Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT01788293 |
| Other study ID # |
PVI - HR |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 2013 |
| Est. completion date |
January 1, 2018 |
Study information
| Verified date |
February 2021 |
| Source |
Hospital Regional de Presidente Prudente |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Oximetry monitoring is common practice in patients undergoing anesthesia. PVI continuous
evaluation may be a possibility of agility and ease of obtaining accurate information about
the state of cardiovascular responsiveness to volume expansion.
This prospective and randomized study will try to demonstrate that the assessment of PVI is a
simple and cost-saving method as compared to cardiac output or oxygen delivery monitoring
technologies. Such a simple approach has therefore the potential for widespread application
as it is not routinely feasible for anesthetists to use cardiac output or oxygen delivery
monitoring technologies in many institutions, as well as in many countries.
Description:
Introduction
Several studies have shown that cardiac output optimization improve postoperative outcome and
to decrease the cost of surgery [Boyd et al., 1993; Gan et al., 2002; Kern & Shoemaker, 2002
; Pearse et al., 2005 ; Poeze et al., 2005 ; Sinclair et al., 1997; Wakeling et al., 2005].
Respiratory variations in the arterial pulse pressure and in the pulse oximetry
plethysmographic waveform amplitude have been extensively studied in mechanically ventilated
patients, and have been demonstrated to be sensitive to changes in ventricular preload as
well as reliable predictors of fluid responsiveness in adults [Cannesson et al 2007;
Cannesson et al., 2008; Natalini et al., 2006; Solus-Biguenet et al., 2006; Zimmermann et
al., 2010].
A few studies have evaluated the impact of a pulse-pressure-variations-guided fluid
management on perioperative outcome [Buettner et al., 2008; Fukui et al., 2007; Fukui et al.,
2009; Kobayashi et al., 2008; Lopes et al., 2007; Mayer et al, 2009; Oubaha & Poelaert, 2009;
Sakamoto et al., 2009]. However, results from these studies are not conclusive and further
studies are required to better explore this topic [Cannesson, 2010].
Pulse oximeters are part of the routine monitoring during anesthesia and in the intensive
care unit [Dorlas & Nijboer, 1985]. The main interest of the pulse oxymeter is to display
arterial oxygenation continuously. Pleth variability index (PVI) is an automatic measure of
the dynamic change in perfusion index (PI) that occurs during a complete respiratory cycle.
PVI is provided currently by one pulse oximeter manufacturer (Masimo Radical 7 ™, Masimo
Corporation, Irvine, CA, USA). The PVI calculation measures changes in PI over a time
interval sufficient to include one or more complete respiratory cycles as and is displayed
continuously [Cannesson et al., 2008; Zimmermann et al., 2010]. PVI quantifies the
variability in plethysmograph waveform due to respiration and is thought to be a surrogate
measure of intravascular volume [Cannesson et al., 2008; Zimmermann et al., 2010]. Cannesson
et al. reported that a PVI value above 14% predicted fluid responsiveness [Cannesson et al.,
2008]. Therefore, the clinical and intra-operative goal of "maximizing stroke volume by
volume loading" can be achieved by reducing PVI below 14 % [Cannesson et al., 2008;
Zimmermann et al., 2010]. Forget et al [2010] demonstrated that PVI based goal-directed fluid
management reduced the volume of intraoperative fluid infused and reduced intraoperative and
postoperative lactate levels. However, to our knowledge there is no study that evaluate the
impact of PVI guided fluid management on perioperative outcome.
Materials and Methods
Patients This procol has been approved by the local Ethics Committee (Hospital Regional de
Presidente Prudente Presidente Prudente, São Paulo, Brazil). The written informed consent
will be obtained from each patient. Adults patients underwent high-risk surgery will be
selected and randomized to either a control group (group C) or an intervention group (group
I).
Patients will be selected according to a pre-operative decision (by the surgeon and the
intensivist) that post-operative care would be undertaken in the ICU because of
co-morbidities or/and the surgical procedure. Patients < 18 years, with cardiac arrhythmias,
with a body mass index > 40, and those undergoing surgery with an open thorax, neurosurgery
or emergency surgery, will be excluded.
Intraoperative monitoring
On the day of surgery, they will receive their respective medication in association with
anesthetic premedication. Immediately after the arrival in the operating room heart rate,
pulse oximetry, blood pressure and capnography will be monitored with a multiparameter
bedside monitor (DX 2023, Dixtal™, São Paulo, Brazil). A 20-G catheter line (Smith Medical
International™, Lancashire, Uk) will be inserted in the radial artery for continuous arterial
pressure measurement and recording. The radial catheter will be connected to a Dixtal® DX
2023 monitor (São Paulo, Brazil).
The patients will be anesthetized with loading doses of propofol (2 mg/kg), sufentanil (0,2 -
0,3 µg/kg) and atracurium (0.6 mg/kg). Anesthesia will be maintained by infusion of the same
products. After induction of anesthesia, patients underwent tracheal intubation. Artificial
ventilation will be provided by a Fabius plus ™ ventilator (Dräger™, Lübeck, Germany)
(respiration rate = 12 strokes/min, tidal volume = 8 to 10 ml/kg).
Each respiratory cycle will be identified from the capnogram, systolic and diastolic arterial
pressures will be measured on a beat-to-beat basis. In patients of intervention group PVI
values will be determined over each respiratory cycle (Masimo Radical 7 ™, Masimo
Corporation, Irvine, CA, USA).
Protocol Randomization will be done pre-operatively using sealed envelopes. During the
surgical procedure, patients will be managed according to our institution's standard of care.
Group C will receive per-operative fluid at the discretion of the anesthetist, whereas group
I will receive additional hydroxyethylstarch 6% (HES) bolus in order to minimize and maintain
PVI below 14 %. This PVI cut-off value was chosen according to previous reports [Cannesson et
al., 2008; Zimmermann et al., 2010].
During the postoperative period, both groups were managed by intensivists (in the ICU) and
clinicians (in the wards) not involved in the intraoperative management or in data
collection. These individuals were not informed of patient allocation.
Data collection
Over the study period all data will be collected prospectively and patients will be followed
up until hospital discharge. Pre and intraoperative data collection will be undertaken by one
of the investigators, whereas post-operative data collection will be undertaken by another,
who was not aware of the allocation group. Before surgery, sex, age, weight, height, history
of renal failure requiring dialysis or not, cirrhosis, chronic obstructive pulmonary disease,
hypertension, peripheral vascular disease, coronary artery disease, other cardiac disease,
diabetes mellitus, and cerebrovascular disease will be recorded. The body mass index will be
calculated according to the standard formula (BMI = weight/height2). Serum creatinine,
prothrombin time, hemoglobin, and platelets will be obtained from routine pre-operative
biological tests. During the surgical procedure, tidal volume, ventilatory frequency, infused
volume of crystalloid solutions, HES, and blood products will be recorded. Heart rate, mean
arterial pressure, percutaneous arterial oxygen saturation, and hemoglobin will be collected
both at the beginning and the end of the surgical procedure. The duration of surgery will be
also recorded. After the surgical procedure, the following parameters will be collected both
at ICU admission and 24h later: mean arterial pressure, heart rate, percutaneous arterial
oxygen saturation. During the 24h following ICU admission, venous lactate will be measured
every 6h and the mean lactate value will be calculated over the first 24h ICU period. The
need for continuous vasoactive (dobutamine or/and norepinephrine) support will be recorded.
Postoperative ICU infections (pneumonia, abdominal, urinary tract, line related sepsis and
wound infections), respiratory complications (pulmonary embolism, acute lung injury, and
respiratory support > 24h exclusive of acute lung injury), cardiovascular complications
(arrhythmia, hypotension, acute pulmonary edema, acute myocardial infarction, stroke, and
cardiac arrest exclusive of fatal outcome), abdominal complications (clostridium difficile
diarrhoea, acute bowel obstruction, upper gastro-intestinal bleed, and anastomotic leak),
hematologic complications (platelet count < 100000/µl or prothrombin time > 1.5 times
control), and renal complications (urine output < 500 ml/day or serum creatinine > 170 µmol/L
or dialysis for acute renal failure) were collected according to criteria previously used by
other investigators [Bennett-Guerrero et al., 1999; Gan et al., 2002; Lopes et al., 2007;
Pearse et al., 2005].
Statistical analysis
Data will be analyzed comparing patients in group C with those in group I on an intention-to
treat basis. The primary outcome measure will be the duration of postoperative hospital stay.
On the basis of our own hospital registry, the mean duration of postoperative hospital stay
in group C is a priori estimated at 15 ± 7 days (median ± median absolute deviation).
According to previous publications we postulated that the mean duration of postoperative
hospital stay in group I could be 35% lower [Lopes et al., 2007; Mythen & Webb, 1995;
Sinclair et al., 1997]. A sample size of 35 patients in each group was calculated for a 0.05
difference (two sided) with a power of 80% [Schulz & Grimes, 2005]. An intermediate analysis
after the enrolment of the first 35 patients was planed, in order to readjust the population
sample size if necessary. Secondary outcome measures were the number of post-operative
complications per patient, as well as the duration of mechanical ventilation and ICU stay.
Results are expressed as median ± median absolute deviation. The median absolute deviation is
a variation of the average absolute deviation that is even less affected by outlying values
because these values have less influence on the calculation of the median than they do on the
mean. In general, for data with extreme values, the median absolute deviation or
interquartile range can provide a more stable estimate or variability than the standard
deviation.
The Mann-Whitney U test was used to compare between groups patient characteristics as well as
the duration of mechanical ventilation, ICU stay and hospital stay. In group I, the effects
of volume expansion with HES administration in PVI will be assessed using a nonparametric
Wilcoxon rank sum test within each group of patients. A Fisher exact test was performed to
compare nominal data. Linear correlations were tested using the Spearman rank method. A
p-value lower than a 0.05 chosen level is regarded as statistically significant. All
statistical analyses are performed using the StatView TM software for Windows (version 4.57,
Abacus Concepts Inc., Berkeley, CA, USA).
