Ventilator WeaningNCT07771101
Can a Pain Monitor Predict When Postoperative Intensive Care Unit Patients Are Ready to Breathe on Their Own? A Pilot Study
An observational study of Ventilator Weaning and Airway Extubation, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The goal of this observational study is to learn if a chest monitor that tracks heart rhythm can help predict whether adults on a breathing machine after surgery will be able to breathe on their own once the breathing tube is removed. It is being done in adults recovering from surgery in the intensive care unit (ICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator Weaning, Airway Extubation, Respiration, Artificial
- How many people
- 50 participants
- Where
- 1 siteSouth Korea
- Study dates
- 11 Aug 2026to 12 Aug 2027
- How long will I take part?
- 28 Days
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants are drawn from adult patients admitted to the surgical intensive care unit (ICU) of Seoul Metropolitan Government Seoul National University Boramae Medical Center, a public academic hospital in Seoul, South Korea, following surgery. The surgical ICU cares for postoperative patients across multiple surgical specialties, including general surgery, thoracic and cardiovascular surgery, and other surgical disciplines requiring postoperative critical care. Eligible participants are identified from among those requiring invasive mechanical ventilation after surgery and sedated according to standard ICU sedation practice at this institution.
Who may be able to join
- Age 18 years or older
- Admitted to the surgical intensive care unit (ICU) after surgery
- Currently on a breathing machine (mechanical ventilation) through a tube in the airway
- Receiving dexmedetomidine as the main sedative medication, with a stable, predefined level of sedation
- Participant or their legal representative agrees to take part in the study
Who cannot join
- Permanent irregular heart rhythm (atrial fibrillation or atrial flutter)
- Complete heart block or a heart rhythm that is fully controlled by a pacemaker
- Already has a tracheostomy (a breathing tube placed through the neck)
- A decision has already been made at ICU admission to withhold or withdraw life-sustaining treatment
- Deeply sedated without receiving any sedative medication, suggesting the low alertness may be due to a brain-related problem rather than medication
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Seoul Metropolitan Government Seoul National University Boramae Medical Center
Seoul, 07061
Saeyeon Kim, M.D., Ph.D., 82-1577-0075, kimaticu@gmail.com
Sangbae Park, M.S.N., 82-1577-0075, parkbreeze@gmail.com
About this study
Official title: Association Between Early Autonomic Dysfunction Measured by the Analgesia Nociception Index (ANI) and Prolonged Mechanical Ventilation in Postoperative ICU Patients
The goal of this observational study is to learn if a chest monitor that tracks heart rhythm can help predict whether adults on a breathing machine after surgery will be able to breathe on their own once the breathing tube is removed. It is being done in adults recovering from surgery in the intensive care unit (ICU).
The main questions it aims to answer are:
Read more
Can heart rhythm patterns, measured soon after ICU admission and during a breathing test, show whether a patient is likely to breathe well without the machine? Do these patterns change in a helpful way when the breathing tube is removed?
Participants will:
Have soft, sticky patches placed on their chest, similar to those used for a regular heart monitor Have their heart rhythm recorded for 5 minutes at four times: soon after ICU admission, before a breathing test, during the breathing test, and right after the breathing tube is removed Continue to receive their usual ICU care; doctors will not see the monitor's readings, so these readings will not affect any treatment decisions
Read the detailed description
<Background and Rationale>
Delayed liberation from invasive mechanical ventilation after surgery is associated with increased risk of ventilator-associated pneumonia, prolonged sedation and analgesic exposure, ICU-acquired weakness, delirium, and longer ICU and hospital stays. Identifying patients at risk of extubation failure before or during a spontaneous breathing trial (SBT) could allow clinicians to better time weaning attempts and reduce these complications.
The autonomic nervous system plays a broader physiological role than heart rate control alone, contributing to respiratory muscle regulation, the cholinergic anti-inflammatory pathway, and the stress response. Heart rate variability (HRV) is a validated, non-invasive marker of autonomic function, and reduced HRV has been associated with multiorgan dysfunction and mortality in critically ill patients. The weaning process, particularly the SBT, imposes substantial autonomic and cardiorespiratory stress through abrupt changes in intrathoracic pressure, preload and afterload, and oxygen demand, resembling a physiological stress test.
Several studies have examined HRV around the time of SBT and its association with weaning or extubation outcomes, generally showing that reduced total power or altered low-frequency/high-frequency ratios are associated with SBT failure. However, prior studies have relied on offline, retrospective HRV processing methods that are not readily applicable at the bedside, and none have evaluated HRV parameters derived from a real-time, point-of-care Analgesia Nociception Index (ANI) monitor in relation to extubation outcomes. In addition, no prior study has evaluated whether autonomic function measured at ICU admission, prior to any weaning attempt, predicts subsequent extubation success, nor has this question been examined specifically in postoperative surgical ICU patients.
The ANI monitor (MDoloris Medical Systems, France) is a commercially available, non-invasive device that derives HRV-based indices from surface ECG in real time, producing an instantaneous index (ANIi), a smoothed mean index (ANIm), and a signal quality/magnitude index (Energy, based on SDNN). ANI monitoring is an established, nationally approved technology for intraoperative nociception monitoring in Korea since 2021, but its use as a physiologic prognostic tool in the ICU, specifically for predicting extubation outcomes, remains unexplored.
<Study Design>
This is a single-center, prospective, observational pilot cohort study conducted in the surgical ICU of a tertiary academic hospital. As a pilot study, no formal sample size calculation was performed; findings are intended to generate preliminary effect estimates and inform the sample size calculation for a subsequent multicenter study.
To minimize confounding from sedative agents with differing autonomic effects, enrollment is restricted to patients sedated with dexmedetomidine as the primary agent, since dexmedetomidine acts directly on alpha-2 receptors to suppress sympathetic activity, in contrast to GABA-mediated agents such as propofol or benzodiazepines, which have been shown to affect HRV parameters differently.
<Measurement Procedures>
ANI-derived HRV parameters (ANIi, ANIm, Energy) are measured non-invasively via chest-surface ECG patches for 5 minutes at each of four standardized time points: (1) baseline, on the day of ICU admission after confirming stable sedation (RASS -2 to -5 maintained for at least 30 minutes); (2) immediately before the SBT, at transition to pressure support ventilation, using the pre-existing ventilator settings; (3) during the SBT, 10-15 minutes after transition to pressure support ventilation (recommended settings: pressure support 8 cmH2O, PEEP 5 cmH2O, adjustable at clinician discretion, with actual settings recorded); and (4) immediately after extubation, regardless of subsequent success or failure. If ICU admission and extubation occur on the same day, baseline and pre-SBT measurements are obtained separately.
The ANI monitor display is shielded from the treating clinical team throughout the study period so that monitoring values do not influence clinical decision-making. The decision to proceed with SBT and extubation remains entirely at the discretion of the treating physicians and follows standardized institutional SBT initiation/termination criteria (based on oxygen saturation, respiratory rate, heart rate change from baseline, blood pressure, work of breathing, and mental status), which are recorded for use as covariates but do not constitute a study intervention.
Only the SBT and extubation attempt performed on the initial intubation episode (i.e., the final weaning attempt prior to the first extubation) are included in the primary analysis; SBTs or extubation attempts occurring after reintubation are excluded from primary analysis.
<Data Collection>
In addition to the ANI parameters, the following data are collected via electronic medical record review: demographic and baseline characteristics (age, sex, height, weight, surgery type, elective/emergency status, comorbidities); severity scores at ICU admission (SOFA, APACHE II); sedation and analgesia data (agent, dose, RASS, use of patient-controlled analgesia); hemodynamic and ventilatory parameters (vasopressor use, ventilator settings including FiO2, PEEP, respiratory rate, tidal volume, and actual SBT settings); inflammatory and hematologic laboratory values (CRP, procalcitonin, lactate, complete blood count); and clinical outcomes including length of ICU/hospital stay, mortality, and delirium status (CAM-ICU). No additional invasive procedures, blood draws, or interventions beyond standard ICU care are performed for research purposes; ANI monitoring uses only chest-surface ECG patches, similar to routine cardiac monitoring.
<Statistical Analysis Plan>
Continuous variables will be assessed for normality using the Shapiro-Wilk test and summarized as mean (SD) or median (IQR) accordingly; categorical variables will be summarized as frequencies and percentages, with Fisher's exact test applied when expected cell counts are below 5.
Associations between each ANI parameter at each time point and the primary outcome will be assessed using univariable logistic regression, reported as odds ratios with 95% confidence intervals. A multivariable model adjusting for SOFA score and cumulative opioid dose (fentanyl equivalents) will be performed; these two covariates were selected a priori based on their established association with weaning outcomes in the literature, with the number of covariates deliberately limited given the small pilot sample size, following the events-per-variable principle to avoid model overfitting.
Because three time points (baseline, pre-SBT, and during-SBT ANI) are each tested as primary predictors, this multiplicity is explicitly acknowledged as exploratory analysis, and formal multiplicity correction (e.g., Bonferroni) is applied exploratorily rather than as a primary inferential adjustment, consistent with the pilot nature of the study. For parameters showing a significant association, receiver operating characteristic curve analysis will be performed to explore the area under the curve and candidate cut-off values.
Secondary analyses include univariable logistic regression for the association between post-extubation ANI and 48-hour reintubation, and for the association between the within-day change in ANI (pre-SBT to during-SBT, ΔANI) and successful extubation. Length of stay will be analyzed using Spearman correlation after assessing normality. All statistical tests are two-sided, with significance defined as p < 0.05.
Statistical analysis will be performed after completion of enrollment for the pilot cohort (target: up to approximately 50 participants over a 6-month enrollment period), with a total study duration of 12 months from IRB approval, including follow-up medical record review.
- Keywords
- Heart Rate Variability, Autonomic Nervous System, Intensive Care Units, Analgesia Nociception Index, Postoperative Care, Spontaneous Breathing Trial, Critical Illness
- Medical subject headings
- Respiratory Aspiration, Critical Illness
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of participants with successful extubation
A participant's breathing tube is removed (extubated) after a period of mechanical ventilation, following a trial in which the ventilator support is reduced to see if the participant can breathe adequately on their own (a spontaneous breathing trial). Extubation is considered successful if the participant does not need the breathing tube reinserted within 48 hours. If a participant dies within this 48-hour window without having the breathing tube reinserted, this is not counted as a failed extubation and is recorded as a separate outcome. This outcome will be analyzed in relation to heart rate variability measurements (an indicator of autonomic nervous system activity, obtained non-invasively from a chest monitor) taken at the time of intensive care unit admission, before the breathing trial, and during the breathing trial.
Measured: Within 48 hours after extubation
Secondary outcomes (5)
Proportion of Participants with Reintubation Following Post-Extubation ANI Measurement
Reintubation is defined as reinsertion of a breathing tube within 48 hours after extubation. This outcome will be analyzed in relation to heart rate variability values measured by a chest monitor immediately after extubation, to explore whether values recorded right after the breathing tube is removed are associated with the need to reinsert it.
Measured: Within 48 hours after extubation
Proportion of Participants with Successful Extubation, by Change in Heart Rate Variability During the Breathing Trial
The change in heart rate variability value (a measure of autonomic nervous system activity obtained from a chest monitor) between the measurement taken just before the breathing trial and the measurement taken during the breathing trial will be calculated for each participant. Successful extubation is defined as no reinsertion of the breathing tube within 48 hours after extubation. This outcome will be analyzed according to the magnitude of change in heart rate variability
Measured: From immediately before the breathing trial to 48 hours after extubation
Length of Stay in the Intensive Care Unit and Hospital
Length of stay is defined as the number of days from intensive care unit (ICU) admission to ICU discharge, and from hospital admission to hospital discharge, respectively.
Measured: From ICU admission until ICU discharge or hospital discharge, up to 28 days
Proportion of Participants who Died in the Intensive Care Unit, in the Hospital, or Within 28 Days
Death occurring during the intensive care unit (ICU) stay, during the hospital stay, and within 28 days of study enrollment will each be recorded separately as three distinct measures of mortality.
Measured: From ICU admission up to 28 days, or until hospital discharge, whichever occurs first
Proportion of Participants with Delirium as Assessed by CAM-ICU
Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), a validated bedside screening tool administered by trained staff. A participant is considered positive for delirium if they show both (1) an acute change or fluctuation in mental status and (2) inattention, together with either (3a) disorganized thinking or (3b) an altered level of consciousness. This tool produces a binary result (delirium present or absent) rather than a numeric score.
Measured: Daily during the intensive care unit stay, up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2026
- Study start11 Aug 2026
- Primary completion12 Feb 2027 (estimated)
- Study completion12 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Ventilator WeaningStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
- Target duration
- 28 Days
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- SMG-SNU Boramae Medical Center
- Responsible party
- Sponsor
- Investigators
- Saeyeon Kim, M.D., Ph.D., Principal investigator, SMG-SNU Boramae Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07771101
- Sponsor's protocol ID
- 30-2026-30
- Status last verified
- Aug 2026
- First submitted
- 13 Aug 2026
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: All individual participant data (IPD) collected during this study that underlie the results reported in future publications will be shared, including de-identified demographic, clinical, laboratory, and Analgesia Nociception Index (ANI)-derived heart rate variability measurements. Data will be shared, after de-identification, beginning after publication of the primary study results and ending 5 years after study completion, consistent with the data retention period specified in the informed consent document. Sharing will be conducted in accordance with Article 18 of the Korean Bioethics and Safety Act and institutional review board approval, upon reasonable request to the corresponding author, for purposes such as independent verification of results or meta-analysis.
Publications
Lee H, Jeon SB, Lee KS. Continuous heart rate variability and electroencephalography monitoring in severe acute brain injury: a preliminary study. Acute Crit Care. 2021 May;36(2):151-161. doi: 10.4266/acc.2020.00703. Epub 2021 Mar 18.
PubMed 33730778Joe HB, Chae YJ, Song SH, Yi IK. Comparison of the effects of dexmedetomidine and propofol on the cardiovascular autonomic nervous system during spinal anesthesia: preliminary randomized controlled observational study. J Clin Monit Comput. 2023 Dec;37(6):1541-1551. doi: 10.1007/s10877-023-01062-w. Epub 2023 Aug 12.
PubMed 37572236Bodenes L, N'Guyen QT, Le Mao R, Ferriere N, Pateau V, Lellouche F, L'Her E. Early heart rate variability evaluation enables to predict ICU patients' outcome. Sci Rep. 2022 Feb 15;12(1):2498. doi: 10.1038/s41598-022-06301-9.
PubMed 35169170Aragon-Benedi C, Caballero-Lozada AF, Perez-Calatayud AA, Marulanda-Yanten AM, Oliver-Fornies P, Boselli E, De Jonckheere J, Bergese SD; ANI-COVID-19 Research Group. Prospective multicenter study of heart rate variability with ANI monitor as predictor of mortality in critically ill patients with COVID-19. Sci Rep. 2022 Dec 16;12(1):21762. doi: 10.1038/s41598-022-25537-z.
PubMed 36526646Aragon-Benedi C, Oliver-Fornies P, Galluccio F, Yamak Altinpulluk E, Ergonenc T, El Sayed Allam A, Salazar C, Fajardo-Perez M. Is the heart rate variability monitoring using the analgesia nociception index a predictor of illness severity and mortality in critically ill patients with COVID-19? A pilot study. PLoS One. 2021 Mar 24;16(3):e0249128. doi: 10.1371/journal.pone.0249128. eCollection 2021.
PubMed 33760875Giordano G, Alessandri F, Tosi A, Zullino V, Califano L, Petramala L, Galardo G, Pugliese F. Heart Rate Variability During Weaning from Invasive Mechanical Ventilation: A Systematic Review. J Clin Med. 2024 Dec 15;13(24):7634. doi: 10.3390/jcm13247634.
PubMed 39768558da Silva RB, Neves VR, Montarroyos UR, Silveira MS, Sobral Filho DC. Heart rate variability as a predictor of mechanical ventilation weaning outcomes. Heart Lung. 2023 May-Jun;59:33-36. doi: 10.1016/j.hrtlng.2023.01.007. Epub 2023 Jan 26.
PubMed 36706686Seely AJ, Bravi A, Herry C, Green G, Longtin A, Ramsay T, Fergusson D, McIntyre L, Kubelik D, Maziak DE, Ferguson N, Brown SM, Mehta S, Martin C, Rubenfeld G, Jacono FJ, Clifford G, Fazekas A, Marshall J; Canadian Critical Care Trials Group (CCCTG). Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients? Crit Care. 2014 Apr 8;18(2):R65. doi: 10.1186/cc13822.
PubMed 24713049Huang CT, Tsai YJ, Lin JW, Ruan SY, Wu HD, Yu CJ. Application of heart-rate variability in patients undergoing weaning from mechanical ventilation. Crit Care. 2014 Jan 23;18(1):R21. doi: 10.1186/cc13705.
PubMed 24456585Vignon P. Cardiopulmonary interactions during ventilator weaning. Front Physiol. 2023 Sep 7;14:1275100. doi: 10.3389/fphys.2023.1275100. eCollection 2023.
PubMed 37745230Pontet J, Contreras P, Curbelo A, Medina J, Noveri S, Bentancourt S, Migliaro ER. Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients. J Crit Care. 2003 Sep;18(3):156-63. doi: 10.1016/j.jcrc.2003.08.005.
PubMed 14595568Pham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, Mancebo J, Penuelas O, Piquilloud L, Pesenti A, Wunsch H, van Haren F, Brochard L, Laffey JG; WEAN SAFE Investigators. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023 May;11(5):465-476. doi: 10.1016/S2213-2600(22)00449-0. Epub 2023 Jan 21.
PubMed 36693401
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Early Autonomic Dysfunction Measured by the Analgesia Nociception Index (ANI) and Prolonged Mechanical Ventilation in Postoperative ICU Patients
- ClinicalTrials.gov ID
- NCT07771101
- Acronym / sponsor ID
- 30-2026-30
- Keywords
- Heart Rate Variability, Autonomic Nervous System, Intensive Care Units, Analgesia Nociception Index, Postoperative Care, Spontaneous Breathing Trial, Critical Illness
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- SMG-SNU Boramae Medical Center
- Study start
- 11 Aug 2026 (actual)
- Primary completion
- 12 Feb 2027 (estimated)
- Study completion
- 12 Aug 2027 (estimated)
- First posted
- 18 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to learn if a chest monitor that tracks heart rhythm can help predict whether adults on a breathing machine after surgery will be able to breathe on their own once the breathing tube is removed. It is being done in adults recovering from surgery in the intensive care unit (ICU).
The main questions it aims to answer are:
Can heart rhythm patterns, measured soon after ICU admission and during a breathing test, show whether a patient is likely to breathe well without the machine? Do these patterns change in a helpful way when the breathing tube is removed?
Participants will:
Have soft, sticky patches placed on their chest, similar to those used for a regular heart monitor Have their heart rhythm recorded for 5 minutes at four times: soon after ICU admission, before a breathing test, during the breathing test, and right after the breathing tube is removed Continue to receive their usual ICU care; doctors will not see the monitor's readings, so these readings will not affect any treatment decisions
Detailed description
<Background and Rationale>
Delayed liberation from invasive mechanical ventilation after surgery is associated with increased risk of ventilator-associated pneumonia, prolonged sedation and analgesic exposure, ICU-acquired weakness, delirium, and longer ICU and hospital stays. Identifying patients at risk of extubation failure before or during a spontaneous breathing trial (SBT) could allow clinicians to better time weaning attempts and reduce these complications.
The autonomic nervous system plays a broader physiological role than heart rate control alone, contributing to respiratory muscle regulation, the cholinergic anti-inflammatory pathway, and the stress response. Heart rate variability (HRV) is a validated, non-invasive marker of autonomic function, and reduced HRV has been associated with multiorgan dysfunction and mortality in critically ill patients. The weaning process, particularly the SBT, imposes substantial autonomic and cardiorespiratory stress through abrupt changes in intrathoracic pressure, preload and afterload, and oxygen demand, resembling a physiological stress test.
Several studies have examined HRV around the time of SBT and its association with weaning or extubation outcomes, generally showing that reduced total power or altered low-frequency/high-frequency ratios are associated with SBT failure. However, prior studies have relied on offline, retrospective HRV processing methods that are not readily applicable at the bedside, and none have evaluated HRV parameters derived from a real-time, point-of-care Analgesia Nociception Index (ANI) monitor in relation to extubation outcomes. In addition, no prior study has evaluated whether autonomic function measured at ICU admission, prior to any weaning attempt, predicts subsequent extubation success, nor has this question been examined specifically in postoperative surgical ICU patients.
The ANI monitor (MDoloris Medical Systems, France) is a commercially available, non-invasive device that derives HRV-based indices from surface ECG in real time, producing an instantaneous index (ANIi), a smoothed mean index (ANIm), and a signal quality/magnitude index (Energy, based on SDNN). ANI monitoring is an established, nationally approved technology for intraoperative nociception monitoring in Korea since 2021, but its use as a physiologic prognostic tool in the ICU, specifically for predicting extubation outcomes, remains unexplored.
<Study Design>
This is a single-center, prospective, observational pilot cohort study conducted in the surgical ICU of a tertiary academic hospital. As a pilot study, no formal sample size calculation was performed; findings are intended to generate preliminary effect estimates and inform the sample size calculation for a subsequent multicenter study.
To minimize confounding from sedative agents with differing autonomic effects, enrollment is restricted to patients sedated with dexmedetomidine as the primary agent, since dexmedetomidine acts directly on alpha-2 receptors to suppress sympathetic activity, in contrast to GABA-mediated agents such as propofol or benzodiazepines, which have been shown to affect HRV parameters differently.
<Measurement Procedures>
ANI-derived HRV parameters (ANIi, ANIm, Energy) are measured non-invasively via chest-surface ECG patches for 5 minutes at each of four standardized time points: (1) baseline, on the day of ICU admission after confirming stable sedation (RASS -2 to -5 maintained for at least 30 minutes); (2) immediately before the SBT, at transition to pressure support ventilation, using the pre-existing ventilator settings; (3) during the SBT, 10-15 minutes after transition to pressure support ventilation (recommended settings: pressure support 8 cmH2O, PEEP 5 cmH2O, adjustable at clinician discretion, with actual settings recorded); and (4) immediately after extubation, regardless of subsequent success or failure. If ICU admission and extubation occur on the same day, baseline and pre-SBT measurements are obtained separately.
The ANI monitor display is shielded from the treating clinical team throughout the study period so that monitoring values do not influence clinical decision-making. The decision to proceed with SBT and extubation remains entirely at the discretion of the treating physicians and follows standardized institutional SBT initiation/termination criteria (based on oxygen saturation, respiratory rate, heart rate change from baseline, blood pressure, work of breathing, and mental status), which are recorded for use as covariates but do not constitute a study intervention.
Only the SBT and extubation attempt performed on the initial intubation episode (i.e., the final weaning attempt prior to the first extubation) are included in the primary analysis; SBTs or extubation attempts occurring after reintubation are excluded from primary analysis.
<Data Collection>
In addition to the ANI parameters, the following data are collected via electronic medical record review: demographic and baseline characteristics (age, sex, height, weight, surgery type, elective/emergency status, comorbidities); severity scores at ICU admission (SOFA, APACHE II); sedation and analgesia data (agent, dose, RASS, use of patient-controlled analgesia); hemodynamic and ventilatory parameters (vasopressor use, ventilator settings including FiO2, PEEP, respiratory rate, tidal volume, and actual SBT settings); inflammatory and hematologic laboratory values (CRP, procalcitonin, lactate, complete blood count); and clinical outcomes including length of ICU/hospital stay, mortality, and delirium status (CAM-ICU). No additional invasive procedures, blood draws, or interventions beyond standard ICU care are performed for research purposes; ANI monitoring uses only chest-surface ECG patches, similar to routine cardiac monitoring.
<Statistical Analysis Plan>
Continuous variables will be assessed for normality using the Shapiro-Wilk test and summarized as mean (SD) or median (IQR) accordingly; categorical variables will be summarized as frequencies and percentages, with Fisher's exact test applied when expected cell counts are below 5.
Associations between each ANI parameter at each time point and the primary outcome will be assessed using univariable logistic regression, reported as odds ratios with 95% confidence intervals. A multivariable model adjusting for SOFA score and cumulative opioid dose (fentanyl equivalents) will be performed; these two covariates were selected a priori based on their established association with weaning outcomes in the literature, with the number of covariates deliberately limited given the small pilot sample size, following the events-per-variable principle to avoid model overfitting.
Because three time points (baseline, pre-SBT, and during-SBT ANI) are each tested as primary predictors, this multiplicity is explicitly acknowledged as exploratory analysis, and formal multiplicity correction (e.g., Bonferroni) is applied exploratorily rather than as a primary inferential adjustment, consistent with the pilot nature of the study. For parameters showing a significant association, receiver operating characteristic curve analysis will be performed to explore the area under the curve and candidate cut-off values.
Secondary analyses include univariable logistic regression for the association between post-extubation ANI and 48-hour reintubation, and for the association between the within-day change in ANI (pre-SBT to during-SBT, ΔANI) and successful extubation. Length of stay will be analyzed using Spearman correlation after assessing normality. All statistical tests are two-sided, with significance defined as p < 0.05.
Statistical analysis will be performed after completion of enrollment for the pilot cohort (target: up to approximately 50 participants over a 6-month enrollment period), with a total study duration of 12 months from IRB approval, including follow-up medical record review.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 28 Days
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants are drawn from adult patients admitted to the surgical intensive care unit (ICU) of Seoul Metropolitan Government Seoul National University Boramae Medical Center, a public academic hospital in Seoul, South Korea, following surgery. The surgical ICU cares for postoperative patients across multiple surgical specialties, including general surgery, thoracic and cardiovascular surgery, and other surgical disciplines requiring postoperative critical care. Eligible participants are identified from among those requiring invasive mechanical ventilation after surgery and sedated according to standard ICU sedation practice at this institution.
Key inclusion criteria (5 listed)
- Age 18 years or older
- Admitted to the surgical intensive care unit (ICU) after surgery
- Currently on a breathing machine (mechanical ventilation) through a tube in the airway
- Receiving dexmedetomidine as the main sedative medication, with a stable, predefined level of sedation
- Participant or their legal representative agrees to take part in the study
Key exclusion criteria (5 listed)
- Permanent irregular heart rhythm (atrial fibrillation or atrial flutter)
- Complete heart block or a heart rhythm that is fully controlled by a pacemaker
- Already has a tracheostomy (a breathing tube placed through the neck)
- A decision has already been made at ICU admission to withhold or withdraw life-sustaining treatment
- Deeply sedated without receiving any sedative medication, suggesting the low alertness may be due to a brain-related problem rather than medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
proportion of participants with successful extubation
Time frame: Within 48 hours after extubation
A participant's breathing tube is removed (extubated) after a period of mechanical ventilation, following a trial in which the ventilator support is reduced to see if the participant can breathe adequately on their own (a spontaneous breathing trial). Extubation is considered successful if the participant does not need the breathing tube reinserted within 48 hours. If a participant dies within this 48-hour window without having the breathing tube reinserted, this is not counted as a failed extubation and is recorded as a separate outcome. This outcome will be analyzed in relation to heart rate variability measurements (an indicator of autonomic nervous system activity, obtained non-invasively from a chest monitor) taken at the time of intensive care unit admission, before the breathing trial, and during the breathing trial.
5 secondary outcomes
Proportion of Participants with Reintubation Following Post-Extubation ANI Measurement
Time frame: Within 48 hours after extubation
Proportion of Participants with Successful Extubation, by Change in Heart Rate Variability During the Breathing Trial
Time frame: From immediately before the breathing trial to 48 hours after extubation
Length of Stay in the Intensive Care Unit and Hospital
Time frame: From ICU admission until ICU discharge or hospital discharge, up to 28 days
Proportion of Participants who Died in the Intensive Care Unit, in the Hospital, or Within 28 Days
Time frame: From ICU admission up to 28 days, or until hospital discharge, whichever occurs first
Proportion of Participants with Delirium as Assessed by CAM-ICU
Time frame: Daily during the intensive care unit stay, up to 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Results publication: PubMed 33730778Lee H, Jeon SB, Lee KS. Continuous heart rate variability and electroencephalography monitoring in severe acute brain injury: a preliminary study. Acute Crit Care. 2021 May;36(2):151-161. doi: 10.4266/acc.2020.00703. Epub 2021 Mar 18.
- Results publication: PubMed 37572236Joe HB, Chae YJ, Song SH, Yi IK. Comparison of the effects of dexmedetomidine and propofol on the cardiovascular autonomic nervous system during spinal anesthesia: preliminary randomized controlled observational study. J Clin Monit Comput. 2023 Dec;37(6):1541-1551. doi: 10.1007/s10877-023-01062-w. Epub 2023 Aug 12.
- Results publication: PubMed 35169170Bodenes L, N'Guyen QT, Le Mao R, Ferriere N, Pateau V, Lellouche F, L'Her E. Early heart rate variability evaluation enables to predict ICU patients' outcome. Sci Rep. 2022 Feb 15;12(1):2498. doi: 10.1038/s41598-022-06301-9.
- Results publication: PubMed 36526646Aragon-Benedi C, Caballero-Lozada AF, Perez-Calatayud AA, Marulanda-Yanten AM, Oliver-Fornies P, Boselli E, De Jonckheere J, Bergese SD; ANI-COVID-19 Research Group. Prospective multicenter study of heart rate variability with ANI monitor as predictor of mortality in critically ill patients with COVID-19. Sci Rep. 2022 Dec 16;12(1):21762. doi: 10.1038/s41598-022-25537-z.
- Results publication: PubMed 33760875Aragon-Benedi C, Oliver-Fornies P, Galluccio F, Yamak Altinpulluk E, Ergonenc T, El Sayed Allam A, Salazar C, Fajardo-Perez M. Is the heart rate variability monitoring using the analgesia nociception index a predictor of illness severity and mortality in critically ill patients with COVID-19? A pilot study. PLoS One. 2021 Mar 24;16(3):e0249128. doi: 10.1371/journal.pone.0249128. eCollection 2021.
- Results publication: PubMed 39768558Giordano G, Alessandri F, Tosi A, Zullino V, Califano L, Petramala L, Galardo G, Pugliese F. Heart Rate Variability During Weaning from Invasive Mechanical Ventilation: A Systematic Review. J Clin Med. 2024 Dec 15;13(24):7634. doi: 10.3390/jcm13247634.
- Results publication: PubMed 36706686da Silva RB, Neves VR, Montarroyos UR, Silveira MS, Sobral Filho DC. Heart rate variability as a predictor of mechanical ventilation weaning outcomes. Heart Lung. 2023 May-Jun;59:33-36. doi: 10.1016/j.hrtlng.2023.01.007. Epub 2023 Jan 26.
- Results publication: PubMed 24713049Seely AJ, Bravi A, Herry C, Green G, Longtin A, Ramsay T, Fergusson D, McIntyre L, Kubelik D, Maziak DE, Ferguson N, Brown SM, Mehta S, Martin C, Rubenfeld G, Jacono FJ, Clifford G, Fazekas A, Marshall J; Canadian Critical Care Trials Group (CCCTG). Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients? Crit Care. 2014 Apr 8;18(2):R65. doi: 10.1186/cc13822.
- Results publication: PubMed 24456585Huang CT, Tsai YJ, Lin JW, Ruan SY, Wu HD, Yu CJ. Application of heart-rate variability in patients undergoing weaning from mechanical ventilation. Crit Care. 2014 Jan 23;18(1):R21. doi: 10.1186/cc13705.
- Results publication: PubMed 37745230Vignon P. Cardiopulmonary interactions during ventilator weaning. Front Physiol. 2023 Sep 7;14:1275100. doi: 10.3389/fphys.2023.1275100. eCollection 2023.
- Results publication: PubMed 14595568Pontet J, Contreras P, Curbelo A, Medina J, Noveri S, Bentancourt S, Migliaro ER. Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients. J Crit Care. 2003 Sep;18(3):156-63. doi: 10.1016/j.jcrc.2003.08.005.
- Results publication: PubMed 36693401Pham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, Mancebo J, Penuelas O, Piquilloud L, Pesenti A, Wunsch H, van Haren F, Brochard L, Laffey JG; WEAN SAFE Investigators. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023 May;11(5):465-476. doi: 10.1016/S2213-2600(22)00449-0. Epub 2023 Jan 21.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) collected during this study that underlie the results reported in future publications will be shared, including de-identified demographic, clinical, laboratory, and Analgesia Nociception Index (ANI)-derived heart rate variability measurements. Data will be shared, after de-identification, beginning after publication of the primary study results and ending 5 years after study completion, consistent with the data retention period specified in the informed consent document. Sharing will be conducted in accordance with Article 18 of the Korean Bioethics and Safety Act and institutional review board approval, upon reasonable request to the corresponding author, for purposes such as independent verification of results or meta-analysis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Saeyeon Kim, M.D., Ph.D. principal investigator
SMG-SNU Boramae Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ventilator Weaning and Airway Extubation, run by Seoul National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sangbae Park, M.S.N. (82-1577-0075, parkbreeze@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
proportion of participants with successful extubation (time frame: Within 48 hours after extubation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07771101, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.