Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04758546 |
| Other study ID # |
7/10/2020 Nº 10 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2021 |
| Est. completion date |
March 31, 2023 |
Study information
| Verified date |
April 2023 |
| Source |
Hospital Virgen de la Salud |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hypothesis:
1. In patients with less than 4 high risk factors for reintubation excluding body mass
index >30 and hypercapnia during the spontaneous breathing trial (SBT) (low and
intermediate risk for extubation failure), who receive preventive therapy with high flow
nasal cannula (HFNC), the use of SBT with "HIGH minimal ventilator settings" (PS 8 +
PEEP 5 cm H2O Vs PS 5 + PEEP 0 cm H2O), increase the proportion of patients with simple
weaning (extubation after the first SBT).
2. In patients with low and intermediate risk for extubation failure, who receive
preventive therapy with HFNC, the use of Walsh screening criteria reduces the mechanical
ventilation time compared with the use of Boles criteria.
Study design: This is a multicenter randomized open trial with 4 arms.
1. Screening with PaO2/FiO2 > 180 and PEEP ≤ 10cm H2O; SBT with "HIGH minimal ventilator
settings" (PS 8 + PEEP 5 cm H2O).
2. Screening with PaO2/FiO2 > 180 and PEEP ≤ 10 cm H2O; SBT with "LOW minimal ventilator
settings" (PS 5 + PEEP 0 cm H2O).
3. Screening with PaO2/FiO2 ≥ 150 and PEEP ≤ 8 cm H2O; SBT with "HIGH minimal ventilator
settings" (PS 8 + PEEP 5 cm H2O).
4. Screening with PaO2/FiO2 ≥ 150 and PEEP ≤ 8 cm H2O; SBT with "LOW minimal ventilator
settings" (PS 5 + PEEP 0 cm H2O).
Primary Outcome Measure:
1. - Percentage of first spontaneous breathing trial tolerated.
2. - Time on mechanical ventilation.
Description:
Discontinuation of mechanical ventilation is a three-step process including:
1. - Readiness testing.
It evaluates the criteria to determine whether a patient might be able to be
successfully and safety weaned from mechanical ventilation. The detection of readiness
to try a spontaneous breathing test has controversial questions, in special concerning
to oxygenation. From a conservative to an aggressive criteria we can list:
1. PaO2/FiO2 > 200 on PEEP ≤ 5 cm H2O (Esteban et al, 1999).
2. PaO2/FiO2 ≥ 150 on PEEP ≤ 8 cm H2O (Boles et al, 2007).
3. PaO2/FiO2 > 180 on PEEP ≤ 10 cm H2O (Walsh et al, 2004). We will compare Walsh and
Boles in their different considerations for oxygenation criteria. Since Walsh
criteria require a higher level of PEEP we understand that this criteria is more
aggressive and in this way it allow to an early detection of readiness to SBT, but
there is not any evidence of this statement.
2. - Spontaneous breathing trial (SBT). It tries to simulate (but not only) post-extubation
work of breathing to promptly determine the time to extubation. There is also disparity
about SBT minimal ventilator settings:
1. Inspiratory pressure with a range between automatic tube compensation (ATC) and
inspiratory pressure of 5 - 8 cm H2O. Theoretically, if we use a higher support
pressure during SBT it would be easier to pass the test. One could think that this
may rise the risk of reintubation but there are various trials that have not
confirmed this assumption.
2. Guidelines does not make any recommendation about expiratory pressurization,
although the trials conducted use levels of Positive End-Expiratory Pressure
(PEEP), between 0 and 5 cm H2O.
3. Furthermore, we consider that "minimal ventilator settings" must be adjusted to
additional parameters not previously considered, like preventive therapy applied
after the extubation.
4. All spontaneous breathing trials will last 30 minutes.
3. - Extubation follow-up care. Therapies targeted to prevent post-extubation respiratory
failure like high flow nasal cannula (HFNC), noninvasive ventilation (NIV) and
respiratory physiotherapy for improving airway clearance, have been proposed.
The variability of preventive therapies and its settings generate different "minimal
ventilator settings".
In view of all that has been set out above, there are two essential points that has not been
analyzed as far we understand:
1. The different screening criteria available have not been compared with each other about
allowing early detection of readiness, even less with the individual risk of
postextubation failure and still less with the preventive therapy that would be applied
for each group.
2. The different inspiratory support pressure as well as PEEP level, have not been compared
with other different values, even less with the individual risk of postextubation
failure and still less with the preventive therapy that would be applied for each group.
The detailed weaning criteria include the following:
- Clinical evaluation:
- Adequate cough reflex and good clearance of respiratory secretions.
- Resolution or stabilization of the initial reason for intubation.
- Patient awake with RASS between +1 and -2 according the Richmond Assessment
Sedation Scale (RASS).
- Data evaluation:
- Cardiovascular stability with minimal or no need of vasopressors (HR ≤ 140 lpm,
blood systolic pressure between 90-160 mmHg with minimal or no need of vasopressors
and without increase in the last 24 hours).
- Successful oxygenation defined by SpO2 >90% on FiO2 ≤ 40% or PaO2/FiO2
≥150 with PEEP up to ≤8 cmH2O (Boles et al, 2007) or PaO2/FiO2 >180 con PEEP ≤10 cm
H2O (Walsh et al, 2004).
- Respiratory rate ≤35 bpm without respiratory acidosis.
- Hemoglobin >7g/dL.
- Temperature between 36-38,5ºC.
- Blood potassium between 3-5 mmol/L.
- Blood sodium between 128-150 mmol/L.
Detailed definition of high risk factors for extubation failure: age older than 65 years;
heart failure as the primary indication for mechanical ventilation; moderate to severe
chronic obstructive pulmonary disease; an Acute Physiology and Chronic Health Evaluation II
(APACHE II) score higher than 12 on extubation day; body mass index of more than 30
(calculated as weight in kilograms divided by height in meters squared); airway patency
problems, including high risk of developing laryngeal edema; inability to deal with
respiratory secretions (inadequate cough reflex or suctioning >2 times within 8 hours before
extubation); difficult or prolonged weaning, in brief, a patient failing the first attempt at
disconnection from mechanical ventilation; 2 or more comorbidities defined with Charlson
score; and mechanical ventilation for more than 7 days.
The detailed risk categories are the following:
- Low risk: Patients without risk factors who benefit from HFNC.
- Intermediate risk: Patients with 1 to 3 risk factors excluding obese (BMI >30 Kg/m2) and
those who develop hypercapnia during the SBT, that can benefit from HFNC.
- High risk: Obese (BMI >30 Kg/m2) and patients with 4 or more risk factors including
hypercapnia during the SBT. This group may benefit from prevention with NIV.
Sample size estimation:
- Basal parameters in low risk patients treated with post-extubation HFNC: estimated 30%
of the entire population. Reintubation rate 4.9% and 1(1-3) days on mechanical
ventilation. Estimated reduction in the intervention group: 1 day in the 25% of the
patients.
- Basal parameters in intermediate risk patients treated with HFNC: estimated 70% of the
entire population. Reintubation rate 12.24% and 4 (2 - 9) days on mechanical
ventilation. Estimated reduction 1 day in the 33% of the patients).
Calculated standard deviation 3.5 days. CI 95% and power 80%, loss rate 10%, and one-tail
analysis: 260 patients per group.
Simple randomization immediately after finishing the spontaneous breathing trial. An
intention to treat analysis will be performed.
Detailed HFNC treatment: High-flow oxygen (Optiflow, Fisher and Paykel Healthcare) will be
applied immediately after extubation through specific nasal cannula. Flow will be initially
set at 10 L/min and titrated upwards in 5-L/min steps until patients experience discomfort.
Temperature will be initially set to 37°C, unless reported too hot by patients, and FIO2 will
be regularly adjusted to the target peripheral capillary oxygen saturation (SPO2) of greater
than 92%. After 48 hours, high-flow will be stopped and, if necessary, patients will receive
conventional oxygen therapy.
Criteria for spontaneous breathing trial failure are: agitation, anxiety, depressed mental
status, diaphoresis, cyanosis, evidence of increasing respiratory effort, increased accessory
muscle activity, facial signs of distress, dyspnea, PaO2 lower than 60 mmHg or SpO2 lower
than 90% on inspired fraction of oxygen higher than .5, PaCO2 higher than 50 mmHg or
increased more than 8 mmHg from baseline value, arterial pH lower than 7.32 or decreased more
than .07 from baseline value, respiratory rate higher than 35 breaths per minute or increased
more than 50% from baseline value, heart rate higher than 140 beats per minute or increased
more than 20% from baseline value, systolic arterial pressure higher than 180 mmHg or
increased more than 20% from baseline value, systolic arterial pressure lower than 90 mmHg,
or cardiac arrhythmias.
Patients who tolerate the spontaneous breathing trial will be reconnected with the previous
ventilator settings for rest and clinical evaluation of airway patency, respiratory
secretions, and upper airway obstruction before extubation.
