>> Good morning, ladies and gentlemen, Mr. President, Mr. Bushner, it's a great pleasure
and also a great [inaudible] to present our clinical trial today.
That compared effect of post-extubation high flow nasal oxygen alone
or with noninvasive ventilation on re-intubation among patients
at high risk of extubation failure.
If you are interested in the study, you can find more details in the full article published today
in "The Journal of American Medical Association."
These are my conflicts of interest.
The study was funded by the French Ministry of Health.
Fisher and Baker provided to all participating centers the high flow nasal oxygen equipment.
And I also report personal fees from Fisher and Baker for lectures
or to attend scientific meetings.
The decision to extubate in the ICU is a daily challenge for clinicians because in a number
of cases, patients fail extubation and need re-intubation.
The usual rate of re-intubation is around 10-15% in the ICU.
But mortality of these patients as indicated
in black box is particularly high, ranging from 25 to 50%.
Meaning the same mortality, for example as [inaudible] patients.
Noninvasive ventilation maybe useful after extubation,
and last clinical practice guidelines suggest that noninvasive ventilation should be used
to prevent post-extubation respiratory failure in patients at high risk of re-intubation.
But this was a conditional recommendation with a low certainty of evidence because few studies,
few randomized control trial found significant decreased re-intubation rate
as compared to standard oxygen.
The most famous study is probably this one from [inaudible] that included 100 patients
in 3 centers, only hypo apneic patients and this was a positive study
that found significant decreased mortality at day 90.
I'm rather pro noninvasive ventilation but I was not completely convinced by the study,
because there was no difference in the ICU and it's difficult to think
that noninvasive ventilation applied only 24 hours
after extubation may decrease mortality long term mortality
without have a strong impact in the ICU.
Patients treated with noninvasive ventilation had less post-extubation respiratory failure,
but re-intubation rates did not defer probably
because the study wasn't a cohort to show such difference.
And finally, in clinical practice in this large survey from [inaudible] including more
than 8000 patients in many countries, many ICU, the re-intubation rate,
the overall re-intubation rate was 12%, but only 10% were treated
with noninvasive ventilation after extubation.
High flow nasal oxygen could also be useful after extubation.
And this study, another Spanish study, 600 patients were included not hypo apneic patients.
And despite a small difference as indicated by the arrow, 24 hours after extubation
when the treatment was stopped, there was no difference
and high flow nasal oxygen was considered as not inferior to noninvasive ventilation.
To keep looking for the most efficient strategy of oxygenation after extubation,
we conducted the [inaudible] trial, medical center randomized clinical trial.
Including only patients at high risk of extubation failing in the ICU
and to determine whether high flow nasal oxygen
with non-invasive ventilation immediately applied after extubation may reduce the rate
of re-intubation as compared to high-flow alone.
Our trial included more than 600 patients at high risk.
They were randomized, they were stratified, according to PCO2 liter in order
to have the same proportion of hypo apneic patients in the two groups.
And they received high-flow nasal oxygen alone, or high-flow nasal oxygen with an IV.
And our primary outcome was re-intubation within the 7 days following extubation.
We included patients at high risk, meaning patients older than 65
or with underlying cardiac respiratory disease, according to our previews, preliminary study.
Because in this group, we found re-intubation rates exceeding 20%.
Underlying chronic lung disease included COPD, obesity,
hyperventilation syndrome, respiratory pulmonary disease.
And underlying chronic cardiac disease including left ventricular dysfunction.
History of cardiogenic pulmonary edema, ischemic heart disease, or atrial fibrillation.
And all patients were previously intubated at least 24 hours prior to extubation.
And they were all ready for extubation.
Meaning, they had successfully undergone a spontaneous breathing trial.
Based on another previous study that we perform, we found that just before the study,
we found that patients treated with NIV had decreased risk for re-intubation.
And in this study, we found that NIV
and [inaudible] incision was associated with 15% re-intubation rate.
And therefore, by combining noninvasive ventilation and high-flow,
we hypothesized that we could further reduce reintubation rate to 10%, and we expected rate
around 18% in the control group, the high-flow group.
The methodology was previously published.
Patients in the control group received high-flow with a flow
of 50 liters per minute for at least 48 hours.
And patients in the interventional group received high-flow and noninvasive ventilation.
Noninvasive ventilation was delivered
for at least 12 hours a day during the 48 hours after extubation.
When to stop the treatment.
When there were no signs of respiratory failure, 48 after extubation.
But the treatment could be continued until completely respiratory recovery.
And in case of established post extubation respiratory failure, NIV was discouraged
in accordance to clinical guidelines because in this setting,
NIV may worsen outcome by [inaudible] re-intubation.
This our pre-specified criteria for re-intubation.
At least two criteria to define several respiratory failure.
Respiratory rate above 35, clinical signs of respiratory distress, respiratory acidosis
or hypoxemia defined as the need of FiO2 at least 80% to have adequate oxygenation.
And obviously comma, cardiac arrest.
The result?
We screen more than 3000 patients, the exclusion criteria where long term treatment with NIV,
neuromuscular disease, and planned extubation.
Patients intubated less than 24 hours, and especially patients
with do not re-intubate order at time of extubation.
Finally, we included 302 patients in the high-flow oxygen group
and 339 patients in the NIV group.
These are the main characteristics.
The main reason for intubation was acute respiratory failure in nearly half of patients.
More than 70% of patients were older than 65.
Nearly half of patients had underlying cardiac disease.
And nearly 30% of patients had underlying respiratory lung disease.
Overall around 30% of patients had difficult or prolonged weaning, meaning that they had failed
at least one spontaneous breathing trial prior to extubation.
This is the main result [inaudible] may occurs in the two groups
and representing the proportion of patients requiring re-intubation in a range
in the NIV group, and in blue the high-flow oxygen group we found re-intubation rate of 18%
in patients treated with high-flow and 12% in patients treated with NIV where we close
to the expected rates if you remember previous slide.
NIV was delivered with a pressure support of 8 centimeter of water [inaudible]
and a peak level of 5 centimeter of water.
Very important, patients received in mean 13 hours of noninvasive ventilation
within the first 24 hours after extubation.
And time to re-intubation did not differ between the two groups.
These are the main secondary outcomes.
Patients treated with NIV had lower post-extubation respiratory failure
as compared to the others, 21 versus 29.
The rate of reintubation up until ICU discharge was also significantly lower in patients treated
with NIV as opposed to those treated with high-flow alone, 12 versus 20.
Mortality in the ICU did not differ between the two groups.
And to reinforce our results, the proportion of patients
who met re-intubation criteria was lower in patients treated with NIV as compared
to patients treated with high-flow alone.
Now the group analysis, you remember that we stratified according to PCO2 level.
And you can see the primary outcome in hyper apneic at left.
And in non-hyper apneic patients at right.
Reintubation rate was significantly lower with non-invasive ventilation
in hyper apneic patients as compared to high-flow oxygen alone.
Whereas it was not the case in non-hyper apneic patients.
But it's very important to understand
that there was no interaction between PCO2 and reintubation.
Meaning that there was no difference, no heterogeneity of treatment effect
between hyper apneic and non-hyper apneic patients.
And, for example, the rates of re-intubation in the ICU were significantly lower using NIV
as compared to patients treated with high-flow alone, with the reintubation in the ICU.
In conclusion, in mechanically ventilated patients at high risk of re-intubation,
the use of high-flow nasal oxygen with NIV applied immediately after extubation
as a prophylactic measure significantly decreased the risk of re-intubation as compared
with high-flow nasal oxygen alone.
Thank you.
[ Applause ]
>> Hi, Daniel Thomas from Germany.
I have two questions.
What is your nurse to patient ratio if you provide 13 hours of NIV within 24 hours?
And the second question is you show pretty impressive data
that re-intubation increases risk for death,
but in your study you had totally no effect on death.
How do you explain that?
Was it difference in tracheostomy at the end or something like that?
>> The first question, what was the first question 13?
>> What is your nurse to patient ratio
that you can actually provide in real life 13 hours of NIV?
>> Our protocol to apply noninvasive ventilation, we use a first station
of four hours, and then stations of two hours.
And we promoted the use of noninvasive ventilation throughout the night,
the entire period of night.
And the main objective was to apply at least 12 hours of noninvasive ventilation.
And the second question about mortality, it's normal not to show a difference of mortality,
and for that the study was planned to found a significant difference in terms of reintubation
because as you see on the figure, the mortality is around 35% in patients who need reintubation.
And therefore, we should plan a study with three times scale with more patients
to show a difference of mortality.
For example, the difference of mortality 3%,
our difference for mortality for re-intubation is 6%.
And therefore, we didn't expect to find a difference of mortality.
Only one-third of patients died and therefore we need three times more patients
to show a difference of mortality.
What we wanted to show was a difference of re-intubation, just re-intubation.
>> Thank you.
And sincerely congratulation.
You had a high percentage of patients who had chronic cardiac failure.
Did you try to stratify your sample, maybe a post hoc analysis just to see
if there were differences between those who had cardiac failure and those who hadn't?
>> No, we didn't, no.
We stratified only on PCO2, maybe we will do future analysis.
But I don't remember nearly half of patients had cardiac disease, but a smaller proportion
of patients had left ventricular dysfunction.
For example, patients had also ischemic cardiopathy,
but without cardiac failure for example.
But will do maybe a group analysis to determine what is the best group.
>> For discriminating the effect of noninvasive intubation on the cardiac function.
>> But in my opinion, maybe hyper apneic was a good option to stratify our patients
because we have previous studies with better, could have better beneficial effects
as compared to non-hyper apneic patients.
And it's true that we show that the difference was probably more stronger
in hyper apneic patients.
>> Thank you.
>> Last question in the back.
>> Yes, [inaudible] thank you for your very nice study.
And following what was Professor Antonelli [assumed spelling] comment,
regarding cardiac dysfunction, I saw you included patient
with systolic impairment, but what about diastolic?
>> It's too difficult to assess diastolic dysfunction in practice.
>> I know it is more connected with [inaudible] than systolic.
>> But who is going to detect diastolic dysfunction very accurately
in the room, but I think it's too difficult.
>> Okay, that's fair.
>> Sorry.
>> Thank you very much, Arnell.
>> Thank you.
[ Applause ]