Chest Compression in Neonatal Cardiac Arrest: Cerebral Blood Flow Measurements in Experimental Models
Round 1
Reviewer 1 Report
I appreciate the opportunity to review the manuscript for publication in Healthcare titled Chest compression in neonatal cardiac arrest: cerebral blood flow measurements in experimental models. The authors are well published experts in neonatal resuscitation and the manuscript is well written.
Combining a review of carotid blood laser Doppler results in varying patterns of compression to ventilation during CPR in neonatal models with a general review of techniques of measuring cerebral blood flow didn’t flow well into the discussion. I suggest the manuscript be revised and split into two manuscripts The articles reviewed and the discussion generated in the current manuscript are better detailed in Dr. Schmolzer’s recent publication: Georg M. Schmölzer, MD, PhD. Chest Compressions During Sustained Inflation During Cardiopulmonary Resuscitation in Newborn Infants Translating Evidence From Animal Studies to the Bedside. JACC Basic Transl Sci. 2019;4:116–121.
I suggest the Authors (1) review the use of their patterns of compression to ventilation in neonatal models compared to patterns of compression to ventilation in older models of CPR with the intent to discuss why neonates might be different and why using recommendations based on adult data and expert opinion might be incorrect and (2) write a separate review of measurement of surrogates of cerebral blood flow in neonatal animal models and whether laser Doppler carotid measurements, cerebral perfusion pressure, NIRs, etc… has been correlated with neurologic outcome in neonates (or older models) and what studies need to be done.
Author Response
Dear reviewer,
Thank you for your comments and suggestions. We understand your concerns about the interest to the 'general' audience. We have accommodated your suggestions to some extent, but have not removed all the information about the methods for CBF measurements. We hope that we are able to explain why in our following point-by-point response to your comments:
Combining a review of carotid blood laser Doppler results in varying patterns of compression to ventilation during CPR in neonatal models with a general review of techniques of measuring cerebral blood flow didn’t flow well into the discussion. I suggest the manuscript be revised and split into two manuscripts The articles reviewed and the discussion generated in the current manuscript are better detailed in Dr. Schmolzer’s recent publication: Georg M. Schmölzer, MD, PhD. Chest Compressions During Sustained Inflation During Cardiopulmonary Resuscitation in Newborn Infants Translating Evidence From Animal Studies to the Bedside. JACC Basic Transl Sci. 2019;4:116–121.
I suggest the Authors (1) review the use of their patterns of compression to ventilation in neonatal models compared to patterns of compression to ventilation in older models of CPR with the intent to discuss why neonates might be different and why using recommendations based on adult data and expert opinion might be incorrect and (2) write a separate review of measurement of surrogates of cerebral blood flow in neonatal animal models and whether laser Doppler carotid measurements, cerebral perfusion pressure, NIRs, etc… has been correlated with neurologic outcome in neonates (or older models) and what studies need to be done.
Response: The reviewer is correct that the 2019 manuscript by Schmölzer et al (JACC Basic Transl Sci) is more detailed in many aspects than our review submitted to Healthcare. There are also other quite recent reviews detailing systemic and pulmonary hemodynamic recovery, as well as ventilation parameters and inflammation/oxidative stress. However, the previously published reviews lack a thorough assessment of cerebral perfusion during CPR. Our present review therefore attempts to fill a gap by looking at different CC techniques exclusively from the perspective of brain circulation. We do not wish to change the entire scope of our review, but agree with the reviewer that the following should be done to make the paper more useful to neonatal practitioners:
How patterns of compression to ventilation in neonatal models compared to patterns of compression to ventilation in older models of CPR have (somewhat) different results. Why neonates might be different and why using recommendations based on adult data and expert opinion might be incorrectReviewer 2 Report
Thanks for having the opportunity to review this paper.
This review article discusses an interesting topic: what evidence is available from animal studies for the different modes of cardiopulmonary resuscitation in neonates. This topic would be of interest to any practicing neonatologist. However, the manuscript is written in a very technical way with too many technical details given about the methods for measuring cerebral blood flow and oxygenation. It also uses a large number of specialist abbreviations which make it for a difficult read. In the current format and proportions I think this manuscript is more useful for a researcher already studying this field and using or learning these techniques. Currently, it is not really accessible or of interest to a general neonatologist.
Specific comments:
Abstract:
- Currently the abstract is disorganised. For example, after discussing results (what the reviewed studies have found) the author continue the abstract with methodical details about blood flow measurements. I would suggest that the authors use the classic approach: objectives (already given appropriately) - methods (which experimental animals, mode of measuring the cerebral blood flow and oxygenation - results (major findings of the studies), conclusion (1 sentence summarising the paper)
Introduction:
- What is the difference between “cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV)” and how do they impact differentially on the brain?
- Fraction of inspired oxygen (FiO2)… it only acts via increasing the blood oxygen content which is listed next.
Methods:
- Search method: “A search in Medline Ovid was performed July 2019” - it would have been useful to search other databases such as Web of Science etc.
- “with the search words hypoxia AND cardiac massage AND infant, newborn AND animals” - I think this search strategy is too restricted. For example papers which only contain the term “chest compression” rather than cardiac massage will not be identified. Also in addition to infant OR newborn, “neonat*” should have been included with a boolean “OR”
Results:
- 3.1 This section is well written, thorough and clear. I would suggest to write a summary sentence at the end of each subsection.
- 3.2 I think this section should come before 3.1 as 3.1 is discussing studies where these methods were used. I also feel that the detail given in this section is too much for a paper written to clinicians and comparing different chest compression methods. The level of detail given here would be more appropriate for a paper written for researchers using this technique.
Discussion:
Appropriate
Other comment:
Can you please define all abbreviations (particularly the different chest compression methods and measurement techniques) in one place, ideally at the beginning of the paper. Currently they are being defined in different parts of the paper which makes it difficult for the reader to find them. These are not abbreviations every neonatologist is familiar with.
Author Response
Dear reviewer,
Thank you for your thoughtful comments and suggestions. In the following, we provide a point-by-point response to each comment/suggestion:
This review article discusses an interesting topic: what evidence is available from animal studies for the different modes of cardiopulmonary resuscitation in neonates. This topic would be of interest to any practicing neonatologist. However, the manuscript is written in a very technical way with too many technical details given about the methods for measuring cerebral blood flow and oxygenation. It also uses a large number of specialist abbreviations which make it for a difficult read. In the current format and proportions I think this manuscript is more useful for a researcher already studying this field and using or learning these techniques. Currently, it is not really accessible or of interest to a general neonatologist.
Response: We understand and agree with your concerns. We have removed some of the details from the revised manuscript: We now only include the three methods for CBF measurement that we consider most relevant (two of which can be used clinically as well)
Abstract:
- Currently the abstract is disorganised. For example, after discussing results (what the reviewed studies have found) the author continue the abstract with methodical details about blood flow measurements. I would suggest that the authors use the classic approach: objectives (already given appropriately) - methods (which experimental animals, mode of measuring the cerebral blood flow and oxygenation - results (major findings of the studies), conclusion (1 sentence summarising the paper)
Response: We have restructured the abstract according to the reviewer’s suggestions
Introduction:
- What is the difference between “cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV)” and how do they impact differentially on the brain?
Response: We have included very brief information about this is the revised manuscript, section 3.1.1:
”CBFV obtained with Doppler ultrasound can be a good indicator of CBF, and CBF can theoretically be calculated from CBF and vessel cross sectional area.”
- Fraction of inspired oxygen (FiO2)… it only acts via increasing the blood oxygen content which is listed next.
Response: We have revised this sentence to: “Blood oxygen content as determined by fraction of inspired oxygen (FiO2), pulmonary gas exchange and haemoglobin (Hb) concentration also influence cerebral oxygen delivery [2].”
Methods:
- Search method: “A search in Medline Ovid was performed July 2019” - it would have been useful to search other databases such as Web of Science etc.
Response: We performed a search in Web of Science and did not identify additional studies of relevance to our topic.
- “with the search words hypoxia AND cardiac massage AND infant, newborn AND animals” - I think this search strategy is too restricted. For example papers which only contain the term “chest compression” rather than cardiac massage will not be identified. Also in addition to infant OR newborn, “neonat*” should have been included with a boolean “OR”
Response: The search words used in Medline were all MeSH terms, and thus should include e.g. “cardiac massage” and “neonat*”
Results:
- 3.1 This section is well written, thorough and clear. I would suggest to write a summary sentence at the end of each subsection.
Response: A summary sentence has been added at the end of each subsection.
- 3.2 I think this section should come before 3.1 as 3.1 is discussing studies where these methods were used. I also feel that the detail given in this section is too much for a paper written to clinicians and comparing different chest compression methods. The level of detail given here would be more appropriate for a paper written for researchers using this technique.
Response: We have put section 3.2 before section 3.1 in the revised manuscript and removed quite a bit of the details about experimental cerebral blood flow measurements.
Discussion:
Appropriate
Other comment:
Can you please define all abbreviations (particularly the different chest compression methods and measurement techniques) in one place, ideally at the beginning of the paper. Currently they are being defined in different parts of the paper which makes it difficult for the reader to find them. These are not abbreviations every neonatologist is familiar with.
Response: We have included a list of abbreviations at the beginning of the paper
Round 2
Reviewer 2 Report
Thanks for revising your paper. Your revision has made your manuscript more clear and accessible for non-specialist readers.
My only concern with the revision is the incorrect numbering sections. Also, you said that you have removed all but the most relevant methods. I agree with this. However, in your revised manuscript the rest of the methods still appear, again, after the results section. Accordingly. there is now two sections 3.2 with the title "cerebral hemodynamic measurements".
