{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:29:41Z","timestamp":1788395381007,"version":"build-2803163510"},"reference-count":23,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T00:00:00Z","timestamp":1531094400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Cesarean delivery is performed under spinal anesthesia, and vasodilation is the main cause for a drop in blood pressure. The compression of the aorta and inferior vena cava by the gravid uterus is of additional clinical importance. Hypotension may occur during cesarean delivery even if prophylactic infusion of phenylephrine is practiced. We have tested if a 3 minute supine observation, can identify a subset of women with decreasing systolic arterial pressure (SAP) under spinal anesthesia.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We performed a prospective observational study at Oslo University Hospital on healthy pregnant women for planned cesarean delivery. Continuous measurements of calibrated invasive SAP and estimated cardiac output were recorded for 76 women in a 3 minutes measurement with the woman in the left lateral position, followed by supine position for 3 minutes. Using functional data clustering, principal component analysis and curve smoothing, to filter way noise and reduce the dimensionality of the signal, we clustered the women into separate SAP groups. \u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    We identified two significantly different groups of women during supine position; one characterized by initial drop in SAP, the other showed initial increase. After spinal anesthesia, the mean SAP curve of the women in the first group showed a drop in blood pressure, which was more rapid than for the other women. A minor difference in cardiac output was observed between the two groups of women with the mean cardiac output curve for the first group being higher.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    This work indicates that supine position affect clinically relevant cardiovascular measurements in pregnant women. A simple test may identify patients with increased risk of spinal anesthesia induced hypotension.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.15142.1","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T07:05:07Z","timestamp":1531119907000},"page":"1028","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["A three minutes supine position test reveals higher risk of spinal anesthesia induced hypotension during cesarean delivery. An observational study."],"prefix":"10.12688","volume":"7","author":[{"given":"Markos","family":"Erango","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoldo","family":"Frigessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-8117","authenticated-orcid":false,"given":"Leiv Arne","family":"Rosseland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,7,9]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"Cd002251","DOI":"10.1002\/14651858.CD002251.pub2","article-title":"Techniques for preventing hypotension during spinal anaesthesia for caesarean section.","author":"A Cyna","year":"2006","journal-title":"Cochrane Database Syst Rev."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"1354-1366","DOI":"10.1172\/JCI102373","article-title":"Studies on autonomic blockade. 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Comparison between the effects of tetraethylammonium chloride (TEAC) and high selective spinal anesthesia on blood pressure of normal and toxemic pregnancy.","volume":"29","author":"N Assali","year":"1950","journal-title":"J Clin Invest."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1120-1129","DOI":"10.1213\/ANE.0000000000001174","article-title":"Hemodynamics of Phenylephrine Infusion Versus Lower Extremity Compression During Spinal Anesthesia for Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Study.","volume":"122","author":"J Kuhn","year":"2016","journal-title":"Anesth Analg."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"319-325","DOI":"10.1097\/ACO.0000000000000453","article-title":"The use of vasopressors during spinal anaesthesia for caesarean section.","volume":"30","author":"W Ngan Kee","year":"2017","journal-title":"Curr Opin Anaesthesiol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"541-551","DOI":"10.1097\/ALN.0b013e31829416dd","article-title":"Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.","volume":"119","author":"L Rosseland","year":"2013","journal-title":"Anesthesiology."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1453-1457","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"370","author":"E von Elm","year":"2007","journal-title":"Lancet."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"856-863","DOI":"10.1097\/ALN.0b013e31818a401f","article-title":"Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion.","volume":"109","author":"E Langesaeter","year":"2008","journal-title":"Anesthesiology."},{"key":"ref-8","doi-asserted-by":"crossref","DOI":"10.1002\/(SICI)1521-4036(199804)40:1<56::AID-BIMJ56>3.0.CO;2-#","article-title":"Functional Data Analysis. 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An observational study.","author":"M Erango","year":"2018","journal-title":"F1000Research."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T15:53:38Z","timestamp":1544111618000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,9]]},"references-count":23,"URL":"https:\/\/doi.org\/10.12688\/f1000research.15142.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.16496.r36887","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.16496.r36886","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.16496.r35875","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.16496.r36887","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.16496.r36886","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.16496.r35875","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,9]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.16496.r35875, Kim Ekelund, Department of Anesthesia, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, 23 Jul 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1#referee-response-35875","order":0,"name":"referee-response-35875","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Leiv Arne Rosseland<\/b>; \n<i>Posted: 23 Jul 2018<\/i>;  &nbsp; Thank you for the positive review of the manuscript. We will respond to the comments and questions and when we have received more referee assessments a revised manuscript will be prepared, including the editing of repeated phrases and the missing information in figure legends. &nbsp; \n<b>Specific questions\/answers:<\/b> \u201dThey were asked to assess specifically the extra pain caused by to the arterial cannulation\u201d Q: What does this mean? A: The parturients were informed about that arterial cannulation is painful. They were asked to consider if this extra pain could be accepted before considering giving their consent. In the revised manuscript we will describe this better. &nbsp; \u201cThe indications for elective cesarean section were maternal request 43%, previous cesarean delivery 25%, breech presentation 8%, other obstetric reasons 13%, and other non-obstetric maternal or neonatal medical conditions 11%.\u201d Q: Why is this important in the present study? A: The generalizability of the study relies on the sample being representative of the population and the information about the included women and the indication for cesarean is included for this reason. &nbsp; \n<b>Statistical analysis:<\/b> Q: Although it seems to be a thorough explanation, I do not understand the majority. But I was intensively looking for a description of an algorithm, since this is mentioned later in the paper: P6: \u201cThe clustering algorithm puts each woman in one of two groups, so to divide them in the best way.W P8: &nbsp;\u201dThe external validity of a classification algorithm based on functional data analysis and clustering, as suggested in this paper,\u2026\u201d P8: \u201cThe algorithm should also be evaluated using a non-invasive continuous monitoring device.\u201d Q: What algorithm are the authors referring to? &nbsp; In our paper we have used one after the other, three statistical procedures on our data, three algorithms, implemented as packages in the software language R. First we recognise that the measurements made for each women, though they come as a sequence of measures taken in discrete points, represent a function: measures of the pressure exist at any time point, and must be quite smooth. This means that measures made after each other, cannot change too much. The first algorithm estimates such a function for every women. The data for every women are then represented by such a function. The next procedure is finding the most important components of such function, by calculating the principal components and by using the first two components. At this point we have reduced the dimension of the very much, as every women is described by just two numbers (one per principal component). The third procedure is clustering: the women are now assigned to one of two clusters, so that within a cluster they are quite similar and across clusters they are quite different. The three procedures realise our algorithm. &nbsp; Results I have read and re-read the paper the sections regarding the three clusters. I have a hard time understanding the reasons why this subdivision is necessary and more important clinical relevant. Q: The authors compare the three clusters in supine position and after spinal. But in the present paper I am not presented with data from the supine position. A: The data from supine and left lateral position in the three clusters are presented in Supplementary Table 3.We agree that the clinical relevance of this information (the three clusters) is not obvious. Without this information one might question why we have chosen only the PCA analysis with two clusters. Was there more information hidden that would be revealed when applying three? Or four? Hence, this is kept for methodological reasons. &nbsp; Discussion \u201dA statistically significant difference in mean CO was observed between the two groups of women and the group with lowest SAP had a higher CO. The difference in CO was probably of limited clinical significance but indicates that the difference in the compensation of spinal anesthesia induced vasodilatation is the mechanism behind this observation. Women are more dependent on sympathetic tone during pregnancy than in non-pregnant state and the effect of spinal anesthesia is a rapid and prominent vasodilatation, leading to a decrease in blood pressure and increase in CO7,16. All women in this study received standard phenylephrine bolus and infusion, and this prophylaxis was effective as the mean SAP was stable.\u201d Q: Treat the patient not the picture! How were the women doing? Was this clinical relevant? A: On average, the women were well treated with the combination of intra-venous fluid + phenylephrine prophylaxis\/treatment. However, some patients will develop hypotension and the idea was to analyze if the simple supine position test could predict hypotension. The study should be regarded as an explorative assay, not a pragmatic clinical study. We believe we have demonstrated both the existence of a specific physiologic effect of supine position and that modern signal analyses may be useful in the development of prediction models. The clinical relevance of this has to be tested and proven in future trials. &nbsp; \u201cPrincipal component analyses have been used for making predictive models. In this. population it would be interesting to identify patients at risk of severe spinal anesthesia induced hypotension and tailor the prophylactic treatment.\u201d Q: I would be interesting if the authors would share some ideas on how prevent hypotension \u2013 an anti-hypotensive adjusted prophylactic treatment? A: Patients at risk according to this test (or further developments of the test, or other tests) should be treated state of the art to prevent hypotension. This includes lowering the local anesthetic dose injected spinally, increasing the dose of prophylactic phenylephrine (or at least included phenylephrine prophylaxis), left tilting the operating table adequately, and last but not least, consider using beat-to-beat monitoring, invasive or non-invasive monitor. We will include this information &nbsp;in the revised discussion. &nbsp; Heart rate variability, time domain analysis, and pulse transit time measures are all mentioned in the discussion, and maybe potentially relevant in this clinical setting. Q: However, as a reader, I cannot see the obvious link between these investigations and the three minutes supine position test. I would like to have more information, linking to the right population, and to the results of the present study in the discussion, if this information should be considered. A: We will like to keep this information in the discussion of different methods used and studied for prevention of spinal induced hypotension. If any of these methods prove sensitive and specific as prediction models, it is clinically relevant in the future. We will revise the discussion to make this clearer. &nbsp; Q: Finally, I would have preferred if the authors have been more strict on answering their Aims (P5). A: Thank you. We will try to indicate more specifically the answers to the aims in results and discussion.","URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1#referee-comment-3850","order":1,"name":"referee-comment-3850","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16496.r36886, Gianpaolo Scalia Tomba, Department of Mathematics, University of Rome Tor Vergata, Rome, Italy, 08 Aug 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1#referee-response-36886","order":2,"name":"referee-response-36886","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16496.r36887, Julian Stander, School of Computing, Electronics and Mathematics, University of Plymouth, Plymouth, UK, 13 Aug 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1028\/v1#referee-response-36887","order":3,"name":"referee-response-36887","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}