Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT05803876 |
Other study ID # |
APHP230072 |
Secondary ID |
2022-A02647-36 |
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
July 20, 2023 |
Est. completion date |
August 2025 |
Study information
Verified date |
December 2023 |
Source |
Assistance Publique - Hôpitaux de Paris |
Contact |
Joaquim MATEO, MD |
Phone |
+33 (0)149958374 |
Email |
joaquim.mateo[@]aphp.fr |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial 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 patient's 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 brain's oxygen needs?
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
patient's 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 brain's 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 patient's 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 microg/mL.
Blood pressure variations will be performed as follows:
In current practice of investigators :
- anesthetic induction is performed under vasopressors (norepinephrine diluted to 5 µg/mL)
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 (dVm/dPAM 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 patient's 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 patient's 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 patient's 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 hospital's 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 = 0.05 and a power of 85%, and an effect size of 0.3
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 rho=0.5 between Vm and the covariates. This correction gives us a
sample size of 32*2 = 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, mean(standard
deviation) for continuous variables, and median[IQR] 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 0.05 is considered significant.