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Completed

NCT Number: NCT05635201

Changes in Autonomic Nervous Activity and Blood Pressure After Anesthesia Induction: Remimazolam Versus Propofol

The goal of this clinical trial is to compare the effects of changes in autonomic nervous activity on changes in blood pressure after anesthesia induction between propofol and remimazolam in patients undergoing low-risk surgery. The main questions it aims to answer are:

* Does remimazolam shift sympathovagal balance toward parasympathetic predominance less than propofol? * Does the less shift in sympathovagal balance toward parasympathetic predominance attenuate the reduction in blood pressure? Participants will be administered either propofol or remimazolam for anesthesia induction, after which the autonomic nervous activity and blood pressure will be measured.

Researchers will compare the propofol and remimazolam groups to see if remimazolam causes less shift in sympathovagal balance toward parasympathetic predominance and subsequently attenuates the reduction in blood pressure.

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Key information

Conditions

General Anesthetics

Age range

20 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Daegu Catholic University Medical Center

Daegu, 42472, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age between 20 and 60 years
  • American Society of Anesthesiologists physical status of 1
  • Elective low-risk surgery requiring general anesthesia, the duration of which is shorter than 2 hours and 30 minutes (e.g., Laparoscopic cholecystectomy, Functional endoscopic sinus surgery, etc.)
  • Body mass index less than 30 kg/m2

Exclusion criteria

  • Arrhythmias or cardiac conduction disorders
  • Disease or medical conditions affecting autonomic nervous activity (hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, cerebrovascular accident, chronic kidney disease, thyroid dysfunction, etc.)
  • Valvular heart disease
  • Use of medications affecting autonomic nervous activity or cardiac conduction (e.g., beta blocker)
  • Limited mouth opening, limited head and upper neck extension, history of obstructive sleep apnea, or Modified Mallampati class 3 or 4
  • Serum electrolyte abnormalities
  • Severe hypovolemia
  • Psychiatric diseases

Treatment and study plan

Anesthesia induction with propofol

Drug

After a 10-minute-long acclimation, general anesthesia is induced with 2% propofol at the effect-site concentration of 4 μg/ml based on the Marsh Pharmacokinetic model. The effect-site concentration was maintained at 4 μg/ml until the trachea was intubated. Five minutes after the anesthesia induction, remifentanil was administered at the effect-site concentration of 4 ng/ml based on the Minto pharmacokinetic model until the trachea was intubated. With the initiation of remifentanil infusion, 1 mg/kg of rocuronium was administered following the calibration of the neuromuscular monitoring device. With the train-of-four count of 0, the trachea was intubated. Then, the effect-site concentrations of propofol and remifentanil were decreased to 3 μg/ml and 0 ng/ml, respectively, until the surgical incision was made.

Anesthesia induction with remimazolam

Drug

After a 10-minute-long acclimation, general anesthesia is induced with a 2-minute-long infusion of remimazolam at a rate of 12 mg/kg/hr, after which the infusion rate was reduced to 1 mg/kg/hr and was maintained until the surgical incision was made. Five minutes after the anesthesia induction, remifentanil was administered at the effect-site concentration of 4 ng/ml based on the Minto pharmacokinetic model until the trachea was intubated. With the initiation of remifentanil infusion, 1 mg/kg of rocuronium was administered following the calibration of the neuromuscular monitoring device. With the train-of-four count of 0, the trachea was intubated. Then, the effect-site concentration of remifentanil was decreased to 0 ng/ml until the surgical incision was made.

Primary outcomes

  1. Difference in low-to-high frequency power ratio (LF/HF) of heart rate variability (HRV) between 5-minute-pre-anesthesia and 5-minute-post-anesthesia induction

    Time frame: Between 5 minutes before and after anesthesia induction

    Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

Secondary outcomes

  1. Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Low-frequency power (LF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.04 and 0.15 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF represents the combined sympathetic and parasympathetic modulation of heart rate via baroreceptor reflexes, but is mainly modulated by sympathetic nervous activity.

  2. Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    Low-frequency power (LF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.04 and 0.15 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF represents the combined sympathetic and parasympathetic modulation of heart rate via baroreceptor reflexes, but is mainly modulated by sympathetic nervous activity.

  3. Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Low-frequency power (LF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.04 and 0.15 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF represents the combined sympathetic and parasympathetic modulation of heart rate via baroreceptor reflexes, but is mainly modulated by sympathetic nervous activity.

  4. Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Low-frequency power (LF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.04 and 0.15 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF represents the combined sympathetic and parasympathetic modulation of heart rate via baroreceptor reflexes, but is mainly modulated by sympathetic nervous activity.

  5. High-frequency power (HF) of heart rate variability (HRV) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    High-frequency power (HF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.15 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. HF represents the parasympathetic modulation of heart rate in response to respiration.

  6. High-frequency power (HF) of heart rate variability (HRV) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    High-frequency power (HF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.15 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. HF represents the parasympathetic modulation of heart rate in response to respiration.

  7. High-frequency power (HF) of heart rate variability (HRV) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    High-frequency power (HF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.15 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. HF represents the parasympathetic modulation of heart rate in response to respiration.

  8. High-frequency power (HF) of heart rate variability (HRV) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    High-frequency power (HF) of heart rate variability (HRV) were calculated by integrating power spectra between 0.15 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. HF represents the parasympathetic modulation of heart rate in response to respiration.

  9. Total power (TP) of heart rate variability (HRV) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Total power (TP) of heart rate variability (HRV) were calculated by integrating power spectra between 0 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. TP represents the overall activity of the autonomic nervous system.

  10. Total power (TP) of heart rate variability (HRV) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    Total power (TP) of heart rate variability (HRV) were calculated by integrating power spectra between 0 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. TP represents the overall activity of the autonomic nervous system.

  11. Total power (TP) of heart rate variability (HRV) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Total power (TP) of heart rate variability (HRV) were calculated by integrating power spectra between 0 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. TP represents the overall activity of the autonomic nervous system.

  12. Total power (TP) of heart rate variability (HRV) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Total power (TP) of heart rate variability (HRV) were calculated by integrating power spectra between 0 and 0.4 Hz, which were obtained from the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. TP represents the overall activity of the autonomic nervous system.

  13. Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

  14. Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

  15. Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

  16. Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

  17. Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  18. Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  19. Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  20. Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  21. Standard deviation of the RR intervals of normal sinus beats originating from the sinoatrial node of the right atrium (SDNN) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  22. Standard deviation of the RR intervals of normal sinus beats originating from the sinoatrial node of the right atrium (SDNN) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  23. Standard deviation of the RR intervals of normal sinus beats originating from the sinoatrial node of the right atrium (SDNN) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  24. Standard deviation of the RR intervals of normal sinus beats originating from the sinoatrial node of the right atrium (SDNN) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  25. The percentage of adjacent normal-to-normal sinus beat RR intervals that have a more than 50 milliseconds difference between them (pNN50) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  26. The percentage of adjacent normal-to-normal sinus beat RR intervals that have a more than 50 milliseconds difference between them (pNN50) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  27. The percentage of adjacent normal-to-normal sinus beat RR intervals that have a more than 50 milliseconds difference between them (pNN50) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  28. The percentage of adjacent normal-to-normal sinus beat RR intervals that have a more than 50 milliseconds difference between them (pNN50) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.

  29. Standard deviation 1 (SD1) of a Poincaré plot during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD1 is calculated as the standard deviation of the distance of each point from the line of identity (y=x). SD1 reflects the short-term HRV as the length of the transverse axis of the ellipse. SD1 correlates with the baroreflex sensitivity and HF.

  30. Standard deviation 1 (SD1) of a Poincaré plot during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD1 is calculated as the standard deviation of the distance of each point from the line of identity (y=x). SD1 reflects the short-term HRV as the length of the transverse axis of the ellipse. SD1 correlates with the baroreflex sensitivity and HF.

  31. Standard deviation 1 (SD1) of a Poincaré plot during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD1 is calculated as the standard deviation of the distance of each point from the line of identity (y=x). SD1 reflects the short-term HRV as the length of the transverse axis of the ellipse. SD1 correlates with the baroreflex sensitivity and HF.

  32. Standard deviation 1 (SD1) of a Poincaré plot during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD1 is calculated as the standard deviation of the distance of each point from the line of identity (y=x). SD1 reflects the short-term HRV as the length of the transverse axis of the ellipse. SD1 correlates with the baroreflex sensitivity and HF.

  33. Standard deviation 2 (SD2) of a Poincaré plot during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD2 is calculated as the standard deviation of the distance of each point from the line passing through the centroid, which vertically intersects the line of identity (y=x). SD2 reflects the long-term HRV as the length of the long axis of the ellipse. SD2 correlates with the baroreflex sensitivity and LF.

  34. Standard deviation 2 (SD2) of a Poincaré plot during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD2 is calculated as the standard deviation of the distance of each point from the line passing through the centroid, which vertically intersects the line of identity (y=x). SD2 reflects the long-term HRV as the length of the long axis of the ellipse. SD2 correlates with the baroreflex sensitivity and LF.

  35. Standard deviation 2 (SD2) of a Poincaré plot during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD2 is calculated as the standard deviation of the distance of each point from the line passing through the centroid, which vertically intersects the line of identity (y=x). SD2 reflects the long-term HRV as the length of the long axis of the ellipse. SD2 correlates with the baroreflex sensitivity and LF.

  36. Standard deviation 2 (SD2) of a Poincaré plot during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    A Poincaré plot is a scatter plot where each pair of preceding and succeeding RR intervals is plotted on the abscissa and ordinate, respectively. After fitting the ellipse around the plot, SD2 is calculated as the standard deviation of the distance of each point from the line passing through the centroid, which vertically intersects the line of identity (y=x). SD2 reflects the long-term HRV as the length of the long axis of the ellipse. SD2 correlates with the baroreflex sensitivity and LF.

  37. Mean arterial blood pressure during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Measured at any time during 5 minutes before anesthesia induction

  38. Mean arterial blood pressure during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    Mean arterial blood pressure corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction

  39. Mean arterial blood pressure during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Measured at any time during 5 minutes after endotracheal intubation

  40. Mean arterial blood pressure during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Measured at any time during 5 minutes before surgical incision

  41. Systolic blood pressure during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Measured at any time during 5 minutes before anesthesia induction

  42. Systolic blood pressure during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    The lowest systolic blood pressure during 5 minutes after anesthesia induction

  43. Systolic blood pressure during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Measured at any time during 5 minutes after endotracheal intubation

  44. Systolic blood pressure during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Measured at any time during 5 minutes before surgical incision

  45. Bispectral index (BIS) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    The BIS value corresponding to blood pressure measured during 5 minutes before anesthesia induction

  46. Bispectral index (BIS) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    The BIS value corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction

  47. Bispectral index (BIS) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after anesthesia induction

    The BIS value corresponding to blood pressure measured during 5 minutes after endotracheal intubation

  48. Bispectral index (BIS) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    The BIS value corresponding to blood pressure measured during 5 minutes before surgical incision

Other outcomes

  1. Deceleration capacity (DC) during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    The quasi-periodic decelerations in short-term heart rate are calculated using a phase-rectified signal averaging technique. The calculated deceleration (deceleration capacity: DC) represents parasympathetic nervous activity.

  2. Deceleration capacity (DC) during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    The quasi-periodic decelerations in short-term heart rate are calculated using a phase-rectified signal averaging technique. The calculated deceleration (deceleration capacity: DC) represents parasympathetic nervous activity.

  3. Deceleration capacity (DC) during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    The quasi-periodic decelerations in short-term heart rate are calculated using a phase-rectified signal averaging technique. The calculated deceleration (deceleration capacity: DC) represents parasympathetic nervous activity.

  4. Deceleration capacity (DC) during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    The quasi-periodic decelerations in short-term heart rate are calculated using a phase-rectified signal averaging technique. The calculated deceleration (deceleration capacity: DC) represents parasympathetic nervous activity.

  5. Diastolic blood pressure during 5 minutes before anesthesia induction

    Time frame: 5 minutes before anesthesia induction

    Measured at any time during 5 minutes before anesthesia induction

  6. Diastolic blood pressure during 5 minutes after anesthesia induction

    Time frame: 5 minutes after anesthesia induction

    Diastolic blood pressure corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction

  7. Diastolic blood pressure during 5 minutes after endotracheal intubation

    Time frame: 5 minutes after endotracheal intubation

    Measured at any time during 5 minutes after endotracheal intubation

  8. Diastolic blood pressure during 5 minutes before surgical incision

    Time frame: 5 minutes before surgical incision

    Measured at any time during 5 minutes before surgical incision

Sponsors and collaborators

Lead sponsor

Daegu Catholic University Medical Center

Other

Collaborators

  • Hana Pharm Co., Ltd.

Registry information

Official study title

Effects of Changes in Autonomic Nervous Activity on Changes in Blood Pressure After Anesthesia Induction: Remimazolam Versus Propofol

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Dec 2, 2022
Registry last updated
Oct 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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