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

General Anesthetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05635201
• Other study ID #: CR-22-138
• Status: Completed
• Phase: Phase 3
• Start date: December 19, 2022
• Est. completion date: September 30, 2023

Study information

• Verified date: October 2023
• Source: Daegu Catholic University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• General Anesthetics

Intervention

Drug:
• Anesthesia induction with propofol
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
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.

Locations

Country	Name	City	State
Korea, Republic of	Daegu Catholic University Medical Center	Daegu

Sponsors (2)

Lead Sponsor	Collaborator
Daegu Catholic University Medical Center	Hana Pharm Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Deceleration capacity (DC) during 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.	5 minutes before anesthesia induction
Other	Deceleration capacity (DC) during 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.	5 minutes after anesthesia induction
Other	Deceleration capacity (DC) during 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.	5 minutes after endotracheal intubation
Other	Deceleration capacity (DC) during 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 minutes before surgical incision
Other	Diastolic blood pressure during 5 minutes before anesthesia induction	Measured at any time during 5 minutes before anesthesia induction	5 minutes before anesthesia induction
Other	Diastolic blood pressure during 5 minutes after anesthesia induction	Diastolic blood pressure corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction	5 minutes after anesthesia induction
Other	Diastolic blood pressure during 5 minutes after endotracheal intubation	Measured at any time during 5 minutes after endotracheal intubation	5 minutes after endotracheal intubation
Other	Diastolic blood pressure during 5 minutes before surgical incision	Measured at any time during 5 minutes before surgical incision	5 minutes before surgical incision
Primary	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	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.	Between 5 minutes before and after anesthesia induction
Secondary	Low-frequency power (LF) of heart rate variability (HRV) during 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.	5 minutes before anesthesia induction
Secondary	Low-frequency power (LF) of heart rate variability (HRV) during 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.	5 minutes after anesthesia induction
Secondary	Low-frequency power (LF) of heart rate variability (HRV) during 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.	5 minutes after endotracheal intubation
Secondary	Low-frequency power (LF) of heart rate variability (HRV) during 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 minutes before surgical incision
Secondary	High-frequency power (HF) of heart rate variability (HRV) during 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.	5 minutes before anesthesia induction
Secondary	High-frequency power (HF) of heart rate variability (HRV) during 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.	5 minutes after anesthesia induction
Secondary	High-frequency power (HF) of heart rate variability (HRV) during 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.	5 minutes after endotracheal intubation
Secondary	High-frequency power (HF) of heart rate variability (HRV) during 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.	5 minutes before surgical incision
Secondary	Total power (TP) of heart rate variability (HRV) during 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.	5 minutes before anesthesia induction
Secondary	Total power (TP) of heart rate variability (HRV) during 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.	5 minutes after anesthesia induction
Secondary	Total power (TP) of heart rate variability (HRV) during 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.	5 minutes after endotracheal intubation
Secondary	Total power (TP) of heart rate variability (HRV) during 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.	5 minutes before surgical incision
Secondary	Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 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.	5 minutes before anesthesia induction
Secondary	Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 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.	5 minutes after anesthesia induction
Secondary	Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 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.	5 minutes after endotracheal intubation
Secondary	Low-to-high-frequency power ratio (LF/HF) of heart rate variability (HRV) during 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.	5 minutes before surgical incision
Secondary	Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes before anesthesia induction	RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before anesthesia induction
Secondary	Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes after anesthesia induction	RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after anesthesia induction
Secondary	Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes after endotracheal intubation	RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after endotracheal intubation
Secondary	Root mean square of the successive differences of the RR intervals (RMSSD) during 5 minutes before surgical incision	RMSSD represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before surgical incision
Secondary	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	SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before anesthesia induction
Secondary	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	SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after anesthesia induction
Secondary	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	SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after endotracheal intubation
Secondary	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	SDNN represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before surgical incision
Secondary	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	pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before anesthesia induction
Secondary	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	pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after anesthesia induction
Secondary	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	pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes after endotracheal intubation
Secondary	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	pNN50 represents the parasympathetic nervous activity mediated by a respiratory sinus arrhythmia.	5 minutes before surgical incision
Secondary	Standard deviation 1 (SD1) of a Poincaré plot during 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.	5 minutes before anesthesia induction
Secondary	Standard deviation 1 (SD1) of a Poincaré plot during 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.	5 minutes after anesthesia induction
Secondary	Standard deviation 1 (SD1) of a Poincaré plot during 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.	5 minutes after endotracheal intubation
Secondary	Standard deviation 1 (SD1) of a Poincaré plot during 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.	5 minutes before surgical incision
Secondary	Standard deviation 2 (SD2) of a Poincaré plot during 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.	5 minutes before anesthesia induction
Secondary	Standard deviation 2 (SD2) of a Poincaré plot during 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.	5 minutes after anesthesia induction
Secondary	Standard deviation 2 (SD2) of a Poincaré plot during 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.	5 minutes after endotracheal intubation
Secondary	Standard deviation 2 (SD2) of a Poincaré plot during 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.	5 minutes before surgical incision
Secondary	Mean arterial blood pressure during 5 minutes before anesthesia induction	Measured at any time during 5 minutes before anesthesia induction	5 minutes before anesthesia induction
Secondary	Mean arterial blood pressure during 5 minutes after anesthesia induction	Mean arterial blood pressure corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction	5 minutes after anesthesia induction
Secondary	Mean arterial blood pressure during 5 minutes after endotracheal intubation	Measured at any time during 5 minutes after endotracheal intubation	5 minutes after endotracheal intubation
Secondary	Mean arterial blood pressure during 5 minutes before surgical incision	Measured at any time during 5 minutes before surgical incision	5 minutes before surgical incision
Secondary	Systolic blood pressure during 5 minutes before anesthesia induction	Measured at any time during 5 minutes before anesthesia induction	5 minutes before anesthesia induction
Secondary	Systolic blood pressure during 5 minutes after anesthesia induction	The lowest systolic blood pressure during 5 minutes after anesthesia induction	5 minutes after anesthesia induction
Secondary	Systolic blood pressure during 5 minutes after endotracheal intubation	Measured at any time during 5 minutes after endotracheal intubation	5 minutes after endotracheal intubation
Secondary	Systolic blood pressure during 5 minutes before surgical incision	Measured at any time during 5 minutes before surgical incision	5 minutes before surgical incision
Secondary	Bispectral index (BIS) during 5 minutes before anesthesia induction	The BIS value corresponding to blood pressure measured during 5 minutes before anesthesia induction	5 minutes before anesthesia induction
Secondary	Bispectral index (BIS) during 5 minutes after anesthesia induction	The BIS value corresponding to the lowest systolic blood pressure during 5 minutes after anesthesia induction	5 minutes after anesthesia induction
Secondary	Bispectral index (BIS) during 5 minutes after endotracheal intubation	The BIS value corresponding to blood pressure measured during 5 minutes after endotracheal intubation	5 minutes after anesthesia induction
Secondary	Bispectral index (BIS) during 5 minutes before surgical incision	The BIS value corresponding to blood pressure measured during 5 minutes before surgical incision	5 minutes before surgical incision