Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02569008 |
| Other study ID # |
13.0116 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
October 2, 2015 |
| Last updated |
October 8, 2015 |
| Start date |
January 2014 |
| Est. completion date |
February 2015 |
Study information
| Verified date |
October 2015 |
| Source |
St George's, University of London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United Kingdom: Research Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
This study evaluate the effect of different doses of crystalloids on the changes on cardiac
output (CO) and on the proportion of responders and non-responders and aims to determine the
minimal volume required to increase the mean systemic filling pressures (Pmsf) in
post-cardiac surgical patients.
Description:
OBJECTIVES
1. To determine if different doses of fluids in a fluid challenge affect the change in CO
and the proportion of responders / non-responders
2. To determine the minimal amount of volume required for performing an effective fluid
challenge.
1. To define the least significant change of the Pmsf measured by Pmsf-arm.
2. To define the stop-flow time required to measure Pmsf-arm
3. To study the changes generated by a fluid challenge in the microcirculation and
correlate those changes with the changes in the Pmsf.
STUDY DESIGN
1. TYPE OF STUDY This is an quasi-randomised open-label study. The purpose of this study
is non-commercial.
2. STUDY OF MINIMAL VOLUME Once the participant is admitted to the ICU, and the monitors
are in place, the fluid challenge will be administered. Each fluid challenge will be
administered with a syringe (50 ml) in five minutes. In order to observe the effect of
the volume on Pmsf-arm, the total sample of patients will be divided in 4 groups: in
group one Pmsf-arm will be measured at baseline and after 1 ml/kg of body weight; in
group 2 after 2 ml/Kg; in group 3 after 3 ml/kg and finally in group 4 after 4 ml/Kg.
The fluid challenge will be completed in everybody after the measurement of Pmsf-arm,
in order to respect clinical practice. Pmsa will be observed also. The total duration
of the fluid challenge will be 5 minutes. The fluid challenge will be repeated in
accordance with the clinical protocol or with the clinician advice.
The first 20 patients will receive 4 ml/kg (normal clinical practice) between the base
line and the second measurement of Pmsf-arm. The subsequent 20 patients will receive
3ml/kg between the two measurements of Pmsf-arm, and then 1ml/kg will be added to
complete the normal fluid challenge. The following 20 patients will receive 2 ml/Kg
between the two measurement of Pmsf-arm, and then the remaining 2 ml/kg will be given
to complete the normal fluid challenge. And finally, the last 20 patients will receive
1 ml/kg between the two measurements of Pmsf-arm, and 3 ml/kg will be added to complete
clinical practice.
3. STUDY OF MICROCIRCULATION In 25 patients, functional capillary density (FCD)
microvascular flow index (MFI), proportion of perfused vessels (PPV) and microvascular
heterogeneity index (MHI) will be measured with a side-stream dark-field (SDF) camera
at five time points: (1)Baseline, (2) At the end of the fluid challenge (4 ml / kg in 5
minutes), (3) 5 minutes after the end of the fluid challenge, (4) 10 minutes after the
end of the fluid challenge, (5) 15 minutes after the end of the fluid challenge.
The ventilation settings, sedation and vasoactive support will be kept constant during
the study period, unless other clinical instruction, in which case the data will be
excluded from the analysis.
4. HAEMODYNAMIC MEASUREMENTS
4.1 CLINICAL MONITORING These measurements are using normally in clinical practice and will
be used during the study but do not constitute any change in clinical practice.
- Mean arterial pressure (MAP) will be measured with a radial artery catheter (p.e.
115.090 Vygon, Ecouen, France).
- Central venous pressure (CVP) will be measured with a venous central catheter (p.e.
CV-15854, Arrow International, Reading, USA) inserted in the internal jugular vein or
the subclavian vein. This line will be ideally inserted in the anaesthetic room after
induction of general anaesthesia. Once the study finishes, this line will be removed
unless the clinical team taking care of the patient decided to use it.
- Both catheters will be connected to a pressure transducer (T001650A, Edwards
Lifesciences LLC, Irvine, USA) and to a multi-parameter monitor (InfinityTM Delta,
Dragger Medical Systems, USA). Zero levels of blood pressures were referenced to the
intersection of the anterior axillary line and the fifth intercostal space.
- Cardiac output will be monitored using LiDCO TM plus (LiDCO Ltd, Cambridge, UK)
4.2 DETERMINATION OF PMSF-ARM Pmsf can be estimated measuring the venous pressure (Pv) and
the arterial pressure (Pa) in on limb after rapid vascular occlusion. This estimation
assumes Pa and Pv equilibrium following a rapid vascular occlusion as described by Maas et
al[2]. In order to determine stop-flow time (or time of arterial / venous balance), we will
perform a pilot study in 10 patients. We will measure the radial arterial pressure and
venous pressure in the same hand and we will then stop the blood-flow during 30 -60 seconds
using an automatic pneumatic tourniquet (APT pneumatic tourniquet, Anetic Aid, Ltd.
Guiseley, UK) to pressures 50 mmHg above systolic pressure. Measures will be taken three
times in order to assess repeatability. The time required to equilibrate arterial and venous
pressure will be the stop-flow time, and will be the time that we need to wait with the
tourniquet inflated. In Maas study was between 25 - 30 seconds.
4.3 MICROCIRCULATION MEASUREMENTS
In order to study microcirculatory changes, sublingual microcirculatory videos will be
obtained using a side-stream dark field-imaging device (SDF; Microscan, MicroVissionMedical,
Amsterdam, the Nederlands) derived from the orthogonal polarized spectral imaging
technology. Images acquisition and analysis will be performed according international
recommendations [3] with dedicated software analysis (Automated Vascular Analysis (AVA) v.
1.0; Academic Medical Center, University of Amsterdam, Amsterdam, the Nederlands). These
recommendations are summarised below:
- Image acquisition will include five sublingual good quality sequences of 20 seconds
each at every observation time-point.
- Scoring will include measurement of perfused capillary density and evaluation of
heterogeneity. We will measure:
1. Functional capillary density (FCD): this can be calculated counting the number of
intersection of capillaries with arbitrary grid lines and measurement of total
capillary length relative to image area.
2. Microcirculatory flow index (MFI): this is based on determination of the
predominant type of flow in four quadrants. Flow is characterised as absent (0),
intermittent (1), sluggish (2) or normal (3). The values of the four quadrants is
averaged.
3. Proportion of perfused vessels (PPV %): calculated as the total number of vessels
minus the number of vessels with intermittent flow or no flow divided by the total
number of vessels.
4. Flow heterogeneity index (FHI): the difference between the highest MFI minus the
lowest site MFI divided by the mean flow velocity of all sublingual sites at a
single time point.
SETTING General and cardiothoracic intensive care unit, St George's Healthcare Trust.
