Time-varying effect of hemodynamics in intensive care via neuromuscular electrical stimulation：a prospective, single-center, self-controlled study

Time-varying effect of hemodynamics in intensive care via neuromuscular electrical stimulation：a prospective, single-center, self-controlled study | 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 Article Time-varying effect of hemodynamics in intensive care via neuromuscular electrical stimulation：a prospective, single-center, self-controlled study Lixiang Ye, Yubo Li, Chengcheng Su, Zhaozhao Xu, Shuxiang Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6749490/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 21 You are reading this latest preprint version Abstract Objective: This study aimed to investigate the pattern of changes in hemodynamic indices after the use of neuromuscular electrical stimulation in intensive carepatients. Methods: Forty icu inpatients with Caprini risk score ≥5 from Qianfoshan Hospital in Shandong Province received neuromuscular electrical stimulation. Doppler ultrasound was used to collect hemodynamic indexes (peak blood flow velocity, peak blood flow, and vessel diameter) of the popliteal vein of the patients before the application of NMES, 0.5h、1h、1.5h、2h during application as well as 0.5h and 1h after the discontinuation of NMES, respectively, to analyze the time-variable variations of hemodynamic indexes. Results: The peak venous flow velocity, diameter of the popliteal vein, and blood flow volume following NMES intervention were significantly higher than pre-intervention levels (P < 0.05). During the initial phase of intervention (from initiation to 1 hour post-intervention), hemodynamic parameters progressively increased, but no further elevation was observed between 1 and 2 hours of intervention. At 1 hour after NMES discontinuation, the peak venous flow velocity, diameter, and blood flow volume in the popliteal vein showed no statistically significant differences compared to pre-intervention values (P > 0.05), indicating a return to baseline levels. Conclusion: NMES accelerates venous blood flow velocity in the lower extremities of ICU patients, is feasible, safe, and effective in the absence of the use of other conventional physical measures. The hemodynamic parameters plateau after 1 hour of application and return to baseline values within 1 hour of discontinuation, providing valuable insights for future research on the clinical utilization of NMES. Health sciences/Medical research Physical sciences/Engineering/Mechanical engineering Neuromuscular Electrical Stimulation Hemodynamic Effects Intensive Care Unit Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction It is well known that intensive care unit patients spend most of their time bedridden and inactive, which can lead to a range of complications such as intensive care unit acquired weakness(ICU-AW), pressure injury, and blood clots [1-3] . In turn, mobility restriction is associated with decreased blood flow velocity and the development of deep vein thrombosis (DVT) [4] . Previous studies have demonstrated that neuromuscular electrical stimulation (NMES) can enhance blood flow velocity and prevent deep vein thrombosis [5-7] . However, time-varying effect of hemodynamics of popliteal vein under NMES intervention remain unclear, which constitutes the rationale for conducting this study. The NMES can be used as one of the options, As a way of mechanical interventions, NMES releases current pulses by electrodes attached to the skin that produces neuronal action potential acting on the common peroneal nerve, induces muscle contraction with dorsiflexion of the foot, which in turn changes the blood flow rate and improves venous and lymphatic reflux of lower extremities with fewer complications and high compliance [8-9] . In 2014, the UK National Institute for Health and Care Excellence (NICE) published a medical technology guideline, for the first time endorsing the use of NMES device named "geko™" in high-risk VTE patients where pharmacological and conventional mechanical prophylaxis cannot be utilized [10] . At the same time, the device was approved by the U.S. Food and Drug Administration (FDA) for the prevention of VTE [11] . Although improved portable wearable devices have emerged for NMES over the past decades, treatment protocols have not been standardized and treatment parameters such as pulse width, stimulation frequency, stimulation intensity, and waveform have not been established with a clear consensus for clinical use, and the present study may be able to add relevant aspects. Patients need to be dynamically assessed for VTE risk and bleeding risk during the whole hospitalization period, and patients admitted to the ICU are often part of the high-risk VTE population. Although the effect of intravenous drugs is obvious and fully supported by clinical practice, the use of drugs may lead to an increase in the risk of bleeding in patients. Therefore, for patients with bleeding tendency, relevant guidelines mostly recommend the use of physical therapy to prevent the occurrence of lower extremity DVT [16-18] . While NMES belongs to one of the modalities in mechanical prophylaxis, prolonged use may lead to adverse effects such as localized muscle overcontraction and decreased neural sensitivity [19] . Therefore, for patients who require NMES, there is a need to clarify the hemodynamic changes of NMES, when it peaks, and when it returns to baseline values after withdrawal, in order to give a reference for the duration of NMES use, and the length of the interval between uses, and a study was initiated for this purpose. NMES has emerged in the healthcare field, with existing studies healthcare training for the elderly, enhancing mechanical ventilation and stimulation of neurodevelopment. And its significance in clinical application is to improve muscle strength, alleviate edema, prevent atrophy, reduce pain, and accelerating blood circulation in patients [12-14] . It is believed that higher metabolite clearance and reduced edema will translate into a reduction in perceived muscle soreness and an accelerated recovery of neuromuscular function and biochemical profile [15] and NMES has that role. Consequently, NMES promote a beneficial effect with the reduction of complications in patients with intensive care unit. However, there are no reports on the effect of NMES on hemodynamics over time in patients admitted to the ICU, and such effects in this context has yet to be fully elucidated. At the same time, it should be taken into account that ICU patients in an absolutely bedridden state represent a specific group of individuals. The application is more promising in units such as ICUs, where comatose patients predominate, have no autonomy and are unable to actively cooperate, because of their ease of wear and use. When encountering overweight patients, most Intermittent Pneumatic Compression(IPC) requires lifting the whole leg, which is not easy to use, and this time NMES is more convenient and highlights its superiority. Although some studies have shown that NMES improves hemodynamic parameters, they have not been able to explain the study of NMES on the pattern of hemodynamic changes over time. Considering the wide use of this strategy among icu patients, it may be significant to clarify the real physiological effects of NMES, to fill this gap in scientific evidence. Accordingly, the aim of this study was to investigate the time-varying effects of applied neuromuscular electrical stimulation on popliteal vein hemodynamics in intensive care patients, and to provide theoretical basis for the rational clinical use of NMES. 2 Materials and Methods 2.1 Study Design This was an interventional, single-centre, self-controlled trial. It was conducted in an 30-bed, level 3, medical ICU at the Affiliated Hospital of Shandong First Medical University during a 3-month period (from January 2025 to March 2025). The study was approved by the Institutional Review Board of Thousand Buddha Mountain Hospital in Shandong Province(No. R202410240370, October 24, 2024). It was prospectively registered (ChiCTR2400093997, 16/12/2024). Informed consent was signed by relative caregiver prior to inclusio. The trial is reported according to CONSORT guidelines [20] . 2.2 Participants Critically ill patients after 1- to 3- days of ICU admission, whose treatment was expected to require at least 5 days in the ICU, were included in the study. The inclusion criteria of the study were as follows:(1) Age ≥18 years; (2) Caprini risk score ≥5 (high risk) assessed after admission to the ICU; (3) no DVT by ultrasonography after admission to the ICU; (4) No autonomic consciousness. Exclusion criteria include(1) Thrombophlebitis of the lower limbs and epilepsy; (2)Implanted cardiac pacemakers; (3)Unable to carry out the procedure due to the presence of ulcers, trauma, dermatitis, and infections on the skin at the peroneal nerve (where the electrode sheet is affixed); (4)People who are allergic to the electrode sheet. (5) brain death, and inability to obtain informed consent.Patients were screened according to strict inclusion and exclusion criteria, and the intervention was carried out after the icu patient or the patient's family had signed an informed consent form, and no other physical measures were taken in the patients included in the study. 2.3 Neuromuscular Electrical Stimulation NMES(Manufactured by China Tino Medical Technology Corporation, Hangzhou, Zhejiang Province, Model CS-200) paste position: the electrode sheet will be pasted in the patient's common peroneal nerve, the common peroneal nerve by the peroneal head below the fibular bone, the fibular bone on the upper part of the lateral through, that is, paste in the fibular head under the one finger can be.The peroneal head is a rounded protuberance on the outside of the lower leg, just below the knee joint.The length of the intervention was 2h once a day in the afternoon, done for 3 consecutive days.The stimulation intensity is NMES pulse frequency 1Hz, pulse width is maximum 560μS, 7 levels of intensity can be adjusted, it is recommended that 3~4 levels, this study takes 3~4 levels. It is used as shown in Figure.1. 2.4 Interventions When the included patients were identified, the electrode sheets were attached to their legs, and then the NMES small device was magnetized on the corresponding position to turn it on and start it up. The length of the intervention was 2h once a day in the afternoon, done for 3 consecutive days. Measurements were performed using a color Doppler ultrasound device (Mindray Bio-Medical Electronics Co.， Ltd.， Shenzhen， Guangdong Province， model UMT-500) at the following time points: before NMES intervention， during NMES application at 0.5 hours， 1 hour， 1.5 hours， 2 hours， and after NMES discontinuation at 0.5 hours and 1 hour. The popliteal vein of one side of the lower limb of the patient was measured randomly using the lottery method(Before the measurement, an uninformed researcher wrote the words “left” and “right” on two identical cards, placed the cards in an opaque black box, and then randomly selected a card by the researcher after sufficiently shaking it to check the words on the selected card. If it is “left”, the left leg will be chosen for the measurement; if it is “right”, the right leg will be chosen, and the card will be put back into the box for the next time). The patients were also randomly assigned to four uninformed sonographers using the closed-envelope method. In addition, the same model of NMES was used in all patients participating in the trial, with stimulation intensities of 3 to 4 levels. The same sonographer measured the same patient using the same ultrasound detector and the same measurement method, and the final data were double-checked and entered by the researcher and the nurse in charge. 2.5 Outcomes and Measurement of Popliteal vein blood flow velocity Outcomes include (1) Peak Flow Velocity (PFV): The maximum linear velocity of a mass of blood moving through the tube per unit of time, expressed in centimeters per second (cm/s); (2)Blood Flow Volume(BFV) :The peak blood flow per minute through a cross-section of the popliteal vein is calculated as:peak blood flow (ml/min) = radius (cm) × radius (cm) × π (circular constant) × peak venous blood flow velocity (cm/s) × 60. (3) Vessel Diameter (VD): the diameter (in cm) of the inner lumen of the popliteal vein. During the measurement, the patients breathed calmly, took the head-high-feet-low position, and slightly abducted and flexed the lower limb on the measurement side. The ultrasound probe was placed at the popliteal vein, the probe was perpendicular to the skin, the popliteal vein was localized by transverse cut, then longitudinal cut, the ultrasound parameters were adjusted so that the acoustic beam and the direction of the venous blood flow were at 60°, and the image was frozen after the clear blood flow signal was displayed, and the spectrum of the spectrum was taken for a cycle of measurement. Patients who met the inclusion criteria used the NMES for 3 consecutive days, with two hours of intervention per day, and the values of the parameters were recorded at different time intervals before, during, and after the intervention, and then averaged over the 3 days. 2.6 Sample Size Estimation and Statistical analysis The indicated sample size in the trial registry was 40. We first calculated the mean difference in peak popliteal venous flow rate before and after the application of NMES based on the results of the pre-experiment to be 4.65 cm/s, with a standard deviation of 2.29 cm/s. At this level of effect, 33 patients would have been required in the study with type I error level of 0.05 (p-value threshold 0.05) and a type II error of 0.20 (power 80%), we added 7 patients due to the consideration of 10% sample attrition. Sociodemographic characteristics underwent descriptive characterization, with quantitative variables displaying normal distribution expressed as mean ± standard deviation, whereas non-normally distributed metrics were reported as median (interquartile range). Nominal variables were summarized using frequency counts with proportional percentages. To assess differences in popliteal venous flow rate across different time points (PFV、VD、BFV), Friedman's ANOVA test was initially analyzed. If Friedman's ANOVA showed significant differences, post-hoc analyses were conducted via the Wilcoxon signed-rank test with Bonferroni correction to assess temporal variations between baseline measurements and follow-up intervals(comparing baseline with time points 0.5h, 1h, 1.5h, and 2h after the NMES intervention, and 0.5h and 1h after withdrawal of the NMES), and examine relationships between interventions at different time points. Normally distributed data were analyzed using the paired-sample t-test. A p value of < 0.05 was considered statistically significant, and when the Bonferroni correction was applied it was set at p < 0.008 (0.05/number of comparisons). All statistical procedures were performed using IBM SPSS Statistics for Windows, versions 26. (IBM Corp., Chicago, IL, USA). 3 Results Forty ICU patients were screened and enrolled onto the study. The study included 23 male and 17 female participants, with a median APACHE II score of 23 (IQR: 19-26), a median Caprini score of 9 (IQR: 8.25-10.0), and a mean age of 59.83 ± 14.34 years. Among 40 enrolled patients, the most common comorbidities at admission included hypertension (62.5%, n=25), coronary heart disease (45.0%, n=18), diabetes mellitus (22.5%, n=9), and pneumonia (30.0%, n=12). Three participants withdrew due to NMES intolerance, and eight discontinued therapy prematurely (<3 consecutive days) following transfer or discharge. All participants completed the intervention protocol of 2 hours daily for three consecutive days, with a 100% completion rate. No adverse events or harms were reported during the study period. Regarding the Peak Flow Velocity, Friedman's ANOVA showed that under NMES intervention, there were statistically significant differences in PFV across different time points (χ² = 179.767, p < 0.05). The Wilcoxon signed-rank test with Bonferroni correction showed that the PFV was significantly higher during the application of the NMES at 0.5h (Z = -5.35, p < 0.001), at 1h (Z = -5.511, p < 0.001), at 1.5h (Z = -5.498, p < 0.001), at 2h (Z = -5.511, p < 0.001), and 0.5h post-weaning (Z = -5.443, p < 0.001) compared to pre-intervention levels. However, no statistically significant difference was observed at 1h post-weaning (Z = -1.788, p = 0.074) compared to pre-intervention. When compared to 0.5h during intervention, significant differences were found at 1h (Z = -4.535, p < 0.001), 1.5h (Z = -4.41, p < 0.001), and 2h (Z = -4.933, p < 0.001) during the application of the NMES. In contrast, No statistically significant differences were detected between 1h and either 1.5h (Z = -0.796, p = 0.426) or 2h (Z = -0.973, p = 0.331) during intervention. This indicates that the PFV gradually increased during the period from the initiation of NMES intervention up to 1h during intervention and subsequently tended to stabilize after 1h of intervention (Fig.2). Detailed comparisons across all time points are presented in Table 1. Regarding the vessel diameter, significant differences were observed between the values at 1h, 1.5h, and 2h of NMES application, as well as 0.5h post-weaning, when compared to pre-intervention and 1h post-weaning (all p 0.05). This indicates that the vascular radius expanded to a stabilized value after 1h of NMES application and returned to baseline levels 1h after cessation(Fig.3). Regarding the blood flow volume, Friedman's ANOVA revealed statistically significant differences in BFV across different time points under NMES intervention (χ² = 174.264, p < 0.05). The Wilcoxon signed-rank test with Bonferroni correction showed that BFV at 1h (Z = -5.511, p < 0.001), 1.5h (Z = -5.497, p < 0.001), and 2h (Z = -5.511, p < 0.001) during intervention, as well as 0.5h post-weaning (Z = -5.511, p < 0.001), differed significantly from both pre-intervention and 1h post-weaning. No statistically significant difference was observed between 1h post-weaning and pre-intervention (Z=-1.642, p =0.101). Combined with the significant difference between 0.5h and 1h during intervention (Z = -4.436, p < 0.001) of NMES application, these results indicate that BFV gradually increased during the first hour of NMES intervention and returned to baseline levels 1h after cessation. Furthermore, No statistically significant differences were observed between 1.5h (Z = -0.524, p = 0.6) and 2h during intervention(Z = -1.066, p = 0.286) when compared to PFV at 1h post-intervention, suggesting that BFV stabilized following the first hour of NMES intervention(Fig.4). 4 Discussion This study aimed to assess the hemodynamic effects of NMES, using a pulse frequency of 1 Hz and pulse width of 280–373 μs, in ICU patients, in a bedridden state. This tool has been suggested as a blood flow enhancer and is being explored for use in high-risk VTE patients who are unable to use pharmacologic and conventional who cannot utilize pharmacological or conventional mechanical prophylaxis. And there is moderate evidence suggesting that NMES may serve as a viable tool to optimize this process [5] . Therefore, the present study may strengthen the evidence for NMES as a means of accelerating venous blood flow velocity and further explore the pattern of blood flow changes after NMES intervention. This study suggests that PFV, VD, and BFV after NMES intervention were statistically significant compared with those before intervention ( p < 0.05) and after 1h of withdrawal compared with other time points ( p 0.05). These data indicate that the hemodynamic effects of NMES on the popliteal vein gradually increased from the initiation of intervention to 1 hour during intervention, ceased further enhancement after 1 hour of intervention, and returned to pre-intervention baseline levels at 1 hour post-withdrawal. The findings provide reference significance for determining the time to peak PFV, VD, and BFV, the recovery time to baseline values, optimal application duration, and appropriate intervals between sessions for the therapeutic purposes of NMES, which may include DVT prophylaxis, reduction of edema, and prevention of muscular dystrophy, among other purposes that are not discussed here without the relevant metrics. Studies over the years have also shown that other mechanical interventions such as intermittent pneumatic compression pump (IPC) and graduated compression stocking (GCS) improve hemodynamic parameters in clinical and healthy populations [21] , but some studies has shown their lower compliance rates [22] . This suggests that mechanical prophylaxis of thrombosis has not been effectively implemented, thereby increasing the risk of DVT in patients. NMES can induce rapid and consistent muscle pump activation through ankle joint movement, generating stronger physiological hemodynamic forces compared to other mechanical prophylactic measures such as GCS or IPC. This is attributed to its ability to fully empty the deep venous sinuses. In addition, it has been shown that skeletal muscle contraction releases myokines [23] , which act and mediate anti-inflammatory effects [24-26] , and systemic inflammatory diseases are highly correlated with thrombotic tendencies [27-28] . Therefore muscle contraction-induced anti-inflammatory effects may also contribute to the hematological effects of NMES in preventing thrombosis. The significant advantages of NMES is its virtually no risk of complications, absence of associated bleeding risks, ease in locating optimal stimulation points, and straightforward operability [29] . However, there are relative gaps in the areas of whether prolonged interventions beyond this time will result in a decline in hemodynamic indices; whether changes will occur as a result of excessive muscle contraction when intervening for a certain amount of time; and whether it is necessary to withdraw the machine when a downward trend occurs to allow time for bodily functions to adjust. The present study was able to show that PFV, VD, and BFV stabilized after 1 h on the machine, and that blood flow velocities returned to pre-intervention baseline values when the machine was withdrawn for 1 h, a time point that can be used as a reference for continued time on the machine. There are several limitations to be noted regarding this study. First, a common limitation of self-controlled studies is the inability to control time-dependent confounding factors. However, our study population were patients in the ICU, in relatively isolated environments, 90% of the patients included in the study were comatose and bedridden, with no autonomous consciousness, and researchers were blinded to the intervention status, to minimize the possible confounders and to control the bias to the greatest extent possible. Second, the degree of foot dorsiflexion response after NMES intervention is not the same in different patients, potentially attributable to factors such as adipose tissue thickness or insufficient stimulation intensity. Although identical equipment, stimulation intensity, and frequency were applied to all participants, the actual degree of physiological intervention might differ among individuals. Lastly, the time nodes of our measurements were half an hour apart, and the data analysis was also conducted in this way. It is therefore possible to peak between 0.5 h-1 h and return to baseline values between 0.5 h-1 h after removing the machine, as these critical timepoints could not be definitively determined through our current sampling strategy. 5 Conclusion NMES is a mechanical strategy with promising applications, and the present study further demonstrated that the intervention of NMES can accelerate venous blood flow in the lower extremities of ICU patients, and that hemodynamic indices stabilized after 1 h of intervention and returned to baseline values 1 h after withdrawal. Considering the limitations of this study, more large-sample, multicenter, high-quality randomized controlled trials are needed in the future to provide further evidence support and standardize its clinical application. Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of Thousand Buddha Mountain Hospital in Shandong Province (No. R202410240370) Consent for publication We obtained signed consent from all participants to use and publish their data for this study using our institutional form. Availability of data and material The dataset analyzed in this study is available upon request from the first author. Competing interests The authors declare that they have no competing interests. Funding This work was supported by a postgraduate medical grant from Shandong Second Medical University and a research grant from Qianfoshan Hospital. Authors' contributions Ye Lixiang was mainly responsible for finding information and writing the paper; Li Yubo was mainly responsible for communicating with the patients or their families and getting them to sign the informed consent form; Su Chengcheng was mainly responsible for collecting and organizing the data; Xu Zhaozhao was mainly responsible for analyzing the data and making the pictures; and Zhang Shuxiang was mainly responsible for communicating with the manufacturer of NMES and contacting the ICU for cooperation. Acknowledgements Not applicable. References Williams KJ, Ravikumar R, Gaweesh AS, Moore HM, Lifsitz AD, Lane TR, Shalhoub J, Babber A, Davies AH. A Review of the Evidence to Support Neuromuscular Electrical Stimulation in the Prevention and Management of Venous Disease. Adv Exp Med Biol. 2017;906:377-386. García-Pérez-de-Sevilla G, Sánchez-Pinto Pinto B. 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Table Table 1:Detailed comparison between different time points Additional Declarations No competing interests reported. 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University","correspondingAuthor":false,"prefix":"","firstName":"Yubo","middleName":"","lastName":"Li","suffix":""},{"id":485394745,"identity":"291c5460-75ef-4ecb-b566-d08fc76ee757","order_by":2,"name":"Chengcheng Su","email":"","orcid":"","institution":"Shandong Second Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengcheng","middleName":"","lastName":"Su","suffix":""},{"id":485394746,"identity":"0c26b055-e626-4936-9384-37813a714d2f","order_by":3,"name":"Zhaozhao Xu","email":"","orcid":"","institution":"Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhaozhao","middleName":"","lastName":"Xu","suffix":""},{"id":485394747,"identity":"3ccfa692-33f0-4108-8057-ed4fc67bfae6","order_by":4,"name":"Shuxiang Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYHACxsc//0jIsbE3HyBaC7MxY4OFMR/PsQSitbAJMzZUJM6TyFEgTr18/xkz5sIdEultDDkMDD8qthHWwjgjLe3xzDMSuW0MZw8w9py5TVgLswTzcQMeNqAWxr4EZsY2IrSw8R9skwBqSWdj5jEgTgsPQ/Ixad42iQQ2NmK1SEikJRvOOCNh2MbDlnCQKL8AQ8zwwYeKOnn5+Y8PPvhRQYQWFHCARPWjYBSMglEwCnABAJLmNkCiZ0xHAAAAAElFTkSuQmCC","orcid":"","institution":"Qianfoshan Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shuxiang","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-05-26 09:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6749490/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6749490/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-29464-7","type":"published","date":"2025-12-03T15:57:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86830468,"identity":"1a581aa4-51a6-47b9-9caf-f006b3df3e04","added_by":"auto","created_at":"2025-07-16 05:56:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":258202,"visible":true,"origin":"","legend":"\u003cp\u003eSites of NMES intervention\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6749490/v1/47dcb13ea592b317c3a08294.png"},{"id":86830469,"identity":"8efe77a2-3c3c-47da-ab00-afe5d497d186","added_by":"auto","created_at":"2025-07-16 05:56:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":37011,"visible":true,"origin":"","legend":"\u003cp\u003eBox Plot of Peak Flow Velocity (solid line = median, dash-dot line = mean)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6749490/v1/3955c1716cf915a3e8311017.png"},{"id":86830481,"identity":"14df43dc-515e-4ab2-b429-162de12e3aac","added_by":"auto","created_at":"2025-07-16 05:56:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33834,"visible":true,"origin":"","legend":"\u003cp\u003eBox Plot of Vessel Diameter (solid line = mean)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6749490/v1/1ee38a7376cd85869540cb32.png"},{"id":86830470,"identity":"42836d90-51b6-421d-abec-71e853c17322","added_by":"auto","created_at":"2025-07-16 05:56:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":38653,"visible":true,"origin":"","legend":"\u003cp\u003eBox Plot of Blood Flow Volume (solid line = median, dash-dot line = mean)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6749490/v1/6955d2334210ec970ac109aa.png"},{"id":97723836,"identity":"9bbcc2d4-a77d-4dfc-88ce-414c32f8c473","added_by":"auto","created_at":"2025-12-08 16:08:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":949567,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6749490/v1/4858bce0-78da-4db3-b0c1-3653ba04ce61.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTime-varying effect of hemodynamics in intensive care via neuromuscular electrical stimulation：a prospective, single-center, self-controlled study\u003c/p\u003e","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIt is well known that intensive care unit patients spend most of their time bedridden and inactive, which can lead to a range of complications such as intensive care unit acquired weakness(ICU-AW), pressure injury, and blood clots\u003csup\u003e[1-3]\u003c/sup\u003e. In turn, mobility restriction is associated with decreased blood flow velocity and the development of deep vein thrombosis (DVT)\u003csup\u003e[4]\u003c/sup\u003e. Previous studies have demonstrated that neuromuscular electrical stimulation (NMES) can enhance blood flow velocity and prevent deep vein thrombosis\u003csup\u003e[5-7]\u003c/sup\u003e. However, time-varying effect of hemodynamics of popliteal vein under NMES intervention remain unclear, which constitutes the rationale for conducting this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe NMES can be used as one of the options, As a way of mechanical interventions, NMES releases current pulses by electrodes attached to the skin that produces neuronal action potential acting on the common peroneal nerve, induces muscle contraction with dorsiflexion of the foot, which in turn changes the blood flow rate and improves venous and lymphatic reflux of lower extremities with fewer complications and high compliance\u003csup\u003e[8-9]\u003c/sup\u003e. In 2014, the UK National Institute for Health and Care Excellence (NICE) published a medical technology guideline, for the first time endorsing the use of NMES device named \"geko™\" in high-risk VTE patients where pharmacological and conventional mechanical prophylaxis cannot be utilized\u003csup\u003e[10]\u003c/sup\u003e. At the same time, the device was approved by the U.S. Food and Drug Administration (FDA) for the prevention of VTE\u003csup\u003e[11]\u003c/sup\u003e. Although improved portable wearable devices have emerged for NMES over the past decades, treatment protocols have not been standardized and treatment parameters such as pulse width, stimulation frequency, stimulation intensity, and waveform have not been established with a clear consensus for clinical use, and the present study may be able to add relevant aspects.\u003c/p\u003e\n\u003cp\u003ePatients need to be dynamically assessed for VTE risk and bleeding risk during the whole hospitalization period, and patients admitted to the ICU are often part of the high-risk VTE population. Although the effect of intravenous drugs is obvious and fully supported by clinical practice, the use of drugs may lead to an increase in the risk of bleeding in patients. Therefore, for patients with bleeding tendency, relevant guidelines mostly recommend the use of physical therapy to prevent the occurrence of lower extremity DVT\u003csup\u003e[16-18]\u003c/sup\u003e. While NMES belongs to one of the modalities in mechanical prophylaxis, prolonged use may lead to adverse effects such as localized muscle overcontraction and decreased neural sensitivity\u003csup\u003e[19]\u003c/sup\u003e. Therefore, for patients who require NMES, there is a need to clarify the hemodynamic changes of NMES, when it peaks, and when it returns to baseline values after withdrawal, in order to give a reference for the duration of NMES use, and the length of the interval between uses, and a study was initiated for this purpose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNMES has emerged in the healthcare field, with existing studies healthcare training for the elderly, enhancing mechanical ventilation and stimulation of neurodevelopment. And its significance in clinical application is to improve muscle strength, alleviate edema, prevent atrophy, reduce pain, and accelerating blood circulation in patients\u003csup\u003e[12-14]\u003c/sup\u003e. It is believed that higher metabolite clearance and reduced edema will translate into a reduction in perceived muscle soreness and an accelerated recovery of neuromuscular function and biochemical profile\u003csup\u003e[15]\u003c/sup\u003e and NMES has that role. Consequently, NMES promote a beneficial effect with the reduction of complications in patients with intensive care unit.\u0026nbsp;However, there are no reports on the effect of NMES on hemodynamics over time in patients admitted to the ICU, and such effects in this context has yet to be fully elucidated.\u003c/p\u003e\n\u003cp\u003eAt the same time, it should be taken into account that ICU patients in an absolutely bedridden state represent a specific group of individuals. The application is more promising in units such as ICUs, where comatose patients predominate, have no autonomy and are unable to actively cooperate, because of their ease of wear and use. When encountering overweight patients, most Intermittent Pneumatic Compression(IPC) requires lifting the whole leg, which is not easy to use, and this time NMES is more convenient and highlights its superiority. Although some studies have shown that NMES improves hemodynamic parameters, they have not been able to explain the study of NMES on the pattern of hemodynamic changes over time. Considering the wide use of this strategy among icu patients, it may be significant to clarify the real physiological effects of NMES, to fill this gap in scientific evidence. Accordingly, the aim of this study was to investigate the time-varying effects of applied neuromuscular electrical stimulation on popliteal vein hemodynamics in intensive care patients, and to provide theoretical basis for the rational clinical use of NMES.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cp\u003e2.1\u0026nbsp;\u0026nbsp;Study Design\u003c/p\u003e\n\u003cp\u003eThis was an interventional, single-centre, self-controlled trial. It was conducted in an 30-bed, level 3, medical ICU at the Affiliated Hospital of Shandong First Medical University during a 3-month period (from January 2025 to March 2025). The study was approved by the Institutional Review Board of Thousand Buddha Mountain Hospital in Shandong Province(No. R202410240370, October 24, 2024). It was prospectively registered (ChiCTR2400093997, 16/12/2024). Informed consent was signed by relative caregiver prior to inclusio. The trial is reported according to CONSORT guidelines\u003csup\u003e[20]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e2.2\u0026nbsp;\u0026nbsp;Participants\u003c/p\u003e\n\u003cp\u003eCritically ill patients after 1- to 3- days of ICU admission, whose treatment was expected to require at least 5 days in the ICU, were included in the study. The inclusion criteria of the study were as follows:(1) Age\u0026nbsp;≥18 years; (2) Caprini risk score\u0026nbsp;≥5 (high risk) assessed after admission to the ICU; (3) no DVT by ultrasonography after admission to the ICU; (4) No autonomic consciousness. Exclusion criteria include(1) Thrombophlebitis of the lower limbs and epilepsy; (2)Implanted cardiac pacemakers; (3)Unable to carry out the procedure due to the presence of ulcers, trauma, dermatitis, and infections on the skin at the peroneal nerve (where the electrode sheet is affixed); (4)People who are allergic to the electrode sheet. \u0026nbsp;(5) brain death, and inability to obtain informed consent.Patients were screened according to strict inclusion and exclusion criteria, and the intervention was carried out after the icu patient or the patient's family had signed an informed consent form, and no other physical measures were taken in the patients included in the study.\u003c/p\u003e\n\u003cp\u003e2.3\u0026nbsp;\u0026nbsp;Neuromuscular Electrical Stimulation\u003c/p\u003e\n\u003cp\u003eNMES(Manufactured by China Tino Medical Technology Corporation, Hangzhou, Zhejiang Province, Model CS-200) paste position: the electrode sheet will be pasted in the patient's common peroneal nerve, the common peroneal nerve by the peroneal head below the fibular bone, the fibular bone on the upper part of the lateral through, that is, paste in the fibular head under the one finger can be.The peroneal head is a rounded protuberance on the outside of the lower leg, just below the knee joint.The length of the intervention was 2h once a day in the afternoon, done for 3 consecutive days.The stimulation intensity is NMES pulse frequency 1Hz, pulse width is maximum 560μS, 7 levels of intensity can be adjusted, it is recommended that 3~4 levels, this study takes 3~4 levels. It is used as shown in Figure.1.\u003c/p\u003e\n\u003cp\u003e2.4\u0026nbsp;\u0026nbsp;Interventions\u003c/p\u003e\n\u003cp\u003eWhen the included patients were identified, the electrode sheets were attached to their legs, and then the NMES small device was magnetized on the corresponding position to turn it on and start it up. The length of the intervention was 2h once a day in the afternoon, done for 3 consecutive days. Measurements were performed using a color Doppler ultrasound device (Mindray Bio-Medical Electronics Co.，\u0026nbsp;Ltd.，\u0026nbsp;Shenzhen，\u0026nbsp;Guangdong Province，\u0026nbsp;model UMT-500) at the following time points: before NMES intervention，\u0026nbsp;during NMES application at 0.5 hours，\u0026nbsp;1 hour，\u0026nbsp;1.5 hours，\u0026nbsp;2 hours，\u0026nbsp;and after NMES discontinuation at 0.5 hours and 1 hour. The popliteal vein of one side of the lower limb of the patient was measured randomly using the lottery method(Before the measurement, an uninformed researcher wrote the words\u0026nbsp;“left”\u0026nbsp;and\u0026nbsp;“right”\u0026nbsp;on two identical cards, placed the cards in an opaque black box, and then randomly selected a card by the researcher after sufficiently shaking it to check the words on the selected card. If it is\u0026nbsp;“left”, the left leg will be chosen for the measurement; if it is\u0026nbsp;“right”, the right leg will be chosen, and the card will be put back into the box for the next time).\u003c/p\u003e\n\u003cp\u003eThe patients were also randomly assigned to four uninformed sonographers using the closed-envelope method. In addition, the same model of NMES was used in all patients participating in the trial, with stimulation intensities of 3 to 4 levels. The same sonographer measured the same patient using the same ultrasound detector and the same measurement method, and the final data were double-checked and entered by the researcher and the nurse in charge.\u003c/p\u003e\n\u003cp\u003e2.5\u0026nbsp;\u0026nbsp;Outcomes and Measurement of Popliteal vein blood flow velocity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOutcomes include (1) Peak Flow Velocity (PFV): The maximum linear velocity of a mass of blood moving through the tube per unit of time, expressed in centimeters per second (cm/s); (2)Blood Flow Volume(BFV) :The peak blood flow per minute through a cross-section of the popliteal vein is calculated as:peak blood flow (ml/min) = radius (cm)\u0026nbsp;×\u0026nbsp;radius (cm)\u0026nbsp;×\u0026nbsp;π\u0026nbsp;(circular constant)\u0026nbsp;×\u0026nbsp;peak venous blood flow velocity (cm/s)\u0026nbsp;×\u0026nbsp;60. (3) Vessel Diameter (VD): the diameter (in cm) of the inner lumen of the popliteal vein. \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring the measurement, the patients breathed calmly, took the head-high-feet-low position, and slightly abducted and flexed the lower limb on the measurement side. The ultrasound probe was placed at the popliteal vein, the probe was perpendicular to the skin, the popliteal vein was localized by transverse cut, then longitudinal cut, the ultrasound parameters were adjusted so that the acoustic beam and the direction of the venous blood flow were at 60°, and the image was frozen after the clear blood flow signal was displayed, and the spectrum of the spectrum was taken for a cycle of measurement. Patients who met the inclusion criteria used the NMES for 3 consecutive days, with two hours of intervention per day, and the values of the parameters were recorded at different time intervals before, during, and after the intervention, and then averaged over the 3 days.\u003c/p\u003e\n\u003cp\u003e2.6\u0026nbsp;\u0026nbsp;Sample Size Estimation and Statistical analysis\u003c/p\u003e\n\u003cp\u003eThe indicated sample size in the trial registry was 40. We first calculated the mean difference in peak popliteal venous flow rate before and after the application of NMES based on the results of the pre-experiment to be 4.65 cm/s, with a standard deviation of 2.29 cm/s. At this level of effect, 33 patients would have been required in the study with type I error level of 0.05 (p-value threshold 0.05) and a type II error of 0.20 (power 80%), we added 7 patients due to the consideration of 10% sample attrition.\u003c/p\u003e\n\u003cp\u003eSociodemographic characteristics underwent descriptive characterization, with quantitative variables displaying normal distribution expressed as mean\u0026nbsp;±\u0026nbsp;standard deviation, whereas non-normally distributed metrics were reported as median (interquartile range). Nominal variables were summarized using frequency counts with proportional percentages.\u003c/p\u003e\n\u003cp\u003eTo assess differences in popliteal venous flow rate across different time points (PFV、VD、BFV), Friedman's ANOVA test was initially analyzed. If Friedman's ANOVA showed significant differences, post-hoc analyses were conducted via the Wilcoxon signed-rank test with Bonferroni correction to assess temporal variations between baseline measurements and follow-up intervals(comparing baseline with time points 0.5h, 1h, 1.5h, and 2h after the NMES intervention, and 0.5h and 1h after withdrawal of the NMES), and examine relationships between interventions at different time points. Normally distributed data were analyzed using the paired-sample t-test. A \u003cem\u003ep\u003c/em\u003e value of \u0026lt; 0.05 was considered statistically significant, and when the Bonferroni correction was applied it was set at p \u0026lt; 0.008 (0.05/number of comparisons). All statistical procedures were performed using IBM SPSS Statistics for Windows, versions 26. (IBM Corp., Chicago, IL, USA).\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003eForty ICU patients were screened and enrolled onto the study. The study included 23 male and 17 female participants, with a median APACHE II score of 23 (IQR: 19-26), a median Caprini score of 9 (IQR: 8.25-10.0), and a mean age of 59.83\u0026nbsp;±\u0026nbsp;14.34 years. Among 40 enrolled patients, the most common comorbidities at admission included hypertension (62.5%, n=25), coronary heart disease (45.0%, n=18), diabetes mellitus (22.5%, n=9), and pneumonia (30.0%, n=12). Three participants withdrew due to NMES intolerance, and eight discontinued therapy prematurely (\u0026lt;3 consecutive days) following transfer or discharge. All participants completed the intervention protocol of 2 hours daily for three consecutive days, with a 100% completion rate. No adverse events or harms were reported during the study period.\u003c/p\u003e\n\u003cp\u003eRegarding the\u0026nbsp;Peak Flow Velocity, Friedman's ANOVA showed that under NMES intervention, there were statistically significant differences in PFV across different time points (χ²\u0026nbsp;= 179.767, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). The Wilcoxon signed-rank test with Bonferroni correction showed that the PFV was significantly higher during the application of the NMES at 0.5h (Z = -5.35, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), at 1h \u0026nbsp; (Z = -5.511, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), at 1.5h (Z = -5.498, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), at 2h (Z = -5.511, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and 0.5h post-weaning (Z = -5.443, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) compared to pre-intervention levels. However, no statistically significant difference was observed at 1h post-weaning (Z = -1.788, p = 0.074) compared to pre-intervention. When compared to 0.5h during intervention, significant differences were found at 1h (Z = -4.535, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), 1.5h (Z = -4.41, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and 2h (Z = -4.933, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) during the application of the NMES. In contrast, No statistically significant differences were detected between 1h and either 1.5h (Z = -0.796, p = 0.426) or 2h (Z = -0.973, p = 0.331) during intervention. This indicates that the PFV gradually increased during the period from the initiation of NMES intervention up to 1h during intervention and subsequently tended to stabilize after 1h of intervention (Fig.2). Detailed comparisons across all time points are presented in Table 1.\u003c/p\u003e\n\u003cp\u003eRegarding the vessel diameter, significant differences were observed between the values at 1h, 1.5h, and 2h of NMES application, as well as 0.5h post-weaning, when compared to pre-intervention and 1h post-weaning (all\u003cem\u003e\u0026nbsp;p\u003c/em\u003e \u0026lt; 0.05). However, no statistically significant difference was found between pre-intervention and 1h post-weaning (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05). This indicates that the vascular radius expanded to a stabilized value after 1h of NMES application and returned to baseline levels 1h after cessation(Fig.3).\u003c/p\u003e\n\u003cp\u003eRegarding the blood flow volume, Friedman's ANOVA revealed statistically significant differences in BFV across different time points under NMES intervention (χ²\u0026nbsp;= 174.264, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). The Wilcoxon signed-rank test with Bonferroni correction showed that BFV at 1h (Z = -5.511, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), 1.5h (Z = -5.497, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and 2h (Z = -5.511, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) during intervention, as well as 0.5h post-weaning (Z = -5.511, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), differed significantly from both pre-intervention and 1h post-weaning. No statistically significant difference was observed between 1h post-weaning and pre-intervention (Z=-1.642,\u003cem\u003ep\u003c/em\u003e=0.101). Combined with the significant difference between 0.5h and 1h during intervention (Z = -4.436, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) of NMES application, these results indicate that BFV gradually increased during the first hour of NMES intervention and returned to baseline levels 1h after cessation. Furthermore, No statistically significant differences were observed between 1.5h (Z = -0.524, p = 0.6) and 2h during intervention(Z = -1.066, p = 0.286) when compared to PFV at 1h post-intervention, suggesting that BFV stabilized following the first hour of NMES intervention(Fig.4).\u0026nbsp;\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study aimed to assess the hemodynamic effects of NMES, using a pulse frequency of 1 Hz and pulse width of 280–373\u0026nbsp;μs, in ICU patients, in a bedridden state. This tool has been suggested as a blood flow enhancer and is being explored for use in high-risk VTE patients who are unable to use pharmacologic and conventional who cannot utilize pharmacological or conventional mechanical prophylaxis. And there is moderate evidence suggesting that NMES may serve as a viable tool to optimize this process\u003csup\u003e[5]\u003c/sup\u003e. Therefore, the present study may strengthen the evidence for NMES as a means of accelerating venous blood flow velocity and further explore the pattern of blood flow changes after NMES intervention.\u003c/p\u003e\n\u003cp\u003eThis study suggests that PFV, VD, and BFV after NMES intervention were statistically significant compared with those before intervention (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05) and after 1h of withdrawal compared with other time points (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), whereas there was no statistical significance between pre-intervention and 1h of withdrawal (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05). These data indicate that the hemodynamic effects of NMES on the popliteal vein gradually increased from the initiation of intervention to 1 hour during intervention, ceased further enhancement after 1 hour of intervention, and returned to pre-intervention baseline levels at 1 hour post-withdrawal. The findings provide reference significance for determining the time to peak PFV, VD, and BFV, the recovery time to baseline values, optimal application duration, and appropriate intervals between sessions for the therapeutic purposes of NMES, which may include DVT prophylaxis, reduction of edema, and prevention of muscular dystrophy, among other purposes that are not discussed here without the relevant metrics.\u003c/p\u003e\n\u003cp\u003eStudies over the years have also shown that other mechanical interventions such as intermittent pneumatic compression pump (IPC) and graduated compression stocking (GCS) improve hemodynamic parameters in clinical and healthy populations\u003csup\u003e[21]\u003c/sup\u003e, but some studies has shown their lower compliance rates\u003csup\u003e[22]\u003c/sup\u003e. This suggests that mechanical prophylaxis of thrombosis has not been effectively implemented, thereby increasing the risk of DVT in patients. NMES can induce rapid and consistent muscle pump activation through ankle joint movement, generating stronger physiological hemodynamic forces compared to other mechanical prophylactic measures such as GCS or IPC. This is attributed to its ability to fully empty the deep venous sinuses. In addition, it has been shown that skeletal muscle contraction releases myokines\u003csup\u003e[23]\u003c/sup\u003e, which act and mediate anti-inflammatory effects\u003csup\u003e[24-26]\u003c/sup\u003e, and systemic inflammatory diseases are highly correlated with thrombotic tendencies\u003csup\u003e[27-28]\u003c/sup\u003e. Therefore muscle contraction-induced anti-inflammatory effects may also contribute to the hematological effects of NMES in preventing thrombosis. The significant advantages of NMES is its virtually no risk of complications, absence of associated bleeding risks, ease in locating optimal stimulation points, and straightforward operability\u003csup\u003e[29]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eHowever, there are relative gaps in the areas of whether prolonged interventions beyond this time will result in a decline in hemodynamic indices; whether changes will occur as a result of excessive muscle contraction when intervening for a certain amount of time; and whether it is necessary to withdraw the machine when a downward trend occurs to allow time for bodily functions to adjust. The present study was able to show that PFV, VD, and BFV stabilized after 1 h on the machine, and that blood flow velocities returned to pre-intervention baseline values when the machine was withdrawn for 1 h, a time point that can be used as a reference for continued time on the machine.\u003c/p\u003e\n\u003cp\u003eThere are several limitations to be noted regarding this study. First, a common limitation of self-controlled studies is the inability to control time-dependent confounding factors. However, our study population were patients in the ICU, in relatively isolated \u0026nbsp;environments, 90% of the patients included in the study were comatose and bedridden, with no autonomous consciousness, and researchers were blinded to the intervention status, to minimize the possible confounders and to control the bias to the greatest extent possible. Second, the degree of foot dorsiflexion response after NMES intervention is not the same in different patients, potentially attributable to factors such as adipose tissue thickness or insufficient stimulation intensity. Although identical equipment, stimulation intensity, and frequency were applied to all participants, the actual degree of physiological intervention might differ among individuals. Lastly, the time nodes of our measurements were half an hour apart, and the data analysis was also conducted in this way. It is therefore possible to peak between 0.5 h-1 h and return to baseline values between 0.5 h-1 h after removing the machine, as these critical timepoints could not be definitively determined through our current sampling strategy.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eNMES is a mechanical strategy with promising applications, and the present study further demonstrated that the intervention of NMES can accelerate venous blood flow in the lower extremities of ICU patients, and that hemodynamic indices stabilized after 1 h of intervention and returned to baseline values 1 h after withdrawal. Considering the limitations of this study, more large-sample, multicenter, high-quality randomized controlled trials are needed in the future to provide further evidence support and standardize its clinical application.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Thousand Buddha Mountain Hospital in Shandong Province (No. R202410240370)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe obtained signed consent from all participants to use and publish their data for this study using our institutional form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset analyzed in this study is available upon request from the first author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by a postgraduate medical grant from Shandong Second Medical University and a research grant from Qianfoshan Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYe Lixiang was mainly responsible for finding information and writing the paper; Li Yubo was mainly responsible for communicating with the patients or their families and getting them to sign the informed consent form; Su Chengcheng was mainly responsible for collecting and organizing the data; Xu Zhaozhao was mainly responsible for analyzing the data and making the pictures; and Zhang Shuxiang was mainly responsible for communicating with the manufacturer of NMES and contacting the ICU for cooperation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWilliams KJ, Ravikumar R, Gaweesh AS, Moore HM, Lifsitz AD, Lane TR, Shalhoub J, Babber A, Davies AH. 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Physiol Rev88:1379\u0026ndash;1406\u003c/li\u003e\n\u003cli\u003eStarkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK(2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 17:884\u0026ndash;886\u003c/li\u003e\n\u003cli\u003eAksu K, Donmez A, Keser G (2012) Inflammation-induced thrombosis: mechanisms, disease associations and management.Curr Pharm Des 18:1478\u0026ndash;1493 \u003c/li\u003e\n\u003cli\u003eJezovnik MK, Poredos P (2010) Idiopathic venous thrombosis is related to systemic inflammatory response and to increased levels of circulating markers of endothelial dysfunction. Int Angiol29:226\u0026ndash;231\u003c/li\u003e\n\u003cli\u003eYang J, Qi H, Huang J, Xu M, Xue Z, Wang Y. Effectiveness of neuromuscular electrical stimulation on venous thromboprophylaxis in surgical patients: A systematic review and meta-analysis. Complement Ther Clin Pract. 2025 Feb;58:101932. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1:Detailed comparison between different time points\u003c/p\u003e\n\u003cp\u003e\u003cimg 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more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neuromuscular Electrical Stimulation, Hemodynamic Effects, Intensive Care Unit","lastPublishedDoi":"10.21203/rs.3.rs-6749490/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6749490/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study aimed to investigate the pattern of changes in hemodynamic indices after the use of neuromuscular electrical stimulation in intensive carepatients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Forty icu inpatients with Caprini risk score ≥5 from Qianfoshan Hospital in Shandong Province received neuromuscular electrical stimulation. Doppler ultrasound was used to collect hemodynamic indexes (peak blood flow velocity, peak blood flow, and vessel diameter) of the popliteal vein of the patients before the application of NMES, 0.5h、1h、1.5h、2h during application as well as 0.5h and 1h after the discontinuation of NMES, respectively, to analyze the time-variable variations of hemodynamic indexes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The peak venous flow velocity, diameter of the popliteal vein, and blood flow volume following NMES intervention were significantly higher than pre-intervention levels (P \u0026lt; 0.05). During the initial phase of intervention (from initiation to 1 hour post-intervention), hemodynamic parameters progressively increased, but no further elevation was observed between 1 and 2 hours of intervention. At 1 hour after NMES discontinuation, the peak venous flow velocity, diameter, and blood flow volume in the popliteal vein showed no statistically significant differences compared to pre-intervention values (P \u0026gt; 0.05), indicating a return to baseline levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eNMES accelerates venous blood flow velocity in the lower extremities of ICU patients, is feasible, safe, and effective in the absence of the use of other conventional physical measures. The hemodynamic parameters plateau after 1 hour of application and return to baseline values within 1 hour of discontinuation, providing valuable insights for future research on the clinical utilization of NMES.\u003c/p\u003e","manuscriptTitle":"Time-varying effect of hemodynamics in intensive care via neuromuscular electrical stimulation：a prospective, single-center, self-controlled study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-16 05:56:08","doi":"10.21203/rs.3.rs-6749490/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-25T18:42:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-25T06:41:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-22T05:46:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-21T14:17:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-21T02:10:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-19T00:14:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-13T13:07:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"272514689865404804220896690531715740302","date":"2025-07-13T12:45:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211271916835347484489518469728455253094","date":"2025-07-13T12:43:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71685594855951025562831089436847445060","date":"2025-07-11T08:13:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-11T07:52:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190034516589353939775207546710638329640","date":"2025-07-11T07:03:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"112752829680794267994664337761764331462","date":"2025-07-11T06:08:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330823877180466005863712905047291834594","date":"2025-07-10T09:34:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212793452662583054923431731408020160169","date":"2025-07-09T15:47:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135072357686733127315036575642049484254","date":"2025-07-09T15:38:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-09T15:32:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T15:29:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-12T06:19:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-11T04:36:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-26T09:45:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4166816-489b-4db3-a6b3-cd738825627b","owner":[],"postedDate":"July 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51577972,"name":"Health sciences/Medical research"},{"id":51577973,"name":"Physical sciences/Engineering/Mechanical engineering"}],"tags":[],"updatedAt":"2025-12-08T16:01:01+00:00","versionOfRecord":{"articleIdentity":"rs-6749490","link":"https://doi.org/10.1038/s41598-025-29464-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-03 15:57:33","publishedOnDateReadable":"December 3rd, 2025"},"versionCreatedAt":"2025-07-16 05:56:08","video":"","vorDoi":"10.1038/s41598-025-29464-7","vorDoiUrl":"https://doi.org/10.1038/s41598-025-29464-7","workflowStages":[]},"version":"v1","identity":"rs-6749490","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6749490","identity":"rs-6749490","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}