Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01285622 |
| Other study ID # |
UofL IRB#10.0537 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2011 |
| Est. completion date |
November 28, 2018 |
Study information
| Verified date |
March 2021 |
| Source |
University of Louisville |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The investigators propose a prospective observational trial. The investigators plan to enroll
40 female subjects scheduled for elective robotic gynecological surgery under general
anesthesia. Hemodynamic data will be recorded at the following intervals: after induction of
anesthesia (Baseline), after initiation of pneumoperitoneum, after positioning the patient in
Trendelenburg position, and every 15 minutes thereafter. At the end of surgery measurements
will be recorded after reversal of Trendelenburg position and after deflation of the
peritoneum.
Forearm - fingertip temperature gradients will be measured by Mon-a-thermometer (Mallinckrodt
Medical, Inc. St. Louis, MO) and disposable Mon-a-therm thermocouples. Vasoconstriction will
be identified when forearm - fingertip temperature gradient is ≥ 00C and PI <1.
Intra-abdominal pressures will be recorded during each measurement of hemodynamic parameters.
Trendelenburg position will be measured with an angle ruler.
The aim of our study is to test the hypothesis that stroke volume will drop significantly
after initiation of pneumoperitoneum and that it will increase after placement in
Trendelenburg position in patients undergoing robotic gynecological procedures. Secondly, the
investigators will test the hypothesis that PVI changes correlate with changes in stroke
volume and pulse pressure variation (PPV) and can predict an increase in stroke volume after
a fluid bolus. The third hypothesis is that delta PVI is independent of the vaso-status of
precapillaries at the measured site.
Description:
BACKGROUND
Optimal intraoperative volume management is a mainstay during general anesthesia. Adequate
intraoperative fluid administration enhances preload and supports optimal cardiac output.
Intraoperative optimization of cardiac output using volume expansion decreases postoperative
morbidity and duration of hospital stay.1 Optimization of intraoperative cardiac output
depends on the ability to assess its preload dependence and fluid responsiveness. Static
indicators of fluid responsiveness such as central venous pressure (CVP), pulmonary capillary
wedge pressure (PCWP), or left ventricular end diastolic area index are invasive or are not
easily available and have been shown to be poor predictors of fluid responsiveness.2-9
Dynamic indicators, such as respiratory variations in arterial pulse pressure (PPV)3 or
stroke volume variations (SVV)5, relying on the respiratory variations in stroke volume or
its surrogates in mechanically ventilated patients have been shown to be superior to static
indicators for prediction of fluid responsiveness. 8,10-12 Both techniques rely on pulse
contour or pulse power analysis derived from an arterial line and are invasive. Respiratory
variations of preload can also be assessed in pulse Doppler aortic flow velocity2,11 or by
esophageal Doppler.13
Recently, it has been shown that respiratory variations in the pulse oximeter plethysmography
waveform amplitude (∆POP) are sensitive to changes in preload14 and can predict fluid
responsiveness in mechanically ventilated patients.15 Pulse oximeter plethysmography waveform
amplitudes are strongly related to the respiratory variations in arterial pulse pressure
(PPV) 16,17 and are sensitive to changes in ventricular preload.14
Recently published studies have shown promising results regarding the ability of ∆POP to
predict fluid responsiveness in the intensive care unit15 and in the operating room.18
Pulse oximeter plethysmography waveform amplitude variations cannot be easily calculated from
a bedside monitor. Thus a plethysmography variability index (PVI, Masimo Corp.) has been
created. PVI is a new algorithm that automatically calculates ∆POP. PVI is a measure of the
dynamic change in perfusion index (PI) that occurs during a specific period of time,
sufficiently long enough to include at least one complete respiratory cycle. For PI
calculation, the infrared pulsatile signal is indexed against the non-pulsatile infrared
signal and expressed as a percentage (PI- (AC/DC×100) reflecting the amplitude of the pulse
oximeter waveform. PVI calculation is accomplished by measuring changes in PI over time as
PVI = (Pimax-Pimin/Pimax) - 100.
In patients undergoing robotic procedures needing a pneumoperitoneum and steep Trendelenburg
position, it is unknown if cardiac output decreases predictably during pneumoperitoneum and
to what extent the steep Trendelenburg position offsets the decrease in cardiac output. In
addition, pulse pressure variation (PPV) has been shown to reliably predict the response to
fluid administration in an animal model in pneumoperitoneum.20 However, no human data are
available in this setting.
Thus, the aim of our study is to test the hypothesis that stroke volume will drop
significantly after initiation of pneumoperitoneum and that it will increase after placement
in Trendelenburg position in patients undergoing robotic gynecological procedures. Secondly,
the investigators will test the hypothesis that PVI changes correlate with changes in stroke
volume and pulse pressure variation (PPV) and can predict an increase in stroke volume after
a fluid bolus. The third hypothesis is that delta PVI is independent of the vaso-status of
precapillaries at the measured site.
METHODS
The investigators propose a prospective observational trial with approval of the Human
Studies Committees at the University of Louisville and University Hospital Research Integrity
Office. All subjects or their legal representatives must give informed, written consent
before being enrolled in the study. The study will be conducted under Good Clinical Practice
Guidelines.
Inclusion criteria The investigators plan to enroll 40 female subjects scheduled for elective
robotic gynecological surgery under general anesthesia.
Exclusion criteria
Patients with atrial fibrillation or other significant arrhythmia (Lown grade 3 or greater)
and patients with aortic regurgitation will be excluded.
Protocol
Anesthesia will be induced with propofol (2 mg/kg), rocuronium (0.6 mg/kg) and fentanyl (2
µg/kg) to facilitate intubation. A #8 endotracheal tube will be inserted in the trachea and
secured at 22 cm. Anesthesia will be maintained with sevoflurane to maintain the BIS value
between 40 and 60. Fentanyl will be given as an infusion at a rate of 2 µg/kg/h. The
ventilator will be set at pressure-controlled mode and patients will be ventilated with an
airway pressure corresponding to a tidal volume of 8 mL/kg up to a maximum airway pressure of
35 cmH20. Inspired oxygen will be kept near 50% but will be increased if necessary to
maintain a hemoglobin oxygen saturation >95%. PEEP will be set at 5 cmH20. Respiratory rate
will be 12 breaths per minute.
Each patient will receive an arterial catheter (radial artery) with a transducer and
continuous real-time cardiovascular monitor (LiDCO rapid, LiDCO Ltd, London, UK) attached to
it. A pulse oximeter (LNOP Adt, Masimo Corp, Irvine, CA) will be attached to the index finger
of the patient's same hand and connected to a bedside monitor (Radical 7, Masimo Corp,
Irvine, CA); the oximeter will be wrapped to prevent interference from outside light. PVI
calculates the respiratory variations in the plethysmography waveform amplitude (Perfusion
index [PI]) using the maximum and minimum PI values over a given time period. Arterial
waveform will be recorded continuously.
Intraoperative fluid management will be performed with plasmolyte 2 mL/kg/h. Fluid boluses
will be given as guided by SVV. Hetastarch will be given as a bolus in 250 mL increments to a
maximum of 50 mL/kg. The fluid bolus will be given over 5 minutes. A bladder (foley) catheter
will be inserted after induction of anesthesia. This is part of conventional care and will
allow for more accurate fluid volume tracking.
Once the patient is in Trendelenburg position and a measurement yields that SVV or PVI stays
above 10%, fluid boluses of 250 mL of hetastarch will be given over 5 minutes until SVV or
PVI falls below 10%. The fluid bolus will also be repeated if there is a rise in stroke
volume of 10%.
Anesthesia will continue until surgery is completed. Paralysis will be continued throughout
the anesthesia period with the goal to maintain a train of four (TOF) at 1 to 2 twitches. At
the end of surgery the patient's trachea will be extubated according to routine extubation
criteria.
During abdominal CO2 insufflation the intra-abdominal pressure will be kept at 15 cmH2O. The
Trendelenburg position will be 30º, which corresponds to the maximum inclination of the OR
table.
Measurements
Hemodynamic data (blood pressure, cardiac index, pulse pressure variation) will be measured
by pulse power analysis. PVI will be measured by pulse oximetry. Hemodynamic data (MAP, SVV,
PPV, CO, PI and PVI) will be recorded at the following intervals: after induction of
anesthesia (Baseline), after initiation of pneumoperitoneum, after positioning the patient in
Trendelenburg position, and every 15 minutes thereafter. At the end of surgery measurements
will be recorded after reversal of Trendelenburg position and after deflation of the
peritoneum.
Forearm - fingertip temperature gradients will be measured by Mon-a-thermometer (Mallinckrodt
Medical, Inc. St. Louis, MO) and disposable Mon-a-therm thermocouples. Vasoconstriction will
be identified when forearm - fingertip temperature gradient is ≥ 00C and PI <1.
Intra-abdominal pressures will be recorded during each measurement of hemodynamic parameters.
Trendelenburg position will be measured with an angle ruler.
Data Analysis Sample size analysis: Preliminary data have shown a likelihood of 75% to see an
increase of stroke volume after positioning the patient in Trendelenburg position. Taking
into consideration the annual patient population of 200 patients and assuming a confidence
interval of 65-80% at the 0.05 significance level a total of 35 patients will be needed.
Thus, the investigators plan to study 40 patients. An interim analysis will be performed
after 20 patients.
The investigators will use paired t-tests and repeated measures ANOVA for all numerical
measurements, when comparing data (BP, HR, and SV), before and after interventions (baseline
to insufflation, insufflation to Trendelenburg position, and stroke volume before and after
fluid bolus). Chi-square tests will be used for categorical data such as change in SVV and
PPV. Logistic regression, Bland-Altmann plot and ROC curves will be used to predict the
agreement and precision of SVV and PVI changes. Results will be considered statistically
significant when P < 0.05.
Significance
The change of hemodynamics during the non-physiologic (iatrogenic) events of abdominal
insufflation and placing the patient in steep Trendelenburg position has not been elucidated.
Shedding light on hemodynamic derangements may help the clinician to optimize stroke volume
and cardiac output early in the process of robotic surgery. The evaluation of a non-invasive
device (perfusion variability index) to determine feasibility may allow measuring dynamic
hemodynamic parameters non-invasively in the future.
This observational trial does not impose any additional risks on the patient. Arterial
cannulation for invasive blood pressure measurements is conventional care during robotic
surgery; the applied devices (LiDCO, pulsoximetry and skin thermometers) are non-invasive
devices.
Gender and Minority Inclusion
There is no data indicating that ethnicity affects hemodynamic changes during robotic
surgery. The investigators accordingly will accept patients from all minority groups. Based
on the population of greater Louisville, the investigators expect that 85% of the subjects
will be Caucasian. The investigators will include female patients only in the study, as the
investigators will only enroll patients for gynecological pathologies.
Potential Risks
The proposed study will be conducted with approval of the Human Studies Committees at the
University of Louisville. The investigators must receive written, informed consent from
participating patients or authorized representatives. The principal investigator and all
collaborators have completed an IRB-certified human subject protection training course.
The investigators will only enroll patients scheduled for robotic surgery undergoing steep
Trendelenburg position. The risks of steep Trendelenburg position are swelling of the upper
body, specifically eyes, and the larynx and pharyngeal structures. Swelling may cause the
risk of delayed extubation or, very seldom, postanesthesia re-intubation. Increased
intracerebral pressure may cause headache.
Insufflation of the abdomen may cause subcutaneous emphysema and shoulder pain due to
irritation of the phrenic nerve.
Arterial cannulation may rarely cause hematoma at the wrist and arterial thrombosis and
infection of the cannulation site.
All potential complications will be explained to the patient twice. First, the patient will
have the information presented to them as part of the conventional care consents for surgery
and anesthesia. Second, when investigators have a consenting discussion with the potential
subjects about the research protocol.
