Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT03921164 |
Other study ID # |
APHP180410 |
Secondary ID |
2018-A02737-48 |
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
January 27, 2021 |
Est. completion date |
July 2023 |
Study information
Verified date |
February 2021 |
Source |
Assistance Publique - Hôpitaux de Paris |
Contact |
Joaquim MATEO, MD |
Phone |
+33 1 49 95 83 74 |
Email |
joaquim.mateo[@]aphp.fr |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
In patients under general anesthesia, the prevention of intraoperative hypotension to
maintain blood pressure (BP) close to the initial blood pressure, i.e. before anesthesia, is
essential to reduce the risk of death and improve surgical outcomes. Vasoactive agents are
commonly used to correct this hypotension (Phenylephrine Ephedrine Noradrenaline). These
three vasoconstrictors have specific effects on the afterload of the heart and can impair its
function. The analysis of the left ventricular pressure-volume curve (PV Loop) allows
continuous information on the post-charge state of the left ventricle and the changes induced
by the vasoconstrictors to be observed. However, the investigators currently have no way of
monitoring these effects. In clinical practice if these loops are obtained non-invasively
they can be used in the evaluation of cardiac function of at-risk patients in perioperative
and also in intensive care to allow therapeutic adaptation.
Description:
Investigators have conducted several studies on the differential effects of different
vasopressors used in general anesthesia to correct sympatholysis-induced hypotension
occurring under anesthetic drugs and after eliminating hypovolemia or overdose in
anesthetics.
In a pilot study investigators described a method for analyzing Velocity-Pressure
interactions to monitor ventricular afterload in the operating room with the construction of
Velocity-Pressure aortic loops (VP Loop).
These loops were constructed from an aortic velocity signal measured by esophageal Doppler
and aortic blood pressure signal from a femoral catheter. The Global Afterload Angle (GALA)
measured on the loop were then higher in patients at cardiovascular risk (RCV+) at 68 ± 6°
compared to 41 ± 15° in patients (RCV-) (p<0.001). In addition, GALA variations were
associated with variations in the three components of ventricular afterload: compliance,
resistance and waves reflection. Finally, under the effect of vasopressors, there was a
modification in the shape of the VP Loop and the value of GALA, showing GALA as a reliable
marker potential for ventricular afterload in patients under general anesthesia.
In order to develop a totally non-invasive method that would produce a pressure velocity
curve, the investigators propose to combine an estimation of aortic pressure by a tonometry
method and an estimation of ventricular volumes by three-dimensional echocardiography.
The main objective of this study is then to compare VP Loop parameters obtained
non-invasively to VP loop obtained invasively according to patient cardiovascular risk
factors.
Cardiac afterload can be schematically defined by the combination of three components:
peripheral vascular resistance (PVR), total arterial compliance (Ctot) and aortic wave
reflections (WR). WR could be assessed by pulse wave pressure analysis with the augmentation
index (Aix) or after pulse wave pressure separation into a forward and backward wave with the
wave reflection index (WRi) or the wave reflection area (WRa).
Invasive Aortic pressure measurements: As required by the standard of care of the
interventional neuroradiology procedure, the neuroradiologist also cannulated the femoral
artery. At the end of the procedure, during catheter withdrawal, pressure waveforms are
recorded in the descending thoracic aorta just in front of the esophageal Doppler probe.
Descending aortic velocity is measured with a transesophageal Doppler CardioQ-ODM+ monitor
(Deltex Medical, Chichester, UK) in order to construct the VP Loop in descending thoracic
aorta.
Non-invasive Non-invasive Aortic velocity recording VP Loop in aorta is measured in the
flushing chamber of the left ventricle from the apical five chamber view by trans-thoracic
echocardiography (TTE) (Philips, EPIQ 7).
Estimation of ventricular diastolic pressure by measuring mitral and aortic flow gradients by
echocardiography (EPIQ G7 Philips© or similar) Determination of left ventricular volumes
during the cardiac cycle by echocardiography (3D EPIQ G7 Philips© or similar).
Non-invasive central pressure measurement by an arterial tonometer reconstructing the central
aortic curve (ShygmoCor, AtCor©) The SphygmoCor radial tonometer (AtCor Medical, Pty Ltd,
Sydney, Australia) is the most widely used tonometer in clinical research for non-invasive
central pressure measurement and pulse wave analysis. The central blood pressure is then
estimated using a validated radial-aortic transfer function.
The tonometer requires prior calibration by mean (MAP) and diastolic (PAD) blood pressure
measured with the conventional brachial cuff as validated in the literature.
VP Loop construction Digitalization of pressure and velocity signals are performed with the
IntelliVue MP60 monitor (Philips, Eindhoven, The Netherlands) at a sampling frequency of 125
Hz and saved using ixTrend software (IXELLENCE, Wildau, Germany) on a computer. Briefly, the
velocity coordinates is plotted on the x axis and the pressure coordinates on the y axis. The
investigators characterize the VP Loop by 4 points (A, B, C, D), allowing us to identify 3
angles: Alpha, Beta and GALA.
The goal of this study is to compare these parameters of cardiac after load obtained
non-invasively with the same parameters invasively obtained.
Experimental design: This is a single-center, interventional, category II prospective study
(minimal risks and constraints)
Population concerned: Patients will be included if their perioperative risk required a
continuous monitoring of mean arterial pressure (MAP) and cardiac output (CO). The study
involves major patients under general anesthesia in interventional neuroradiology.
Research Proceedings For all patients, data from trans-esophageal Doppler, trans-thoracic
echocardiography (TTE) and hemodynamic data are collected at the end of the procedure. During
catheter withdrawal, pressure waveforms are recorded in the descending thoracic aorta just in
front of the esophageal Doppler probe. All data from monitoring are connected to the main
monitor.
Individual benefit: There is no benefit for the patient
Collective benefit: Targeting mean arterial pressure (MAP) with boluses of selective
peripheral vasopressors (without positive inotropic or chronotropic effects) could have
deleterious effects on cardiac output. Thus, it seems important to use a combined analysis of
MAP and CO with low invasive methods to estimate the Afterload-related cardiac performance
(ACP) in surgical patients considered with "high cardiovascular risk".
Risks and minimal constraints added by the research:
No added risk. Patients are included if their perioperative risk required a continuous
monitoring of MAP and CO. The standard of care for the interventional neuroradiology
procedure needs a catheterization of the femoral artery using the Seldinger technique and
insertion of a catheter. All the other ones measures are obtained non-invasively. Patients
are assigned to one of two groups according to their risk of increased arterial stiffness as
reported in cardiological publications. The criteria investigators used are as follows: age >
50 years old as a major criterion 20 and cardio-vascular risk factors (history of congestive
heart failure, history of cardiovascular event, current smoking, diabetes mellitus,
dyslipidemia, and arterial hypertension) as minor criteria. Patients were classified into the
high risk group (Hi-risk) if they had at least one major criterion or two minor criteria or
into the low risk group (Lo-risk) if they presented with no or one minor criterion. During
their interventional neuroradiology procedure, all patients' routine monitoring will consist
of electrocardiogram, pulsated oxygen saturation, endtidal carbon dioxide (CO2), respiratory
rate, tidal volume and monitoring of neuromuscular function.
For all patients whatever the comorbidities, anesthesia induction will be performed using a
target-controlled infusion (Orchestra® Base Primea Fresenius Kabi France). According to our
standard of care, intra-operative episodes of hypotension (mean arterial pressure (MAP) < 65
mmHg or < 80% baseline) are treated by Norepinephrine bolus of 10 µg. For all patients, data
from trans-esophageal Doppler, trans-thoracic echocardiography (TTE) and hemodynamic data are
collected at the end of the procedure.
Number of selected subjects Selection of patients up to 55 analyzable patients Number of
centers: 1 Research center Agenda inclusion period: 12 months duration of participation
(treatment + follow-up): duration of the interventional neuroradiology procedure: 1 day Total
duration: 12 months Number of planned inclusions by center and month: 2-3 Number of subjects
required: 55
Statistics: Continuous data are expressed in median [interquartile] and qualitative data in n
(%). The risk α has been set at 5%. The categorical variables will be compared by
Mann-Whitney test and the continuous variables by Wilcoxon test.
The concordance between the two methods will be evaluated by the intra-class correlation
coefficient as well as by the Bland-Altman representation (with determination of bias and
approval limits) for the various parameters of interest.
Selection of patients until 55 analyzable patients is obtained (signal quality obtained and
possible analysis). The estimate of the number of subjects to be included is based on the
main evaluation criterion, the intra-class correlation coefficient. Thus, to highlight, an
intra-class correlation coefficient of 0.9 with a confidence interval of 0.1, for an alpha
risk of 5%, it is necessary to include 56 patients.