Reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions: a systematic review and meta-analysis

Reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions: a systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions: a systematic review and meta-analysis Tianyu Liu, Chao Xu, Min Wang, Zheng Niu, Dunyi Qi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.300/v6 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 May, 2019 Read the published version in BMC Anesthesiology → Version 6 posted 4 You are reading this latest preprint version Show more versions Abstract Background: Goal-directed volume expansion is increasingly used for fluid management in mechanically ventilated patients. The Pleth Variability Index (PVI) has been shown to reliably predict preload responsiveness; however, a lot of research on PVI has been published recently, and update of the meta-analysis needs to be completed. Methods: We searched PUBMED, EMBASE, Cochrane Library, Web of Science (updated to November 7, 2018) and the associated references. We also contacted relevant authors and researchers. Results: Twenty-five studies with 975 patients were included in this meta-analysis. All patients were mechanically ventilated. The area under the curve (AUC) of receiver operating characteristics (ROC) to predict preload responsiveness in patients was 0.82 (95% confidence interval (CI) 0.79 - 0.85). The pooled sensitivity was 0.77 (95% CI 0.67-0.85) and the pooled specificity was 0.77 (95% CI 0.71-0.82). The results of subgroup of patients without undergoing surgery (AUC =0.86, Youden index =0.65) and the results of subgroup of patients in ICU (AUC =0.89, Youden index =0.67) were reliable. Conclusion: The reliability of the PVI is limited, but the PVI can play an important role in bedside monitoring for mechanically ventilated patients who are not undergoing surgery. Patients who are expanded with colloid may be more suitable for PVI. Internal Medicine Specialties Pleth variability index Preload responsiveness Mechanically ventilated patients Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Goal-directed fluid therapy has proven benefits for the hemodynamic stability of perioperative and shock patients. Some recent studies have reported that moderate intraoperative volume expansion, and adequate maintenance of cardiac output (CO) can reduce the complications after surgery and the time spent in the intensive care unit (ICU)[1-3]. Inappropriate fluid administration is often harmful to patients; thus, accurate detection of the patient’s hemodynamics can effectively improve the patient’s prognosis (such as decrease in serum lactate, the length of stay in hospital and incidence of postoperative organ complications ) [4-6]. A pulse oximeter is a noninvasive routine intraoperative monitor in most hospitals, and it is one of the preferred instruments for bedside monitoring [7]. The Massimo pulse oximeter (Massimo Corp., Irvine, CA, USA) adds a module for monitoring of respiratory changes in the pulse oximetry plethysmographic waveform, derived from the perfusion index (PI) [8]. PI is defined as pulsatile and non-pulsatile tissues ratio of absorbed light. Pleth variability index (PVI) reflects the variation of PI in the respiratory cycle. PVI can be continuously monitored on the display screen by connecting the probe of pulse oximeter. It is generated by the pulse oxygen probe and the absorption of red and infrared light at the measuring site. Several trials have contributed to investigating the reliability of the PVI in predicting preload responsiveness [9-33]. On this basis, three system reviews evaluate the high accuracy of PVI[34-36]. A series of studies have shown that the PVI can reliably predict preload responsiveness during mechanical ventilation; however, some of these studies are not convincing because the sample size was less than 30 [11, 12, 17, 19, 29, 33]. Broch O et al. reported that the PVI reliably predicted preload responsiveness only in patients with high perfusion level (PI＞4%) [9]. Le Guen et al supported that the accuracy of PVI is limited during kidney transplantation [22]. Moreover, Maughan BC et al. indicated that PVI also cannot reliably predict preload responsiveness during cardiac surgery [26]. There seems to be no consensus on the reliability of PVI for different patients. The purpose of this review is to assess the reliability of the PVI to predict preload responsiveness in different mechanically ventilated patients (patients in different locations, with different types of surgery, different ages, and different methods of expansion). Methods and materials Search strategy PUBMED, EMBASE, Cochrane Library, and Web of Science databases (last updated to November 7, 2018) were searched by two reviewers independently , using the keywords as follow : (plethysmography OR pleth OR plethysmographic) AND (variability OR variation) AND (index OR indices OR indexes). The references of all reviewed articles were viewed to look for valuable studies. Relevant authors and researchers had been contacted for complete data. Eligibility criteria We included diagnostic trials that evaluated the reliability of the PVI to predict fluid responsiveness in patients with mechanical ventilation. We excluded reviews, case reports, comments, experiments on animals, or in vitro studies and articles that were not published in English. Quality assessment Two reviewers independently assessed the quality of reviewed studies using the QUADAS-2 scale by Review Manager 5.3（Cochrane Library, Oxford, UK) [37]. Disagreement was resolved by discussion with third reviewer. Data extraction The study characteristics and outcomes were examined and extracted by two reviewers independently . The following data were recorded using Microsoft Excel 2016 (Microsoft Corp, Redmond, WA): first author, year of publication, characteristics of patient, place of study, number of patients studied, tidal volume, amount of fluid infusion, the f value for defining responders to preload responsiveness, true positive rate , false positive rate , false negative rate , true negative rate , best cut-off value, sensitivity, specificity, the pooled area under the curve (AUC) of receiver operating characteristics (ROC) and r value. For further data analysis, we also assessed the pooled sensitivity, pooled specificity, pooled AUC, Youden index (sensitivity plus specificity minus one) and 95% credibility interval (CI) of them. Statistical treatment Data calculation and graphics synthesis was performed by Stata (version 14.0). Threshold effect and nonthreshold effect both will lead to heterogeneity. We used Spearman correlation coefficient (Mixed Model) to evaluate the threshold effect and used Cochrane-Q value of the AUC to evaluate nonthreshold effect. The heterogeneity was represented by the I2 statistic: when I2＜25% , it means low heterogeneity exists, when 25%＜I2＜50% ,it means moderate heterogeneity exists, and when I2≥50%, it means significant heterogeneity exists. Sensitivity analyses (test each article individually whether it is a source of heterogeneity) and meta-regression (patient’s surgeries; patient’s age; choice of patients volume expansion methods) were used to find the source of heterogeneity. We used Deeks’ Funnel Plot Asymmetry Test For Diagnostic Odds Ratio to determine whether significant publication bias exists in the articles included in the analysis [38]. Results Literature search and study characteristics The original literature search included 1,068 articles, of which 1007 articles were excluded by reviewing title and abstracts because they were duplicates, irrelevant studies, animal experiments, conference summaries, case reports or review articles. After careful browsing of the remaining 61 studies, 31 studies were excluded because they lacked the full-text article. Four studies were excluded because the lack of relevant data on outcomes. One study was excluded because its abstract was published in English, while its full-text was published in Chinese. The retrieved ,included and excluded articles for meta-analysis are summarized in Fig. 1. Characteristics of the 25 retrieved studies are summarized in Additional file 1. Quality assessment and Publication bias Quality assessment of 25 retrieved studies is shown in Fig. 2 and Fig.3. The result of Deeks’ Funnel Plot Asymmetry Test for Diagnostic Odds Ratio is that the P value=0.76, indicates that no significant publication bias exists in the included literature. Results of retrieved studies The results of each retrieved studies are shown in Additional file 2. Twenty-five studies that included 1035 patients. The best cut-off value for PVI varied between 7% and 20%, while 1 study [18] did not provide information regarding the cut-off value. In 3 studies [20, 22, 32], the same patient receives more than one volume expansion, and the final data analysis uses the data for each volume expansion. Two studies [20,23] evaluated preload responsiveness at two different period of surgery, so we divided the results of each study into two parts. Results of meta-analysis The Spearman correlation coefficient was 0.07 ( P <0.01), indicates that although a significant threshold effect exists, the effect on the results is small. The Cochrane-Q value of the AUC was 39.175 (95% CI 0.79-0.85, P <0.001) and I2=95%, indicates significant heterogeneity exists. Because of the significant heterogeneity of the pooled results, we performed a further subgroup analysis based on the patient's condition. The results of the meta-analysis are described in Table 1 and Fig. 4. The pooled AUC was 0.82 (95% confidence interval (CI) 0.79 - 0.85). The pooled sensitivity was 0.77 (95% CI 0.67-0.85) and the pooled specificity was 0.77 (95% CI 0.71-0.82). The results shown that the accuracy of PVI predicting preload reactivity is not as high as reported in previous meta-analyses[34-36]. Our new discovery is the result of patients without undergoing surgery (AUC=0.86, Youden index=0.65) was reliable. Heterogeneity The pooled I2 value was 95%, indicating statistically significant heterogeneity. After performance of meta-regression, we found the choice of intravenous colloid injection as a means of preload responsiveness was a significant cause ( p =0.02) of the heterogeneity; however, following the exclusion of the 17 studies which used intravenous colloid injection [10-16, 19-21, 23, 24, 29-33]， the heterogeneity remained significant（I2=84%）. The sensitivity analysis showed that 2 [16, 27] of the studies may have contributed to the heterogeneity; however, following the exclusion of the two studies, the heterogeneity remained significant（I2=95%）. Significant heterogeneity exists in both the overall group and most of the subgroups, which may be because of patient’s complex conditions, different surgical methods and the different fluid management methods. The heterogeneity was relatively low in the subgroup of patients undergoing noncardiac surgery(I2=63%), which may be because of the patients undergoing cardiac surgery are often non-sinus rhythms and have a greater impact on tissue perfusion. No significant heterogeneity exists in the subgroups of patients without undergoing surgery (I2=33%), which may be because certain surgical stimuli (such as pain) and procedures (such as liver surgery for inferior vena cava) may cause changes in vascular tension or hemodynamics. No significant heterogeneity exists in the crystalloid subgroup (I2=23%), potentially because of the small number of studies (n=4). With the data emerging from our meta-analysis, no certain assertion can be made. The study provides interesting data and the results of the subgroups of patients without undergoing surgery should be reliable. Discussion Applicable patients The PVI has higher accuracy for mechanically ventilated patients with a regular rhythm and nonthoracotomy [39]. The PVI reflects the degree of change in PI caused by breathing over a period of time, so PVI is greatly affected by cardiopulmonary exercise. The PVI has ability to reliably predict preload responsiveness, provided that the pressure changes in the chest cavity are sufficiently obvious enough and the cardiopulmonary interaction between different respiratory cycles is stable. Therefore, the PVI and other dynamic parameters of cardiopulmonary interaction are more suitable for patients with mechanical ventilation rather than spontaneous breathing. The results of the meta-analysis also showed that PVI was less reliable in the subgroup of cardiac surgery (Youden index =0.45) than in the non-cardiac surgery subgroup (Youden index =0.49). Perfusion situation Under the monitoring of a pulse oximeter, the pulsating blood flow absorbs red and infrared light (AC), and the tissue and skin also absorb red and infrared light (DC). The ratio of the two parameter can calculate the PI : PI=（AC-DC）×100% PVI reflects the degree of change in PI caused by breathing over a period of time. The formula is as follows: PVI=[（PImax-PImin）/PImax]×100% Reliability of the PVI is largely affected by adequacy of perfusion [40]. Peripheral perfusion deficiency can result in impaired blood flow to a stable constant partly caused by skin and other factors that signal the volume in the tissue. To date, a pulsed oximeter, which is used to calculate the PVI, will not be able to determine whether the reduction of chest pressure is caused by the variety of cardiovascular system capacity or low perfusion of the monitored site, so any influence on peripheral perfusion factors, that is, the factors that affect PI, can affect the reliability of the PVI [34]. The sensitivity of the subgroup of cardiac surgery is lower than that of the other subgroups and overall (0.67 95% CI 0.40-0.87). Broch O et al. [9] reported that the PVI reliably predicted preload responsiveness only in patients with high perfusion level (PI＞4%). When using the PVI to guide goal-directed volume expansion, anesthetists should pay attention to factors that can affect perfusion situation of the monitored site (such as peripheral vascular disease, severe heart failure, application of vasoactive drugs, and damage of the monitored site). Types of volume expansion The results of the synthesis show that the subgroups with colloid injection (Youden index=0.59 AUC=0.83) are more reliable than the subgroups with crystalloid injection (Youden index=0.46 AUC=0.79). This may be because the colloidal fluid has a better effect on the macrocirculation and the microcirculation [41], thus increasing the reliability of the PVI. The best cut-off value The included results show that the PVI has a wide range of best cut-off value for defining responders to preload responsiveness, which range from 7% to 20%. The different conditions for each study (the patients’ underlying disease, volume stroke, age, type of surgery, in operating room or in ICU), and patients’ different fluid management (the application of vasoactive drugs, rate of intravenous infusion and type of volume expansion) may contribute to high variability. We suggest that readers can refer to the cut-off values reported in the corresponding articles when applying PVI to different patients. Monitored site The monitored site can affect the morphology and respiratory variation of the PVI[42-45]. Desgranges et al. [12] compared finger, forehead and ear as monitored site, reporting that the choice of three monitored sites has no significant impact on accuracy. While Hood et al. [19] reported that the PVIfinger can reliably predict increases in SV, while the PVIearlobe can not reliably predict increases in SV in dynamic intraoperative conditions. Fischer et al. [15] demonstrated PVIforehead was more accurate than PVIfinger in patients after cardiac surgery. For safety and convenience, the PVIfinger remains the preferred choice for most patients, with the PVIforehead and PVIearlobe as stable alternatives [12]. Limitations Our systematic review has several limitations. First, significant heterogeneity exists in both the overall group and most subgroups; thus, differences between patients and surgeries should be considered in the application of the PVI. Second, we only included mechanically ventilated patients, which limited the results extrapolated to all patients. Studies on the monitoring of the PVI on patients with spontaneous breathing must be conducted. Third, subgroup analyses of the child subgroup and the passive leg raise subgroup were not performed because of insufficient studies. Fourth, the best cut-off value for the PVI varied within great ranges, and the best cut-off value for different types of patients and surgeries remains to be studied. Finally, although PVI is more reliable for patients in the ICU, most of these patients are also applying other more accurate invasive monitoring (such as arterial blood pressure monitoring), so PVI is more recommended as a supplement of pulse oxygen. Conclusions The PVI, as a noninvasive and automatic hemodynamic monitoring, has limited ability to predict the fluid responsiveness of mechanically ventilated patients, except patients without undergoing surgery and patients in ICU. The PVI can plays an important role in bedside monitoring for mechanically ventilated patients who are not undergoing surgery, such as patients after cardiac surgery and shock patients. Patients who are expanded with colloid may be more suitable for PVI. For different individuals, the optimal PVI cut-off value must be further determined. Abbreviations PVI: Pleth Variability Index; PI: perfusion index; CI：confidence interval ；AUC: area under the curve; ICU: intensive care unit; Declarations Acknowledgements： Not Applicable. Funding No funding was received for this study. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions Liu, Xu, and Qi made substantial contributions to conception and design of the study; Wang and Niu searched literature, extracted data from the collected literature and analyzed the data; Liu wrote the manuscript; Wang and Niu revised the manuscript; All authors approved the final version of the manuscript. Ethics approval and consent to participate Not applicable Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests Author details 1Key Laboratory of Anesthesia and Analgesia, Xuzhou Medical University and 2 Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jangsu, China References 1. Bundgaard-Nielsen M, Holte K, Secher NH, Kehlet H: Monitoring of peri-operative fluid administration by individualized goal-directed therapy . Acta anaesthesiologica Scandinavica 2007, 51 (3):331-340. 2. 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Tables Table 1 Results of meta-analysis Setting(numbers of studies) Sensitivity(95% CI) Specificity(95% CI) Youden index AUC(95% CI)-ROC I2(%) PVI across all settings(n=27) 0.77(0.67-0.85) 0.77(0.71-0.82) 0.54 0.82(0.79-0.85) 95 PVI in OR(n=18) 0.76(0.67-0.84) 0.76(0.68-0.82) 0.52 0.82(0.79-0.85) 81 PVI in ICU(n=4) 0.79(0.41-0.95) 0.88(0.77-0.94) 0.67 0.89(0.86-0.92) 89 PVI in adult(n=22) 0.77(0.65-0.85) 0.77(0.70-0.82) 0.54 0.82(0.79-0.85) 95 PVI in cardiac surgery(n=9) 0.67(0.40-0.87) 0.78(0.66-0.87) 0.45 0.80(0.77-0.84) 89 PVI in noncardiac surgery(n=12) 0.78(0.64-0.88) 0.71(0.58-0.82) 0.49 0.80(0.76-0.83) 63 PVI without surgery(n=6) 0.85(0.69-0.94) 0.80(0.70-0.87) 0.65 0.86(0.82-0.89) 33 PVI with colloid injection(n=17) 0.77(0.67-0.85) 0.82（0.77-0.86) 0.59 0.83(0.80-0.86) 87 PVI with crystalloid injection(n=4) 0.77(0.60-0.88) 0.69(0.52-0.81) 0.46 0.79(0.75-0.82) 23 Abbreviations: AUC, area under the curve; ROC, receiving operating characteristics. Supplementary Files supplement2.docx supplement2.docx Cite Share Download PDF Status: Published Journal Publication published 18 May, 2019 Read the published version in BMC Anesthesiology → Version 6 posted Submission checks completed at journal 07 Nov, 2019 Editorial decision: Accept 24 Apr, 2019 Editor assigned by journal 24 Apr, 2019 Editor invited by journal 23 Apr, 2019 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-300","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":83856,"identity":"28439fc9-0e38-4c1c-983c-254539d05338","order_by":1,"name":"Tianyu Liu","email":"","orcid":"","institution":"Xuzhou Medical College Affiliated Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tianyu","middleName":"","lastName":"Liu","suffix":""},{"id":83857,"identity":"03c8d430-8262-4897-ab46-ad5114baa221","order_by":2,"name":"Chao Xu","email":"","orcid":"","institution":"Xuzhou Medical College Affiliated 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Qi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYFCCBMYHHwxs5NjY2w8QrYXZcEZFmjEfz5kEorWwCfOcOZw4T8LBgDgNfMdzzBhntqWlt0kwJDD8qNhGWIvkmTdmDz622eS2STceYOw5c5uwFoMbOeaGQFty22QOJDAzthGnxUyat+1wOptEggEJWoDeTyBei+SZZ8WgQDZsAwbyQaL8wnc8eSMoKuXl29sPPvhRQYQWhgMciOg4QIR6kDL2B8QpHAWjYBSMgpELAFehQrSE6+h6AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0432-5422","institution":"Xuzhou Medical College Affiliated Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Dunyi","middleName":"","lastName":"Qi","suffix":""}],"badges":[],"createdAt":"2019-02-05 15:19:45","currentVersionCode":6,"declarations":"","doi":"10.21203/rs.2.300/v6","doiUrl":"https://doi.org/10.21203/rs.2.300/v6","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-019-0744-4","type":"published","date":"2019-05-18T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2611040,"identity":"a8eadb43-d1d3-41cb-9a1a-8bcfa20b9d35","added_by":"dbe1c910-fa3f-4a3a-a5c6-af99624d3e99","created_at":"2020-09-25 20:52:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":323291,"visible":true,"origin":"","legend":"The search, inclusion and exclusion of the literature.","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/figure_1.jpg"},{"id":2611041,"identity":"0b1f6a8a-adc0-490f-9c23-f5407d4d6359","added_by":"dbe1c910-fa3f-4a3a-a5c6-af99624d3e99","created_at":"2020-09-25 20:52:01","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":143100,"visible":true,"origin":"","legend":"The results of quality assessment of the included articles (overview).","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/figure_2.jpg"},{"id":2611044,"identity":"8590d004-478f-4177-ad5e-0be7e9accea2","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:52:01","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":344652,"visible":true,"origin":"","legend":"The results of quality assessment of each articles.","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/figure_3.jpg"},{"id":2611042,"identity":"d5095708-aa2e-405f-a543-de10ca44ac79","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:52:01","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1719461,"visible":true,"origin":"","legend":"The summary receiver operating characteristics (SROC) of the included articles.","description":"","filename":"figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/figure_4.jpg"},{"id":13466725,"identity":"0ff2ca61-33fe-4dde-9973-387b3c7e43b4","added_by":"auto","created_at":"2021-09-16 20:52:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1830656,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/6115490b-ec7e-4859-bbea-d6a1ef73d437.pdf"},{"id":2611440,"identity":"0d86f31f-ef56-4e2f-a4a7-3af3f334ad01","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:52:16","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":51915,"visible":true,"origin":"","legend":"","description":"","filename":"supplement2.docx","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/supplement_2.docx"},{"id":2611043,"identity":"23e12288-c75b-461e-8282-f7823a3503c9","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:52:01","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":21097,"visible":true,"origin":"","legend":"","description":"","filename":"supplement2.docx","url":"https://assets-eu.researchsquare.com/files/rs-300/v6/supplement_2.docx"}],"financialInterests":"","formattedTitle":"Reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions: a systematic review and meta-analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eGoal-directed fluid therapy has proven benefits for the hemodynamic stability of perioperative and shock patients. Some recent studies have reported that moderate intraoperative volume expansion, and adequate maintenance of cardiac output (CO) can reduce the complications after surgery and the time spent in the intensive care unit (ICU)[1-3]. Inappropriate fluid administration is often harmful to patients; thus, accurate detection of the patient’s hemodynamics can effectively improve the patient’s prognosis (such as decrease in serum lactate, the length of stay in hospital and incidence of postoperative organ complications ) [4-6].\u003c/p\u003e\n\u003cp\u003eA pulse oximeter is a noninvasive routine intraoperative monitor in most hospitals, and it is one of the preferred instruments for bedside monitoring [7]. The Massimo pulse oximeter (Massimo Corp., Irvine, CA, USA) adds a module for monitoring of respiratory changes in the pulse oximetry plethysmographic waveform, derived from the perfusion index (PI) [8]. PI is defined as pulsatile and non-pulsatile tissues ratio of absorbed light. Pleth variability index (PVI) reflects the variation of PI in the respiratory cycle.\u003c/p\u003e\n\u003cp\u003ePVI can be continuously monitored on the display screen by connecting the probe of pulse oximeter. It is generated by the pulse oxygen probe and the absorption of red and infrared light at the measuring site.\u003c/p\u003e\n\u003cp\u003e Several trials have contributed to investigating the reliability of the PVI in predicting preload responsiveness [9-33]. On this basis, three system reviews evaluate the high accuracy of PVI[34-36]. A series of studies have shown that the PVI can reliably predict preload responsiveness during mechanical ventilation; however, some of these studies are not convincing because the sample size was less than 30 [11, 12, 17, 19, 29, 33]. Broch O et al. reported that the PVI reliably predicted preload responsiveness only in patients with high perfusion level (PI＞4%) [9]. Le Guen et al supported that the accuracy of PVI is limited during kidney transplantation [22]. Moreover, Maughan BC et al. indicated that PVI also cannot reliably predict preload responsiveness during cardiac surgery [26]. There seems to be no consensus on the reliability of PVI for different patients. The purpose of this review is to assess the reliability of the PVI to predict preload responsiveness in different mechanically ventilated patients (patients in different locations, with different types of surgery, different ages, and different methods of expansion).\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cp\u003e\u003cb\u003eSearch strategy \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003ePUBMED, EMBASE, Cochrane Library, and Web of Science databases (last updated to November 7, 2018) were searched by two reviewers independently , using the keywords as follow : (plethysmography OR pleth OR plethysmographic) AND (variability OR variation) AND (index OR indices OR indexes). The references of all reviewed articles were viewed to look for valuable studies. Relevant authors and researchers had been contacted for complete data.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eEligibility criteria\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eWe included diagnostic trials that evaluated the reliability of the PVI to predict fluid responsiveness in patients with mechanical ventilation. We excluded reviews, case reports, comments, experiments on animals, or in vitro studies and articles that were not published in English.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eQuality assessment\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eTwo reviewers independently assessed the quality of reviewed studies using the QUADAS-2 scale by Review Manager 5.3（Cochrane Library, Oxford, UK) [37]. Disagreement was resolved by discussion with third reviewer.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eData extraction\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe study characteristics and outcomes were examined and extracted by two reviewers independently . The following data were recorded using Microsoft Excel 2016 (Microsoft Corp, Redmond, WA): first author, year of publication, characteristics of patient, place of study, number of patients studied, tidal volume, amount of fluid infusion, the f value for defining responders to preload responsiveness, true positive rate , false positive rate , false negative rate , true negative rate , best cut-off value, sensitivity, specificity, the pooled area under the curve (AUC) of receiver operating characteristics (ROC) and r value.\u003c/p\u003e\n\u003cp\u003eFor further data analysis, we also assessed the pooled sensitivity, pooled specificity, pooled AUC, Youden index (sensitivity plus specificity minus one) and 95% credibility interval (CI) of them.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eStatistical treatment\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eData calculation and graphics synthesis was performed by Stata (version 14.0). Threshold effect and nonthreshold effect both will lead to heterogeneity. We used Spearman correlation coefficient (Mixed Model) to evaluate the threshold effect and used Cochrane-Q value of the AUC to evaluate nonthreshold effect. The heterogeneity was represented by the I2 statistic: when I2＜25% , it means low heterogeneity exists, when 25%＜I2＜50% ,it means moderate heterogeneity exists, and when I2≥50%, it means significant heterogeneity exists. Sensitivity analyses (test each article individually whether it is a source of heterogeneity) and meta-regression (patient’s surgeries; patient’s age; choice of patients volume expansion methods) were used to find the source of heterogeneity. We used Deeks’ Funnel Plot Asymmetry Test For Diagnostic Odds Ratio to determine whether significant publication bias exists in the articles included in the analysis [38].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eLiterature search and study characteristics \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe original literature search included 1,068 articles, of which 1007 articles were excluded by reviewing title and abstracts because they were duplicates, irrelevant studies, animal experiments, conference summaries, case reports or review articles. After careful browsing of the remaining 61 studies, 31 studies were excluded because they lacked the full-text article. Four studies were excluded because the lack of relevant data on outcomes. One study was excluded because its abstract was published in English, while its full-text was published in Chinese. The retrieved ,included and excluded articles for meta-analysis are summarized in Fig. 1.\u003cb\u003e \u003c/b\u003eCharacteristics of the 25 retrieved studies are summarized in Additional file 1.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eQuality assessment and Publication bias \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eQuality assessment of 25 retrieved studies is shown in Fig. 2 and Fig.3. \u003c/p\u003e\n\u003cp\u003eThe result of Deeks’ Funnel Plot Asymmetry Test for Diagnostic Odds Ratio is that the P value=0.76, indicates that no significant publication bias exists in the included literature.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eResults of retrieved studies\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe results of each retrieved studies are shown in Additional file 2. Twenty-five studies that included 1035 patients. The best cut-off value for PVI varied between 7% and 20%, while 1 study [18] did not provide information regarding the cut-off value. In 3 studies [20, 22, 32], the same patient receives more than one volume expansion, and the final data analysis uses the data for each volume expansion. Two studies [20,23] evaluated preload responsiveness at two different period of surgery, so we divided the results of each study into two parts.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eResults of meta-analysis\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe Spearman correlation coefficient was 0.07 (\u003ci\u003eP\u003c/i\u003e \u0026lt;0.01), indicates that although a significant threshold effect exists, the effect on the results is small. The Cochrane-Q value of the AUC was 39.175 (95% CI 0.79-0.85, \u003ci\u003eP\u003c/i\u003e \u0026lt;0.001) and I2=95%, indicates significant heterogeneity exists. Because of the significant heterogeneity of the pooled results, we performed a further subgroup analysis based on the patient's condition. The results of the meta-analysis are described in Table 1 and Fig. 4. The pooled AUC was 0.82 (95% confidence interval (CI) 0.79 - 0.85). The pooled sensitivity was 0.77 (95% CI 0.67-0.85) and the pooled specificity was 0.77 (95% CI 0.71-0.82). The results shown that the accuracy of PVI predicting preload reactivity is not as high as reported in previous meta-analyses[34-36]. Our new discovery is the result of patients without undergoing surgery (AUC=0.86, Youden index=0.65) was reliable.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eHeterogeneity\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe pooled I2 value was 95%, indicating statistically significant heterogeneity. After performance of meta-regression, we found the choice of intravenous colloid injection as a means of preload responsiveness was a significant cause (\u003ci\u003ep\u003c/i\u003e =0.02) of the heterogeneity; however, following the exclusion of the 17 studies which used intravenous colloid injection [10-16, 19-21, 23, 24, 29-33]， the heterogeneity remained significant（I2=84%）.\u003c/p\u003e\n\u003cp\u003eThe sensitivity analysis showed that 2 [16, 27] of the studies may have contributed to the heterogeneity; however, following the exclusion of the two studies, the heterogeneity remained significant（I2=95%）.\u003c/p\u003e\n\u003cp\u003eSignificant heterogeneity exists in both the overall group and most of the subgroups, which may be because of patient’s complex conditions, different surgical methods and the different fluid management methods. The heterogeneity was relatively low in the subgroup of patients undergoing noncardiac surgery(I2=63%), which may be because of the patients undergoing cardiac surgery are often non-sinus rhythms and have a greater impact on tissue perfusion. No significant heterogeneity exists in the subgroups of patients without undergoing surgery (I2=33%), which may be because certain surgical stimuli (such as pain) and procedures (such as liver surgery for inferior vena cava) may cause changes in vascular tension or hemodynamics. No significant heterogeneity exists in the crystalloid subgroup (I2=23%), potentially because of the small number of studies (n=4).\u003c/p\u003e\n\u003cp\u003e With the data emerging from our meta-analysis, no certain assertion can be made. The study provides interesting data and the results of the subgroups of patients without undergoing surgery should be reliable.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cb\u003eApplicable patients\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe PVI has higher accuracy for mechanically ventilated patients with a regular rhythm and nonthoracotomy [39]. The PVI reflects the degree of change in PI caused by breathing over a period of time, so PVI is greatly affected by cardiopulmonary exercise. The PVI has ability to reliably predict preload responsiveness, provided that the pressure changes in the chest cavity are sufficiently obvious enough and the cardiopulmonary interaction between different respiratory cycles is stable. Therefore, the PVI and other dynamic parameters of cardiopulmonary interaction are more suitable for patients with mechanical ventilation rather than spontaneous breathing. The results of the meta-analysis also showed that PVI was less reliable in the subgroup of cardiac surgery (Youden index =0.45) than in the non-cardiac surgery subgroup (Youden index =0.49).\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003ePerfusion situation\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eUnder the monitoring of a pulse oximeter, the pulsating blood flow absorbs red and infrared light (AC), and the tissue and skin also absorb red and infrared light (DC). The ratio of the two parameter can calculate the PI : \u003c/p\u003e\n\u003cp\u003e PI=（AC-DC）×100%\u003c/p\u003e\n\u003cp\u003ePVI reflects the degree of change in PI caused by breathing over a period of time. The formula is as follows:\u003cb\u003e \u003c/b\u003e \u003c/p\u003e\n\u003cp\u003e PVI=[（PImax-PImin）/PImax]×100%\u003c/p\u003e\n\u003cp\u003eReliability of the PVI is largely affected by adequacy of perfusion [40]. Peripheral perfusion deficiency can result in impaired blood flow to a stable constant partly caused by skin and other factors that signal the volume in the tissue. To date, a pulsed oximeter, which is used to calculate the PVI, will not be able to determine whether the reduction of chest pressure is caused by the variety of cardiovascular system capacity or low perfusion of the monitored site, so any influence on peripheral perfusion factors, that is, the factors that affect PI, can affect the reliability of the PVI [34]. The sensitivity of the subgroup of cardiac surgery is lower than that of the other subgroups and overall (0.67 95% CI 0.40-0.87). Broch O et al. [9] reported that the PVI reliably predicted preload responsiveness only in patients with high perfusion level (PI＞4%).\u003c/p\u003e\n\u003cp\u003eWhen using the PVI to guide goal-directed volume expansion, anesthetists should pay attention to factors that can affect perfusion situation of the monitored site (such as peripheral vascular disease, severe heart failure, application of vasoactive drugs, and damage of the monitored site).\u003c/p\u003e\n\u003cp\u003e \u003c/p\u003e\n\u003cp\u003e\u003cb\u003eTypes of volume expansion\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the synthesis show that the subgroups with colloid injection (Youden index=0.59 AUC=0.83) are more reliable than the subgroups with crystalloid injection (Youden index=0.46 AUC=0.79). This may be because the colloidal fluid has a better effect on the macrocirculation and the microcirculation [41], thus increasing the reliability of the PVI.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eThe best cut-off value\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe included results show that the PVI has a wide range of best cut-off value for defining responders to preload responsiveness, which range from 7% to 20%. The different conditions for each study (the patients’ underlying disease, volume stroke, age, type of surgery, in operating room or in ICU), and patients’ different fluid management (the application of vasoactive drugs, rate of intravenous infusion and type of volume expansion) may contribute to high variability. We suggest that readers can refer to the cut-off values reported in the corresponding articles when applying PVI to different patients.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eMonitored site\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe monitored site can affect the morphology and respiratory variation of the PVI[42-45]. Desgranges et al. [12] compared finger, forehead and ear as monitored site, reporting that the choice of three monitored sites has no significant impact on accuracy. While Hood et al. [19] reported that the PVIfinger can reliably predict increases in SV, while the PVIearlobe can not reliably predict increases in SV in dynamic intraoperative conditions. Fischer et al. [15] demonstrated PVIforehead was more accurate than PVIfinger in patients after cardiac surgery. For safety and convenience, the PVIfinger remains the preferred choice for most patients, with the PVIforehead and PVIearlobe as stable alternatives [12].\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eOur systematic review has several limitations. First, significant heterogeneity exists in both the overall group and most subgroups; thus, differences between patients and surgeries should be considered in the application of the PVI. Second, we only included mechanically ventilated patients, which limited the results extrapolated to all patients. Studies on the monitoring of the PVI on patients with spontaneous breathing must be conducted. Third, subgroup analyses of the child subgroup and the passive leg raise subgroup were not performed because of insufficient studies. Fourth, the best cut-off value for the PVI varied within great ranges, and the best cut-off value for different types of patients and surgeries remains to be studied. Finally, although PVI is more reliable for patients in the ICU, most of these patients are also applying other more accurate invasive monitoring (such as arterial blood pressure monitoring), so PVI is more recommended as a supplement of pulse oxygen.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe PVI, as a noninvasive and automatic hemodynamic monitoring, has limited ability to predict the fluid responsiveness of mechanically ventilated patients, except patients without undergoing surgery and patients in ICU. The PVI can plays an important role in bedside monitoring for mechanically ventilated patients who are not undergoing surgery, such as patients after cardiac surgery and shock patients. Patients who are expanded with colloid may be more suitable for PVI. For different individuals, the optimal PVI cut-off value must be further determined.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePVI: Pleth Variability Index; PI: perfusion index; CI：confidence interval ；AUC: area under the curve; ICU: intensive care unit;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003eAcknowledgements：\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eFunding\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eAvailability of data and materials \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eAuthors’ contributions \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eLiu, Xu, and Qi made substantial contributions to conception and design of the study; Wang and Niu searched literature, extracted data from the collected literature and analyzed the data; Liu wrote the manuscript; Wang and Niu revised the manuscript; All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eEthics approval and consent to participate Not applicable\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication Not applicable.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eCompeting interests\u003c/b\u003e \u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eAuthor details\u003c/b\u003e 1Key Laboratory of Anesthesia and Analgesia, Xuzhou Medical University and 2 Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jangsu, China\u003c/p\u003e"},{"header":"References","content":"\u003cp class=\"endNote_Bibliography\"\u003e1. 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Shelley KH, Jablonka DH, Awad AA, Stout RG, Rezkanna H, Silverman DG: \u003cb\u003eWhat is the best site for measuring the effect of ventilation on the pulse oximeter waveform?\u003c/b\u003e \u003ci\u003eAnesthesia and analgesia \u003c/i\u003e2006, \u003cb\u003e103\u003c/b\u003e(2):372-377, table of contents.\u003c/p\u003e"},{"header":"Tables","content":"\u003cbody\u003e\u003cp\u003e\u003cb\u003eTable 1 Results of meta-analysis\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003e \u003c/p\u003e\n\u003ctable class=table\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eSetting(numbers of studies)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eSensitivity(95% CI)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eSpecificity(95% CI)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eYouden index\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eAUC(95% CI)-ROC\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eI2(%)\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003ca name=\"_GoBack\"/\u003ePVI across all settings(n=27) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.67-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.71-0.82)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.54\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.82(0.79-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e95\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI in OR(n=18)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.76(0.67-0.84)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.76(0.68-0.82)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.52\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.82(0.79-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e81\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI in ICU(n=4)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.79(0.41-0.95)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.88(0.77-0.94)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.67\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.89(0.86-0.92)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e89\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI in adult(n=22)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.65-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.70-0.82) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.54\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.82(0.79-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e95\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI in cardiac surgery(n=9)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.67(0.40-0.87)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.78(0.66-0.87)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.45\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.80(0.77-0.84)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e89\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI in noncardiac surgery(n=12)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.78(0.64-0.88)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.71(0.58-0.82)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.49\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.80(0.76-0.83)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI without surgery(n=6)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.85(0.69-0.94)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.80(0.70-0.87)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.65\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.86(0.82-0.89)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI with colloid injection(n=17)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.67-0.85)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.82（0.77-0.86)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.59\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.83(0.80-0.86)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e87\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePVI with crystalloid injection(n=4)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.77(0.60-0.88)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.69(0.52-0.81)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.46\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.79(0.75-0.82)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003eAbbreviations: AUC, area under the curve; ROC, receiving operating characteristics.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pleth variability index, Preload responsiveness, Mechanically ventilated patients, Meta-analysis","lastPublishedDoi":"10.21203/rs.2.300/v6","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.300/v6","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Goal-directed volume expansion is increasingly used for fluid management in mechanically ventilated patients. The Pleth Variability Index (PVI) has been shown to reliably predict preload responsiveness; however, a lot of research on PVI has been published recently, and update of the meta-analysis needs to be completed. Methods: We searched PUBMED, EMBASE, Cochrane Library, Web of Science (updated to November 7, 2018) and the associated references. We also contacted relevant authors and researchers. Results: Twenty-five studies with 975 patients were included in this meta-analysis. All patients were mechanically ventilated. The area under the curve (AUC) of receiver operating characteristics (ROC) to predict preload responsiveness in patients was 0.82 (95% confidence interval (CI) 0.79 - 0.85). The pooled sensitivity was 0.77 (95% CI 0.67-0.85) and the pooled specificity was 0.77 (95% CI 0.71-0.82). The results of subgroup of patients without undergoing surgery (AUC =0.86, Youden index =0.65) and the results of subgroup of patients in ICU (AUC =0.89, Youden index =0.67) were reliable. Conclusion: The reliability of the PVI is limited, but the PVI can play an important role in bedside monitoring for mechanically ventilated patients who are not undergoing surgery. Patients who are expanded with colloid may be more suitable for PVI.\u003c/p\u003e","manuscriptTitle":"Reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":6,"date":"2019-04-30 19:36:34","doi":"10.21203/rs.2.300/v6","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2019-11-07T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2019-04-24T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-04-24T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-04-23T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":5,"date":"2019-04-19 16:23:20","doi":"10.21203/rs.2.300/v5","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-04-18T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":4,"date":"2019-04-15 21:27:52","doi":"10.21203/rs.2.300/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-04-15T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-04-12T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-04-12T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-04-12T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":3,"date":"2019-04-10 19:55:34","doi":"10.21203/rs.2.300/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-04-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-04-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-04-08T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-02-05T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2019-03-13 15:46:49","doi":"10.21203/rs.2.300/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-04-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-04-01T12:00:00+00:00","index":3,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"editorInvitedReview","content":"","date":"2019-04-01T12:00:00+00:00","index":4,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"reviewerAgreed","content":"","date":"2019-03-27T12:00:00+00:00","index":6,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-03-27T12:00:00+00:00","index":6,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"reviewerAgreed","content":"","date":"2019-03-25T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-03-25T12:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-03-25T12:00:00+00:00","index":5,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-03-25T12:00:00+00:00","index":1,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"editorInvitedReview","content":"","date":"2019-03-25T12:00:00+00:00","index":2,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"reviewersInvited","content":"","date":"2019-03-24T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-03-24T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-03-24T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvited","content":"","date":"2019-03-10T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-03-10T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-02-05T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-02-06 18:02:05","doi":"10.21203/rs.2.300/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2019-02-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-02-27T12:00:00+00:00","index":9,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"editorInvitedReview","content":"","date":"2019-02-25T12:00:00+00:00","index":6,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **'I declare that I have no competing interests**\n\nComments to Author:\n---\nReviewer's comments temporarily unavailable."},{"type":"editorInvitedReview","content":"","date":"2019-02-18T12:00:00+00:00","index":5,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **No conflict of interest**\n\nComments to Author:\n---\nIn this work the authors describe the reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients under various conditions. PVI is subject to the same limitations as other functional hemodynamic parameters such as SVV and PPV, including reduced reliability during arrhythmias, right heart failure, spontaneous breathing activity, and low tidal volume (\u003c8ml/kg). There are certain clinical scenarios where it is not recommended or not possible to use. In general, PVI is less accurate and therefore not recommended for spontaneously breathing patients, for patients with cardiac arrhythmia, for patients with extremely low PI, such as some ICU patients treated with vasopressors. PVI is also not recommended for patients undergoing open chest or laparoscopic surgery. Lastly, it may be unnecessary to use PVI for patients who require an arterial line. PVI also has some limitations specific to its technology such as movement artifacts. A similar work has already been published in a lower number of patients where the results are similar: \"Accuracy of pleth variability index to predict fluid responsiveness in mechanically ventilated patients: a systematic review and metaanalysis\" (J Clin Monit Comput, 2016, 30:265-274).\n\nHowever, the current work is an update of what has been published so far.\nI think is still necessary to descrive better the PI as well as the PVI method. Furthermore, the cut off related to the suggestive value of responsiveness is not described. Finally it is necessary to correct Spearman which must be written with a capital letter and figure 2 is not clear for which it is better specified.\n\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-16T12:00:00+00:00","index":4,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nThe study is a meta-analysis to determine the reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients.\nThe study is interesting and the effort made by the authors noteworthy.\nIt is not easy to perform a study of this type that requires time and dedication.\nDespite this necessary premise, there are substantial observations that must be made.\nThe meta-analysis studies are a source of valuable information, but can also be a source of serious confounding.\nThe first fundamental rule of a meta-analysis study is to compare studies that can be comparable.\nAs is often heard, you can not compare apples with oranges.\nThe selection of the studies to be included in the meta-analysis is fundamental to avoid selection bias that invalidate the whole study.\nTo avoid selection bias, it is necessary to try to insert well-designed studies with adequate sample size in the meta-analysis.\nAnother precaution to take is to include studies that investigate the same outcomes in similar patients.\nUnfortunately, the authors have tried to put together too different studies, often with low sample size and inadequate quality.\nThe authors then found themselves facing the problem of heterogeneity and tried to handle it correctly.\nBeing the result of a serious problem of selection bias, the authors have not been able to explain the origin of heterogeneity, because it is substantially unexplainable.\nThis makes any conclusion of the study impossible.\nA good way to solve the selection bias problem could be to limit the meta-analysis to at least clinically similar studies (for example, only studies on cardiac surgery patients), in this way trying to reduce inexplicable heterogeneity.\nI am very sorry for my judgment because I know how much effort there is behind this kind of studies. I hope that with appropriate adjustments, the study will be able to provide reliable information.\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-16T12:00:00+00:00","index":3,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nThe study is a meta-analysis to determine the reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients.\nThe study is interesting and the effort made by the authors noteworthy.\nIt is not easy to perform a study of this type that requires time and dedication.\nDespite this necessary premise, there are substantial observations that must be made.\nThe meta-analysis studies are a source of valuable information, but can also be a source of serious confounding.\nThe first fundamental rule of a meta-analysis study is to compare studies that can be comparable.\nAs is often heard, you can not compare apples with oranges.\nThe selection of the studies to be included in the meta-analysis is fundamental to avoid selection bias that invalidate the whole study.\nTo avoid selection bias, it is necessary to try to insert well-designed studies with adequate sample size in the meta-analysis.\nAnother precaution to take is to include studies that investigate the same outcomes in similar patients.\nUnfortunately, the authors have tried to put together too different studies, often with low sample size and inadequate quality.\nThe authors then found themselves facing the problem of heterogeneity and tried to handle it correctly.\nBeing the result of a serious problem of selection bias, the authors have not been able to explain the origin of heterogeneity, because it is substantially unexplainable.\nThis makes any conclusion of the study impossible.\nA good way to solve the selection bias problem could be to limit the meta-analysis to at least clinically similar studies (for example, only studies on cardiac surgery patients), in this way trying to reduce inexplicable heterogeneity.\nI am very sorry for my judgment because I know how much effort there is behind this kind of studies. I hope that with appropriate adjustments, the study will be able to provide reliable information.\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-16T12:00:00+00:00","index":2,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nThe study is a meta-analysis to determine the reliability of pleth variability index in predicting preload responsiveness of mechanically ventilated patients.\nThe study is interesting and the effort made by the authors noteworthy.\nIt is not easy to perform a study of this type that requires time and dedication.\nDespite this necessary premise, there are substantial observations that must be made.\nThe meta-analysis studies are a source of valuable information, but can also be a source of serious confounding.\nThe first fundamental rule of a meta-analysis study is to compare studies that can be comparable.\nAs is often heard, you can not compare apples with oranges.\nThe selection of the studies to be included in the meta-analysis is fundamental to avoid selection bias that invalidate the whole study.\nTo avoid selection bias, it is necessary to try to insert well-designed studies with adequate sample size in the meta-analysis.\nAnother precaution to take is to include studies that investigate the same outcomes in similar patients.\nUnfortunately, the authors have tried to put together too different studies, often with low sample size and inadequate quality.\nThe authors then found themselves facing the problem of heterogeneity and tried to handle it correctly.\nBeing the result of a serious problem of selection bias, the authors have not been able to explain the origin of heterogeneity, because it is substantially unexplainable.\nThis makes any conclusion of the study impossible.\nA good way to solve the selection bias problem could be to limit the meta-analysis to at least clinically similar studies (for example, only studies on cardiac surgery patients), in this way trying to reduce inexplicable heterogeneity.\nI am very sorry for my judgment because I know how much effort there is behind this kind of studies. I hope that with appropriate adjustments, the study will be able to provide reliable information.\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-15T12:00:00+00:00","index":8,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n\nComments to Author:\n---\nPag 1\n1)should report the acronym ROC\nPag 2\n2)the English can be improved\nPag 3\n3)see previous note\n4)This concept is not clear... Can be expressed differently?\nPag 4\n5) Add year\nPag 5\n6) Confusing... I suggest to reorganize it\n7) The various patient's population included represents, (because the different physiological patterns and characteristics of this), an huge bias in this study.\nPag 6\n8) Not necessary this clarification\n9) discussion with third reviewer?\n10) Please review how to report the data extraction\nPag 7\n11)write also extended form\n12) and do you mean DOR instead?\nPag 10\n13) I suggest to report the results in a simplified way:\n- organize the results in categories\n- lists it cleary\n-eliminate not useful statistical data from the report\n\nPlease review http://www.equator-network.org/reporting-guidelines/prisma/ for the method description.\nIn case of disagreement a third reviewer should assess the data.\nThe studies included having different population's categories shouldn't analyzed in a single systematic review and metanalysis, I suggest to restrict the study at one category in order to avoid biases.\nBecause the methods are not adequate also the conclusions consequently results simplified.\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-15T12:00:00+00:00","index":7,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n\nComments to Author:\n---\nPag 1\n1)should report the acronym ROC\nPag 2\n2)the English can be improved\nPag 3\n3)see previous note\n4)This concept is not clear... Can be expressed differently?\nPag 4\n5) Add year\nPag 5\n6) Confusing... I suggest to reorganize it\n7) The various patient's population included represents, (because the different physiological patterns and characteristics of this), an huge bias in this study.\nPag 6\n8) Not necessary this clarification\n9) discussion with third reviewer?\n10) Please review how to report the data extraction\nPag 7\n11)write also extended form\n12) and do you mean DOR instead?\nPag 10\n13) I suggest to report the results in a simplified way:\n- organize the results in categories\n- lists it cleary\n-eliminate not useful statistical data from the report\n\nPlease review http://www.equator-network.org/reporting-guidelines/prisma/ for the method description.\nIn case of disagreement a third reviewer should assess the data.\nThe studies included having different population's categories shouldn't analyzed in a single systematic review and metanalysis, I suggest to restrict the study at one category in order to avoid biases.\nBecause the methods are not adequate also the conclusions consequently results simplified.\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-15T12:00:00+00:00","index":1,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Unable to assess**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nThe authors evaluated reliability of pleth variability index (PVI) in predicting preload responsiveness of mechanically ventilated patients in various conditions by meta-analysis. The issue is important for optimal fluid therapy in critically ill patients. This reviewer raises several major concerns especially on design of the study.\n\n\u003cMajor comments\u003e\n1. Design of the study\nAs the authors commented in the Introduction, a lot of study on reliability of PVI in predicting fluid responsiveness has been reported. Indeed it is a good idea that the results are analyzed according to patient population, patient background such as vascular tone might be largely different within each patient population. Therefore, conclusion according to meta-analysis in this study may not be valid.\n\n2. Purpose and conclusion\nThe purpose of this study was the comparison of reliability of PVI to predict preload responsiveness between (i) undergoing operation or without operation, (ii) undergoing cardiac surgery or noncardiac surgery, (iii) adults or children ,(iv) different types of volume expansion (in the Introduction). However, the conclusion in the Abstract was \"PVI can play an important role in bedside monitoring for mechanically ventilated patients who are not undergoing surgery.\" This corresponds to (i) above. How about other comparisons?\n"},{"type":"reviewerAgreed","content":"","date":"2019-02-14T12:00:00+00:00","index":11,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-12T12:00:00+00:00","index":9,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-12T12:00:00+00:00","index":10,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-12T12:00:00+00:00","index":8,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-12T12:00:00+00:00","index":7,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-10T12:00:00+00:00","index":6,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-10T12:00:00+00:00","index":5,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-09T12:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-09T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-09T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-09T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-02-09T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-02-05T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-02-05T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-02-05T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5c7421bd-382a-4950-b9fb-769bdac34b0d","owner":[],"postedDate":"April 30th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":11550,"name":"Internal Medicine Specialties"}],"tags":[],"updatedAt":"","versionOfRecord":{"articleIdentity":"rs-300","link":"https://doi.org/10.1186/s12871-019-0744-4","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2019-05-18 12:00:00","publishedOnDateReadable":"May 18th, 2019"},"versionCreatedAt":"2019-04-30 19:36:34","video":"","vorDoi":"10.1186/s12871-019-0744-4","vorDoiUrl":"https://doi.org/10.1186/s12871-019-0744-4","workflowStages":[]},"version":"v6","identity":"rs-300","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-300","version":["v6"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}