Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04038398 |
| Other study ID # |
EK Nr: 1614/2019 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2019 |
| Est. completion date |
December 1, 2020 |
Study information
| Verified date |
July 2019 |
| Source |
Medical University of Vienna |
| Contact |
Claudius Doerr, MD, PHD |
| Phone |
043 1 4040041000 |
| Email |
claudius.doerr[@]meduniwien.ac.at |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The proper management of brain oxygenation is an essential component of all anesthesiologic
procedures. Nevertheless, the brain remains one of the least monitored organs in the
perioperative phase and intensive care therapy. In the current study the effects of
continuous positive airway pressure (CPAP) with different ventilation parameters (FiO2 21% -
50% - 100%) on cerebral and peripheral oxygenation (rSO2) will be examined.
The INVOS Brain oximeter (IBO) is a reliable trend monitor for changes in regional cerebral
oxygenation (rSO2). Therefore rSO2 will be measured on the forehead and the arm. In a
randomised way the rSO2 will be monitored for 30 minutes (3x10min) with different FiO2
settings. The randomisation refers to the order of the applied FiO2, each patient is
therefore its own control. Additionally vital parameters (heart rate, blood pressure, SpO2)
will be recorded and blood gas analysis will be performed.
Description:
Near infrared spectroscopy (NIRS), is a non-invasive method for the measurement of blood flow
in tissues, first used for cerebral tissue oxygenation in 1977. NIRS is a spectroscopic
technique, which uses electromagnetic waves (700-950nm), an emitter and a detector. In the
last 20 years there was an enormous development in the instrumentation and application of
NIRS. This technique now allows to measure the oxygenation of the brain tissue. The INVOS
Brain oximeter is a reliable trend monitor for changes in regional cerebral oxygenation
(rSO2) and correlates with the hemoglobin saturation in venous, capillary and arterial blood,
using an algorithm based upon the Beer-Lambert law. The INVOS Cerebral oximeter system uses
light, with wavelengths between 730-810 nm, that penetrates layers of the human body, among
them the skin, the scull and the brain. It is either scattered within the tissue or absorbed
by present chromophores. In the rather transparent near infrared region, there are many
absorbing light chromophores, but only three are important as far as the oxygenation is
concerned, namely haemoglobin (HbO2), deoxyhaemoglobin (Hb) and cytochrome oxidase (CtOx).
Oxygenated and deoxygenated haemoglobin absorb light at different wavelengths, allowing a
differentiation of these two forms of haemoglobin. The sensors, ("SomaSensors"), are applied
to the patients forehead with an integrated medical-grade adhesive. The method is applied by
using two source-detector distances in the sensor: a "near" one (shallow), 3 cm from the
source and a "far" one (deep), 4 cm from the source. Both samples penetrate the tissue
beneath the light source equally well, with the difference that the 4cm source-detector
measures signals deeper in the brain or other parts of the body. The subtraction of the near
sample from the far one should leave a signal originating predominantly in the brain cortex.
The proper management of brain oxygenation is an essential component of all anesthesiologic
and intensive-care procedures. Nevertheless, the brain remains one of the least monitored
organs in the perioperative phase and intensive care therapy. Up until now, the
anesthesiological application of NIRS as a method for measuring the cerebral oxygenation has
only been investigated in a health population, patients undergoing cardiac surgery or
cerebrovascular surgery, elderly patients undergoing major abdominal surgery and neonatal
infants. If NIRS detects a decrease of rSO2 in these fields, there are specific guidelines of
interventions to regain a sufficient oxygen supply in the brain.
Therefore, it is already strongly involved in the patients care in the perioperative setting.
A routine use of NIRS on the ICUs has not yet been established. For this reason most studies
on rSO2 were performed during surgery. These studies indicate that the measured cerebral
oxygenation is affected by the relative proportion of blood in the arterial or venous part of
the capillary bed, the haemoglobin concentration, and the systemic saturation.
The precise consequences of alterations in the systemic saturation (SaO2) on the cerebral
oxygenation (rSO2) remain unknown. It is a current assumption that rSO2 is directly
correlated to Sa02, so that an increase of SaO2 also leads to an increase of rSO2.
The amount of oxygen in the arterial blood depends on the inspired oxygen and the pulmonary
gas exchange. These two starting points are primarily affected by the individual's
respiratory ventilation. Patients with chronic respiratory failure, or just a temporary
(acute) breathing deficiency (e.g. after general anaesthesia), are routinely treated with the
continuous positive airway pressure (CPAP) therapy, a non-invasive form of ventilation. It is
also commonly used in the treatment of sleep apnea and in neonates (especially premature
infants). In these patients CPAP ventilation may prevent the need of tracheal (re-)
intubation, or enable earlier extubation. The therapy was developed by Dr. George Gregory and
colleagues in the neonatal ICU at the University of California, San Francisco in 1971, and
then modified by Professor Colin Sullivan at Royal Prince Alfred Hospital in Sydney,
Australia, in 1981. Initially the CPAP therapy was mainly used by patients for the treatment
of obstructive sleep apnea at home. Nowadays it is commonly used in ICUs as a form of
non-invasive mechanical ventilation. There it is usually reserved for subgroups of patients
where the oxygen treatment via a facemask is insufficient. Patients on CPAP therapy are
closely monitored in the ICU setting. The treatment supports the patient's spontaneous
breathing by building up a positive end expiratory pressure (PEEP). Typically CPAP is a
discontinuous therapy on the ICU that means Patients take it off during meals, or just use it
if they require temporarily respiratory relief. The pressure applied by most patients ranges
between 5 and 12 cmH2O. The patient can individually determine his or her own respiratory
frequency as well as the depth of respiration.
The primary study goal is the evaluation of the effect of ventilation with different FiO2
settings applied via NIV on rSO2 in relation to the vital parameters, haemoglobin, SaO2
(analyzed by BGA) and SpO2. These combined measurements can be used to further describe the
effect of NIV on rSO2. So far, this kind of study has not been performed on patients in the
ICU. Therefore, this project aims at gaining new insights into the influence of NIV on the
cerebral oxygenation.
This study will be carried out in patients with good access to the forehead. The NIRS
measurement (IBO) will be performed on the temporoparietal cortex on both sides of the head
and as a control on both shoulders/upper arms. During the whole investigation the SaO2, the
blood pressure (continuously invasive or non invasive in 3 minute-intervals), the heartrate
and the ECG will be recorded. These vital signs are part of the routine ICU monitoring.
NIRS measurement will be performed CPAP therapy (FIO2 : 21% - 50% - 100%) for each 10
minutes. The patients will be randomized into two groups, with changed FIO2 application
orders.
Condition 1: CPAP 6 mbar PEEP, 0 ASB, FIO2: 21%
Condition 2: CPAP 6 mbar PEEP, 0 ASB, FIO2: 50%
Condition 3: CPAP 6 mbar PEEP, 0 ASB, FIO2: 100%
The order of condition 1 and 3 will be randomized.
Group 1: 21% -> 50% -> 100%
Group 2: 100% -> 50% -> 21%
As a standard setting of NIV with CPAP 6 mbar pressure support will be preferred, if another
setup is required, it will be noted in the CRF. After each 10min-period an arterial and
central venous blood sample will be drawn, to perform a blood gas analysis (BGA). CPAP and
NIRS measurements are both non-invasive in nature. ABP on the other hand is an invasive
procedure, which will only be performed if an arterial access is already available. It will
also be used for drawing a blood sample (each 2ml) for the BGA. No additional invasive iv.
line will be installed for the study.
So far there is little data concerning the effects of NIV therapy on rSO2 in patients with
respiratory failure on an ICU setting.
However, there are pilot studies on other breathing deficiencies like obstructive sleep apnea
syndrome. They investigated NIV in OSAS patients with the help of NIRS. A periodic decrease
in HbO2, blood volume (BV) and the tissue oxygenation index (TOI) which is practically the
same as rSO2, could be shown. These studies demonstrate that the mentioned periodic decrease
can be eliminated through CPAP therapy.
A number of other studies investigated a different parameter, namely the cerebral blood flow.
For this they used transcranial Doppler Ultrasound in patients with OSAS as well as healthy
volunteers under CPAP therapy. The results of these studies are not consistent, as they show
both de- and increases in the cerebral blood flow during CPAP therapy. The inconsistency of
cerebral blood flow is not completely understood. A possible explanation is the relative
change in PaCO2, which is already higher in OSAS patients compared to healthy individuals.
That would also mean that applying CPAP therapy in healthy volunteers may be harmful, since
the lowering in PaCO2 might cause a vasoconstrictive reaction in the brain supplying vessels,
lowering the cerebral oxygenation. OSAS patients are more adapted to high levels of PaCO2.
Therefore, the vascular response (vasoconstriction or vasodilatation) to an alteration in
PaCO2 may differ between patients with pulmonary diseases in comparison to healthy
individuals. 30-33
We want to investigate differences in rSO2 in patients undergoing CPAP therapy with different
FiO2 settings each for 10min, in order to evaluate the immediate effect of NIV on cerebral
oxygenation in ICU patients with breathing deficiency in order to conclude on the accuracy
and liability of the NIRS technique.
Primary study objective:
Influence of NIV on rSO2
The following parameters will be measured, calculated and noted in the CRF:
- Blood pressure (BP)
- Heart rate (HR)
- SpO2 (FingerClip- peripheral oxygen saturation)
- rSO2 (left and right hemisphere and shoulder)
- BGA: pO2, pCO2, pH, Haemoglobin (Hb), Hk, SO2, pCO2, BE, SBC
- Ventilation: PEEP, Minute volume, Tidal volume, Respiratory rate, FiO2
- ASA Classification (1-4)
Additionally, the occurrence of vomiting and nausea, headache and agitation during the CPAP
therapy will be registered with yes and no. The indication of CPAP in each patient will be
documented.
Additionally other side effects will be registered (according to the CRF):
-side effects under CPAP
In our previous study (Doerr et al., 2018) a mean difference of 5.9 between COT vs. CPAP with
a standard deviation of 4.2 was observed. Based on that result we expect half the difference
(2.95) between both FIO2 21% vs 50% and FIO2 50% vs 100%. Based on a paired t-test with a
total sample size of 25 (+ 5 accounted for drop-outs) this results in a power of 0.8.
