Discussion
Q (Dr. Fernando Supagerri Dias):I have a question. Some videos on YouTube that have run about the use of two patients could be ventilated by one machine. I have a lot of concerns about this technique. And people say that in situations with a lot of patients to be ventilated, this strategy could be used. What do you think about this? I'm afraid to use one ventilator, one machine for two patients.
A (Dr. Youzhong An): As I know in Wuhan, in China, we use the ventilator one for a single patient. So it's not for two patients. It's only for a single patient. But I want to hear the evaluation from Du Bin for that. I don't think it's a good idea - the one ventilator goes two patients and more. So you couldn't observe what's real and you don’t know the response of the patients. So you couldn't adjust the parameters for the ventilators. But for me, we didn't meet these kinds of problems. So actually in Wuhan at the same time, we have thousands of licensed ventilators. So it's not a big problem now in China.
Q (Dra. Flavia Machado): May I ask another question to Prof. Youzhong? Now things are going much nicer, or at least we've heard, that in China things are under control. Can you talk a little bit about that because as we see in the WHO register, the new cases are very few? So how's it going and if it's better, what do you believe makes it become better?
A (Dr. Youzhong An): Yeah. It's a good question. So we do pay
attention to the second outbreak at the moment. We did much better
than January, so I think that we have some different experience
compared to the European countries and the United States. Because we
have full centralization and at the very beginning the outbreak in
Wuhan is much like now in Italy, Spain, and the United States.
But after that, the government sent a lot of healthcare workers to
Wuhan, but it's not the only thing that's very important. The very
important thing is early testing of the patients, early diagnosis of
the patients, because when I came to Wuhan - it's about eight weeks
ago - we found that it was a total loss of the control and a lot of
patients and the local healthcare workers were exhausted at that time.
And we were worried about how many patients will come and how many ICU
beds we'll need.
And then we use clinical diagnosis, not only the PCR, but also the CT
scan, the chest x-ray, the academic history for screening the
patients. And after that, we centralize all of the patients as
possible to several shelters - the big shelters. Each of the shelters
could accommodate nearly thousands of patients. And then when all of
the patients that were tested or diagnosed and quarantined in the
shelter, and we could know how many patients are there. And we gave
them the triage: how many mild patients, how many severe patients, and
how many critically-ill patients, and then we tried our best to give
oxygen therapy and ventilation. Then several hundred were intubated
and used mechanical ventilation.
At the moment, we discharge the patients by two types of PCR negative.
Even so, there were still a few patients that were recurrent - maybe
the PCR positive again - that's a big problem. We pay more attention
to these kinds of the patients: if the PCR turns positive again and
they have the contagious, the infectable or even the worse condition.
Now we pay attention to that.
Q (Dr. Fábio Regatieri): Professor, if the
patients are positive again in PCR, you believe they are reinfected or
it's a limitation of the method of the diagnosis?
The PCR is not still safe (reliable)?
What do you think about this?
A (Dr. Youzhong An): It's a good question. So at the very
beginning, we use only the PCR but there are false negative and the
false positive that occurred at very early times. The accuracy is only
maybe 30, 40 percent. Then we try to use some clinical diagnosis, just
as I mentioned, not only the PCR but also the CAT scan, the chest
x-ray. And very important is we need to know the academic histories,
what the contact is and whom the patients contacted before and if
there are any patients he or she contacted.
(Dr.Bin Du is back from disconnection, and continue his answer to the
1st question about the use of two patients could be ventilated.
A (Dr. Youzhong An): It's a good question. So at the very
beginning, we use only the PCR but there are false negative and the
false positive that occurred at very early times. The accuracy is only
maybe 30, 40 percent. Then we try to use some clinical diagnosis, just
as I mentioned, not only the PCR but also the CAT scan, the chest
x-ray. And very important is we need to know the academic histories,
what the contact is and whom the patients contacted before and if
there are any patients he or she contacted.
(Dr.Bin Du is back from disconnection, and continue his answer to the
1st question about the use of two patients could be ventilated.
A (Dr. Bin Du): No. I am not aware of any single case managed
by multiple patients ventilated with one ventilator. This did not
happen here in Wuhan. However, I should say that ventilating two
patients with one ventilator requires that the patients to be of the
same size and the same lung mechanics, which might be very difficult.
We have no way to monitor how large and what is the total volume for
two individual patients, so I don't think it's (possible)... unless
you have very similar patients.
Q (Dra. Flávia Machado): Can I come back to my question that Prof. Youzhong was answering because I'm not sure I understood the answer? Are you saying that you believe 20% of the patients that have a clinical diagnosis of COVID are PCR negative and you're treating them as false negatives, and isolating them as if they were positive? Is that what you said?
A (Dr. Youzhong An): So for that type of the patients, we at first very early quarantined all of them and tested again and again to find if we have at least two or three times that it's a negative, and even we referred to the chest... CAT scan. And if no symptoms and no CAT scan changes and we didn't find any pneumonia and even they have no symptoms and asymptomatic and the PCR is still negative, we diagnose that they are not COVID-19. And I think in the shelter, maybe some people are false positive. Even in the hospital there are a few of the cases that the final diagnosis is not COVID-19. But it's not too many. But how about Du Bin's opinion?
Q (Dr. Bin Du): I did not get the question. What
is the question?
Q (Dra. Flávia Machado): Du Bin, we have a problem here. For
instance, now at this time of COVID-19 epidemics, if the patient is
coming with a PCR that it's negative, we are taking him out of
isolation. If a single negative PCR, my question is, even if it's a
clinical picture is suggestive of COVID-19, if the PCR is negative, we
are taking them out of the isolation. So the question is, do you think
this is safe? Are you seeing too many false-negative patients after
the first PCR became positive?
A (Dr. Bin Du): Well, Flavia, I would say this is not an
appropriate approach because as Dr. An said that there are many
patients that who had - I mean initially - who had negative PCR test
but eventually turn out to be positive. I mean according to the
repeated PCR test. I even know a case that in my hospital back in
Beijing who had repeated about five or six times on PCR. I mean all
the previous PCR test was negative until the last one because the
clinicians suspected that even though it was a negative PCR test, they
suspected this is a case of COVID-19. So I have no perfect explanation
for the false-negative results with regards to the PCR test. I think
among all the possible explanations, I think there are several, such
as the different manufacturers of the test kit about the sampling
technique. I do believe their sampling technique might play a very
important role. And I'm not quite sure if the viral shedding will
persist day after day, or it will fluctuate that the viral shedding
will occur periodically. I am not quite sure about the last
explanation. But anyway, this happened not in the minority of the
cases. So I would say that only do not isolate patients based on only
one negative PCR test, (it) might be inappropriate..
A (Dra. Flávia Machado): Thank you. I understood quite well.
Q (Dr. Luciano Azevedo): Can I ask one question? Could you two professors please comment on the use of hydroxychloroquine or the use of antivirus in China? Did you use a lot of patients? Did use only in the more severe ones or? Can you comment, please?
A (Dr. Youzhong An): In our hospital in Tongji Hospital, we use
some chloroquine but I don't think there are significant differences
between the control and test group. Either for hydroquine or normal
quine, there is no significant difference up till now. But not so many
cases, I think are maybe 20, or 20 more.
A (Dr. Bin Du): I agree with Dr. An in saying that actually in
Wuhan multiple antivirals have been tested clinically, but not in a
clinical trial. So I don't believe we have solid data or convincing
data supporting or against one over the other. But anyway, according
to the information that I have right now, there is no effective
antiviral agent against the COVID-19, against the SARS-COVID-2.
A (Dr. Youzhong An): And even have some the side infections for
the eye and the liver function.
A (Dr. Bin Du): Yeah. And I think there is a question raised by
Isadora about the nasal high-flow... nasal cannula. It has been used
very often here in Wuhan and other cities in Hubei province. However,
according to my judgment, the failure rate might be high either due to
persistent hypoxemia at rest or exertional. Or it could be persistent
dyspnea or respiratory distress. Even on the high-flow nasal cannula.
So I will not suggest a trial of the high-flow nasal cannula for
longer than one or two days.
Q (Dr. Fábio Regatieri): Professors, I have a question about the time of evolution from the first symptoms in the patient until he needs mechanical ventilation. There is an average time in the cases who begins more severe that you can notice?
A (Dr. Bin Du): The timeline? The presenting signs and symptoms
of COVID-19 usually start with the, ever, dry cough. However, some of
the patients will develop, diarrhea, nausea, and vomiting instead of
the respiratory symptoms assign. But that’s a minority. They seem okay
during the first week. So it is very common for these patients at the
end of the first week, they will develop shortness of breath or
dyspnea or respiratory distress and hypoxemia. So it's about five to
seven days, after disease onset, they will have signs of respiratory
failure.
And here in Wuhan, they will be admitted to the hospital whenever they
had respiratory failure, and then on day 10 to day 14, they will be
admitted to the ICU if the respiratory failure is severe enough to be
admitted to the ICU. And if he or she was intubated... invasive
mechanical ventilation, the need for the survivors, and the duration
of mechanical ventilation usually two to three weeks. You never
weaning the patient within one week. Never.
A (Dr. Fábio Regatieri): Okay, thank you.
Q (Dr. Gustavo Ferreira Araújo): I'd like to
address the ventilation beginning. I have heard some relates in using
the oxygen cannula and the patient benefit from that, so we can
postpone and some patients even don't need ventilation.
But is there a trigger... moment trigger or a system trigger to get
patients on ventilation?
Q (Dr. Bin Du): So the indication for mechanical ventilation,
is your question sir?
A (Dr. Gustavo Ferreira Araújo): Yes, yes. The beginning of
ventilation, please.
A (Dr. Youzhong An): So in my opinion, we need to observe and
monitor not only SPO2 but also the patient’s effort. We use the
high-flow nasal cannula and another oxygen therapy, but if the patient
is very severe, shortness of breath, you could watch the patients have
a very big effort to breathe and even the value of SpO2 maybe 90 or 92
or 93, I think that intubation is the only choice for this kind of
patients.
But in Wuhan, we don't have enough experienced staff to ventilate the
patients. We sedated the patients and paralyze the patient at the very
beginning, and so to decrease the patient-ventilator fighting. And we
try to keep the trans-pulmonary pressure is no more than 20, even 16.
But for me, I don't care about the plateau pressure, but I focus on
the driving pressure. And so we need to keep the driving pressure
within the limit. So it's my opinion. How about Du Bin?
A (Dr. Bin Du): Concerning the timing or indication for
mechanical ventilation, I would say: the first is hypoxemia. Well,
some patients had what we called the silent hypoxemia, which means
whenever you saw the patient, he or she was doing quite okay. There
are no signs of respiratory distress. There are no signs of shortness
of breath or dyspnea. However, when you do the oximetry on the
patient, it read as low as 70 percent, which means I would advise that
to have the SPO2 in every patient. Whatever it turns out to be.
Whether he is in shortness of breath or not, do test SPO2 and so this
is one of the indications. The second one is respiratory distress or
significant inspiratory effort as mentioned by Dr. An. For example in
patients who are ventilated with an NIV, non-invasive mechanical
ventilation, a tidal volume higher than let's say 800, 900 or even
1,000 ml suggests failure and you should consider immediate
endotracheal intubation. I think these are the two indications for
mechanical ventilation.
A (Dr. Youzhong An): I agree. It's very important what Prof.
Du said. When I came to Wuhan there are not so many early-stage
patients. And the patients cannot respond as a short of the breath,
like respiratory distress, even the heart rate is slow, and the heart
rate may be only 70 and even 60 and 80, so that's not a good thing,
because for the oximetry it is only maybe 70% and 80%. So the slow
heart rate and the slow breath rate is not a good thing. It means that
a patient has a very severe damage to their cardiac function and the
breathing function. Do you agree with me Du Bin?
A (Dr. Bin Du): Well, I'm not quite sure, you are talking about
how early or how late these patients are. I do believe that majority
of patients in Wuhan are ventilated till quite late. At the late
stage. I think you have the same experience.
A (Dr. Youzhong An): Yes. The EKG is not significant abnormal
and even the troponin is not so high as a typical myocardial (injury).
A (Dr. Bin Du): Leave the question to the audience. Leave the
question to the other to ask first, okay? May I suggest?
Q (Dr. Fernando Supagerri Dias): I have a question about the patients that develop circulatory shock in this situation. Could you synthesize the best approach for these patients? Vasopressor, I'm sure is not adrenaline; fluids rescuing therapy? and for monitoring the hemodynamic in these patients? (such as) Echoes, pulse pressure variation? How do you manage these patients in the event they develop?
A (Dr. Bin Du): So it's a question about circulatory shock.
Circulatory shock is common in ICU patients. I mean ICU patients
rather than the patients in general wards, with the prevalence of
about 20% or even higher. And just as Dr. An mentioned minutes ago
that even a higher proportion of patients will have evidence of
cardiac injury as suggested by elevated biomarkers of cardiac injury
such as troponin I level, hyper-sensitive cardiac troponin I. Most of
them. And with regards to circulatory shock, I would say that septic
shock is not so common. It's not so common until at the late stage.
Whenever the patient had secondary infection pneumonia or bloodstream
infection. That might be a septic shock. But for the other patients,
you should be aware of the cardiac function, of the cardiogenic shock,
rather than vessel dilatory.
So with regards to vasopressors, yes, the noradrenaline has been used,
although in some of the cases the doctors might administer the
inotropes such as the dobutamine, dopamine and sometimes adrenaline.
Echo has been used widely, especially in February when we are no
longer short of medical devices. And in some cases the doctors, the
clinicians did observe a few patients with so-called acute core
pulmonary, which might be secondary to.
A (Dr. Youzhong An): Yes, I am quite risky for these COVID-19
patients, and so the cardiac function injury is very often. I think
that we use Echo and we could find that it's not congestive heart
failure. But the left ventricle is usually normal and even so smaller
than the normal. But the core pulmonary, like the right ventricle,
it's sometimes enlarged and mild hypertension for pulmonary artery.
And like Prof. Du Bin said that even we have the hypercapnia, the
PACO2 is very high, and if this kind of phenomenon was observed and we
think the pulmonary capillary was damaged very severe and no gas
exchange, and even the blood from the right heart to the left heart
was damaged, that's a problem, and that means the right heart is
hyperdynamic, but the left heart, the left ventricle have not enough
blood to pump to the body.
A (Dr. Fernando Suparregi Dias): This should be a case for
dobutamine.
A (Dr. Youzhong An): We sometimes use dobutamine even
levosimendan.
Q (Dr. Fernando Supagerri Dias): Levosimendan? Did you have a good experience with the levosimendan?
A (Dr. Youzhong An): Yeah. For me, we have two cases to use that. For these two patients, we think this affects. But it's only two cases.
Q (Dr. João Manoel Silva): I would like to know about D-DIMER. Do you use the anticoagulants for this patient?
A (Dr. Bin Du): Anticoagulation such as Heparin or low-molecular-weight Heparin, right? Well, I know that some of the colleagues here will promote or, use the anticoagulation in patients, but out of prophylaxis or out of the context of the DVT prophylaxis. If we are talking about DVT prophylaxis, my answer will be "yes" for the majority of the patients. However, if we are talking about anticoagulation in COVID-19 patients, I don't think so. I don't think we have much good experience or good results from that. No.
Q (Dr. João Manoel da Silva): Okay, and about
PEEP. Which is your experience about PEEP and judgment about PEEP?
Q (Dr. Luciano Azevedo): And also if I can add on recruitment
maneuvers and also on prone position, overall on mechanical
ventilation please, thank you.
A (Dr. Bin Du) : Okay, sure. For mechanical ventilation, I
noticed that Davide Chiumello from Italy said that, COVID-19 is not
like ARDS. I agree with him because it's very rare for you to see a
chest X-ray or chest CT scan to have the consolidation in the
dependent lung. And with regards to the ventilatory strategy, I would
say low tidal volume, ventilation has been widely used as you may
imagine.
However, the PEEP setting might be very interesting because whenever
you increase the PEEP, especially during the initial stage, shortly
after endotracheal intubation, whenever you increase the PEEP or you
perform the recruitment maneuver, the response might be very good.
However, it might be accompanied or associated with a much higher
increase in plateau pressure. For example, I had one patient that I
decrease the PEEP level from 10 to 5, and what I observed is that the
plateau pressure decreased from 30 something to 20. Decreased by 10 or
more than 10 centimeters of the pressure of water. So it means, even a
low PEEP level as 10 might increase the risk of overdistension, which
means that the majority of the patients might have a PEEP level
between 5 and 10 to avoid the alveolar overdistension.
And prone positioning works in about 70 to 80 percent of the patients.
So I would highly recommend prone positioning on top, recruitment
maneuver, or higher PEEP in those patients who had the poor arterial
oxygenation whenever on mechanical ventilation.
A (Dr. Youzhong An): Even some patients not very critical and
not ventilated and we could let them have the prone position, right?
A (Dr. Bin Du): Yes, exactly, and even for patients who are on
NIV or high flow nasal cannula. I know that not a small number of
patients will be put on the prone positioning by their treating
physicians with a very good response.
Q (Dr. Fernando Supagerri Dias): And about the use of the nitric oxide, did you have experience in these patients?
A (Dr. Bin Du): Nitric oxide is not approved by China FDA. So
it's not used in mainland China.
A (Dr. Fernando Supagerri Dias): Okay. Thank you.
Q (Dr. Luciano Azevedo): Can I ask you something about inflammatory cytokine storms on these patients? There are a lot of suggestions from several countries saying that we could use for instance corticosteroids or anti-interleukin-6 blockers like monoclonal antibodies. Did you have any experience with that? Could you comment?
A (Dr. Bin Du): Well, corticosteroids are a highly
controversial issue or topic in viral pneumonia. So you can imagine
that there are a lot of different opinions. I do believe some of my
colleagues - the majority of them are chest physicians -
pulmonologists. They would favor the use of the corticosteroids, and
they will think, escalating the dose of corticosteroids whenever the
patient deteriorated. And there is another group of physicians,
doctors, who do not believe that the corticosteroids will benefit the
patient.
And my impression is that the long-term high dose corticosteroids will
do more harm than benefit, in the long duration of viral shedding, in
worsening the lymphocytopenia and might leading to a higher risk of
the secondary infection. So I'll never use a long-term higher dose of
corticosteroids.
However, I'm not quite sure about the efficacy or safety of the short
term use of corticosteroids, let's say corticosteroids of no longer
than five days, and with a dose of the methylprednisolone of about 80
milligrams per day. So I'm not quite sure about that, but anyway, a
higher dose - let's say 240 or 160, I don't believe so.
But what I'm not quite sure also is that whenever the patient had
resolved, pulmonary infection, either due to the virus or some
bacteria, and there is evidence of pneumonia according to the CT scan
of fibrosis. You might think about the corticosteroids in the absence
of active infection, but that will be the late stage stuff rather than
an early stage.
Frankly speaking, I don't know what is the definition of cytokine
storm in the context of sepsis or severe infection, and I know the
so-called cytokine storm might differ from different clinical
scenarios, and I don't believe the concept of treating patients with
COVID-19 with IL6 monoclonal antibodies is a correct way, because IL6
is not the key. It's not the most important cytokines as far as we
know. So, I think it's based on the wrong principle, wrong concept. I
will never, never use the IL6 monoclonal antibody.
A (Dr. Youzhong An): Yes, if we use IL6 monoclonal antibodies
and we could find that the IL6 level, in serum will be much higher
than we use the monoclonal antibody before, so the cytokine level in
COVID-19 patients is not as higher as some the bacteremia and the
sepsis patient. I don't think that the cytokine storm, like Dr. Du
said, is the key role in the COVID-19. And for the corticosteroid, we
need to monitor the patient's response. If the patient's chest X-ray
or chest scan develops very quickly and maybe we try to use it for
only a couple of days, maybe two or five days - and we observe what is
the change after we use corticosteroid like the methylprednisolone.
There are one or two milligrams per kilo. It's not a big dose. During
the SARS in 2003, we used a long time and the high dose of
corticosteroids, but they were not so good and a lot of side effects
for the SARS patients.
Q (Dr. Fernando Suparregi): In patients that develop an acute adrenal injury, what's the time to start renal therapy, and did you use continuous or intermittent renal replacement therapy?
A (Dr. Bin Du): Well, around 20% of patients had an acute
kidney injury - very severe ones requiring the hemodialysis. Both
intermittent and continuous has been used here. The major difference
is in human resources. So if you don't have enough human power, you
may consider the intermittent. As what happened in the hospital which
I visited regularly during the past three days, they will offer an
eight-hour daily session of renal replacement therapy for every
patient who requires hemodialysis. However, in other hospitals, we can
see continuous renal replacement therapy whenever they have enough
human power - enough nurses.
A (Dr. Youzhong An): If it is for ECMO patients, it's
continuous.
Q (Dr. Fábio Regatieri): Professor, what do you think about the prone position in ventilation? Is it used for in these cases or it's not established?
A (Dr. Bin Du): Well, although there has been no paper
published yet, I just mentioned that our personal experience was prone
positioning in patients requiring invasive mechanical ventilation,
also in patients with non-invasive mechanical ventilation and even in
some patients treated with the high flow nasal cannula. I mean our
experience is very good. And I have talked with some doctors from
Italy and they had the same observations - the same results - that
prone positioning will be a very good method to improve arterial
oxygenation. So I would say it is the priority whenever you have
difficulty in ventilating the patients.
A (Dr. Fábio Regatieri): Okay. Thank you.
Q (Dr. João Manoel Silva): And about sedation. Which drugs did you use?
A (Dr. Youzhong An): So I think that we use as we all use that the morphine and some like the fentanyl and the sufentanil. And we use the propofol and the midazolam. We keep RASS score minus four or even minus five.
Q (Dr. Marcelo Amato): Hello Prof. Du Bin, nice to
meet you. Prof. Youzhong hello. I would like to ask you a question,
and then I would like to comment. So something that we are very
concerned about here is the transmission of the disease to the
caregivers. I know that in China you had lots of contamination as in
all the countries. You get, let's say a good perception, I know this
is very difficult to have a conclusion, but if contamination from the
exhalation valve of ventilators is from non-invasive ventilation
devices, would it be an issue? Or you have any conclusion about this?
For instance just to make a very specific question, there is a big
issue here: if we some people care about economy – they are worried
about to waste too much money - they use not HEPA filters in the
exhalation valve. They use just an HNI heated humidifier. So do you
have any hint from this?
A (Dr. Youzhong An): So we ventilate several hundred patients
in Wuhan and we don't have any cases of contaminations especially for
healthcare workers. So I don't think the negative pressure room in the
ward is essential. And for us, in most of the hospitals we don't have
enough negative pressure wards. So we keep every ward to have the
windows and even we use some regular fans to make wind from the indoor
to the outdoor, and no patients and the doctors and the nurses were
infected by use of the ventilator.
A (Dr. Marcelo Amato): Okay. Good to know.
Q (Dra. Flávia Machado): And sorry, I was disconnected. Have you already discussed the use of FF2 masks and N95 for more than a single-use? How you're doing this there? Are you re-utilizing them?
A (Dr. Youzhong An): No. For the medical staff working in the
inner ward, we do use N95, but if we leave the ward, even the hospital
we only use the surgical mask, the face mask.
A (Dr. Bin Du): Never think about reuse. Reuse is not a good
idea I will say. I would say that in my opinion, at the current stage,
most of the healthcare workers in Wuhan are over-protected. Because
unlike the recommendations from WHO and health care workers taking
care of the patients with COVID-19 will usually have a cap, an N95
face mask, maybe plus a surgical mask and a coverall, maybe also plus
a long-sleeve gown, and a boot and double gloving. But my impression
is that the N95 face mask is the most important one, and hand washing
is the second most important issue and nothing else.
Q (Dra. Flávia Machado): Yes, but the problem here Bin Du, is that people outside hospitals, they bought a lot of masks. I am aware of the enterprise that bought more than a hundred thousand N95 masks for their employees, so they went out of stock in Brazil. So the problem of reuse, it's not an economic problem, it's a supply problem. So did you have any supply problem?
A (Dr. Bin Du): We did have a supply shortage of PPEs in late January and only February, but not anymore.
Q (Dra. Flávia Machado): And even on that supply problem, you did not run out of any N95?
A (Dr. Bin Du): Well, we do have some problems I mean, in late January. We didn't have enough N95 face masks at that time and we would consider always to have a surgical face mask on top, whatever N90 or just face mask.
Q (Dra. Flávia Machado): But you did not reuse them? Even then?
A (Dr. Bin Du): No.
A (Dra. Flávia Machado): Yeah. This is one of the biggest
issues in Brazil. We will run out of N95. We can't reuse them in my
opinion.
Q (Dr. Marcelo Amato): Sorry, Flavia. What did you say? Did you say that you reuse or you don't?
A (Dra. Flávia Machado): We reuse it. We reuse it for as long as it's okay microscopically for up to seven days.
Q (Dr. Marcelo Amato): Wow, very dangerous, huh?
A (Dra. Flávia Machado): The technique is to put them in paper sacks, and technique to put them again. And now we are afraid that if you use it as a single use of a single-day use, we might run out of them in some ways. This is the biggest issue now and I'm glad to know that you are not using all these lunar caps, these complicated things. As you said, I believe it's very simple. It's just a 30 grams cap and vestment, but I agree that the mask is important at least for healthcare professionals doing mechanical ventilation.
Q (Dr. Cristiano Franke): May I ask professors Bin Du and An, endotracheal intubation, we know it's procedures that have a generation of problems and most dangerous for the healthcare professionals. Do you have any tips for the emergency and intensive doctors to perform endotracheal intubation and in COVID-19 patients?
A (Dr. Bin Du): So any tips, any suggestion for protection during the endotracheal intubation, right? Well, I would say that initially, we don't have the positive pressure stuff whenever we intubated patients. And I have the experience of intubated patients with only goggles, without face shields. No positive, pressure stuffed. And I think it's okay. Whenever you heavily sedate and paralyze the patient, I think it's okay. But it happens. Right now they have enough stuff and it's fine.
Q (Dr. Marcelo Amato): Okay. Thank you. Yeah, I have a very strong feeling that... but for instance, if you do intubation and you are using just the N95, you just throw out after the procedure, right? Because there is a lot of people here in Brazil that they do a dangerous procedure and then they pack the N95 for a few days, reusing them. It's the most dangerous thing because the mask is contaminated by droplets. And then we are putting them back, picking it up with hands, and using it again. So I think this should be avoided by all means.
A (Dr. Bin Du): Oh well, I agree. Whenever you are running out of the N95 face mask.
Q (Dr. Youzhong An): But Du Bin, it's not only the N95. We need the face shield, right? Both the face shield and the N95.
A (Dr. Bin Du): Do you mean during the endotracheal intubation?
Well, whenever you have it - but anyway, if you have the positive
pressure stuff, there's no need for the face shield anymore.
A (Dr. Youzhong An): Yeah, but if you haven't that, and you
maybe use both the face shield and N95.
A (Dr. Bin Du): Well, it's okay. I went to intubated patients
with only goggles.
A (Dra. Flávia Machado): The face shield will protect a little
bit without any N95. Although I have believed, which must tell you
that this is not the ideal world, it will be much worse not having any
N95 in those two or three weeks. So, the rationale for reusing them,
is only the shortage. Nobody's saying that this is the best way to go.
I believe that when the industry in Brazil will start to produce it
and the government allows selling them only to hospitals. We might
stop reusing them.
A (Dr. Marcelo Amato): Yeah, I fully agree with Flavia. But I
think a very easy tip is to use the N95 with a surgical mask on top of
it if you're doing a procedure because then you remove the surgical
mask and the N95 is not so contaminated. It's very easy. I realize
that people are not doing this, and I think we should pay more
attention to this.
A (Dra. Flávia Machado): Yes for procedures, I agree, because
we are using face shields for intubation. But I agree with you, but
not as a routine. Our agency, our sanitary agency, just releases a lot
of recommendations and they are not recommending the use of a surgical
mask over the N95 as a routine, but for procedures, I agree. It's a
good thing.
A (Dr. Paulo Rehder): I have a comment regarding this. In my
hospital in Jeddah, Saudi Arabia, we are using intubation. So just a
lot of sets of intubation with everything is needed. It's mandatory
there to use the video laryngoscope that makes things easier. You’re
not to keep with your face over the mouth of the patient and with full
PPE. The team is led by one intensive care doctor, experienced
anesthesia doctor, and any case that the patient should be intubated
by the most experienced one to reduce the time and make things faster.
All the PPE should be thrown as soon as you finish any procedure,
cannot be reused.
But then we leave them a different situation. After the MERS-CoV, any
patient that receives the diagnosis, most of them are quarantined. We
could see what makes the difference is, once any patient arrives at
the hospital, all of them were isolated in negative pressure rooms or
HEPA filters room. And then once the patient is negative for testing,
and the testing was not ELISA, it was PCR. Once negative, the patient
got released from the isolation. And even repeated the test many times
the, if the patient is not improving, repeat it again. This made
difference because all the patients are dying a lot and the healthcare
professionals, mainly in the ERs, in the emergency rooms - were dying.
And after all, what made the difference was isolation, contact
precautions, and airborne precautions, and this was what changed the
course for this. And the MERS-CoV, there's a difference compared
to the novel coronavirus as 55% mortality. So that's a very different
situation, but the difference also was so effective as the new one.
Anyway, it's PPE, hand washing, and not to reuse anything.
Anything was dispensed at the same time.
Q (Dr. Marcelo Amato): Can I make a question to you both Dr. Du Bin and Youzhong? I know that you have been talking also during this presentation earlier that physicians are using steroids and some are not, and the reasonably good experiences reported in German. I have seen a few cases in which the patient was very inflammatory with signals ground-glass opacity, which is, for us as a pneumologist, a signal that you must have some alveolar inflammation and bronchiolitis. These patients, seem to develop bronchiolitis after the big proliferation phase of the virus, and in my mind, it is very similar to what the typical pneumologist call bronchiolitis obliterans because it starts with ground glass and then evolves to some consolidations. And then I have seen some patients in which after having this bronchiolitis diffuse ground-glass opacities, a big inflammatory phase with PCR very high, D-dimer very high. We give small doses of steroids and then the inflammation fades away and then I have seen that in 5 days, for instance, the infiltrate is gone and then with the decrease in the inflammatory markers. The fear we have, is that okay after 5 days or 10 days we may have a rebound of viral proliferation or some rebound of even the inflammation? Have you seen any of these, or you never experienced this?
A (Dr. Bin Du): Okay. I think I have the same experience with Marcelo. Some patients initially show a very good response to corticosteroids and then whenever you stop, it will rebound. And some of the pulmonologists will reuse the steroids again. And they will continue to not stop anyway. They will taper the dose and as I mentioned, I don't think it's a good idea. I have seen patients who have been on steroids for more than two months. And it seems to me that it is very common for these patients who remain positive for viral shedding for quite a long time, even after 30 days. So I will never consider the use for such a long time.
Q (Dra. Marcelo Amato): Okay, but you taper dose after one week?
A (Dr. Bin Du): I will not. I will never use the steroids for
longer than five days.
A (Dr. Youzhong An): I agree. I think that we had an experiment
like the therapies for maybe three or five days for corticosteroids.
A (Dr. Marcelo Amato): Excellent point. Thank you.
Q (Dr. Youzhong An): And if there is some rebound, I don't know in Brazil you use the convalescent plasma for the patients?
A (Dr. Bin Du): No, they don't have enough. Not yet.
Q (Coordinator) : Doctors, excuse me. We have a question here - all the time it’s appearing - about the parameters in the mechanical ventilation. So the behavior of coronavirus we know is a little bit different and I would like to share this question with you and fellow about the...parameters of the mechanical ventilation. This is the first question and then another question here that appears, about the adaptive ventilation modes. Unfortunately some parts of our country, the doctors are not so familiar with ventilators, also physical therapy. So what about the parameters and the adaptive ventilation modes, like A and B, A and V, volume support something like that for these patients?
A (Dr. Bin Du): Well with regards to mechanical ventilation, I
will say that it makes a huge difference with early versus late
intubation. You can imagine that in Wuhan, most of the patients were
ventilated quite late in their time course of illness, which means
whenever intubated patients put them on the ventilator, you always
have FiO2 over 80% or even 100%, which also means that you should
sedate and paralyze the patients to ensure adequate oxygenation. So
it's very common for us here in Wuhan, that after endotracheal
intubation, you should heavily sedate the patients and paralyze the
patients. So whatever this is the case. I don't believe the volume
control and pressure control will make a difference in terms of the
effect of the ventilating the patient. I saw a lot of patients who
were ventilated with the volume control mode, and some other patients
ventilated gradual control mode. However, the majority of them are, I
think, with a tidal volume of 6 to 8 mL per kilo.
And in terms of PEEP, I should admit that when I first saw the
patients, I often set PEEP of you to know, 15 or even 20 - close
to 20. However, right now, I would rather prefer a lower PEEP. I just
mentioned 5 to 10, if possible.
What else? Tidal volume, PEEP, and frequency. The respiratory rate - I
would say that here in Wuhan, we have a lot of patients with severe
hypercapnia, which has not been observed in other provinces in China
and Italy right now. I have discussed with my colleagues in other
provinces and Italy, and they have not observed such severe
hypercapnia with PCO2 up to 100 or even higher. And I think the
patients they treated were in the early stage of respiratory failure -
which means they intubated them quite earlier. And another clue to
this is that the initial FiO2 setting was 40% to 50% which is never
the case here in Wuhan.So whenever you have severe patients with
severe hypercapnia, the respiratory rate is always 30 something, 35 or
even higher, with minute ventilation about 12 to 15 liters per minute
- even was this high minute ventilation - these patients are still
hypercapnic.
A (Dra. Flávia Machado): People, It's Flavia. I want to thank
our colleagues from China and Mindray. I will have to leave now. Good
luck to everyone.
A (Dr. Bin Du): You too, Flavia. Take care.
A (Dra. Flávia Machado): Thank you so much for your help.
Q (Dr. Fernando Suparregi): I have the last question. There is a lot of patients that need palliative care. When to do this? How to approach a family? Because many families ask to be in touch with the patient, with the family. So can we handle this very delicate situation? So many of these patients die and family doesn't have any contact with them. Can you talk about this?
A (Dr. Bin Du): Well, I would say we have the designated
hospitals for patients with COVID-19 all over China. And in these
hospitals, no visitors allowed. Either the patient is still alive or
dead. So the doctors will communicate with the families by phone and
tell them about the updated information about the patients, to get the
oral consent for any invasive procedures such as endotracheal
intubation, such as ECMO. But if the patient dies unfortunately, they
will be handled by specific staff with notification to the families.
And I don't think members are allowed to see the patient even after
that.
A (Dr. Youzhong An): The patient can communicate with his or
her family member by phone, by mobile phone, and then to sign some
files and the photo, huh Du Bin?
A (Dr. Paulo Rehder): In Saudi Arabia, we have a specific
policy for this. Any patient that, no matter if coronavirus or not,
that is considered as a patient that should not be treated, the
doctor, the consultant should go to the family and explain that no
matter what they are going to do, the patient has no prognosis. After
appraisal from more than two consultants, the patient was designated
for do not resuscitate order. And this should be done by the doctor.
In some hospitals, you have some support from social workers and
psychologists and this helps sometimes, but the main responsibilities
for the doctor is to communicate with the family, maybe by phone these
days. But anyway, it's the responsibility of the doctor to clarify to
the whole family members.
Q (Coordinator): Okay. Returning to the previous question about the ventilation. We would like to hear from Prof. Marcelo about the experience that he already had with this and the ventilation. Could you please share with us professor?
A (Dr. Marcelo Amato): I think the basic message is that I have
the feeling that these patients share many physiological aspects that
are similar to patients with swine flu. I mean severe hypoxemia, which
means that it's a kind of disproportional. And this is striking. So
they have very severe hypoxemia, a little bit dissociated from the
clinical findings and the mechanical findings, which means that they
have relatively good mechanics, but very bad PO2. It means that If we
don't have patients that were under non-invasive ventilation for a
long time like you had in China at the initial phase, typically these
patients they get intubated with very good compliance. And then it's
very easy, if you have good compliance, to have protective ventilation
because driving pressure is typically very long. I think whenever your
driving pressure is low - I mean in some patients we see it below 10,
like a recent patient in which driving pressure was seven - you just
have to be patient and wait a little bit. And this is why I liked to
say that we have to think about mechanical ventilation in these
patients like prolonged anesthesia. It's like an anesthetizing patient
for abdominal surgery for 3 weeks.
And then I share the thoughts that Dr. Du Bin was promoting, that
initially, he was eager to have a kind of higher PEEP use but later on
he is promoting a little bit lower PEEP, something around 10 or even
less in some patients. I generally agree, but I think we still have to
individualize. And I think this is very important. For instance,
anesthesia, if you use 4 of PEEP to every patient - we have proven
this recently - you are promoting decubitus collapse. This means that
in many patients, you are going to promote a very high driving
pressure just because you have atelectasis caused by collapse and
gravity. And then in this case you are doing some harm using such a
low PEEP.
So in fact, I think we should individualize the PEEP for every patient
according to its characteristics, and then we have to use enough PEEP
to avoid decubitus collapse, and this PEEP level varies from patient
to patient. We have a recent study using electrical impedance
tomography and also esophageal pressure measurements, and then we
could show that for patients that they have high pleural pressure, the
PEEP levels that you need to apply during anesthesia are around 14 to
16 centimeters of water. So sometimes the patient needs such a high
PEEP just to avoid decubitus atelectasis, not to treat the bad areas
of the lung. But some other patients they need just 6, so you have
really to individualize and in this way, your driving pressure will be
almost always about below 10 centimeters of water. So I think this is
a general principle and we are trying to treat our patients, either by
titrating people with electrical impedance tomography or by using what
we called minute titration.
Minute titration is kind of, okay, you start from a maximum PEEP that
you believe you can handle for this patient - let's say 20 - and then
you slowly go on with PEEP checking what happens with your driving
pressure. And then if you reach a point of minimum, after which you
start to see an increase in driving pressure again, so let's say you
reduce PEEP from 20, 18, 16, 14, 12, and then when you go to 10 you
start to see an increase in driving pressure again, then I stop and I
keep the PEEP level at 12. It's interesting that using this approach,
we have seen not only an improvement in driving pressure, in CO2
exchange, but also an immediate increase in TO2, and then on average
we had decreased the PEEP level in these patients. I think this is
general.
Q (Dr. Fernando Suparregi): Marcelo? Good to see you. I would like to hear your opinion about the use of mechanical ventilation for more than two or more patients. Think about this, it's a surprising idea for me.
A (Dr. Marcelo Amato): Yeah, I think... sorry I know that we
are thinking about all the creative solutions for the lack of
resources, but I think this is against everything we know about
mechanical ventilation, because, you can handle the cross-infection -
it is possible - you can use a smart circuitry, and then you can avoid
cross-contamination, but it's absolutely against the principle that
you have to individualize mechanical ventilation. So think we should
abolish this idea. I think it doesn't make sense, for instance, if you
put our resources just to fix machines, it would be much better.
A (Dr. Cristiano Franke): The reason is you can save 1 or kill
2, 3 or 4 or which might, I think this is reason yes.
Q (Dr. Marcelo Amato): Can I ask you another question to Prof. Du Bin and Youzhong? So how is the... how many new cases you are observing in the last weeks? You are having new cases or you're just weaning the old ones?
A (Dr. Youzhong An): We don't have new cases. Only the old one.
A (Dr. Marcelo Amato): Okay. Wow, so it's really... the
situation got really under control.
A (Dr. Youzhong An): Yeah.
A (Dr. Marcelo Amato): Wonderful. This is very nice to hear.
A (Dr. Bin Du): We have new imported case, about 47 cases today
all over China. Not in Wuhan because Wuhan is still locked down.
Q (Dr. Marcelo Amato): I see. Also, Wuhan is still locked down but the rest of China not?
A (Dr. Bin Du): Yes. So I just read from the newspaper that CAAC Airlines, the authorities, they limit on the international flight, daily international flight, to individual airlines. Only one international flight from a single stop daily allowed daily.
Q (Dr. Marcelo Amato): And do you have a special feeling about… you cannot keep a city locked down forever, right? So, do you have a kind of forecast when you should remove the lockdown and then we can always think about removing the lockdown but keeping a very high, like we say, vertical surveillance in which any new cases is extremely chased and people do kind of very deep investigation in each new case, and then you can suspend the lockdown? What are your thoughts on this?
A (Dr. Bin Du): The lockdown policy will become invalid on April 8th. And however, I still believe that the government and the CDC staff will maintain a very high vigilance about everyone who comes in and who leaves the Wuhan or even Hubei province.
Q (Dr. Marcelo Amato): So tell me again, the date is the 4th of April?
A (Dr. Youzhong An): No, 8th of April.
A (Dr. Marcelo Amato): 8th of April. Okay. We are very curious
to see what happens because here in Brazil there is a big commotion
due to our very bad orientation of our president. So some people are
trying to remove the lockdown right now, which I think is insane. It's
good to know that you are keeping the lockdown till now, and then just
remove on the 8th of April.
A (Dr. Youzhong An): Yeah, it's more than two months. Two and a
half months.
A (Dr. Marcelo Amato): Needed. Okay. Thank you for sharing
this with us.
Q (Dr. Gustavo Ferreira Araújo): I'm sorry. About mechanical ventilation, did you establish minimal time in days for mechanical ventilation? And another question: the extubation time is a stress hour, do you have any special care at this point?
A (Dr. Bin Du): Well, I don't think we have a restriction or limit on the duration of mechanical ventilation in our patients. And for weaning from the ventilator, I think the majority of us do not perform TPs anymore. We just use the CPAP trial or PS low - let's say pressure support of 7 or even 5 centimeters of water, the pressure of water. However, once I extubated the patients, I just did it with my face shield which is okay. So it's nothing so special. I mean for patients who develop respiratory failure, respiratory failure usually starts in the second week and the beginning of the second week. And whenever the patient got intubated, we usually spend two or three weeks, I mean, on mechanical ventilation. This means, whenever you started to wean the patient from the ventilator, for the majority of the patients, it's already one month after onset of illness. And so the PCR test at this stage is usually negative, often negative. So it doesn't matter.
Q (Dr. Marcelo Amato): And then do you try to be a little bit more conservative in terms of your weaning criteria? So you are a little bit more cautious in terms of prolonging a little bit more to be sure that you have all the parameters okay before doing the weaning? Are you do like every other patient in the ICU?
A (Dr. Bin Du): Well, I think clinicians are prone to be more conservative, when extubating the patients or weaning the patient from the ventilator. I don't know why but it happens.
Q (Dr. Marcelo Amato): Probably. Yeah, yeah. But I think it's a wise procedure because we don't want to reintubate one patient like this and then looked like that, which is your general impression. After all, for H1N1, secondary infections were a nightmare. But looks like that for these patients, it's not so much. What do you think?
A (Dr. Bin Du): Well, MRSA pneumonia is very rare. It did
happen ever. I mean in patients with COVID-19, I've never seen a
single case. I have never seen a single case with MRSA pneumonia.
However, CRE or carbapenem-resistant Acinetobacter are more common.
And for aspergillosis, I saw a couple of troubled cases with IPA,
invasive pulmonary aspergillosis. And I know from the results of the
autopsy, I know that a couple of patients had the IPA, pathological
evidence of IPA.
A (Dr. Youzhong An): Even for Casterisation. We just have
patients whose G-test is so high, but we found the chest x-ray but we
doubt it but we need to proof.
Q (Dr. Marcelo Amato): Maybe because they use
steroids or no relationship?
Q (Dr. Bin Du): Do you mean IPA or?
A (Dr. Marcelo Amato): No, the aspergillus.
A (Dr. Bin Du): Well, I don't know. These patients had
lymphocytopenia. The infrastructure of the respiratory system has been
damaged by the virus. So, both of these might contribute to the
pulmonary aspergillosis. Not necessarily steroids, although I think
that the corticosteroids might increase the likelihood or the risk.
A (Dr. Youzhong An): Most of the secondary infection is
gram-negative. It's like Dr. Du said that maybe some CRE and
pulmonary.
A (Dr. Bin Du): I think there are questions about how long
would you wait to intubate a patient. My experience tells me that
delay of intubation into endotracheal intubation might be a risk
factor for mortality. So never, never delay the endotracheal
intubation whenever the patient failed NIV or high flow nasal cannula
trial. Never delay.
Q (Dr. Youzhong An): Do you think the NIV is very dangerous for the error? I don’t think that it's so dangerous.
A (Dr. Bin Du): Well, it's not safe invasive mechanical
ventilation. Although according to the recommendation or the interim
guidance from the WHO, it might be as safer than the old versions of
the NIV. I mean the old ventilator, it will be never as safe as
invasive mechanical ventilation.
A (Dr. Youzhong An): In the United States, some doctors told me
that they never use NIV for COVID-19.
A (Dr. Bin Du): Well, I know that some of the patients have
been managed quite well by the NIV or high flow nasal cannula, to
avoid endotracheal intubation yes.
Q (Dr. Marcelo Amato): I think it's important to see the ventilatory pattern. I have seen also some cases in which you put it on NIV, the respiratory rate is very low, and you cannot observe that the patient is not doing a high tidal volume. And this is the patient in which you can keep it, and maybe it's the only bridge you need. But I think the major problem is in those that you still see a high tidal volume. This is the patients that you should not wait about. Do you agree?
A (Dr. Bin Du): Sure, I agree.
A (Dr. Marcelo Amato): So I think we should not put a kind of
mark, like, do not use non-invasive ventilation. I think you can do a
trial and if the patient is very calm, very well-adapted, and not a
big effort, it could be a good bridge.
A (Dr. Bin Du): And I also think the 2 to the 6 hour window of
the observation during the NIV trial is so tough. I mean as
recommended by the Who guidance. It's so tough. But anyway, it should
not be longer than one or two days in my opinion. You need experienced
human resources.
Q (Coordinator): There is a question for Prof. Du Bin. We're talking about the mechanical ventilation and some questions appear here about the weaning, the extubation. What are your experience with high flow nasal cannula, or the non-invasive ventilation after extubation with these patients? Because the patients will keep for a longer time in mechanical ventilation and probably the weaning is more complex than the other patients, right? So what is your experience in the extubation?
A (Dr. Bin Du): Well, it has been used. It has been used after
the patients were extubated from the ventilator. They were weaned from
the ventilator and extubated. Both the non-invasive ventilation and
the high flow nasal cannula have been used. Yeah, but not in every
patient. Only in some selected patients according to the discretion of
treating physicians.
A (Dr. Youzhong An): Yeah, for some patients, we x-ray, we also
use a high flow nasal cannula and we... also use NIV several times,
maybe daily, maybe 4 times, 3 times daily, so to have patients get
better oxygen even to keep the lung open.
Q (Coordinator): Okay. One more last question. We know that for... to the FDA it's not so clear… they stating about the use of anesthesia machine for this patient to ventilate in ICU, but it's due to lack of mechanical ventilators in the world, in some countries. Also Brazil, some hospitals, asked us about the use of anesthesia machine to ventilate, to support the patient in an emergency. Dr. Manoel, Dr. Regatieri, could you please share a little bit more about it?
A (Dr. Bin Du): So, is another question for us right? No, the anesthesia machine has not been used here. I mean, to ventilate patients with COVID-19. Not here in Wuhan and not in any of the cities that I am aware of. I'm not aware of any single case.
Q (Dr. Marcelo Amato): This was very common in Italy, right? But not in China.
A (Dr. Bin Du): No.
A (Dr. Fábio Regatieri): I think the anesthesia machine is
capable to ventilate these patients. It's my personal opinion.
A (Dr. Marcelo Amato): Better than sharing the circuit with
just one ventilator.
A (Dr. Fernando Suparregi): Thank you all for sharing your
experience.
The webinar is initiated and organized by Mindray in the interest of the healthcare community to combat COVID-19. Thanks to the contribution of all the panelists who join in the discussion voluntarily with no conflict of interest.