (N=49)"
11) In "Postoperative and intraoperative hyponatremia were detected in all these patients" the
use of "these" implies a substudy. If you did not mean this, I would revise to "in all our study
population" or similar
12) In your discussion changing "The incidence of fluid overload seems low based on the
published literatures." to "Our study found a low incidence of fluid overload compared to
published literature." makes your opening sentence stronger
13) You state "resulting an incidence rate of 0.2%" It is missing the word "in". Additionally,
incidence rates use person-time as a denominator. I suspect this is simply incidence
14 In ". However, in our study, we find that it is not rare in RPOC removal and adhesiolysis of
severe IUA cases. " you should use the past tense
15) In "In the first 250 endometrial resections experience". What 250 resections are you referring
to?
16) In "This risk is heightened in the severe cases, endometrium was predominantly replaced by
scar tissue. " You should add a connector between the two clauses
17) In "Without electronic energy, the scissor does not have any hemostasis function."  Would
this be electrical energy?
18) In "When the myometrial was broken, the bleeding would be more likely to be detected by
the operator" when the mymetrial was broken in whom ? If this is a fact, change to present tense
19) Overall, this third discussion paragraph still need some editing as it has multiply clauses
that don't seem to be connected
20) "In our study, we also find that excessive ". Find should be stated in the past tense, as you
refer to your own study
21) ". In certain kind treatments such as TCRF," is missing the word 'of'. Same later in the same
paragraph
21) Your last sentence is ". And we wish to explore such hysteroscopic complications using
different kind distension media and emerging techniques in future studies."
It is unusual to start a sentence with "and" after a full stop. I would maybe restructure to "Future
studies should focus on...."