Title: Safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for
deep sedation of elderly patients undergoing ERCP
Version: 1 Date: 20 Nov 2023
Reviewer's report:
GENERAL COMMENT
The number of endoscopic procedures requiring sedation has grown over the past decades.
Patient safety and comfort are the key elements in sedation (PMID: 36647160). The combination
of drugs belonging to different classes is rational given that it may allow synergism resulting
from different mechanisms of action therefore consenting increased efficacy and lower side
effects thanks to dose reduction of each individual component of the drug combination.
With this backset, submission ID 60a58b81-8a87-4a99-975e-f7a67059cd4f found that a low-
dose three-drug regime (midazolam, alfentanil, and propofol) was safe and effective for deep
sedation of elderly and very elderly individuals undergoing ERCP procedures for benign biliary
duct disease. Points of strengths of the study include substantially homogeneous comparison
groups and a reasonably large sample of patients over the age of 80 years. However, this
submission has also several limitations which are properly addressed by the authors. Some
suggestions aimed at improving the manuscript are appended below.
SPECIFIC COMMENT
MAJOR
1. Title fails to identify the study adequately. Rephrase it based on the following statement “a
low-dose three-drug regime consisting of midazolam, alfentanil, and propofol seems safe and
effective for deep sedation of elderly and very elderly patients who are the candidates for ERCP
procedures”
2. Keywords: “midazolam”, “alfentanil” and “propofol” must be added
3. Introduction - This section should be fully reworked aimed at: a) Improving conciseness b)
Focusing on the pros and cons of pharmacological association of midazolam-alfentanil-propofol
c) Highlighting the specific rationale and the research question(s). In this connection, authors
may be willing to consider that the statement “there is a paucity of studies” never is a necessary
nor sufficient condition unless otherwise qualified by a robust rationale.
4. Methods a) The reason why a series of patients with benign disease only were selected should
be declared. Moreover, American Society for Gastrointestinal Endoscopy (ASGE) grade for
complexity of ERCP procedure should be reported [PMID: 21377673.]. b) bispectral index
(BIS): given that this is not a popular technique, it definitely deserves some identification. To
this end, it may be suggested to anticipate those notions illustrate under the relative paragraph
of discussion. “All ERCP procedures were performed using standard duodenoscope by expert
endoscopists with more than two years of experience” Please, state how many different operators
were involved in this study (if possible, also indicate the number of procedures per year for each
operator involved).
5. Discussion - This section is too long and poorly focused. Authors may be willing to rework
discussion section following a standard format: a) Summarize novel finding b) Discuss such
findings in relation to previous studies and to the rationale of the study c) Strengths and
limitations of the research. d) Conclusion and research agenda. In particular, the following
paragraph may be either deleted or move to elsewhere in the manuscript “As a gold standard
for treating biliary and pancreatic diseases, ERCP application is growing with the aging of the
global population [14]. Proper sedation of patients is of great significance in ERCP. Elderly
patients are more prone to sedation-related complications, making sedation a significant concern
in this group of patients [4]. Thus, ensuring safe and tolerable sedation is essential for improved
management and better outcomes in elderly patients undergoing ERCP procedures.” Finally,
more emphasis should be placed on how drug doses were titrated to avoid sedation-related
adverse events.
MINOR
1. “ASA guidelines” a reference should be added.
2. If possible, increased variety in phraseology should be added given that “in the present study/
in the current study is repeated multiple times.
3. Indicate whether propofol was administered by an anaesthesiologist or another member of
staff.
4. Find bibliographic reference for definitions of apnea and respiratory depression.
Title: Safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for
deep sedation of elderly patients undergoing ERCP
Version: 1 Date: 20 Nov 2023
Reviewer's report:
GENERAL COMMENT
The number of endoscopic procedures requiring sedation has grown over the past decades.
Patient safety and comfort are the key elements in sedation (PMID: 36647160). The combination
of drugs belonging to different classes is rational given that it may allow synergism resulting
from different mechanisms of action therefore consenting increased efficacy and lower side
effects thanks to dose reduction of each individual component of the drug combination.
With this backset, submission ID 60a58b81-8a87-4a99-975e-f7a67059cd4f found that a low-
dose three-drug regime (midazolam, alfentanil, and propofol) was safe and effective for deep
sedation of elderly and very elderly individuals undergoing ERCP procedures for benign biliary
duct disease. Points of strengths of the study include substantially homogeneous comparison
groups and a reasonably large sample of patients over the age of 80 years. However, this
submission has also several limitations which are properly addressed by the authors. Some
suggestions aimed at improving the manuscript are appended below.
SPECIFIC COMMENT
MAJOR
1. Title fails to identify the study adequately. Rephrase it based on the following statement “a
low-dose three-drug regime consisting of midazolam, alfentanil, and propofol seems safe and
effective for deep sedation of elderly and very elderly patients who are the candidates for ERCP
procedures”
2. Keywords: “midazolam”, “alfentanil” and “propofol” must be added
3. Introduction - This section should be fully reworked aimed at: a) Improving conciseness b)
Focusing on the pros and cons of pharmacological association of midazolam-alfentanil-propofol
c) Highlighting the specific rationale and the research question(s). In this connection, authors
may be willing to consider that the statement “there is a paucity of studies” never is a necessary
nor sufficient condition unless otherwise qualified by a robust rationale.
4. Methods a) The reason why a series of patients with benign disease only were selected should
be declared. Moreover, American Society for Gastrointestinal Endoscopy (ASGE) grade for
complexity of ERCP procedure should be reported [PMID: 21377673.]. b) bispectral index
(BIS): given that this is not a popular technique, it definitely deserves some identification. To
this end, it may be suggested to anticipate those notions illustrate under the relative paragraph
of discussion. “All ERCP procedures were performed using standard duodenoscope by expert
endoscopists with more than two years of experience” Please, state how many different operators
were involved in this study (if possible, also indicate the number of procedures per year for each
operator involved).
5. Discussion - This section is too long and poorly focused. Authors may be willing to rework
discussion section following a standard format: a) Summarize novel finding b) Discuss such
findings in relation to previous studies and to the rationale of the study c) Strengths and
limitations of the research. d) Conclusion and research agenda. In particular, the following
paragraph may be either deleted or move to elsewhere in the manuscript “As a gold standard
for treating biliary and pancreatic diseases, ERCP application is growing with the aging of the
global population [14]. Proper sedation of patients is of great significance in ERCP. Elderly
patients are more prone to sedation-related complications, making sedation a significant concern
in this group of patients [4]. Thus, ensuring safe and tolerable sedation is essential for improved
management and better outcomes in elderly patients undergoing ERCP procedures.” Finally,
more emphasis should be placed on how drug doses were titrated to avoid sedation-related
adverse events.
MINOR
1. “ASA guidelines” a reference should be added.
2. If possible, increased variety in phraseology should be added given that “in the present study/
in the current study is repeated multiple times.
3. Indicate whether propofol was administered by an anaesthesiologist or another member of
staff.
4. Find bibliographic reference for definitions of apnea and respiratory depression.
Please review this paper.
user
Title: Safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for
deep sedation of elderly patients undergoing ERCP
Version: 1 Date: 20 Nov 2023
Reviewer's report:
GENERAL COMMENT
The number of endoscopic procedures requiring sedation has grown over the past decades.
Patient safety and comfort are the key elements in sedation (PMID: 36647160). The combination
of drugs belonging to different classes is rational given that it may allow synergism resulting
from different mechanisms of action therefore consenting increased efficacy and lower side
effects thanks to dose reduction of each individual component of the drug combination.
With this backset, submission ID 60a58b81-8a87-4a99-975e-f7a67059cd4f found that a low-
dose three-drug regime (midazolam, alfentanil, and propofol) was safe and effective for deep
sedation of elderly and very elderly individuals undergoing ERCP procedures for benign biliary
duct disease. Points of strengths of the study include substantially homogeneous comparison
groups and a reasonably large sample of patients over the age of 80 years. However, this
submission has also several limitations which are properly addressed by the authors. Some
suggestions aimed at improving the manuscript are appended below.
SPECIFIC COMMENT
MAJOR
1. Title fails to identify the study adequately. Rephrase it based on the following statement “a
low-dose three-drug regime consisting of midazolam, alfentanil, and propofol seems safe and
effective for deep sedation of elderly and very elderly patients who are the candidates for ERCP
procedures”
2. Keywords: “midazolam”, “alfentanil” and “propofol” must be added
3. Introduction - This section should be fully reworked aimed at: a) Improving conciseness b)
Focusing on the pros and cons of pharmacological association of midazolam-alfentanil-propofol
c) Highlighting the specific rationale and the research question(s). In this connection, authors
may be willing to consider that the statement “there is a paucity of studies” never is a necessary
nor sufficient condition unless otherwise qualified by a robust rationale.
4. Methods a) The reason why a series of patients with benign disease only were selected should
be declared. Moreover, American Society for Gastrointestinal Endoscopy (ASGE) grade for
complexity of ERCP procedure should be reported [PMID: 21377673.]. b) bispectral index
(BIS): given that this is not a popular technique, it definitely deserves some identification. To
this end, it may be suggested to anticipate those notions illustrate under the relative paragraph
of discussion. “All ERCP procedures were performed using standard duodenoscope by expert
endoscopists with more than two years of experience” Please, state how many different operators
were involved in this study (if possible, also indicate the number of procedures per year for each
operator involved).
5. Discussion - This section is too long and poorly focused. Authors may be willing to rework
discussion section following a standard format: a) Summarize novel finding b) Discuss such
findings in relation to previous studies and to the rationale of the study c) Strengths and
limitations of the research. d) Conclusion and research agenda. In particular, the following
paragraph may be either deleted or move to elsewhere in the manuscript “As a gold standard
for treating biliary and pancreatic diseases, ERCP application is growing with the aging of the
global population [14]. Proper sedation of patients is of great significance in ERCP. Elderly
patients are more prone to sedation-related complications, making sedation a significant concern
in this group of patients [4]. Thus, ensuring safe and tolerable sedation is essential for improved
management and better outcomes in elderly patients undergoing ERCP procedures.” Finally,
more emphasis should be placed on how drug doses were titrated to avoid sedation-related
adverse events.
MINOR
1. “ASA guidelines” a reference should be added.
2. If possible, increased variety in phraseology should be added given that “in the present study/
in the current study is repeated multiple times.
3. Indicate whether propofol was administered by an anaesthesiologist or another member of
staff.
4. Find bibliographic reference for definitions of apnea and respiratory depression.
assistant