Physicochemical Characteristics of Cardiological Drugs and Practical Recommendations for Intravenous Administration: A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript clearly outlines the aim of providing practical recommendations for intravenous (IV) administration of cardiological drugs. However, a stronger emphasis on the clinical implications and novelty of these recommendations would enhance the manuscript:

Major Comments:

o   How does this work build upon or differ from previous reviews on IV administration, such as those on antimicrobial agents?

o   Clarify the real-world applications for clinicians managing cardiological emergencies.

o   While the PRISMA framework is followed, the search strategy for databases such as PUBMED and EMBASE should be elaborated further in the main text or as a supplementary file. Include exact search terms and boolean operators.

o   The exclusion of non-English articles could introduce bias; this limitation should be explicitly discussed.

o   The classification of "red flag" drugs is insightful, but the manuscript lacks sufficient discussion on interventions or protocols for mitigating risks during the administration of these drugs. For example, provide specific case studies or examples where such protocols have reduced complications.

o   The PRISMA flow diagram (Figure 1) needs improved clarity; labels should be larger, and colors could be used to differentiate exclusion criteria.

o   Table 1, while comprehensive, would benefit from formatting adjustments to ensure better readability, especially in distinguishing "red flag" drugs from safer options.

o   The discussion could include a comparison of safety profiles between peripheral and central administration techniques.

o   Address gaps in literature concerning specific drug classes like antiarrhythmics or diuretics, and suggest areas for further research.

Minor Comments:

o   The abstract is informative but dense. Consider summarizing the most critical findings (e.g., percentage of drugs safe for PVAD) in a more concise manner.

o   There are minor grammatical inconsistencies in sections, such as "Only RCTs till 31 August 2024 were analyzed" (suggest "were considered for analysis").

o   Enhance readability by reducing redundancy (e.g., "CVADs and PVADs" are repeatedly defined).

o   Ensure that all cited studies (e.g., on phlebitis rates or vesicant properties) are the most recent and relevant. Cross-check citations for accuracy.

o   The limitations are adequately mentioned but could include a more detailed explanation of potential biases introduced by the choice of databases or the exclusion criteria (e.g., non-English studies).

Author Response

Dear Editor,

please find enclosed our revised version of the manuscript entitled “Physicochemical Characteristics of Cardiological Drugs and Practical Recommendations for Intravenous Administration: a Systematic Review.”. We thank the Editor and the reviewers for their constructive criticisms that substantially improved our paper. We hope that the paper will be suitable for publication. We have made a point-by-point answer to the referees’ comments below.

 

Answers to Reviewer 1

Reviewer 1: The manuscript clearly outlines the aim of providing practical recommendations for intravenous (IV) administration of cardiological drugs.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment.

Reviewer 1: Major Comments:   However, a stronger emphasis on the clinical implications and novelty of these recommendations would enhance the manuscript:How does this work build upon or differ from previous reviews on IV administration, such as those on antimicrobial agents?

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. to our knowledge, there are numerous works in the literature on the impact of potentially vaso-lesive drugs. However, the number of systematic reviews is scarce. The Infusion Nurses Society task force recently released a document grouping the main drugs with this property. This document lists medicines of different types grouped for various uses, such as antibiotics, vasoactive agents, etc. Our manuscript is part of a larger project that aims to produce a series of rigorous systematic reviews in which in each one, the physical-chemical properties of drugs belonging to the same category are described (for example, see our previous work on antimicrobials: Borgonovo, F., Quici, M., Gidaro, A., Giustivi, D., Cattaneo, D., Gervasoni, C., Calloni, M., Martini, E., la Cava, L., Antinori, S., Cogliati, C., Gori, A., & Foschi, A. (2023). Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review. Antibiotics 2023, Vol. 12, Page 1338, 12(8), 1338. https://doi.org/10.3390/ANTIBIOTICS12081338). The aim is to make a series of texts available to clinicians, enabling various health organizations to develop policies to safely administer these drugs.

Now, this is clearly exposed in the introduction section.

Reviewer 1: Clarify the real-world applications for clinicians managing cardiological emergencies.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. We have rewritten some parts of the abstract and introduction to clarify the objective of the manuscript better. However, we have modified part of the discussion by highlighting the various factors that should be chosen between CVAD and PVAD.

Reviewer 1: While the PRISMA framework is followed, the search strategy for databases such as PUBMED and EMBASE should be elaborated further in the main text or as a supplementary file. Include exact search terms and boolean operators.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. The search strategy was inserted as supplementary files in the first version of the paper. As suggested by the reviewer, we added this information to the main text.

Reviewer 1: The exclusion of non-English articles could introduce bias; this limitation should be explicitly discussed.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We add this limitation to the paper. “This systematic review includes only English-language articles; this limitation can introduce selection bias, but it allows for the evaluation of paper who can universally understand.”

Reviewer 1: The classification of "red flag" drugs is insightful, but the manuscript lacks sufficient discussion on interventions or protocols for mitigating risks during the administration of these drugs. For example, provide specific case studies or examples where such protocols have reduced complications.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. In the discussion, we quote the paper by Brørs et al., which recently confirmed how strict adherence to clinical practice guidelines for amiodarone infusion effectively reduces the occurrence of phlebitis.

Reviewer 1: The PRISMA flow diagram (Figure 1) needs improved clarity; labels should be larger, and colors could be used to differentiate exclusion criteria.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We increase the dimension of the figure to improve readability, but in our limited experience, no colors are usually used to differentiate exclusion criteria.

Reviewer 1: Table 1, while comprehensive, would benefit from formatting adjustments to ensure better readability, especially in distinguishing "red flag" drugs from safer options.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. The heading is repeated on each page to increase the table's readability. We tried some adjustments to improve the distinction of “red Flag,” but coloring the drug name or the box where the drug is doesn’t improve the readability. For this reason, we have decided to leave the formatting of the table to our previous work on antibiotics and this first version.

Reviewer 1: The discussion could include a comparison of safety profiles between peripheral and central administration techniques.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We added a short sentence describing the different risks between PVAD and CVAD.

Reviewer 1:  Address gaps in literature concerning specific drug classes like antiarrhythmics or diuretics, and suggest areas for further research.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We add a sentence about this future research: “A well-designed RCT is the only solution for this risk issue related to antiarrhythmics or diuretic infusion utilizing a midline catheter instead of a central venous catheter.”

Reviewer 1: Minor Comments: The abstract is informative but dense. Consider summarizing the most critical findings (e.g., percentage of drugs safe for PVAD) in a more concise manner.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. We modified the abstract to improve its readability.

Reviewer 1: There are minor grammatical inconsistencies in sections, such as "Only RCTs till 31 August 2024 were analyzed" (suggest "were considered for analysis").

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. These issues have been fixed.

Reviewer 1: Enhance readability by reducing redundancy (e.g., "CVADs and PVADs" are repeatedly defined).

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. These issues have been fixed (see changes in text)

Reviewer 1: Ensure that all cited studies (e.g., on phlebitis rates or vesicant properties) are the most recent and relevant. Cross-check citations for accuracy.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. We have performed a cross-check citation to increase the accuracy.

Reviewer 1: The limitations are adequately mentioned but could include a more detailed explanation of potential biases introduced by the choice of databases or the exclusion criteria (e.g., non-English studies).

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. As mentioned before, we add the limitation of non-English studies.

 

Answers to Reviewer 2

Reviewer 2: This is a PRISMA-compliant systematic review (registered on PROSPERO) of cardiology medications evaluating the physiochemical association and recommendations for intravenous administration.

Overall, this is a very nicely researched and presented manuscript and reads well. The methodology is sound and appropriate for the type of topic being investigated. The conclusions are consistent with current evidence and will help guide future guidelines and recommendations regarding the selection and use of various intravascular devices based on the administration of these drugs. I only have a couple of comments for the authors.

Response to Reviewer 2 comment:  We thank the reviewer for his/her positive comment.

Reviewer 2: Although minimal, please avoid the use of first-person perspective (us, we, our, etc.) and use third-person (this study, the authors, this research, these findings, the outcomes, etc.) as this creates a more academically and less personalized styled manuscript. This should be applied throughout the entire manuscript where needed also.

Response to Reviewer 2 comment:  We thank the reviewer for his/her suggestion. These issues have been fixed (see changes in text)

 

Reviewer 2: Please replace the term “line/lines” throughout the manuscript/tables/figures with the correct terminology/nomenclature ‘catheters’ or ‘devices’ - “line/lines” is an unfortunate frequently used non-descriptive term that is ambiguous in describing venous catheters. Correct nomenclature and terminology are essential in the proper description of medical devices and yet we continue to use/see the term ‘line/lines' to describe various invasive devices; central venous catheters ("central lines”), peripherally inserted central catheters ("PICC lines”), femoral catheters ("femoral lines”), arterial catheters (arterial lines).. a line is nothing but that - a line!

Response to Reviewer 2 comment:  We thank the reviewer for his/her suggestion. These issues have been fixed (see changes in text)

 

Reviewer 2: The chemical structure of various drug therapies may cause significant injury or harm to patients if an inappropriate intravascular device is used. This helps clinicians to advocate and choose the best device based on the type of cardiological drug that may be required for patient treatment. There have been very few publications in this area that have evaluated such a large selection of medications and made recommendations regarding the type of device they should be administered through. It adds a significant benefit to all clinicians who may select or administer these various medications.

Response to Reviewer 2 comment:  We thank the reviewer for his/her positive comment.

Reviewer 2 Report

Comments and Suggestions for Authors

Physicochemical characteristics of cardiological drugs and practical recommendations for intravenous administration: a Systematic Review by Massimiliano Quici et al.

This is a PRISMA-compliant systematic review (registered on PROSPERO) of cardiology medications evaluating the physiochemical association and recommendations for intravenous administration.

Overall, this is a very nicely researched and presented manuscript and reads well. The methodology is sound and appropriate for the type of topic being investigated. The conclusions are consistent with current evidence and will help guide future guidelines and recommendations regarding the selection and use of various intravascular devices based on the administration of these drugs. I only have a couple of comments for the authors.

Although minimal, please avoid the use of first-person perspective (us, we, our, etc.) and use third-person (this study, the authors, this research, these findings, the outcomes, etc.) as this creates a more academically and less personalized styled manuscript. This should be applied throughout the entire manuscript where needed also.

Please replace the term “line/lines” throughout the manuscript/tables/figures with the correct terminology/nomenclature ‘catheters’ or ‘devices’ - “line/lines” is an unfortunate frequently used non-descriptive term that is ambiguous in describing venous catheters. Correct nomenclature and terminology are essential in the proper description of medical devices and yet we continue to use/see the term ‘line/lines' to describe various invasive devices; central venous catheters ("central lines”), peripherally inserted central catheters ("PICC lines”), femoral catheters ("femoral lines”), arterial catheters (arterial lines).. a line is nothing but that - a line!

The chemical structure of various drug therapies may cause significant injury or harm to patients if an inappropriate intravascular device is used. This helps clinicians to advocate and choose the best device based on the type of cardiological drug that may be required for patient treatment. There have been very few publications in this area that have evaluated such a large selection of medications and made recommendations regarding the type of device they should be administered through. It adds a significant benefit to all clinicians who may select or administer these various medications.

Author Response

Dear Editor,

please find enclosed our revised version of the manuscript entitled “Physicochemical Characteristics of Cardiological Drugs and Practical Recommendations for Intravenous Administration: a Systematic Review.”. We thank the Editor and the reviewers for their constructive criticisms that substantially improved our paper. We hope that the paper will be suitable for publication. We have made a point-by-point answer to the referees’ comments below.

 

Answers to Reviewer 1

Reviewer 1: The manuscript clearly outlines the aim of providing practical recommendations for intravenous (IV) administration of cardiological drugs.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment.

Reviewer 1: Major Comments:   However, a stronger emphasis on the clinical implications and novelty of these recommendations would enhance the manuscript:How does this work build upon or differ from previous reviews on IV administration, such as those on antimicrobial agents?

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. to our knowledge, there are numerous works in the literature on the impact of potentially vaso-lesive drugs. However, the number of systematic reviews is scarce. The Infusion Nurses Society task force recently released a document grouping the main drugs with this property. This document lists medicines of different types grouped for various uses, such as antibiotics, vasoactive agents, etc. Our manuscript is part of a larger project that aims to produce a series of rigorous systematic reviews in which in each one, the physical-chemical properties of drugs belonging to the same category are described (for example, see our previous work on antimicrobials: Borgonovo, F., Quici, M., Gidaro, A., Giustivi, D., Cattaneo, D., Gervasoni, C., Calloni, M., Martini, E., la Cava, L., Antinori, S., Cogliati, C., Gori, A., & Foschi, A. (2023). Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review. Antibiotics 2023, Vol. 12, Page 1338, 12(8), 1338. https://doi.org/10.3390/ANTIBIOTICS12081338). The aim is to make a series of texts available to clinicians, enabling various health organizations to develop policies to safely administer these drugs.

Now, this is clearly exposed in the introduction section.

Reviewer 1: Clarify the real-world applications for clinicians managing cardiological emergencies.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. We have rewritten some parts of the abstract and introduction to clarify the objective of the manuscript better. However, we have modified part of the discussion by highlighting the various factors that should be chosen between CVAD and PVAD.

Reviewer 1: While the PRISMA framework is followed, the search strategy for databases such as PUBMED and EMBASE should be elaborated further in the main text or as a supplementary file. Include exact search terms and boolean operators.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. The search strategy was inserted as supplementary files in the first version of the paper. As suggested by the reviewer, we added this information to the main text.

Reviewer 1: The exclusion of non-English articles could introduce bias; this limitation should be explicitly discussed.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We add this limitation to the paper. “This systematic review includes only English-language articles; this limitation can introduce selection bias, but it allows for the evaluation of paper who can universally understand.”

Reviewer 1: The classification of "red flag" drugs is insightful, but the manuscript lacks sufficient discussion on interventions or protocols for mitigating risks during the administration of these drugs. For example, provide specific case studies or examples where such protocols have reduced complications.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. In the discussion, we quote the paper by Brørs et al., which recently confirmed how strict adherence to clinical practice guidelines for amiodarone infusion effectively reduces the occurrence of phlebitis.

Reviewer 1: The PRISMA flow diagram (Figure 1) needs improved clarity; labels should be larger, and colors could be used to differentiate exclusion criteria.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We increase the dimension of the figure to improve readability, but in our limited experience, no colors are usually used to differentiate exclusion criteria.

Reviewer 1: Table 1, while comprehensive, would benefit from formatting adjustments to ensure better readability, especially in distinguishing "red flag" drugs from safer options.

Response to Reviewer 1 comment: We thank the reviewer for his/her suggestion. The heading is repeated on each page to increase the table's readability. We tried some adjustments to improve the distinction of “red Flag,” but coloring the drug name or the box where the drug is doesn’t improve the readability. For this reason, we have decided to leave the formatting of the table to our previous work on antibiotics and this first version.

Reviewer 1: The discussion could include a comparison of safety profiles between peripheral and central administration techniques.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We added a short sentence describing the different risks between PVAD and CVAD.

Reviewer 1:  Address gaps in literature concerning specific drug classes like antiarrhythmics or diuretics, and suggest areas for further research.

Response to Reviewer 1 comment:  We thank the reviewer for his/her suggestion. We add a sentence about this future research: “A well-designed RCT is the only solution for this risk issue related to antiarrhythmics or diuretic infusion utilizing a midline catheter instead of a central venous catheter.”

Reviewer 1: Minor Comments: The abstract is informative but dense. Consider summarizing the most critical findings (e.g., percentage of drugs safe for PVAD) in a more concise manner.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. We modified the abstract to improve its readability.

Reviewer 1: There are minor grammatical inconsistencies in sections, such as "Only RCTs till 31 August 2024 were analyzed" (suggest "were considered for analysis").

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. These issues have been fixed.

Reviewer 1: Enhance readability by reducing redundancy (e.g., "CVADs and PVADs" are repeatedly defined).

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. These issues have been fixed (see changes in text)

Reviewer 1: Ensure that all cited studies (e.g., on phlebitis rates or vesicant properties) are the most recent and relevant. Cross-check citations for accuracy.

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. We have performed a cross-check citation to increase the accuracy.

Reviewer 1: The limitations are adequately mentioned but could include a more detailed explanation of potential biases introduced by the choice of databases or the exclusion criteria (e.g., non-English studies).

Response to Reviewer 1 comment:  We thank the reviewer for his/her positive comment. As mentioned before, we add the limitation of non-English studies.

 

Answers to Reviewer 2

Reviewer 2: This is a PRISMA-compliant systematic review (registered on PROSPERO) of cardiology medications evaluating the physiochemical association and recommendations for intravenous administration.

Overall, this is a very nicely researched and presented manuscript and reads well. The methodology is sound and appropriate for the type of topic being investigated. The conclusions are consistent with current evidence and will help guide future guidelines and recommendations regarding the selection and use of various intravascular devices based on the administration of these drugs. I only have a couple of comments for the authors.

Response to Reviewer 2 comment:  We thank the reviewer for his/her positive comment.

Reviewer 2: Although minimal, please avoid the use of first-person perspective (us, we, our, etc.) and use third-person (this study, the authors, this research, these findings, the outcomes, etc.) as this creates a more academically and less personalized styled manuscript. This should be applied throughout the entire manuscript where needed also.

Response to Reviewer 2 comment:  We thank the reviewer for his/her suggestion. These issues have been fixed (see changes in text)

 

Reviewer 2: Please replace the term “line/lines” throughout the manuscript/tables/figures with the correct terminology/nomenclature ‘catheters’ or ‘devices’ - “line/lines” is an unfortunate frequently used non-descriptive term that is ambiguous in describing venous catheters. Correct nomenclature and terminology are essential in the proper description of medical devices and yet we continue to use/see the term ‘line/lines' to describe various invasive devices; central venous catheters ("central lines”), peripherally inserted central catheters ("PICC lines”), femoral catheters ("femoral lines”), arterial catheters (arterial lines).. a line is nothing but that - a line!

Response to Reviewer 2 comment:  We thank the reviewer for his/her suggestion. These issues have been fixed (see changes in text)

 

Reviewer 2: The chemical structure of various drug therapies may cause significant injury or harm to patients if an inappropriate intravascular device is used. This helps clinicians to advocate and choose the best device based on the type of cardiological drug that may be required for patient treatment. There have been very few publications in this area that have evaluated such a large selection of medications and made recommendations regarding the type of device they should be administered through. It adds a significant benefit to all clinicians who may select or administer these various medications.

Response to Reviewer 2 comment:  We thank the reviewer for his/her positive comment.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed all the previous comments.