While little is known about the epidemiology of ventilator-acquired pneumonia among COVID-19 patients, some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. Ashish K. Khanna, MD, FCCP, FCCM, is joined by Charles-Hervé Vacheron, MD, to discuss the Cohort exposed/nonexposed study among the REA-REZO surveillance network. (Vacheron CH, et al. Crit Care Med. 2022;50:449-459). Charles-Hervé Vacheron is a doctor in the Department of Anaesthesia and Intensive Care at Centre Hospitalier Lyon Sud in Pierre-Bénite, France.
Estimated Time: 22:24 min
Dr. Khanna: Hello and welcome to the Society of Critical Care Medicine’s Critical Care podcast. I’m your host, Ashish Khanna. Today, I’ll be speaking with Charles-Hervé Vacheron, MD, on the article, “Increased Incidence of Ventilator-Acquired Pneumonia in COVID-19 Patients, A Multicentric Cohort Study.” This was published in the March 2022 Critical Care Medicine. To access the full article, visit ccmjournal.org. Dr. Vacheron is a medical doctor. He’s finishing his PhD and he’s with the Department of Anesthesia and Intensive Care at Centre Hospitalier Léon in Léon, France. Welcome, Dr. Vacheron. We are so happy that you are here with us today.
Dr. Vacheron: Thank you, Dr. Khanna. I’m very happy to be with you too.
Dr. Khanna: Great. Before we start, do you have any financial or academic conflicts of interest or disclosures to report to our listeners?
Dr. Vacheron: I have no other disclosure than my patients in intensive care.
Dr. Khanna: Perfect. Patients first. We all work for our patients and, especially in the last two years, life has taught us a lot about how to better take care of our patients with COVID-19. Very, very impressed with your work. I think this is really interesting work. All of us have always thought and believed that the incidence of ventilator-acquired pneumonia in coronavirus disease was really, really high, but your study has clearly shown and proven this. I’m going to start with a very basic question. Why did you choose to study this subject?
Dr. Vacheron: This is a very interesting question. Thank you for asking me that. I think the beginning of this work comes from the clinical sense that we all have with these COVID patients in intensive care. Briefly, we had a pre-COVID-19 clinical sign. When we had pneumonia, bacterial pneumonia, classical pneumonia, we had a sign of respiratory distress and we intubated the patient for respiratory distress. We maintained these patients for five or six days on mechanical ventilation and if they’re well after that, okay, they could be extubated. With COVID-19, we had to revise our view of pneumonia and viral pneumonia with patients who showed signs of distress very, very late. After intubation, we have a long phase of mechanical ventilation, mainly because we cannot extubate them because of the ventilator-associated pneumonia. I wanted to understand if this was only a point of view of the clinician, and I wanted to show that it was not only in the field that we had problems with ventilator-associated pneumonia but also on the global scale and to understand that there is a real problem with this pneumonia.
Dr. Khanna: Very interesting. This is a great introduction to your work. I see that you use something called Rea-Rezo Surveillance Network for your analyses. Tell our listeners more about this database. How big is this database and what sort of data are available for analysis in this database?
Dr. Vacheron: Once again, thank you for this great question because none of this work could have been done without the physicians and practitioners of the Rea-Rezo Surveillance Network. Briefly, intensive care units in France that are devoted to fighting against nosocomial infection or ICU-acquired infection joined Rea-Rezo. Each patient admitted to intensive care with a small length of stay, like under two days, we didn’t include, but all patients who had a length of stay of more than two days were included in our database. We ask very simple questions, like: When was the patient intubated? Is there ventilator-acquired pneumonia? Is there a bloodstream infection? Did patients receive antibiotics at admission? With these simple questions, we were able to have a panel of ICU-acquired infections at Rea-Rezo, with approximately 100 centers in France. It’s approximately 20% to 30% of the ICU beds in France, which is pretty okay to be representative of the French ICU population.
Dr. Khanna: Interesting. So it looks like it’s a very detailed database and very representative of the French ICU population. Obviously, those are very important features of a good database. Now that you’ve done this important work, can you summarize for our listeners the main findings of your analysis, please?
Dr. Vacheron: Of course. The main finding of our analysis showed that COVID-19 patients matched with non-COVID-19 patients have an increased risk of ventilator-acquired pneumonia, more than two times the risk of ventilator-acquired pneumonia. To be more specific, the incidence rate for VAP was around 15 VAP episodes for over 1000 ventilation days in non-COVID-19 patients and, for COVID-19 patients, it was around 25. Therefore, this increased incidence was well characterized. We also focused on the time of occurrence of the ventilator-acquired pneumonia, and we found that this occurred similarly, at the ninth day after the first ventilator-acquired pneumonia. So we have the ventilator-acquired pneumonia, which occurs approximatively at the same time, which has an increased incidence, and which has approximatively the same bacterial ecology. We have the same germ. We have the same panel of resistance in our COVID-19 patients. In this study, the only difference between ventilator-acquired pneumonia in the COVID-19 patient versus in the non-COVID-19 patient was increased incidence. That’s the only difference.
Dr. Khanna: So again, just to summarize, the biggest difference here is the increased incidence of ventilator-acquired or ventilator-associated pneumonia in COVID-19 patients. No difference in the microbial patterns and resistance patterns to antibiotics. Correct?
Dr. Vacheron: Exactly.
Dr. Khanna: Okay. Great. I also saw that you tested for differences between the first and second episodes of ventilator-acquired pneumonia. Why did you specifically want to do this and what is the relevance of that finding?
Dr. Vacheron: This was a basic consideration that in the literature we mainly focus on the first episode of ventilator-acquired pneumonia, maybe because we don’t have a lot of second episodes. Using the Rea-Rizo database, we have a large panel of patients in the ICU and we were about to study the second episode of VAP. There was an increased incidence, maybe a little less significant, on the first episode, but we also found an increased risk around the eighth day of having a second episode of VAP. In the non-COVID-19 patient, the modelization of the hazard rate of VAP was pretty linear. We have a V curve, an inverted V curve, of hazard rate of VAP for the second episode similar to the first episode, only in the COVID-19 patient. In the non-COVID-19 patient, we have a linear hazard rate of VAP after the first episode.
Dr. Khanna: Tell me, were you surprised when you saw the results of your analysis? It looks like there’s a big, big difference between your COVID-19 group and non-COVID-19 group in terms of ventilator-associated pneumonia. Are you surprised or did you expect these outcomes?
Dr. Vacheron: Honestly, Dr. Khanna, we were not surprised about this incidence. As I explained in the introduction, this work was mainly directed from a clinical feeling of the patients. The interesting point that we were not able to anticipate was the absence of discrepancy between both groups in bacterial ecology. We have globally similar germs in COVID-19 patients and non-exposed COVID-19 patients, which is a little surprising because we might have a lot more germs identified globally in immunocompromised patients. But another finding that was not expected was heightened incidence of VAP on the second episode, which has a very different curve compared to the second episode in non-COVID-19 patients. I hope I am clear in my explanation.
Dr. Khanna: Yes, definitely. Thank you. That is clear and thank you so much for that. I’m going to now talk a little bit about patient characteristics in your COVID-19 and non-COVID-19 groups. In any analysis like that, the first thing the readers and the peer reviewers look at is whether your two groups were appropriately matched because it’s very easy to have confounders. I’m looking at your matching criteria, age, sex, you looked at acute physiology scores, you looked for admission from community or nursing homes, antibiotics at admission, time from admission to mechanical ventilation, and then you looked at length of ICU stay and quite a lot of other good matching criteria in your two groups. The one thing that I don’t see here is the depth of sedation and the use of muscle relaxers. That one part came to me when I looked at your paper. We do know that ventilator-associated pneumonia has been shown to be more in patients who are intubated and paralyzed and/or deeply sedated. Do you feel that there’s something that could have been matched for? Is that something that would have changed your outcomes?
Dr. Vacheron: Thank you for your question. Yes, indeed, there are several matching criteria that could have been done on these patients. We could add the presence of corticosteroid therapy, for example, muscle relaxant therapy, all the risk factors of ventilator-acquired pneumonia. The reason we didn’t choose them is very simple. It’s because, as I explained to you, we are working on the national surveillance network, the Rea-Rizo network, and the physicians are giving their data based on their free time. They are collecting the data and therefore we cannot ask them a lot of different variables. At each meeting we ask them to collect certain data. These data, while very interesting, are not actually collected from the Rea-Rizo Surveillance Network. That’s why we couldn’t ask them. The question is: Would these have changed the results? Maybe, but not in a significant way, in my opinion. We know that, in ARDS, we have an increased incidence of ventilator-acquired pneumonia, which goes to around 18 to 20 VAPs per thousand ventilation days. The use of corticosteroids is currently highly debatable in the occurrence of ventilator-acquired pneumonia. Therefore, this might have changed our results, but I don’t think that will drastically penalize the conclusion of the article.
Dr. Khanna: Sure. And I also see that in your patient outcomes, your total duration of mechanical ventilation, your median days on mechanical ventilation, is significantly higher in your COVID group and so is your length of ICU stay. Again, that is expected. We know that COVID patients stay in the ICU longer, they stay on mechanical ventilation longer. Were you able to adjust for these factors in your final analysis?
Dr. Vacheron: No, no, no. We did not adjust for these factors. To understand why, we have to understand the competing risk analysis. So thank you for letting me explain these problems. The competing risk is the presence of factors that influence the outcome. Here, for example, we know that having ventilator-acquired pneumonia will increase the duration of mechanical ventilation. Therefore, they are intricate. We cannot adjust the duration of mechanical ventilation because we will create a bias regarding our patients. In the competing risk analysis, we simulate the hazard rate of the extubation and on the intubation, cumulative incidence. Therefore, we are able to accurately visualize the occurrence of this event independently of the occurrence of the other event, which is extubation. This is a statistical methodology. I hope I’m clear; I can explain further if you want.
Dr. Khanna: Thank you so much. I did want you to talk about that. That is very, very useful for our listeners. Thank you. This is great work. Again, the more I look at it, the more I feel that this is going to be important for the critical care community all over the world. What do you want critical care doctors and providers all over the world who read your paper to have as a take-home lesson? And how do you feel your work is going to change practice in ICUs and how we manage these patients?
Dr. Vacheron: Very hard question, because we are more descriptive than explicative. What we can say is that the concern of the physician about ventilator-acquired pneumonia among COVID-19 patients, concern to be taken into account of management of our patients, prevention of these, are very, very, very important. There is no need to change my beliefs. Antibiotics are best for ventilator-acquired pneumonia because ecology is globally the same. Some ask whether we should have a more aggressive strategy to prevent VAP. For example, I could cite selective oral decontamination, which has shown to be helpful to prevent VAP. I can cite the good performance of all the strategies we already have in preventing VAP. This is the main message that this paper shows. I believe you will have this question asked about this paper: Does ventilator-acquired pneumonia have an influence on the occurrence of death in these patients? My question currently is: Are these VAPs really the same as VAP in our COVID-19 or non-COVID-19 patients and do they penalize the patients more? We have several patients in our clinical daily patient care that we believe could be extubated and doing well when they are extubated, but VAP increases drastically their length of hospital stay and sometimes they die after VAP. So the question I think that this paper raised is mainly whether the effect of VAP is different on attributable mortality than conventional VAP.
Dr. Khanna: Yes. That’s a very, very important question about attributable mortality. I think this is something that we very often forget and don’t think about when we look at analyses like this. So thank you for bringing that up. I think that’s really, really important. Now, my last question to you today is going to be ideas for other analyses. You just told us that this paper is hopefully going to ask more questions and people will think about other analyses to do in this field of ventilator-acquired pneumonia. Do you have any plans of any follow-up analyses?
Dr. Vacheron: We’re actually trying to understand this attributable mortality. This required a lot of work because we are on the multistate analysis. I believe that your readers are familiar with these analyses but, briefly, these take into account the competing risk analysis, but not only on one level, but on multiple levels. The attributable mortality has been studied widely by someone who has performed a lot of work on ICU-acquired attributable mortality of nosocomial infections. So I believe this is the next question they will ask us. On a more pragmatic level, I believe that a main follow-up study that will follow this is: If we are able to prevent ventilator-acquired pneumonia, are we able to reduce overall mortality? It has been shown on a small panel of patients that, by preventing VAP using selective digestive decontamination, we were able to lower mortality. In our COVID-19 patients in the ICU, I don’t believe that antiviral drugs or other therapeutics could be as effective as preventing VAP in our patients.
Dr. Khanna: Thank you. Thank you. These are really important points. We’re coming to the end of this podcast. Do you have anything else that you would like to tell our listeners specific to your study or your work?
Dr. Vacheron: Read Critical Care Medicine, all the papers in Critical Care Medicine, which are very interesting.
Dr. Khanna: Thank you. That’s a great message.
Dr. Vacheron: Exactly.
Dr. Khanna: I can promise our listeners that I did not tell him to say that. He said it to himself.
Dr. Vacheron: I promise.
Dr. Khanna: Thank you. This concludes another edition of the Society of Critical Care Medicine’s Critical Care Podcast. For this critical care podcast, I’m Ashish Khanna. Thank you so much for listening to us and have a great day.
Ashish K. Khanna, MD, FCCP, FCCM, is a staff intensivist and anesthesiologist, associate professor of anesthesiology and section head for research in the Department of Anesthesiology, Section of Critical Care Medicine, at Wake Forest University School of Medicine in Winston-Salem, North Carolina.
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