- Academic Editors
Background: During cardiac surgery, maintaining a mean arterial
pressure (MAP) within the range of cerebral autoregulation (CA) may prevent
postoperative morbidity. The lower limit of cerebral autoregulation (LLA) can be
determined using the mean velocity index (Mx). The standard Mx is averaged over a
ten second period (Mx
Cerebral Autoregulation (CA) maintains a constant cerebral blood flow despite changes in blood pressure within an individualized range that is specific to each patient [1]. The mean arterial pressure (MAP) value at which cerebral blood flow (CBF) begins to decrease is called the Lower Limit of Autoregulation (LLA). During cardiopulmonary bypass (CPB) in the context of cardiac surgery, maintaining a MAP below the LLA is associated with an increased risk of postoperative morbidity [2, 3, 4, 5, 6]. The large interindividual variations in LLA make it necessary to use an individualized technique for the correct calculation of each patient’s LLA in order to define the “best” MAP, allowing for appropriate CBF [2].
Using continuous transcranial doppler to measure the CBF alongside an invasive arterial catheter to measure the MAP, the LLA can be determined by a continuous calculation of the correlation between cerebral blood flow velocity ( mean velocity of the mean cerebral artery (MV)) and MAP, also known as the mean velocity index (Mx) [2, 5, 7]. The Mx is a moving Pearson correlation coefficient and approaches the value of 1 when there is a high correlation between MAP and MV (outside of autoregulation) and approaches 0 when the MAP is on the plateau of autoregulation. In order to determine the LLA, a range of MAP values are required to obtain a correlated and uncorrelated relationship with the MV [8]. Classically, the LLA was mainly used within the neuro intensive care unit and was calculated using a large time window (at least five minutes to get the first value of Mx, with a new value each minute) [9]. This large averaging time has pros and cons. Extreme and/or aberrant values are less impactful and can be included in the final calculation. Conversely, if these extreme values are real, they will have a smaller effect on the calculated Mx. Additionally, a minimum of 15–20 minutes for the standard LLA calculation may be too long for cardiac surgery setting. Increasing the recording frequency of paired data (MAP and MV) may allow for a faster assessment of LLA and increase the integration of such values into clinical decisions [10].
The main objectives of our study were to demonstrate the clinical feasibility of a quick determination of LLA (qLLA) throughout a 15-minute period during CPB, and to compare this qLLA with the reference LLA (rLLA), which was calculated throughout the entire CPB period. Secondary objectives were to analyse the interindividual variability of qLLA and rLLA.
This was a prospective and observational study with retrospective analysis. Patients undergoing elective cardiac surgery with CPB and aortic clamping for whom transcranial doppler was used between January 2020 to April 2021 were included. This study protocol received the approval of the Institutional Review Board Ramsay Sante, reference number 00010835. All patients gave written informed consent, were verbally asked if they wanted to refuse data recording and received a letter that gave them the option to recuse themselves later. Patients with history of cerebrovascular disease or significant carotid artery stenosis (greater than 60%) were excluded.
Standard monitoring was used throughout the procedure, including EKG
(Philips® healthcare, Amsterdam, The Netherlands), pulse
oximetry, depth of anaesthesia monitoring (State/Response
Entropy®, GE Healthcare, Chicago, IL, USA), regional
cerebral oxygen saturation (INVOS, Medtronic®, Minneapolis,
MN, USA), invasive arterial pressure measurement (Seldicath,
Prodimed®, Paris, France), and temperature monitoring (Mon-a-Therm, Covidien, Mansfield, MA, USA).
Arterial blood pressure was recorded continuously using a radial artery catheter.
Anaesthesia and skeletal muscle relaxation were maintained during CPB with
propofol, remifentanil, and cisatracurium with the goal of maintaining the depth
of anaesthesia monitoring between 40–60. Non-pulsatile CPB
(Medtronic® AP 40 oxygenator fusion) was achieved with a
non-occlusive centrifugal pump (AP 40, Medtronic, Minneapolis, MN, USA) and patients were kept normothermic (
MV was continuously measured via transcranial Doppler (WAKIe®,
Atys medical, Soucieu-en-Jarrest, France) over the right or left middle cerebral
artery with a 2 MHz transducer probe at a depth between 40 and 70 mm. The probe
was held in place with a headband. This technology automatically scans all the
possible orientations and positions itself, with the subsequent positive flow
corresponding to the strongest signal that is manually validated. Additionally,
the orientation of the probe automatically readjusts when the signal quality
decrease. MV was calculated by the area under the doppler envelope signal. The
Doppler envelope is materialized by a white curve that follows the Doppler
signal. If the curve did not adequately follow the Doppler signal despite the
modifications of the gain, the power, and the width of the sample, the patient
was excluded from the analysis. The arterial pressure signal (MAP) was also
continuously recorded by the device. Recording frequency of the MV/MAP pair was 1
Hz. Cerebral autoregulation was calculated continuously using the
Optimap® software (version 1.3.1, Atys medical, Soucieu en Jarrest, France) present in the doppler device.
Optimap® calculates the correlation coefficient between MAP
and MV, termed the Mx. Mx determination requires 30 pairs
of MAP-MV which are continuously calculated by excluding the oldest of the 30
data pairs and including a new data pair as they are recorded. These new values
of Mx (Mxn, Mxn + 1, Mxn + 2) are calculated at a predefined frequency. To
calculate qLLA (using Mx average over 2 second period (Mx
Determination of qLLA and rLLA using Mx
The LLA’s were calculated after the surgery. The qLLA was calculated over a
period of 15 minutes during CPB and the rLLA was calculated throughout
the entire period of CPB. The 15 minutes period was individually chosen by each
observer (n = 2) to contain significant variations in MAP (
Examples of LLA indeterminations. (a) Alternating Mx
The distribution of continuous data was tested for normality using a
Shapiro-Wilk test. Normally distributed variables were compared using a student’s
t-test and expressed as mean
A Cohen’s kappa value of
117 patients were eligible while 55 patients were enrolled (Fig. 3). Patient’s
characteristics are shown in the Table 1. qLLA and rLLA were calculable in 78%
(n = 43) and 47% (n = 26) of the cases, respectively. Mx
Flow chart. Notes: qLLA, MAP threshold below the cerebral
autoregulation plateau calculated with Mx
Variables | Mean or median | |
---|---|---|
Age (years) | 67 ( | |
BMI (kg/cm |
25.6 ( | |
Ejection Fraction (%) | 61 (60–65) | |
Male/female gender | 73% (n = 40)/27% (n = 15) | |
Diabetes | 18% (n = 10) | |
Hypertension | 65% (n = 36) | |
Beta-blocker | 40% (n = 22) | |
Hemoglobin (g/dL) | 14.4 (13.2–15.1) | |
Creatinine (µmol/L) | 81 (70–90) | |
Euroscore II (%) | 1.1 (0.8–1.3) | |
CPB duration (min) | 66 (48–83) | |
Type of surgery | ||
Coronary artery bypass | 42% (n = 23) | |
Valvular replacement | 35% (n = 19) | |
Combined surgery | 11% (n = 6) | |
Ascending aorta | 13% (n = 7) | |
Aortic cross clamp duration (min) | 41 (31–62) | |
Average MAP (mmHg) during CPB | 64 ( | |
Mean CPB pump flow (L/min/m |
2.45 ( | |
SvO |
80 ( | |
PaCO |
48 (47–52) | |
Hemoglobin (g/dL) | 14.4 (13.2–15.1) | |
qLLA (mmHg) | 66 (61–71) | |
rLLA (mmHg) | 66 (66–71) | |
Minimal and maximal MAP used to calculate Mx |
40 (40–51)–80 (75–84) | |
Minimal and maximal MAP used to calculate Mx |
46 (40–51)–80 (70–89) |
Notes: Data are presented in mean (
Experimenters agreed on identical values of LLA in 48% of the cases for qLLA and in 73% of the cases for rLLA. Coefficient kappa was 0.36 (95% CI: 0.20–0.52), and 0.45 (95% CI: 0.24–0.66), for qLLA and rLLA, respectively (fair and moderate agreement). The dispersion for qLLA and rLLA ranged from 46 to 85 mmHg and 60 to 85 mmHg, respectively (Fig. 4).
Individualized qLLA (blue) and rLLA (orange) values. Notes:
qLLA, lower limit of autoregulation determined by the Mx
This feasibility study demonstrates that the calculation of cerebral autoregulation with transcranial doppler was possible in 78% of the cases using a quick assessment of LLA on 15 minutes recording compared to only 47% of the cases using the standard analysis on the total CPB recording. The Gaussian distribution of qLLA values (Fig. 4) similar to the distribution of rLLA values suggests that these values are physiological [2].
The large limits of agreement between qLLA and rLLA (
Of note, two studies determined the CA with the rLLA for a Mx value of 0.4, but they precised that rLLA was also chosen with the lowest Mx value when the value of 0.4 was not reached [12, 13]. Unfortunately, the authors did not precise the rate of these observations.
Compared to the current use of the longer sampling (Mx
There are a few potential reasons for our mitigate results. First, the software
automatically calculates the LLA according to a predefined period, a predefined
sampling of Mx and a predefined threshold value (0.4 for the Mx). As any
potential artifacts are incorporated into the Mx calculation, an observer needs
to “clean out” these specific periods to ensure appropriate values and then
choose individually the 15 minutes period for calculating qLLA. This could
explain the large interobserver variability, as mentioned before. Second, the
observational design of this study prevented from controlling numerous parameters
influencing cerebral autoregulation during cardiopulmonary bypass. We hypothesize
that the true individualized LLA is not constant throughout the perioperative
period, as the impact of PaCO
Moreover, as we did not deliberately change the MAP, ranges of MAP were
sometimes narrow which could explain why no threshold was obtained in 35% of the
cases for rLLA. Most of these cases presented indeed a Mx
This study has limitations. Firstly, there is a limited sample size, due in part to the high rate of unusable MV tracings. We were sometimes transiently faced with a poor Doppler signal despite the initial modifications of the gain, the filtering, and the power of the signal. Hence, the calculation of the mean velocity may have been partially incorrect because of an impropriate signal to noise ratio. Secondly, our institution has only recently started using perioperative transcranial doppler (TCD) technology. As our experience grows, the efficiency and accuracy of the recorded signals will likely improve. During cardiac surgery, an appropriate TCD signal can be challenging to maintain due to patient mobilization and use of electrosurgical unit [17].
Of note, analysis of Mx is one way to calculate cerebral autoregulation and is
not considered to be the gold standard despite strong correlation with
postoperative complications [2, 4, 5]. Other calculation techniques have been
proposed [7], as well as other CBF monitoring techniques, such as cerebral
oximetry [18]. The clinical challenge is to find an appropriate method that can
continuously analyze the relationship between MAP and CBF despite confounding
factors such as hemodilution or PaCO
CPB is a unique state wherein most determinants of cerebral autoregulation
(flow, hematocrit, PaCO
Determination of qLLA during CPB is feasible. However, the large limits of agreement between qLLA and rLLA prevent any interchangeability. Additionally, interobserver variation limits bedside applicability for both qLLA and rLLA in a non-controlled environment. Further studies aimed at modifying MAP to actively determine the LLA may limit the impact of confounding factors.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
All authors contributed substantially to the study and were involved in scientifically significant ways. All authors gave their final approval to the manuscript. They are all agreed to be accountable for all aspects of the work. OD, LG, and RM designed the research study. JN, OD, EB, MD recruited patients and performed the study. JB, AJ and BA provided help and advises about the transcranial doppler technic. All authors contributed to the redaction of the article. All authors read, modified and approved the manuscript.
This study had been submitted to the ethic review board of Ramsay Sante, which accepted the study (The Ethic number is 00010835). The patients were informed their datas would be used in this study and nobody gave an opposition.
Not applicable.
This research received no external funding.
The authors declare no conflict of interest.
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