Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04547491 |
| Other study ID # |
ID 3672 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 15, 2020 |
| Est. completion date |
June 30, 2021 |
Study information
| Verified date |
September 2020 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Intraoperative hypotension (IOH) is a rather common event during general surgery, with
variable incidence that ranges between 5 and 99% based on the definition used. It is
associated to significant complications including acute renal failure, myocardial damage,
stroke and overall increased mortality, reason why the prevention and the reduction of
hypotensive events through an appropriate proactive approach can potentially improve the
patient's outcome. The Hypotension Prediction Index (HPI) is an algorithm derived from the
analysis of the arterial waveform and it is expressed as an absolute value from 0 to 100. It
has been demonstrated that the HPI is able to predict the occurrence of hypotensive events of
patients undergoing major surgery under general anesthesia, providing also a guide for the
appropriate treatment based on further calculated secondary hemodynamic variables that
estimate patient's preload, cardiac contractility and afterload. Aim of this prospective
randomized study is to compare the incidence of IOH during major gynecologic oncologic
surgery among two groups of patients receiving standard hemodynamic monitoring versus HPI
monitoring. The primary hypothesis is that hemodynamic management HPI-guided reduces the
incidence, entity and duration of intraoperative hypotensive events, defined as mean arterial
pressure (MAP) lower than 65 mmHg lasting more than one minute.
Description:
Intraoperative hypotension (IOH) represents a common event during general anesthesia (GA),
with an estimated incidence between 5% and 99%, according to definition adopted [1].
Actually, a mean arterial pressure (MAP) below 65 mmHg is considered an appropriate
definition of IOH [2].
Hypotension mainly occurs during anaesthesia due to three pathophysiological dysregulations:
hypovolemia and consecutively decreased cardiac output, myocardial depression and low
systemic vascular resistance [3]. IOH has been associated with postoperative acute acute
kidney injury and myocardial injury; it seems that the cumulative time spent in hypotension
increases the risk, and this has implications as even relatively short episodes of
hypotension that are treated promptly can over time reach accumulated hypotension time
associated with increased injury rates [4-7]. Therefore, anaesthetic management that aims to
prevent IOH using a "pro-active" treatment protocol might potentially reduce the amount and
severity of IOH, perioperative complications and mortality. In order to detect and treat
these haemodynamic alterations, advanced haemodynamic monitoring combined with a treatment
algorithm can be used [8].
The Hypotension Prediction Index (HPI) algorithm was recently established by Edwards
Lifesciences (Irvine, USA). Based on the Edward´s monitoring platform (HemoSphere), HPI is a
monitoring tool which aims to predict IOH up to 15 min before its onset [9, 10]. HPI is a
unitless number that ranges from 1 to 100, and as the number increases, the risk of an event
occurring in the future increases. The HPI was developed using machine learning methods and
is a data-driven model developed from over 200,000 hypotensive patient events and it predicts
upcoming hypotensive events based on features of the arterial pressure waveform [9].
When HPI rises over 85, the monitor Hemosphere provides a secondary screen showing the
following hemodynamic parameters: stroke volume variation (SVV) as indicator of fluid
responsiveness - preload, radial dP/dtmax as indicator of cardiac contractility, and dynamic
elastance (Eadyn) as dynamic indicator of resistance - afterload. Hemodynamic variables,
hemodynamic diagnostic guidance and the definition of a treatment protocol, should allow for
determination and treatment of the underlying cause of the impending hypotension.
Using an early warning system to predict hypotension does not necessarily lead to reduce
hypotension. There are few randomized clinical trials to investigate the effectiveness of the
use of HPI in reducing the amount of hypotension as measured by time-weighted average [11]
during major noncardiac surgery [3, 12].
Eligible patients will be allocated in one of the two groups of the study according to a
computerized randomization form (ww.randomization.com). Once the patient arrives in the
premedication hall of the operating room, a peripheral intravenous access will be placed.
Based on the patient's allocation group, the following hemodynamic monitoring will be
started:
- Group C - Control: through the EV1000 monitor (with Flotrac sensor)
- Group HPI - Proactive: through the HemoSphere platform (with Acumen Flotrac sensor)
The following timepoints will be recorded:
T0: Machine calibration on the bed in neutral position, recordings of the parameters with
annotation of the baseline MAP; T1: Infusion of RLS at 3ml/kg/h as in standard clinical
practice; T2: cannulation of the radial artery under local anesthesia before induction of
general anesthesia, as in normal standard clinical practice; T3: performance of neuraxial
anesthesia if needed; T4: standard induction of general anesthesia GA) with propofol,
sufentanil and rocuronium bromide; maintenance of GA with sevoflurane and sufentanil; T5:
differentiated hemodynamic management based on the patient's allocation group; T6: surgery
under continuous monitoring.
Group C: Standard Protocol In group C the hemodynamic management will be performed based on
cardiac optimization. Fluid boluses will be given with the use of an individualized
goal-directed therapy (GDT) protocol aiming to optimize stroke volume index (SVI) [13].
Patients will receive 250 ml fluid challenges, within duration of 5 minutes, with a RL
solution. Fluid responsiveness will be defined as a SVI increase ≥10%. Maximal stroke volume
will be defined as the absence of a sustained rise in SVI of at least 10% sustained for 20
minutes or more in response to a fluid challenge. No more than 500 ml of fluid will be
administered for initial determination of the maximal value of SVI before start of the
surgical procedure. Once the maximal value of SVI will be determined after induction of
anesthesia, SVI must be maintained throughout the intervention period with subsequent boluses
of fluids as required.
For the treatment of eventual hypotensive episodes, etilephrine or efedrine will be used,
depending on the clinical situation. If needed, continuous infusion of noradrenaline and/or
other vasopressors or inotropes will be started.
All of the hemodynamic parameters detected with the EV1000 monitor and the measures adopted
will be recorded.
Group HPI: Proactive Protocol In case of HPI>85, hypotension will be prevented according to
the following modalities. The first step will be the optimization of SVV (in case of SVV>13%)
with bolus of 250 ml RLS. In case of dP/dtmax < 400 (or in decreasing trend) dobutamine
infusion 2.5 - 5 mcg/Kg/min will be started. In case of Eadyn < 0,9 norepinephrine infusion
0,1 mcg/kg/min will be started.
All of the data relative to the hemodynamic monitoring and the measures adopted will be
recorded and subsequently analyzed to compare the incidence and duration of the hypotensive
events in the 2 groups. To calculate the entity of the intraoperative hypotension the
following technique will be used: after removal of artifacts, the TWA MAP (time weighted
average mean arterial pressure) <65mmHg will be represented by the area between the threshold
of 65 mmHg and the curve of the measured MAP, divided by the total recorded time in minutes
[12].
Statistical plan The data will be described in their demographic and clinical characteristics
through the application of descriptive statistics. The qualitative variables will be
described using tables of absolute frequencies and percentages; the continuous quantitative
variables will be presented as a median and interquartile range or as a mean and standard
deviation when normally distributed; while the non-normal variables will be presented as
minimum, maximum and median values.
In the two groups of patients, the hypertensive events, defined as a MAP lower than 65mmHg
for > 1 minute (and the severe hypotensive events as having a MAP lower than 60 and 55 mmHg),
will be analyzed in terms of frequency and absolute duration and, to estimate their severity,
as the ratio between the area under the 65 mmHg threshold and the total length, expressed in
minutes, of intraoperative monitoring using the TWA-MAP method. The Chi-squared test will be
used to compare the two incidences. The t-student test for independent samples will be used
to evaluate statistically significant differences among the patients' demographic and
anthropometric characteristics.
The Shapiro-Wilk test will be used to assess the normality of data distribution, while the sd
test will be used to verify the equality of the variance.
The Mann-Whitney test will be used for independent samples to compare the data that are not
normally distributed.
Regarding the assessment of the secondary outcomes, the investigators will report the
relative risks with 95% confidence intervals and p-values based on either the chi square or
Fisher's exact test, as more appropriate according to the frequencies expected and detected.
A p-value <0.05 will be considered statistically significant. All of the analysis will be
performed through the STATA IC 15.1 (Stata Corp) for Windows, Microsoft Excel, Matlab (The
MathWorks Inc., Natick, MA, USA) and the Acumen Analytics software (Edwards Lifesciences,
Irvine, CA).
Sample Size International literature agrees to consider clinically significant a reduction of
75% of the hypotensive events in terms of entity and duration. According to one of our
internal databases (data not yet published), the mean TWA-MAP during gynecological oncology
surgery is 0,5 mmHg. Thus, the estimated mean difference between the two groups according to
the sample size calculations results to be 0.38 mmHg. Based on the previous clinical trials
11,12 the TWA-MAP standard deviation is estimated to be 0.51 mmHg. Dividing the mean
difference by the standard deviation, the resulting dimension has a size effect of 0.74. The
investigators calculated that a sample of 60 patients, 30 for each group, has 80% ability of
discriminating such effect (t-test with α of 0.05).
