Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03929055 |
| Other study ID # |
HFNC |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2018 |
| Est. completion date |
June 1, 2021 |
Study information
| Verified date |
November 2020 |
| Source |
University of Milan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to assess the effect of HFNC on esophageal pressure and
diaphragmatic function in patients with acute respiratory failure
Description:
In recent years, new devices that deliver totally conditioned gas through a nasal cannula at
high flow have emerged as a safe and useful supportive therapy in many clinical situations.
High flow nasal cannula (HFNC) supportive therapy is one such technique that exerts its
potential benefits through a variety of mechanisms. In the last two decades, HFNC supportive
therapy has emerged as a safe, useful therapy in patients with respiratory failure. Several
mechanisms are known to contribute to oxygenation improvement and carbon dioxide reduction,
which are the main potential benefits of using HFNC therapy. However, the exact contributions
of each mechanism have not been conclusively established and these may, in fact, vary from
one patient to another. Recently several clinical trials have analyzed the effectiveness of
HFNC therapy in different clinical situations and have reported promising results such as the
potential to improve clinical outcomes. However, the physiologic mechanisms underlying the
clinical benefits of HFNC are still poorly understood in adult patients. Basic clinical
monitoring during HFNC therapy demonstrated rapid improvement of oxygenation and reduction of
dyspnea in comparison to a standard facial mask. Findings in other populations indicate that
advanced respiratory monitoring might demonstrate other specific physiologic effects such as
the reduction in inspiratory effort and increment in lung volume that may prevent respiratory
muscle exhaustion and lower the tidal volume/end expiratory lung volume (EELV) ratio.
Moreover, It has been hypothesized that the continuous administration of a very high flow of
gas flushes the carbon dioxide (CO2) out of the upper respiratory airway, avoiding the
re-inhalation of the previous exhaled gas. A randomized, crossover, experimental study with
neonatal piglets with lung injury treated with continuous positive airway pressure (CPAP;
minimal leak) or a HFNC with a high or low degree of leak around the nasal prongs showed that
under both HFNC leak conditions PaCO2 decreased and oxygen arterial pressure (PaO2) increased
with increasing flow. This effect of nasopharyngeal dead space washout was associated more
with increases in flow rates than with increases in pressure. Thus, compared with the masks
used with conventional oxygen delivery devices, nasal prongs reduce dead space.
Additionally, high velocity flows likely reduce inspiratory resistance and allow the patient
to breathe from their dead space, rather than through it. This is how high velocity Nasal
Insufflation helps reduce work of breathing, respiratory rate and assists in increasing
alveolar ventilation efficiency.
The relative contribution of the patient's effort during assisted breathing is difficult to
measure in clinical conditions, and the diaphragm, the major muscle of inspiratory function,
is inaccessible to direct clinical assessment. Several methods have been used in the research
setting to assess diaphragmatic contractile activity. Bedside ultrasonography, which is
already crucial in several aspects of critically illness, has been recently proposed as a
simple, non-invasive method of quantification of diaphragmatic contractile activity .
Ultrasound can be used to determine diaphragm excursion which may help to identify patients
with diaphragm dysfunction Ultrasonographic examination can also allow for the direct
visualization of the diaphragm thickness in its zone of apposition. Thickening during active
breathing has been proposed to reflect the magnitude of diaphragmatic effort, similarly to an
ejection fraction of the heart. In spontaneously breathing patients, thickness fraction was
shown to be positively related to tidal volume and thickness measurements during spontaneous
breathing may be influenced by lung volume in a non-linear relationship, and diaphragmatic
thickening was shown to be more pronounced above 50% of vital capacity. It seems reasonable
to expect that the high flow nasal cannula may modify the thickness or diaphragm thickening
and its excursion depend on the level of positive end expiration pressure generated. On the
other hand, it could also happen that with a relevant increase in tidal volume the
diaphragmatic excursion may remain constant. The most likely explanation is that a higher
portion of the tidal volume (VT) is distributed to the non-dependent lung region due to
better compliance of this area, as recently shown with electrical impedance tomography
analysis. Another possible explanation is that patients' respiratory muscles could be
over-assisted and the diaphragm may be passively displaced downward by simply improving gas
exchange efficacy.
The aim of the present study is to compare the HFNC, Helmet continues positive airway
pressure (CPAP) and venturi mask on the inspiratory effort, respiratory rate, gas exchange,
level of dyspnea and diaphragmatic function evaluated by US in a group of patients with acute
respiratory failure (ARF).
Inclusion and exclusion criteria The study has been submitted to our local ethics committee
and patients will receive their written informed consent. All consecutive patients with acute
respiratory failure presenting as respiratory rate higher than 25-30; Pao2 / oxygen
inspiratory fraction (FiO2) ratio less than 300 supported with venturi mask at 30% Fio2.
Patients will be exclude if there will be present one of the following conditions: PaO2/FiO2
less than 100; hemodynamic instability (mean arterial pressure lower than 60 mmHg after fluid
challenge) and impossibility to insert the esophageal monitoring. Sample size calculation is
based on the results of the study by Mauri, in which the application of HFNC at a similar
flow rate to patients suffering from acute hypoxemic respiratory failure determined a
reduction in esophageal pressure swing from 9.4+-4.1 to 7.9+-3.0. If the investigators
hypothesize that a similar effect size is present in our patient population, a sample size of
25 patients will be necessary to achieve a level of significance of 0.05, with a 0.8 power,
for a repeated-measures study design. Normally distributed variables are expressed as mean ±
standard deviations and were analysed by a paired t-test. Non-normally distributed variables
are expressed as medians and were compared by Wilcoxon's signed rank test. Correlations were
analysed by Pearson's coefficient. A level of p<0.05 (two-tailed) was considered
statistically significant.
Experimental settings and Measurements A cross over study. Patients will enter in the three
study phases with the same set clinical FiO2 for 20 minutes: standard Venturi oxygen mask
with FiO2 regulated to achieve 90-04% of oxygen saturation (SpO2) with a flow rate of 35-40
Litters/minute (L/m); high velocity nasal insufflation (Precision Flow) with optimized gas
flow; Helmet CPAP with positive end expiatory pressure (PEEP) set to reach the same
esophageal swing obtained with HFNC. Using a small-bore nasal cannula the study will start
with a flow rate set to 35 L/min, with a starting temperature between 35°C and 37°C and FIO2
at 1.0. Adjustments in flow (within the range of 25 L/min to 40 L/min) and temperature
(typically between 35°C to 37°C) are made to alleviate respiratory distress and optimize
comfort; FIO2 was titrated to maintain SpO2 at 90-94%.
At enrolment, the investigators will collect the patients' main demographics and clinical
data. An esophageal balloon catheter will be placed in the esophagus, as demonstrated by the
appearance of cardiac artefacts and appropriate negative swings of pressure tracings during
inspiration. Esophageal pressure waveforms will be continuously recorded by a dedicated data
acquisition system throughout the study. At each steps ultrasonography of the diaphragm will
be performed using an ultrasound machine (GE Healthcare) equipped with a high-resolution
10-megahertz (MHz) linear probe and a 7.5-MHz convex phased-array probe. Images will be
recorded for subsequent computer- assisted quantitative analysis performed by a trained
investigator. The convex probe will be placed below the right costal margin along the
mid-clavicular line, so that the ultrasound beam are perpendicular to the posterior third of
the corresponding hemi-diaphragm, as previously described. Patients will be scanned along the
long axis of the intercostal spaces, with the liver serving as an acoustic window. M-mode
will then be used to display diaphragm excursion. Diaphragm thickness (DT) will be assessed
in the zone of apposition of the diaphragm to the rib cage. The inferior border of the
costophrenic sinus will be identified as the zone of transition from the artifactual
representation of normal lung to the visualization of the diaphragm and liver. In this area,
the diaphragm is observed as a three-layered structure: a non-echogenic central layer
bordered by two echogenic layers, the peritoneum and the diaphragmatic pleurae.
