Ignite Creation Date:
2024-05-06 @ 6:51 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05803876
Status:
RECRUITING
Last Update Posted:
2023-12-15
First Post:
2023-03-16
Brief Title:
Cerebral Perfusion Variation During Blood Pressure Changes Under General Anesthesia
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Cerebral Perfusion Variation During Blood Pressure Changes Under General Anesthesia Relationship Between Transcranial Doppler Frontal EEG and Cerebral Oximetry a Prospective Observational Study
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DELTAPAMAG
Brief Summary:
The risk associated with arterial hypotension during general anesthesia for surgery has been demonstrated but the threshold at which consequences for perfusion of one or more organs appear varies according to the mechanism of hypotension associated abnormalities HR cardiac output and oxygen transport and the patients terrain
Currently a mean arterial pressure greater than 60 mm Hg and a reduction of less than 30-50 from the value measured before general anesthesia are commonly used treatment thresholds to ensure good perfusion of all organs
Normally cerebral blood flow is auto-regulated which allows cerebral blood flow to adapt to oxygen requirements and to different levels of blood pressure both high and low However this protective mechanism may fail for a degree of hypotension that depends on several factors such as the age or vascular status of the patient
The aim of the study is to measure non-invasively easily and reliably the variations of cerebral perfusion in patients with and without cardiovascular risk factors during controlled variations performed during routine care to set the blood pressure level within the recommended safety standards during general anesthesia
What is the target level of blood pressure tolerable for a patient under general anesthesia Is there a simple and non-invasive way to measure the level of cerebral blood flow autoregulation and especially its adequacy to the brains oxygen needs
Currently a mean arterial pressure greater than 60 mm Hg and a reduction of less than 30-50 from the value measured before general anesthesia are commonly used treatment thresholds to ensure good perfusion of all organs
Normally cerebral blood flow is auto-regulated which allows cerebral blood flow to adapt to oxygen requirements and to different levels of blood pressure both high and low However this protective mechanism may fail for a degree of hypotension that depends on several factors such as the age or vascular status of the patient
The aim of the study is to measure non-invasively easily and reliably the variations of cerebral perfusion in patients with and without cardiovascular risk factors during controlled variations performed during routine care to set the blood pressure level within the recommended safety standards during general anesthesia
What is the target level of blood pressure tolerable for a patient under general anesthesia Is there a simple and non-invasive way to measure the level of cerebral blood flow autoregulation and especially its adequacy to the brains oxygen needs
Detailed Description:
The risk associated with arterial hypotension during general anesthesia for surgery or interventional procedure has been demonstrated but the threshold at which consequences for perfusion of one or more organs appear varies according to the mechanism of hypotension associated abnormalities Heart rate cardiac output and oxygen transport and the patients terrain
Currently a mean arterial pressure greater than 60 mm Hg and a reduction of less than 30-50 from the value measured before general anesthesia are commonly used treatment thresholds to ensure good perfusion of all organs
These values are based on large cohort studies that associate these blood pressure thresholds with the occurrence of postoperative complications or during the resuscitation stay They cannot be generalized to certain subpopulations that are underrepresented such as women and elderly patients
Normally cerebral blood flow is self-regulated which allows cerebral blood flow to adapt to oxygen requirements and to different levels of high and low blood pressure
However this protective mechanism may fail for a degree of hypotension that depends on several factors such as the age or vascular health of the patient For example in patients with preexisting hypertension the autoregulatory capacity of the brain is likely impaired making organs more susceptible to ischemia at low blood pressure
Thus current American College of Cardiology and American Heart Association guidelines in the setting of noncardiac surgery recommend individualizing care for patients with associated cardiovascular comorbidities Arterial stiffness is currently one of the best independent early biomarkers predictive of cardiovascular complications and cardiovascular comorbidity Assessment of arterial stiffness is currently performed by pulse wave velocity PWV measurement Therefore higher blood pressure goals tailored to the physiology of each patient may be preferable for these high-risk patients
Because there is individual variability in cerebral autoregulation a strategy based on a one-size-fits-all recommended blood pressure BP value is nonsense
What is the tolerable target BP level for a patient under general anesthesia Is there a simple and non-invasive way to measure the level of cerebral blood flow autoregulation and more importantly adequacy to the brains oxygen requirements
The aim of the study is to measure non-invasively easily and reliably the variations of cerebral perfusion in patients with or without cardiovascular risk factors during controlled variations performed during routine care to adjust the blood pressure level within the recommended safety standards during general anesthesia The setting of the optimal mean arterial pressure MAP level will be achieved within the ranges of values commonly used taking into account the patients cardiovascular comorbidities In particular the lower limit of MAP of 60 mmHg for patients without cardiovascular risk factors and 80 mmHg for patients with risk factors should never be exceeded in accordance with current French and international recommendations The main objective is to identify a significant linear relationship between the percentage change in mean velocity Vm and the percentage change in the 95 spectral frequency front SEF95 during the MAP change
Cerebral perfusion and cerebral O2 adequacy will be compared and assessed by continuous and simultaneous measurements of cerebral blood flow by transcranial Doppler TCD and cerebral O2 adequacy by near-infrared spectroscopy NIRS and a brain function parameter by intraoperative electroencephalogram EEG - frontal EEG
The classification of patients in the cardiovascular risk group will be determined in addition to their history and treatment by an arterial stiffness parameter pulse wave velocity measured non-invasively before and during the protocol by MESI mTablet automatic digital sphygmomanometer MESI ltd Slovenia
The objective for a given patient is to look for a possible threshold value of pressure that could impact the blood flow velocity Doppler and possibly the EEG and cerebral oximetry
This clinical research work is performed on adult patients undergoing scheduled surgery at Lariboisière Hospital under general anaesthesia
All measurements are obtained non-invasively The monitoring routinely includes continuous electrocardiogram and blood pressure monitoring by non-invasive means Clearsight EV1000 Edwards Sciences in anesthesia pulsed O2 saturation SpO2 ventilatory parameters FR VC FiO2 and anesthesia depth by frontal EEG
Patients over 18 years of age are eligible to participate in this protocol During the anaesthesia consultation they will be given an information letter on the objectives and the course of the study Their non-objection to participate in this study will be collected at the latest during the pre-anesthetic visit the day before the operation after a period of reflection The protocol starts on the day of the operation
For all patients the surgical procedures will be performed under general anesthesia with an intravenous anesthesia protocol with a concentration target Orchestra Base Primea - Fresenius Kabi France and a vasopressor support by norepinephrine diluted to 5 microgmL Blood pressure variations will be performed as follows
In current practice of investigators
anesthetic induction is performed under vasopressors norepinephrine diluted to 5 µgmL with the objective of maintaining a MAP 90 of the value measured during the anesthesia consultation
when blood pressure stability is obtained the dose of norepinephrine is gradually decreased to a MAP target 70 of the baseline value without ever falling below 60 mmHg for patients without low cardiovascular risk factors and 80 mmHg for patients with cardiovascular risk factors
At this stage the data to establish the autoregulatory threshold are not yet analyzed and are not available to adjust the mean arterial pressure level
The change in cerebral blood flow will then be compared with the change in mean arterial pressure dPAM to obtain the slope of the change in mean velocity dVm of the blood in the middle cerebral artery obtained by transcranial Doppler dVmdPAM in percentage In case of a positive correlation between these two parameters cerebral autoregulation will be considered as impaired and in case of no correlation it will be considered as preserved
On the day of the intervention a routine monitoring of the depth of anesthesia from the quantitative frontal EEG Sedline Masimo ensures a continuous recording of the intraoperative EEG data Placement of a frontal O3 Sensor rSO2 Masimo or Foresight sensor rSO2 Edwards electrode for continuous measurement of cerebral tissue O2 saturation StO2 Continuous measurement of blood velocity in the middle cerebral artery by transcranial pulsed Doppler TCD Atys Medical TCD-X The probe attachment system on the patients head is similar to a pair of glasses it is light and comfortable The orientation of the robotic probe is automatically readjusted to ensure stable recording quality over time
Patients over 18 years old are eligible to participate in this protocol
No additional examinations will be performed The physician in charge of the study collecting the data is not involved in the patients management at any time
The monitoring data are currently available and are made available in the clinical research unit of department thanks to
A data extraction system from the PHILIPS IntelliVue monitoring solutions The Data Warehouse Connect software solution allows the collection of all these data with a fine sampling 2ms for the tracings 1s for the numerical data which considerably widens the capacities in terms of data analysis and exploitation
The retrieval system is temporally coupled to the patients events medications doses administered through an IntelliSpace Critical Care and Anesthesia ICCAA information system that is operational in all operating rooms The clinical information system is linked to all medical devices and is fed by nurses to record events and the administration of medications and solutions Thus the data provided are coupled with the digital traces and measurements of the multiparametric monitor transmitted in HL7 to the server of the hospitals IT department
The implementation of the intraoperative frontal EEG monitoring performed routinely in this type of operation does not prolong the duration of the anesthesia The placement and adjustments of the O3 or Foresight electrode and the transcranial Doppler probe takes only 5 to 10 minutes
The physician in charge of the study collecting the data does not participate at any time in the management of the patient The measures cannot influence the prescribing physician since at this stage the data are not yet analyzed and available
The main objective is to identify a significant linear relationship between the percentage change in Vm and the percentage change in the 95 spectral frequency front SEF95 during the MAP change
The objective is to reject the null hypothesis based on the R2 measure of goodness of fit H0 R2 0
Considering a type I error probability 005 and a power of 85 and an effect size of 03 based on preliminary data For a single predictor the physician obtain a sample size of n 32 patients To adjust for possible confounding factors the physician assume a partial correlation coefficient rho05 between Vm and the covariates This correction gives us a sample size of 322 64 patients 11 Finally preliminary data indicate that 30 of the included patients have a poor signal or defective measurements resulting from artifacts or unsuitable experimental conditions The final number of patients to be included is estimated at N 100
Rejection of the primary null hypothesis will be established by a linear regression model
As a secondary objective linear regression will also be evaluated between Vm and EEG markers such as alpha band power time spent in burst-suppression and delta-to-alpha ratio
Descriptive statistics will be reported as n for categorical variables meanstandard deviation for continuous variables and medianIQR for ordinal variables that do not have a normal distribution
All statistical analyses will be performed using R statistical software The R Foundation for Statistical Computing Vienna Austria Results will be expressed as means standard deviation A p-value of less than 005 is considered significant
Currently a mean arterial pressure greater than 60 mm Hg and a reduction of less than 30-50 from the value measured before general anesthesia are commonly used treatment thresholds to ensure good perfusion of all organs
These values are based on large cohort studies that associate these blood pressure thresholds with the occurrence of postoperative complications or during the resuscitation stay They cannot be generalized to certain subpopulations that are underrepresented such as women and elderly patients
Normally cerebral blood flow is self-regulated which allows cerebral blood flow to adapt to oxygen requirements and to different levels of high and low blood pressure
However this protective mechanism may fail for a degree of hypotension that depends on several factors such as the age or vascular health of the patient For example in patients with preexisting hypertension the autoregulatory capacity of the brain is likely impaired making organs more susceptible to ischemia at low blood pressure
Thus current American College of Cardiology and American Heart Association guidelines in the setting of noncardiac surgery recommend individualizing care for patients with associated cardiovascular comorbidities Arterial stiffness is currently one of the best independent early biomarkers predictive of cardiovascular complications and cardiovascular comorbidity Assessment of arterial stiffness is currently performed by pulse wave velocity PWV measurement Therefore higher blood pressure goals tailored to the physiology of each patient may be preferable for these high-risk patients
Because there is individual variability in cerebral autoregulation a strategy based on a one-size-fits-all recommended blood pressure BP value is nonsense
What is the tolerable target BP level for a patient under general anesthesia Is there a simple and non-invasive way to measure the level of cerebral blood flow autoregulation and more importantly adequacy to the brains oxygen requirements
The aim of the study is to measure non-invasively easily and reliably the variations of cerebral perfusion in patients with or without cardiovascular risk factors during controlled variations performed during routine care to adjust the blood pressure level within the recommended safety standards during general anesthesia The setting of the optimal mean arterial pressure MAP level will be achieved within the ranges of values commonly used taking into account the patients cardiovascular comorbidities In particular the lower limit of MAP of 60 mmHg for patients without cardiovascular risk factors and 80 mmHg for patients with risk factors should never be exceeded in accordance with current French and international recommendations The main objective is to identify a significant linear relationship between the percentage change in mean velocity Vm and the percentage change in the 95 spectral frequency front SEF95 during the MAP change
Cerebral perfusion and cerebral O2 adequacy will be compared and assessed by continuous and simultaneous measurements of cerebral blood flow by transcranial Doppler TCD and cerebral O2 adequacy by near-infrared spectroscopy NIRS and a brain function parameter by intraoperative electroencephalogram EEG - frontal EEG
The classification of patients in the cardiovascular risk group will be determined in addition to their history and treatment by an arterial stiffness parameter pulse wave velocity measured non-invasively before and during the protocol by MESI mTablet automatic digital sphygmomanometer MESI ltd Slovenia
The objective for a given patient is to look for a possible threshold value of pressure that could impact the blood flow velocity Doppler and possibly the EEG and cerebral oximetry
This clinical research work is performed on adult patients undergoing scheduled surgery at Lariboisière Hospital under general anaesthesia
All measurements are obtained non-invasively The monitoring routinely includes continuous electrocardiogram and blood pressure monitoring by non-invasive means Clearsight EV1000 Edwards Sciences in anesthesia pulsed O2 saturation SpO2 ventilatory parameters FR VC FiO2 and anesthesia depth by frontal EEG
Patients over 18 years of age are eligible to participate in this protocol During the anaesthesia consultation they will be given an information letter on the objectives and the course of the study Their non-objection to participate in this study will be collected at the latest during the pre-anesthetic visit the day before the operation after a period of reflection The protocol starts on the day of the operation
For all patients the surgical procedures will be performed under general anesthesia with an intravenous anesthesia protocol with a concentration target Orchestra Base Primea - Fresenius Kabi France and a vasopressor support by norepinephrine diluted to 5 microgmL Blood pressure variations will be performed as follows
In current practice of investigators
anesthetic induction is performed under vasopressors norepinephrine diluted to 5 µgmL with the objective of maintaining a MAP 90 of the value measured during the anesthesia consultation
when blood pressure stability is obtained the dose of norepinephrine is gradually decreased to a MAP target 70 of the baseline value without ever falling below 60 mmHg for patients without low cardiovascular risk factors and 80 mmHg for patients with cardiovascular risk factors
At this stage the data to establish the autoregulatory threshold are not yet analyzed and are not available to adjust the mean arterial pressure level
The change in cerebral blood flow will then be compared with the change in mean arterial pressure dPAM to obtain the slope of the change in mean velocity dVm of the blood in the middle cerebral artery obtained by transcranial Doppler dVmdPAM in percentage In case of a positive correlation between these two parameters cerebral autoregulation will be considered as impaired and in case of no correlation it will be considered as preserved
On the day of the intervention a routine monitoring of the depth of anesthesia from the quantitative frontal EEG Sedline Masimo ensures a continuous recording of the intraoperative EEG data Placement of a frontal O3 Sensor rSO2 Masimo or Foresight sensor rSO2 Edwards electrode for continuous measurement of cerebral tissue O2 saturation StO2 Continuous measurement of blood velocity in the middle cerebral artery by transcranial pulsed Doppler TCD Atys Medical TCD-X The probe attachment system on the patients head is similar to a pair of glasses it is light and comfortable The orientation of the robotic probe is automatically readjusted to ensure stable recording quality over time
Patients over 18 years old are eligible to participate in this protocol
No additional examinations will be performed The physician in charge of the study collecting the data is not involved in the patients management at any time
The monitoring data are currently available and are made available in the clinical research unit of department thanks to
A data extraction system from the PHILIPS IntelliVue monitoring solutions The Data Warehouse Connect software solution allows the collection of all these data with a fine sampling 2ms for the tracings 1s for the numerical data which considerably widens the capacities in terms of data analysis and exploitation
The retrieval system is temporally coupled to the patients events medications doses administered through an IntelliSpace Critical Care and Anesthesia ICCAA information system that is operational in all operating rooms The clinical information system is linked to all medical devices and is fed by nurses to record events and the administration of medications and solutions Thus the data provided are coupled with the digital traces and measurements of the multiparametric monitor transmitted in HL7 to the server of the hospitals IT department
The implementation of the intraoperative frontal EEG monitoring performed routinely in this type of operation does not prolong the duration of the anesthesia The placement and adjustments of the O3 or Foresight electrode and the transcranial Doppler probe takes only 5 to 10 minutes
The physician in charge of the study collecting the data does not participate at any time in the management of the patient The measures cannot influence the prescribing physician since at this stage the data are not yet analyzed and available
The main objective is to identify a significant linear relationship between the percentage change in Vm and the percentage change in the 95 spectral frequency front SEF95 during the MAP change
The objective is to reject the null hypothesis based on the R2 measure of goodness of fit H0 R2 0
Considering a type I error probability 005 and a power of 85 and an effect size of 03 based on preliminary data For a single predictor the physician obtain a sample size of n 32 patients To adjust for possible confounding factors the physician assume a partial correlation coefficient rho05 between Vm and the covariates This correction gives us a sample size of 322 64 patients 11 Finally preliminary data indicate that 30 of the included patients have a poor signal or defective measurements resulting from artifacts or unsuitable experimental conditions The final number of patients to be included is estimated at N 100
Rejection of the primary null hypothesis will be established by a linear regression model
As a secondary objective linear regression will also be evaluated between Vm and EEG markers such as alpha band power time spent in burst-suppression and delta-to-alpha ratio
Descriptive statistics will be reported as n for categorical variables meanstandard deviation for continuous variables and medianIQR for ordinal variables that do not have a normal distribution
All statistical analyses will be performed using R statistical software The R Foundation for Statistical Computing Vienna Austria Results will be expressed as means standard deviation A p-value of less than 005 is considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2022-A02647-36 | OTHER | IDRCB | None |