Metabolic and Hemodynamic Responses to Early Passive Range of Motion in Sedated Critically Ill Adults

Metabolic and Hemodynamic Responses to Early Passive Range of Motion in Sedated Critically Ill Adults | 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 Metabolic and Hemodynamic Responses to Early Passive Range of Motion in Sedated Critically Ill Adults Turgay Altunalan, Ahmet Oğuzhan Küçük, Umut Apaydın, Ömer Faruk Şahin, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7139229/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jan, 2026 Read the published version in BMC Anesthesiology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Passive range of motion (PROM) is a common early mobilization technique in intensive care, especially for sedated, mechanically ventilated patients. This study aimed to evaluate the effect of early PROM on oxygen consumption (VO₂) and carbon dioxide production (VCO₂) in mechanically ventilated critically ill adults. Methods: A prospective observational cohort study was conducted in the tertiary ICU of a university hospital between May and September 2023. PROM was initiated within 24–48 hours of admission in hemodynamically stable, sedated patients (RASS: -2 to -4). An experienced physiotherapist performed a standardized 10-minute PROM protocol. VO₂ and VCO₂ were measured via indirect calorimetry before, during, and after the intervention. Cardiovascular parameters were also recorded. Results: Eighteen patients were included. Compared to baseline, VCO₂ increased significantly during PROM (mean change: +12%, p < 0.05), while VO₂ showed a modest but significant increase only at the seventh minute (+9%, p < 0.01). Both returned to near-baseline post-intervention. Systolic blood pressure increased transiently at the seventh minute (p = 0.04); other parameters remained stable. No adverse events were reported. Conclusion: Early PROM exercises in sedated, mechanically ventilated ICU patients induced a mild yet significant rise in metabolic demand, particularly reflected in VCO₂. The findings show that PROM is metabolically safe and does not cause haemodynamic instability. It accelerates the elimination of metabolic waste and can be used as part of early rehabilitation protocols. Early Mobilization Exercise Indirect Calorimetry Intensive care units Range of Motion Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Individuals with critical illness are at risk of developing a variety of complications due to the severity of their condition and extended stays in intensive care units (ICUs) [ 1 ]. These complications often include physical, cognitive, and psychological impairments that may persist long after hospital discharge, collectively known as post-intensive care syndrome (PICS) [ 2 ]. Approximately 50% of ICU survivors develop at least one symptom of PICS, posing significant challenges to long-term recovery [ 3 ]. As survival rates improve, minimizing the burden of PICS has become a key priority for clinicians, researchers, and families [ 4 ]. In response to these challenges, multidisciplinary teams have implemented evidence-based protocols such as the ABCDEF bundle to promote functional recovery and reduce adverse outcomes without increasing risk [ 5 , 6 ]. Within this bundle, the letter “E” highlights the importance of early mobilization and exercise as a non-pharmacological intervention to improve patient outcomes in ICU settings [ 1 , 7 , 8 ]. Early mobilization includes a continuum of activities ranging from a passive range of motion (PROM) exercises to active ambulation [ 9 ]. PROM refers to joint movement conducted without patient participation and is often the primary intervention in sedated and mechanically ventilated individuals [ 10 ]. Its widespread use is attributed to feasibility and safety; however, the physiological responses it induces, particularly cardiorespiratory changes, remain insufficiently explored. Previous research on early mobilization has primarily assessed basic safety parameters, such as blood pressure, heart rate, oxygen saturation, and respiratory rate [ 11 ]. Yet, PROM exercises may also impact metabolic variables like oxygen consumption and carbon dioxide production, which are vital for caloric estimation and understanding cardiopulmonary stress [ 12 ]. Despite its frequent use, limited evidence exists on how PROM affects dynamic cardiorespiratory parameters in critically ill adults. This gap in knowledge restricts our ability to individualize PROM protocols and ensure cardiopulmonary stability during interventions. Therefore, this study aimed to evaluate the cardiorespiratory responses to early PROM in mechanically ventilated adults in the ICU. A secondary aim was to determine whether these parameters remain within safe and stable physiological limits. Methods Study Design This prospective observational cohort study was conducted in the tertiary intensive care unit (ICU) of Karadeniz Technical University, Farabi Hospital, between May and September 2023. An observational design was chosen to examine the feasibility and physiological effects of early passive range of motion (PROM) exercises in critically ill adults prior to conducting large-scale randomized controlled trials (RCTs). A single-center structure ensured procedural consistency and real-time physiological data acquisition. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Karadeniz Technical University (approval number: 2023/27), and written informed consent was obtained from all participants' legally authorized representatives. Participants Eligible participants were adults requiring invasive mechanical ventilation with Richmond Agitation-Sedation Scale (RASS) scores between − 2 and − 4. Inclusion criteria included hemodynamic stability and a minimum of 48 hours in the ICU. Exclusion criteria comprised acute neurological trauma, cerebrovascular events, intercostal catheters with air leakage, FiO₂ >0.6, extracorporeal membrane oxygenation (ECMO), and renal replacement therapy. Patients were enrolled after being clinically stable as determined by the attending intensivist. Intervention PROM was initiated within 24–48 hours of ICU admission by the ABCDEF bundle recommendations. One experienced physiotherapist (15 years) performed all PROM procedures, which lasted 10 minutes and followed a standardized sequence: Minutes 1–2: Right shoulder flexion/abduction Minute 3: Right elbow/wrist flexion-extension Minutes 4–5: Right hip/knee flexion and abduction Minute 5: Right ankle flexion-extension Minutes 6–7: Left hip/knee flexion and abduction Minute 7: Left ankle flexion-extension Minutes 8–9: Left shoulder abduction and flexion Minute 10: Left elbow/wrist flexion-extension PROM was conducted in the supine position. No sedation changes, repositioning, nutrition, or nursing interventions were allowed 30 minutes before and after PROM. All interventions were applied in the morning (10:00–12:00) on the first day the patient was deemed eligible. Data Collection and Measurements Data were extracted from the hospital’s electronic health records and bedside logs by researchers blinded to the study hypothesis. Collected variables included demographics, diagnosis, sedation medications, and severity scores: Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Cardiorespiratory measurements were obtained using the CARESCAPE™ B650 monitor and the CARESCAPE™ Respiratory Module (E-sCAiOVX; GE HealthCare). Oxygen consumption (VO₂) and carbon dioxide production (VCO₂) were measured via indirect calorimetry. All equipment was calibrated per manufacturer guidelines. Baseline measurements were recorded after 30 minutes of clinical rest, PROM was then performed, and follow-up measurements were taken within 3 minutes post-intervention. Sample Size Calculation Based on Medrinal et al.’s findings (15% change in cardiac output; effect size: 0.625), G*Power version 3.1.9.7 (Faul et al., 2007) was used to determine that a sample of 18 participants would provide 80% power at α = 0.05 [ 13 ]. Statistical Analysis Statistical analyses were conducted using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Data normality was tested using the Kolmogorov–Smirnov test. Continuous variables were presented as mean ± standard deviation or median (interquartile range). Paired sample t-tests compared cardiorespiratory parameters across time points. A p-value < 0.05 was considered statistically significant. Results Participant Flow and Characteristics Between May and September 2023, 167 patients were screened in the ICU. Out of these, 30 patients receiving invasive mechanical ventilation and appropriate sedation levels (RASS scores between − 2 and − 4) were identified. Seven patients were excluded due to hemodynamic instability, presence of intercostal catheters with air leaks, acute neurological events, or ECMO therapy. Consequently, 23 patients were included in the final analysis. Participant selection and exclusion criteria are clearly outlined in the participant flow diagram (Fig. 1 ). Demographic and Clinical Characteristics Participants' mean age was 63 (Min-Max: 30–90) years, and 34.8% were male. The median APACHE II and SOFA scores were 21 (IQR: 15–23) and 7 (IQR: 5–10), respectively (Tablo 1). Primary diagnoses and baseline clinical parameters are summarized in Table 1 . Table 1 Characterization of study participants Age (years) / mean (min-max) 63 (30–90) End Points Gender, male / female 15/8 (65.2% / 34.8%) Midazolam, mg/h 0.032 (0-0.1) Height (cm) / mean (min-max) 169 (160–180) Fentanyl, mcg/h 1.7 (0–5) Weight (kg) / mean (min-max) 77 (55–100) Ketamin, mg/h 0.17 (0–1) SOFA score / median (IQR) 7 (5–10) Vasopressor Use, no. (%) 18 (78%) APACHE score/median (IQR) 21 (15–23) Noradrenalin, mcg/kg/h 0.09 (0-0.5) RASS / median (IQR) -4 (-4- -4) ICU Stay, day/median (IQR) 6 (3–14) GCS / median (IQR) 4 (4–6) IMV Duration, day 4 (2–11) Hgb, g/Dl / median (IQR) 9.2 (8.1–10) IMV Duration, day 4 (2–11) Cardiac 4 (17.4) Plt Count, x1000/uL/median (IQR) 196 (92–269) Malignancy 2 (8.7) WBC, x1000/mcL / median (IQR) 11 (8–15) Neurological 6 (26.1) CRP, mg/L / median (IQR) 152 (110–208) Sepsis 1 (4.3) Pulmonary 10 (43.5) Abbreviations: SOFA; Sequential Organ Failure Assessment, APACHE; Acute Physiology and Chronic Health Evaluation, RASS; Richmond Agitation-Sedation Scale, GCS; Glasgow Coma Score, ICU; Intensive care unit, IMV; invasive mechanical ventilation, Hgb; hemoglobin, Plt; platelet, WBC; White blood cell, CRP; c-reactive protein. Cardiorespiratory and Metabolic Responses Baseline oxygen consumption (VO₂) and carbon dioxide production (VCO₂) measurements were taken after a standardized 30-minute rest period with no medical or nursing interventions. Compared to baseline values, significant increases were observed during the PROM intervention (VO₂ baseline: 263.69 ± 109.01 ml/min vs. PROM 7th min : 287.34 ± 126.17 ml/min, p < 0.01; VCO₂ baseline: 182.17 ± 77.19 ml/min vs. PROM 6th min : 198.69 ± 76.20 ml/min, p < 0.01; Sistolic tension baseline: 122.65 ± 21.28 mmHg, PROM 7th min : 127.34 ± 19.28 mmHg, p 0.05; VCO₂: 188.08 ± 81.43 ml/min, p > 0.05; Sistolic tension baseline: 122.87 ± 19.31 mmHg, p > 0.05), (Figs. 1 and 2 ). The magnitude of change during intervention represented approximately 9% increase in VO₂ and 12% increase in VCO₂ compared to baseline, indicating measurable but clinically safe metabolic stress during PROM. There was no significant change in heart rate, diastolic tension, and tidal volume (p > 0.05), (Figs. 3 , 4 and 5 ). Safety and Adverse Events No significant adverse events such as extubation, tube displacement, hemodynamic instability, or desaturation were observed during or after PROM interventions. Discussion The primary aim of this study was to investigate the cardiorespiratory responses to early passive range of motion (PROM) exercises in adults with critical illness requiring invasive mechanical ventilation. The study demonstrated significant carbon dioxide (CO₂) production increases throughout the PROM, excluding the 1st, 8th, and 10th minutes, while oxygen (O₂) consumption significantly increased only at the seventh minute. Both parameters returned to baseline after a defined resting period. No clinically significant alterations were observed in other cardiometabolic parameters. The observed increase in CO₂ production without a parallel rise in O₂ consumption suggests that active muscle contractions were unlikely to be responsible for this metabolic response. Typically, increased O₂ consumption accompanies active muscle contractions due to metabolic demand [ 14 ]. Instead, our findings suggest the increased CO₂ production might result from mobilizing venous blood reservoirs through passive limb movements against gravity. Wollersheim et al. reported similar findings, noting no change in O₂ consumption with increased CO₂ elimination during PROM exercises [ 15 ]. A recent meta-analysis supports this concept, suggesting PROM may prevent muscle wasting not through active muscle engagement but possibly via reduction in nitrosative stress and immune modulation [ 16 ]. Our findings align with this hypothesis, indicating that PROM exercises may enhance metabolic clearance of byproducts, thus mitigating muscle wasting in immobilized patients [ 17 , 18 ]. Unlike Wilkinson et al., who reported no change in VCO₂ with upper-limb PROM ergometry, our inclusion of lower-limb movements may explain the observed metabolic differences [ 19 ]. The observation that the metabolic waste removed from the body increases during the initial seven minutes and subsequently exhibits a downward trend prompts the question of whether the beneficial effects of PROM will also be apparent in short applications of five to seven minutes. The study also demonstrated minimal hemodynamic responses during PROM, characterized by an initial rise followed by stabilization. Specifically, systolic blood pressure exhibited an initial increase, peaking at the seventh minute, corresponding with the completion of right-sided extremities and left hip PROM. These transient changes align with previous findings by Medrinal et al., who observed similar cardiometabolic response patterns during initial phases of PROM [ 13 ]. Such transient increases may reflect acute physiological stress responses, highlighting the importance of initiating PROM exercises gradually and focusing initially on small (distal) joint mobilization to mitigate acute stress reactions [ 20 , 21 ]. There is growing evidence that passive joint exercises do not significantly affect the haemodynamic stability of critically ill patients [ 22 ] even in patients receiving vasopressor support [ 23 ]. Muscle loss in critical illness has been linked to survival rates [ 24 ]. Passive joint movements in sedated and ventilated critically ill patients could be used as a therapy to improve metabolic clearance and circulation and slow muscle breakdown. Notably, no adverse events such as extubation, catheter removal, or hemodynamic instability occurred during the interventions, supporting previous evidence indicating that PROM is safe and feasible, even in patients receiving low-dose vasopressor support [ 25 , 26 ]. Our protocol demonstrated minimal clinically relevant hemodynamic changes, suggesting PROM can be safely applied in the ICU if appropriate precautions and patient-specific adjustments are observed. However, several limitations must be noted. Although statistical power analysis indicated adequate sample size, the generalizability of findings may be limited due to the relatively small and homogenous sample. Additionally, muscle blood flow or muscle activity measurements (e.g., electromyography) were not performed, which could have provided more profound insights into the observed metabolic changes. Future studies should address these limitations by incorporating electromyographic measurements during PROM to investigate the underlying mechanisms more thoroughly. Further research is needed to determine the optimal duration and intensity of PROM exercises for maximizing metabolic benefits and minimizing muscle atrophy in patients with limited mobility. Conclusion The results of this study suggest that PROM exercises significantly increase CO₂ elimination without notably affecting O₂ consumption in critically ill adults requiring sedation and mechanical ventilation. The temporary metabolic shifts observed highlight PROM's potential role in enhancing metabolic clearance in immobilized patients. All observed cardiorespiratory responses remained within clinically acceptable ranges, underscoring the safety of PROM interventions in ICU practice. Further studies should investigate muscle activity and varying exercise sequences to optimize early mobilization protocols. Abbreviations APACHE Acute Physiology and Chronic Health Evaluation ECMO Extracorporeal Membrane Oxygenation ICU Intensive care unit ICU-AW ICU-acquired weakness PICS Post-intensive care syndrome PROM Passive range of motion (RASS) Richmond Agitation-Sedation Scale SOFA Sequential Organ Failure Assessment Declarations Acknowledgments Not applicable. Author’s contributions TA, AOK, and MPK conceptualized the study. Data collection was supervised by AOK, ÖFŞ, and MPK, and analysis was conducted by UA. The manuscript was conceptualized by TA, UA, and ÖFŞ and drafted by AOK and MPK. All authors contributed to revising the manuscript and approval of the final version. All authors read and approved the final manuscript. Funding None. Availability of data and materials The datasets generated during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was approved by the Ethics Committee of The Faculty of Medicine, Karadeniz Technical University, on 14 April 2023 (2023/27). Clinical trial number Not applicable Ethics approval and consent to participate. The study was approved by the Ethics Committee of The Faculty of Medicine, Karadeniz Technical University, on 14 April 2023 (2023/27). This study was conducted following the tenets of the Declaration of Helsinki. Informed consent was obtained from a legally authorized representative of each unconscious patient before enrolment. The legally authorized representatives were informed about the purpose of the study, the methods, the potential risks and benefits, and their rights regarding participation. The confidentiality of the data collected and the patient's privacy were protected. The legally authorized also had the option to withdraw from the study at any time. Competing interests The authors certify that there is no competing interest with any financial organisation regarding the material discussed in the manuscript. Consent for publication Not applicable. References Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit: Crit Care Med. 2013;41:263–306. Kim S-J, Park K, Kim K. 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Cite Share Download PDF Status: Published Journal Publication published 08 Jan, 2026 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 11 Sep, 2025 Reviews received at journal 09 Sep, 2025 Reviews received at journal 08 Sep, 2025 Reviewers agreed at journal 03 Sep, 2025 Reviewers agreed at journal 02 Sep, 2025 Reviewers invited by journal 24 Aug, 2025 Editor invited by journal 21 Aug, 2025 Editor assigned by journal 24 Jul, 2025 Submission checks completed at journal 24 Jul, 2025 First submitted to journal 16 Jul, 2025 You are reading this latest preprint version 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. 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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-7139229","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508573535,"identity":"d0ebade7-ce3f-4cee-a3c5-e672a7359503","order_by":0,"name":"Turgay 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PROM\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/886021a9c33dffeeaeddd1ff.jpeg"},{"id":90463668,"identity":"0028211b-a235-4156-879d-2b5bf89512c8","added_by":"auto","created_at":"2025-09-03 05:05:36","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":224127,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of heart rate before during and after PROM.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/03b841325e66e106128a660d.jpeg"},{"id":90465101,"identity":"27553b97-e3aa-4042-9290-7a06ad3a29d2","added_by":"auto","created_at":"2025-09-03 05:13:36","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31205,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of systolic pressure before during and after PROM.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/f87b4c4731d79b029ad3d1f7.jpeg"},{"id":90463670,"identity":"875f3b2e-9503-4820-b6d1-bf079cd689b0","added_by":"auto","created_at":"2025-09-03 05:05:36","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":203670,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of diastolic pressure before during and after PROM.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/d643618a36549952d9bf1cb3.jpeg"},{"id":90463678,"identity":"6e8c1292-9ae8-4369-b521-1e82df15f26e","added_by":"auto","created_at":"2025-09-03 05:05:36","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":210344,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of tidal volume before during and after PROM.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/2331ef2989739ff5b2f91261.jpeg"},{"id":100070397,"identity":"04d5f3a2-bcb0-4016-97aa-c8c5a3db125e","added_by":"auto","created_at":"2026-01-12 16:17:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1342669,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7139229/v1/0e9043c4-e79d-4b69-a0cd-86c42ebfd0c7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Metabolic and Hemodynamic Responses to Early Passive Range of Motion in Sedated Critically Ill Adults","fulltext":[{"header":"Background","content":"\u003cp\u003eIndividuals with critical illness are at risk of developing a variety of complications due to the severity of their condition and extended stays in intensive care units (ICUs) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These complications often include physical, cognitive, and psychological impairments that may persist long after hospital discharge, collectively known as post-intensive care syndrome (PICS) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Approximately 50% of ICU survivors develop at least one symptom of PICS, posing significant challenges to long-term recovery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. As survival rates improve, minimizing the burden of PICS has become a key priority for clinicians, researchers, and families [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In response to these challenges, multidisciplinary teams have implemented evidence-based protocols such as the ABCDEF bundle to promote functional recovery and reduce adverse outcomes without increasing risk [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Within this bundle, the letter “E” highlights the importance of early mobilization and exercise as a non-pharmacological intervention to improve patient outcomes in ICU settings [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEarly mobilization includes a continuum of activities ranging from a passive range of motion (PROM) exercises to active ambulation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. PROM refers to joint movement conducted without patient participation and is often the primary intervention in sedated and mechanically ventilated individuals [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Its widespread use is attributed to feasibility and safety; however, the physiological responses it induces, particularly cardiorespiratory changes, remain insufficiently explored. Previous research on early mobilization has primarily assessed basic safety parameters, such as blood pressure, heart rate, oxygen saturation, and respiratory rate [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Yet, PROM exercises may also impact metabolic variables like oxygen consumption and carbon dioxide production, which are vital for caloric estimation and understanding cardiopulmonary stress [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite its frequent use, limited evidence exists on how PROM affects dynamic cardiorespiratory parameters in critically ill adults. This gap in knowledge restricts our ability to individualize PROM protocols and ensure cardiopulmonary stability during interventions. Therefore, this study aimed to evaluate the cardiorespiratory responses to early PROM in mechanically ventilated adults in the ICU. A secondary aim was to determine whether these parameters remain within safe and stable physiological limits.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Design\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis prospective observational cohort study was conducted in the tertiary intensive care unit (ICU) of Karadeniz Technical University, Farabi Hospital, between May and September 2023. An observational design was chosen to examine the feasibility and physiological effects of early passive range of motion (PROM) exercises in critically ill adults prior to conducting large-scale randomized controlled trials (RCTs). A single-center structure ensured procedural consistency and real-time physiological data acquisition.\u003c/p\u003e\u003cp\u003eThe study protocol was approved by the Ethics Committee of the Faculty of Medicine, Karadeniz Technical University (approval number: 2023/27), and written informed consent was obtained from all participants' legally authorized representatives.\u003c/p\u003e\u003cp\u003e\u003cb\u003eParticipants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEligible participants were adults requiring invasive mechanical ventilation with Richmond Agitation-Sedation Scale (RASS) scores between − 2 and − 4. Inclusion criteria included hemodynamic stability and a minimum of 48 hours in the ICU. Exclusion criteria comprised acute neurological trauma, cerebrovascular events, intercostal catheters with air leakage, FiO₂ \u0026gt;0.6, extracorporeal membrane oxygenation (ECMO), and renal replacement therapy. Patients were enrolled after being clinically stable as determined by the attending intensivist.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePROM was initiated within 24–48 hours of ICU admission by the ABCDEF bundle recommendations. One experienced physiotherapist (15 years) performed all PROM procedures, which lasted 10 minutes and followed a standardized sequence:\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eMinutes 1–2: Right shoulder flexion/abduction\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinute 3: Right elbow/wrist flexion-extension\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinutes 4–5: Right hip/knee flexion and abduction\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinute 5: Right ankle flexion-extension\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinutes 6–7: Left hip/knee flexion and abduction\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinute 7: Left ankle flexion-extension\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinutes 8–9: Left shoulder abduction and flexion\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMinute 10: Left elbow/wrist flexion-extension\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003cp\u003ePROM was conducted in the supine position. No sedation changes, repositioning, nutrition, or nursing interventions were allowed 30 minutes before and after PROM. All interventions were applied in the morning (10:00–12:00) on the first day the patient was deemed eligible.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Collection and Measurements\u003c/b\u003e\u003c/p\u003e\u003cp\u003eData were extracted from the hospital’s electronic health records and bedside logs by researchers blinded to the study hypothesis. Collected variables included demographics, diagnosis, sedation medications, and severity scores: Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores.\u003c/p\u003e\u003cp\u003eCardiorespiratory measurements were obtained using the CARESCAPE™ B650 monitor and the CARESCAPE™ Respiratory Module (E-sCAiOVX; GE HealthCare). Oxygen consumption (VO₂) and carbon dioxide production (VCO₂) were measured via indirect calorimetry. All equipment was calibrated per manufacturer guidelines. Baseline measurements were recorded after 30 minutes of clinical rest, PROM was then performed, and follow-up measurements were taken within 3 minutes post-intervention.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSample Size Calculation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBased on Medrinal et al.’s findings (15% change in cardiac output; effect size: 0.625), G*Power version 3.1.9.7 (Faul et al., 2007) was used to determine that a sample of 18 participants would provide 80% power at α = 0.05 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were conducted using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Data normality was tested using the Kolmogorov–Smirnov test. Continuous variables were presented as mean ± standard deviation or median (interquartile range). Paired sample t-tests compared cardiorespiratory parameters across time points. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eParticipant Flow and Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBetween May and September 2023, 167 patients were screened in the ICU. Out of these, 30 patients receiving invasive mechanical ventilation and appropriate sedation levels (RASS scores between \u0026minus;\u0026thinsp;2 and \u0026minus;\u0026thinsp;4) were identified. Seven patients were excluded due to hemodynamic instability, presence of intercostal catheters with air leaks, acute neurological events, or ECMO therapy. Consequently, 23 patients were included in the final analysis. Participant selection and exclusion criteria are clearly outlined in the participant flow diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDemographic and Clinical Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eParticipants' mean age was 63 (Min-Max: 30\u0026ndash;90) years, and 34.8% were male. The median APACHE II and SOFA scores were 21 (IQR: 15\u0026ndash;23) and 7 (IQR: 5\u0026ndash;10), respectively (Tablo 1). Primary diagnoses and baseline clinical parameters are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacterization of study participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years) / mean (min-max)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (30\u0026ndash;90)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEnd Points\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, male / female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15/8 (65.2% / 34.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMidazolam, mg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.032 (0-0.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight (cm) / mean (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e169 (160\u0026ndash;180)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFentanyl, mcg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.7 (0\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight (kg) / mean (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77 (55\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eKetamin, mg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.17 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOFA score / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (5\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVasopressor Use, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (78%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPACHE score/median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (15\u0026ndash;23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNoradrenalin, mcg/kg/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.09 (0-0.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRASS / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-4 (-4- -4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eICU Stay, day/median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (3\u0026ndash;14)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGCS / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (4\u0026ndash;6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIMV Duration, day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (2\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHgb, g/Dl / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.2 (8.1\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIMV Duration, day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (2\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePlt Count, x1000/uL/median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e196 (92\u0026ndash;269)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eWBC, x1000/mcL / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (8\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (26.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCRP, mg/L / median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e152 (110\u0026ndash;208)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePulmonary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (43.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: SOFA; Sequential Organ Failure Assessment, APACHE; Acute Physiology and Chronic Health Evaluation, RASS; Richmond Agitation-Sedation Scale, GCS; Glasgow Coma Score, ICU; Intensive care unit, IMV; invasive mechanical ventilation, Hgb; hemoglobin, Plt; platelet, WBC; White blood cell, CRP; c-reactive protein.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCardiorespiratory and Metabolic Responses\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBaseline oxygen consumption (VO₂) and carbon dioxide production (VCO₂) measurements were taken after a standardized 30-minute rest period with no medical or nursing interventions. Compared to baseline values, significant increases were observed during the PROM intervention (VO₂ baseline: 263.69\u0026thinsp;\u0026plusmn;\u0026thinsp;109.01 ml/min vs. PROM\u003csub\u003e7th min\u003c/sub\u003e: 287.34\u0026thinsp;\u0026plusmn;\u0026thinsp;126.17 ml/min, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; VCO₂ baseline: 182.17\u0026thinsp;\u0026plusmn;\u0026thinsp;77.19 ml/min vs. PROM\u003csub\u003e6th min\u003c/sub\u003e: 198.69\u0026thinsp;\u0026plusmn;\u0026thinsp;76.20 ml/min, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Sistolic tension baseline: 122.65\u0026thinsp;\u0026plusmn;\u0026thinsp;21.28 mmHg, PROM\u003csub\u003e7th min\u003c/sub\u003e: 127.34\u0026thinsp;\u0026plusmn;\u0026thinsp;19.28 mmHg, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Measurements returned close to baseline values within 3 minutes post-intervention (VO₂: 269.69\u0026thinsp;\u0026plusmn;\u0026thinsp;110.88 ml/min, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05; VCO₂: 188.08\u0026thinsp;\u0026plusmn;\u0026thinsp;81.43 ml/min, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Sistolic tension baseline: 122.87\u0026thinsp;\u0026plusmn;\u0026thinsp;19.31 mmHg, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The magnitude of change during intervention represented approximately 9% increase in VO₂ and 12% increase in VCO₂ compared to baseline, indicating measurable but clinically safe metabolic stress during PROM.\u003c/p\u003e\u003cp\u003eThere was no significant change in heart rate, diastolic tension, and tidal volume (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSafety and Adverse Events\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo significant adverse events such as extubation, tube displacement, hemodynamic instability, or desaturation were observed during or after PROM interventions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe primary aim of this study was to investigate the cardiorespiratory responses to early passive range of motion (PROM) exercises in adults with critical illness requiring invasive mechanical ventilation. The study demonstrated significant carbon dioxide (CO₂) production increases throughout the PROM, excluding the 1st, 8th, and 10th minutes, while oxygen (O₂) consumption significantly increased only at the seventh minute. Both parameters returned to baseline after a defined resting period. No clinically significant alterations were observed in other cardiometabolic parameters.\u003c/p\u003e\u003cp\u003eThe observed increase in CO₂ production without a parallel rise in O₂ consumption suggests that active muscle contractions were unlikely to be responsible for this metabolic response. Typically, increased O₂ consumption accompanies active muscle contractions due to metabolic demand [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Instead, our findings suggest the increased CO₂ production might result from mobilizing venous blood reservoirs through passive limb movements against gravity. Wollersheim et al. reported similar findings, noting no change in O₂ consumption with increased CO₂ elimination during PROM exercises [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A recent meta-analysis supports this concept, suggesting PROM may prevent muscle wasting not through active muscle engagement but possibly via reduction in nitrosative stress and immune modulation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our findings align with this hypothesis, indicating that PROM exercises may enhance metabolic clearance of byproducts, thus mitigating muscle wasting in immobilized patients [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Unlike Wilkinson et al., who reported no change in VCO₂ with upper-limb PROM ergometry, our inclusion of lower-limb movements may explain the observed metabolic differences [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The observation that the metabolic waste removed from the body increases during the initial seven minutes and subsequently exhibits a downward trend prompts the question of whether the beneficial effects of PROM will also be apparent in short applications of five to seven minutes.\u003c/p\u003e\u003cp\u003eThe study also demonstrated minimal hemodynamic responses during PROM, characterized by an initial rise followed by stabilization. Specifically, systolic blood pressure exhibited an initial increase, peaking at the seventh minute, corresponding with the completion of right-sided extremities and left hip PROM. These transient changes align with previous findings by Medrinal et al., who observed similar cardiometabolic response patterns during initial phases of PROM [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Such transient increases may reflect acute physiological stress responses, highlighting the importance of initiating PROM exercises gradually and focusing initially on small (distal) joint mobilization to mitigate acute stress reactions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. There is growing evidence that passive joint exercises do not significantly affect the haemodynamic stability of critically ill patients [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] even in patients receiving vasopressor support [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Muscle loss in critical illness has been linked to survival rates [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Passive joint movements in sedated and ventilated critically ill patients could be used as a therapy to improve metabolic clearance and circulation and slow muscle breakdown.\u003c/p\u003e\u003cp\u003eNotably, no adverse events such as extubation, catheter removal, or hemodynamic instability occurred during the interventions, supporting previous evidence indicating that PROM is safe and feasible, even in patients receiving low-dose vasopressor support [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our protocol demonstrated minimal clinically relevant hemodynamic changes, suggesting PROM can be safely applied in the ICU if appropriate precautions and patient-specific adjustments are observed.\u003c/p\u003e\u003cp\u003eHowever, several limitations must be noted. Although statistical power analysis indicated adequate sample size, the generalizability of findings may be limited due to the relatively small and homogenous sample. Additionally, muscle blood flow or muscle activity measurements (e.g., electromyography) were not performed, which could have provided more profound insights into the observed metabolic changes.\u003c/p\u003e\u003cp\u003eFuture studies should address these limitations by incorporating electromyographic measurements during PROM to investigate the underlying mechanisms more thoroughly. Further research is needed to determine the optimal duration and intensity of PROM exercises for maximizing metabolic benefits and minimizing muscle atrophy in patients with limited mobility.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study suggest that PROM exercises significantly increase CO₂ elimination without notably affecting O₂ consumption in critically ill adults requiring sedation and mechanical ventilation. The temporary metabolic shifts observed highlight PROM's potential role in enhancing metabolic clearance in immobilized patients. All observed cardiorespiratory responses remained within clinically acceptable ranges, underscoring the safety of PROM interventions in ICU practice. Further studies should investigate muscle activity and varying exercise sequences to optimize early mobilization protocols.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAPACHE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAcute Physiology and Chronic Health Evaluation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECMO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eExtracorporeal Membrane Oxygenation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU-AW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eICU-acquired weakness\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePICS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePost-intensive care syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePROM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePassive range of motion\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e(RASS)\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRichmond Agitation-Sedation Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSOFA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSequential Organ Failure Assessment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTA, AOK, and MPK conceptualized the study. Data collection was supervised by AOK, \u0026Ouml;FŞ, and MPK, and analysis was conducted by UA. The manuscript was conceptualized by TA, UA, and \u0026Ouml;FŞ and drafted by AOK and MPK. All authors contributed to revising the manuscript and approval of the final version. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of The Faculty of Medicine, Karadeniz Technical University, on 14 April 2023 (2023/27).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate.\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of The Faculty of Medicine, Karadeniz Technical University, on 14 April 2023 (2023/27).\u0026nbsp;This study was conducted following the tenets of the Declaration of Helsinki. Informed consent was obtained from a legally authorized representative of each unconscious patient before enrolment. The legally authorized representatives were informed about the purpose of the study, the methods, the potential risks and benefits, and their rights regarding participation. The confidentiality of the data collected and the patient\u0026apos;s privacy were protected. The legally authorized also had the option to withdraw from the study at any time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors certify that there is no competing interest with any financial organisation regarding the material discussed in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBarr J, Fraser GL, Puntillo K, Ely EW, G\u0026eacute;linas C, Dasta JF, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit: Crit Care Med. 2013;41:263\u0026ndash;306.\u003c/li\u003e\n\u003cli\u003eKim S-J, Park K, Kim K. Post\u0026ndash;intensive care syndrome and health-related quality of life in long-term survivors of intensive care unit. Aust Crit Care. 2023;36:477\u0026ndash;84.\u003c/li\u003e\n\u003cli\u003eZhou M, Zhang J, Xu Z, Gu H, Chen Z, Ding Y. Incidence of and risk factors for post\u0026ndash;intensive care syndrome among Chinese respiratory intensive care unit patients: A cross-sectional, prospective study. Aust Crit Care. 2023;36:464\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eLee M, Kang J, Jeong YJ. Risk factors for post\u0026ndash;intensive care syndrome: A systematic review and meta-analysis. Aust Crit Care. 2020;33:287\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eMatsuoka A, Yoshihiro S, Shida H, Aikawa G, Fujinami Y, Kawamura Y, et al. Effects of Mobilization within 72 h of ICU Admission in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2023;12:5888.\u003c/li\u003e\n\u003cli\u003ePun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, et al. Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Crit Care Med. 2019;47:3\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eDaum N, Drewniok N, Bald A, Ulm B, Buyukli A, Grunow JJ, et al. Early mobilisation within 72 hours after admission of critically ill patients in the intensive care unit: A systematic review with network meta-analysis. Intensive Crit Care Nurs. 2024;80:103573.\u003c/li\u003e\n\u003cli\u003eDevlin JW, Skrobik Y, G\u0026eacute;linas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46:e825\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eRuo Yu L, Jia Jia W, Meng Tian W, Tian Cha H, Ji Yong J. Optimal timing for early mobilization initiatives in intensive care unit patients: A systematic review and network meta-analysis. Intensive Crit Care Nurs. 2024;82:103607.\u003c/li\u003e\n\u003cli\u003eNydahl P, Sricharoenchai T, Chandra S, Kundt FS, Huang M, Fischill M, et al. Safety of Patient Mobilization and Rehabilitation in the Intensive Care Unit. Systematic Review with Meta-Analysis. Ann Am Thorac Soc. 2017;14:766\u0026ndash;77.\u003c/li\u003e\n\u003cli\u003eAnekwe DE, Biswas S, Bussi\u0026egrave;res A, Spahija J. Early rehabilitation reduces the likelihood of developing intensive care unit-acquired weakness: a systematic review and meta-analysis. Physiotherapy. 2020;107:1\u0026ndash;10.\u003c/li\u003e\n\u003cli\u003eTomonaga Y, Menges D, Yebyo HG, Fumeaux T, Heise A, Wesch C, et al. Early mobilisation and rehabilitation in Swiss intensive care units: a cross-sectional survey. Swiss Med Wkly. 2022;152:w30125.\u003c/li\u003e\n\u003cli\u003eMedrinal C, Combret Y, Prieur G, Robledo Quesada A, Bonnevie T, Gravier FE, et al. Comparison of exercise intensity during four early rehabilitation techniques in sedated and ventilated patients in ICU: a randomised cross-over trial. Crit Care Lond Engl. 2018;22:110.\u003c/li\u003e\n\u003cli\u003eKovacs G, Herve P, Barbera JA, Chaouat A, Chemla D, Condliffe R, et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J. 2017;50:1700578.\u003c/li\u003e\n\u003cli\u003eWollersheim T, Haas K, Wolf S, Mai K, Spies C, Steinhagen-Thiessen E, et al. Whole-body vibration to prevent intensive care unit-acquired weakness: safety, feasibility, and metabolic response. Crit Care Lond Engl. 2017;21:9.\u003c/li\u003e\n\u003cli\u003eVollenweider R, Manettas AI, H\u0026auml;ni N, de Bruin ED, Knols RH. Passive motion of the lower extremities in sedated and ventilated patients in the ICU - a systematic review of early effects and replicability of Interventions. PloS One. 2022;17:e0267255.\u003c/li\u003e\n\u003cli\u003eJi HM, Won YH. Early Mobilization and Rehabilitation of Critically-Ill Patients. Tuberc Respir Dis. 2024;87:115\u0026ndash;22.\u003c/li\u003e\n\u003cli\u003ePowers SK, Morton AB, Ahn B, Smuder AJ. Redox control of skeletal muscle atrophy. Free Radic Biol Med. 2016;98:208\u0026ndash;17.\u003c/li\u003e\n\u003cli\u003eWilkinson OM, Bates A, Cusack R. An observational feasibility study - does early limb ergometry affect oxygen delivery and uptake in intubated critically ill patients \u0026ndash; a comparison of two assessment methods. BMC Anesthesiol. 2021;21.\u003c/li\u003e\n\u003cli\u003eGenzler L, Johnson PJ, Ghildayal N, Pangarakis S, Sendelbach S. End-tidal carbon dioxide as a measure of stress response to clustered nursing interventions in neurologic patients. Am J Crit Care Off Publ Am Assoc Crit-Care Nurses. 2013;22:239\u0026ndash;45.\u003c/li\u003e\n\u003cli\u003eKawano T, Ono H, Abe M, Umeshita K. Changes in Physiological Indices Before and After Nursing Care of Postoperative Patients With Esophageal Cancer in the ICU. SAGE Open Nurs. 2023;9:23779608231190144.\u003c/li\u003e\n\u003cli\u003eCollings N, Cusack R. A repeated measures, randomised cross-over trial, comparing the acute exercise response between passive and active sitting in critically ill patients. BMC Anesthesiol. 2015;15.\u003c/li\u003e\n\u003cli\u003eCamargo Pires-Neto R, Foga\u0026ccedil;a Kawaguchi YM, Sayuri Hirota A, Fu C, Tanaka C, Caruso P, et al. Very early passive cycling exercise in mechanically ventilated critically ill patients: physiological and safety aspects--a case series. PloS One. 2013;8:e74182.\u003c/li\u003e\n\u003cli\u003eKolck J, Hosse C, Fehrenbach U, Beetz N-L, Auer TA, Pille C, et al. The extent of Skeletal muscle wasting in prolonged critical illness and its association with survival: insights from a retrospective single-center study. BMC Anesthesiol. 2025;25.\u003c/li\u003e\n\u003cli\u003eGenc A, Koca U, Gunerli A. What Are the Hemodynamic and Respiratory Effects of Passive Limb Exercise for Mechanically Ventilated Patients Receiving Low-Dose Vasopressor/Inotropic Support? Crit Care Nurs Q. 2014;37:152\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eLindholz M, Schellenberg CM, Grunow JJ, Kagerbauer S, Milnik A, Zickler D, et al. Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study. Crit Care Lond Engl. 2022;26:362.\u003c/li\u003e\n\u003c/ol\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":"Early Mobilization, Exercise, Indirect Calorimetry, Intensive care units, Range of Motion","lastPublishedDoi":"10.21203/rs.3.rs-7139229/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7139229/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Passive range of motion (PROM) is a common early mobilization technique in intensive care, especially for sedated, mechanically ventilated patients. This study aimed to evaluate the effect of early PROM on oxygen consumption (VO₂) and carbon dioxide production (VCO₂) in mechanically ventilated critically ill adults.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A prospective observational cohort study was conducted in the tertiary ICU of a university hospital between May and September 2023. PROM was initiated within 24–48 hours of admission in hemodynamically stable, sedated patients (RASS: -2 to -4). An experienced physiotherapist performed a standardized 10-minute PROM protocol. VO₂ and VCO₂ were measured via indirect calorimetry before, during, and after the intervention. Cardiovascular parameters were also recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Eighteen patients were included. Compared to baseline, VCO₂ increased significantly during PROM (mean change: +12%, p \u0026lt; 0.05), while VO₂ showed a modest but significant increase only at the seventh minute (+9%, p \u0026lt; 0.01). Both returned to near-baseline post-intervention. Systolic blood pressure increased transiently at the seventh minute (p = 0.04); other parameters remained stable. No adverse events were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Early PROM exercises in sedated, mechanically ventilated ICU patients induced a mild yet significant rise in metabolic demand, particularly reflected in VCO₂. The findings show that PROM is metabolically safe and does not cause haemodynamic instability. 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