Okay, we're going to get back on track and start with our couple of respiratory failure cases. We're delighted to have Bob Bauch and Dr. Gates presenting. You've been through a lot, so we're going to try and make this a little bit fun by giving you some easy questions, and we're going to start with mechanical ventilation and some management of respiratory failure. We're going to build on a single case here of a 32-year-old female with COVID ARDS. You probably haven't seen one of these in a little bit of time, but patient's intubated, begun on mechanical ventilation, remdesivir, dexamethasone, has a chest x-ray with bilateral alveolar infiltrates, has an ideal body weight of 60 kilograms, waits six hours, and you get some new lab, and you can see it there. We've got kind of tachypneic with a respiratory rate of 38 to blood pressure 120 over 75 tachycardic at 105. Actually, the 38 wasn't the tachypnea, that's 30 was the tachypnea, 38 was the temperature. That was 92% on volume assist control at 18 breaths per minute, FiO2 80%, PEEP is 12, tidal volume is 360. We have a peak pressure of 35 centimeters of water pressure, plateau pressure of 32 centimeters of water pressure, and you can see the blood gas, 737, 38, 64, and 92% saturated. Typical x-ray. So, what do you want to do? Do you want to change the tidal volume to 300, increase the PEEP to 15, add some inhaled nitric oxide, or do you want to initiate prone ventilation? There's no pole everywhere, so. Oh, there's no pole for this? Oh, okay. Anybody want to throw something out? Something like the board likes to tell you, there's a couple of attractive choices here, right? So, what's the one thing that is maybe a little glaring as not quite right on this slide? Can you use your microphone so we can hear you? Or you can come up here and join us, we'd be delighted. Oh, yeah. No. So, looking at the... I mean, we have to know, like, six hours later. So... Yeah, so at six hours, what do you have? You have maybe acceptable blood gases. 64 is not bad, but you have room for FiO2 to go further up, and PEEP of 12 is not pretty high, and the tidal volume is, like, you know... Well, what do you think of the tidal volume? If you see the ideal body weight is 60... Six, yeah. ...and you're at 360, is that six mils per kilogram? Yep, that is pretty good. So that would be lung protective, except for what? The... Look at the plateau pressure. Oh, yeah. Yep, plateau is quite high. So you did everything right, except the plateau pressure says maybe it's not quite as right as it should be. So trying to be lung protective, you want to reduce that plateau pressure, right? So at this point in time, you could say, if we skip ahead a couple of things, well, maybe we want to do prone ventilation or maybe we want to use inhaled NO to improve the oxygenation or increase the PEEP, but none of those are going to fix the plateau pressure properly, right? They're all going to fix the oxygen. So if we'd like to be lung protective as our primary goal of ARDS management, we want to get lung protective. So choice one becomes the answer. Everybody okay with that? Well? Sure. So 12 hours later, you have mild temp at 38.3, 130 over 80, blood pressure, tachycardic still at 110, with a respiratory rate of 24. So the patient is breathing over the ventilator, which is set on AC at 18 breaths per minute. On those settings, the patient in the settings would include an FIO2 of 100% and a PEEP of 5. The patient is sat in 92%, and we have reduced the tidal volume to 300. With those vent settings, we have a peak pressure of 32 and a plateau pressure of 39. So as in the previous goal, we did decrease our plateau pressure. We do have an ABG, which, from a ventilatory standpoint, looks pretty good. Our last two of our pH matches our PCO2, so we're in pretty decent shape. But now we have a PAO2 of 59 on 100% FIO2. So the best evidence suggests that we should do what at this point in time? Prone. Okay, and based on what? So we have a PDF ratio less than 150. And so the PERCEIVA trial said, hey, let's do low tidal volume, plain old standard RSNet ventilation for about 12 to 24 hours, and then let's look at our PDF ratio. And it selects out a group of patients who actually have a mortality benefit from proning. And so that group is a PDF of less than 150. If you're reaching your low tidal volume, long protective strategy, peep okay, plateau okay, and your PDF is greater than 150, not a candidate for proning. Okay? And importantly, none of these other choices improve mortality, right? There are two things that improve mortality in ARDS. They are low tidal volume ventilation and proning. The rest of it just helps the numbers here and there. So now we get to 10 days later, still on the vent, has proximal myopathy with strength of 2 to 3 over 5 in most muscle groups. We've improved the oxygenation status in that we only need 40% FiO2, PIPA 5, rapid shallow breathing index frequency over tidal volume ratio of 115. And unfortunately, this patient has failed a 40% pressure support of 5 with the PIPA 5 spontaneous breathing trial for two days in a row and fails after about 25 minutes with rapid shallow breathing. So now what do you do? Do you want to continue to optimize medical management and attempt an SBT daily and think about liberation? Do you want to proceed with a trach and do a daily, some call it a face mask, but we call it trach collar trial where you just take them off and make breathing as easy as possible? Do you want to put a trach in and just put them on either pressure support or CPAP and see how they do? Or do you want to say let's pull and pray and extubate them, put them on high flow nasal cannula and we'll move to the next patient? Now I can tell you that in real life you probably will find all of these scenarios. And the question is what would the board exam ask you to do? And I don't know that they will ask this kind of a question because I think this is controversial. And I could not come up with a true right answer. I would say it's always important to optimize medical management, but we have somebody with a critical illness polymyoneuropathy. And if we were astute in the beginning and would be trying to mobilize our patient and take care of the inflammatory response from the get-go, maybe we would not have gotten here. But at this point in time, it's going to be a long term. It may be that there are some things we can correct, like if there's nutritional deficiencies, electrolyte abnormalities, things that are easy to correct, but we're not likely going to all of a sudden develop good muscle power. So I think you're going to be into a long-term scenario and probably end up going with a trach, and whether you do the daily trach collar trials, which is what I think we learned, because I did some work at an LTAC where they did a trial that showed that when you take people who have a trach and you take them right from the ventilator and you put them on a trach collar, and surprisingly about half of those people actually will wean if you just give them time to do that. Or we do our methodical, let's turn down the pressure support over time and allow people to wean. Either of those, I think, are utilized, and at least in the prolonged mechanical ventilation area of LTACs, going to a trach collar will pick out people who will wean faster. But you're still left with about half that aren't going to wean for whatever length of time it takes for their muscles and nerves to recover. I think the other point is early trach in this situation. I think we were at day 7? We were at day 10. 7 to 10, earlier trach rather than later. You had a question? Use your mic if you can. Yeah, so I think the more recent literature supports early trach in this situation in which, you know, it's clear that it's going to be a prolonged situation, so day seven to ten proceeding with tracheostomy, as opposed to the previous 14 days and then decide. And for those of us old enough, we used to wait 21 days before we thought it was time to do a trach. So usually by day seven to ten, you know whether you're in it for the long run or you have a chance to get people off. And I just threw in some summary information here. I guess if you're going to get a copy of these slides, review these before you go to take your board. But things just to take away, we've already talked about the lung protective ventilatory support strategy, the need for PEEP, and there's still debate about the high versus the low PEEP strategy. Prone ventilation gets a strong yes for improving outcome. ECMO in selected circumstances may be beneficial and you just have to choose your patient correctly. Inhaled nitric oxide has not been shown to improve survival. And high frequency oscillatory ventilation has not been shown to improve survival. Use protocolized sedation and weaning, that put down no benefit to early trach, but that's early data. And the trach trials are better than pressure support in at least the LTCH population. Questions? We're here to catch up on time. So two things regarding the myopathies. So especially during the COVID times, we used to have these patients on the vents for long times and to complicate the matters further, there were a few, like one or two cases with GBS that was suspected because of the COVID, post-COVID, and it just complicated the matter so much. So did you guys see anything like that in myopathies? We were trying to make a differential based on the ENMG studies and all that, and this patient ended up getting plasmapheresis and don't know what happened after that, but any comments on such other causes of myopathies in addition to paralytics? There's lots you can say about that. We all lived through an era where we forgot everything we learned about critical care and looked at the fear coming from other parts of the country and said, we don't want to contaminate our staff or ourselves or whatever. So we're going to take people who look sick, put them on a ventilator early on to minimize the fear of aerosols going everywhere, sedate the hell out of them because we got to leave them in a room and we're going to put the IV pole out in the hallway somewhere so nobody has to go in the room and we're not turning patients. We're going to paralyze them so they won't do anything. And then we figured, well, they're not getting better, let's add steroids. So we set them up for failure and set ourselves up for failure until we slapped ourselves in the face and said, hey, we've been doing modern critical care for the last so many years, what did we forget? And then we changed and we are back to what we think is good care. But the first, I'll say, four to six weeks of COVID management were hellacious. I hate to do that on something that's going to be recorded, but we sort of lost our bearings of what we were supposed to be doing in critical care. And a lot of our principles have trained to just use the right amount of sedation, start mobilizing people, minimize time on the ventilator. All that went for the wayside and it's not surprising. We had a lot of delirium, we had a lot of prolonged neuromuscular blockade, we had lots of people off to trach and to an LTAC. And fortunately, they were young and healthy before that so they could recover. But I think there was a big learning curve, at least at our institution. There was a learning curve. We, for the most part, stuck to the basics, but that intubate, folks, I remember, clear as day, six liters. If you went anywhere past six liters, you got intubated. Insane. We would never think of that. So I think we've learned, but to your point, physical therapy in there with the patients that were appropriate, trying to continue to move them, et cetera, treatment of COVID with steroids, kind of threw a little bit of a monkey wrench in there. But again, minimizing the things that we could, avoiding paralegals when we could, I think has helped. And one thing we did utilize correctly for our ECMO patients, we didn't divert our knowledge. And we work to extubate our patients as soon as possible as long as they're on effective ECMO because you don't need a ventilator. And then once they're extubated, we try and get them up and walking around the unit and making sure that they're interactive, they're on the least amount of sedation, get rid of benzos, have them do PT, have the family out there encouraging them, which was hard with COVID because you had to do it by FaceTime. But those kind of principles work to actually improve outcomes in critical care. So if you can mobilize, get the family involved, keep people from getting delirium, they make a difference. Any other comments? The last answer for the last question, was it face mask or PSV? Probably using the trach with the trach collar face mask. Okay. Thank you. With the caveat being that was in long term, like LTAC settings. There's a small caveat to that. Yeah. It's not a great question. I hope you don't see it again. We're now going to move to some pneumonia in the ICU questions, which will combine both community acquired and ventilator as well as hospital acquired pneumonia. Which of the following is not a risk factor for development of CAP? ACE inhibitor use, PPI use, inhaled corticosteroids, or alcohol use? These are all easy. You probably have thought about this, but ACE inhibitors. We now put in, because you're going to take the boards, or some of you are taking the boards, and you heard over all these sessions how important it is to read the question and figure out what are they trying to ask me. You say our questions are really nice and friendly. It's very short. Ask you exactly what they want to know. We're not trying to give you 40 different scenarios and you try and figure out what are they asking me. But when you talk about pneumonia, especially community acquired, it's a lot of little pearls that give you the clue as to what the diagnosis is. As far as pneumonia, think of historical things like where have they traveled, where do they reside, what were they exposed to, and where were they exposed, maybe on a farm, and they can help you determine what organisms you should think about. Here's some other historical features, some habits if they have IV drug abuse, if they've been on recent antibiotic therapy, if they get pneumonia in the summer or winter, you think about Legionella. If they've in the Four Corners region of the U.S., Hantavirus, although I haven't seen a Hantavirus case in almost a decade or so. With the various viral things, this slide was an old slide. It predates COVID, but that has become everybody now is a viral pneumonia expert. These are sputum characteristics, which I think actually sometimes people put in the question things like they're coughing up rusty sputum, typical for strep pneumonia, current jelly sputum, Klebsiella, foul smelling with anaerobes. When you have a gram stain, they say there's a lot of white cells, but no bacteria. In the setting of a bacterial pneumonia, think of Legionella. Another thing on the physical exam, when you talk about a patient who has a fever, but doesn't have a tachycardia, so you call that a pulse temperature deficit, that you see in people with viral pneumonias, mycoplasma, acidosis, tularemia, and Legionella. And again, when you have a big discrepancy between the infiltrates, look pretty impressive, but the patient's not very sick, think about viral and mycoplasma pneumonia. So just to give you clues as we move forward. And now question two. Which of the following treatment regimens should be started for a healthy 60-year-old man with presumed pneumonia who was admitted to the ICU for treatment with mechanical ventilatory support? We're going to pull out the big guns with zosyn and amikacin, we're going to do levoflaxacin plus tovi, lenazolate plus mero or ceftriaxone plus azithromycin. Number four? And that is correct. And there's actually good data that says, you know, if you're dealing with community-acquired pneumonia, especially in the hospital, the regimen should include azithromycin. So whether you're a fluoroquinolone, although, I don't know, do you guys have to fill out a special form to order a fluoroquinolone in your institution? Yeah, we do too. So as somebody who takes care of a lot of CF patients, it drives me nuts, but at least they all have pseudomonas so I can qualify. But it's hard to order azithromycin these days. Which of the following findings suggest a poor prognosis for a patient with severe community-acquired pneumonia in the ICU? Having sub-segmental infiltrates, a falling procalcitonin level at 24 hours, a high bacterial load for pneumococci, or prior immunization with pneumovex? What makes sense? Probably the one with the high bacterial load, right? And indeed, there is data that came out of Grant Waterer's lab showing that the higher the bacterial load, the higher the mortality. Anybody using procalcitonin to help you diagnose, prognosticate, or decide how long to treat a pneumonia? No. Okay, and actually prior immunization with pneumovex actually helps you do better. So encourage your people to get that. All right, we have a 67-year-old man with cellulitis and diabetic foot ulcer admitted for IV levofloxacin. Not at Rush, maybe? No. On day four, he has worsening renal function and respiratory distress requiring intubation and ventilatory support. Four days later, he has a new right loral infiltrate, fever, elevated white count, and decreased blood pressure. So based on this new clinical setting, what would you like to do? Begin impaired broad-spectrum antibiotic coverage, start Heparin and send for a PE protocol CT, perform BROC and BAL for quantitative cultures, or await culture results prior to starting antibiotic therapy? Number one, thank you. That is the correct answer. So it's just like in our sepsis management, right? You think infection, start your antibiotics. So I would add, which antibiotics? Oh, there we go. That's the next question. Great. Ask it to him. So now that you want new antibiotics, what are you going to do? You want to continue the levofloxacin but add amikacin. You want to go to ceftriaxone and azithromycin, begin lenazolid and meropenem, initiate ampicillin and cefepime. We do have a PharmD in attendance, if anybody's used to asking their opinion. Ron, you want to weigh in? Three? Correct, because you've already had initial therapy, which would have hopefully covered the pseudomonas, but it's likely resistant, if it is. So we failed the initial therapy and now we have a ventilator associated pneumonia so I I think this is the right answer. It's just also utilizing you since you're here touching on lenazulate versus vancomycin in this situation. So the vancomycin probably most institutions is going to be their initial therapy. Anything like lenazulate or daftomycin will likely require some type of approval that the limitations of vancomycin even though it's been around for decades and is that it does take it does take at least about 48 hours depending on the patient the dosing and the levels to actually even figure out if it's adequate serum concentrations especially if it's an MRSA suspected or confirmed infection. So utilizing lenazulate which is actually lenazulate and daftomycin are both generic now so you know it's not necessarily a financial piece of it but it's just recognizing we have drugs that are just as effective or if not more effective but that you know that are adequate concentration right away especially in a decompensating patient. Now there is some data that lenazulate may be better than vancomycin in non-bacterial patients with ventilator associated pneumonia. Do you agree with that or disagree? I'd agree and it's likely that data is likely been trending even if it was done with more patients would have shown that it was even better is likely because you can get adequate concentrations on the first dose rather than 48 to 72 hours. And with some of the ones that have toxin mediated effects you don't need to add clindamycin with lenazulate. That's correct and then there was a comment if you are thinking pneumonia and or skin and soft tissue then lenazulate would probably be your drug and if you're thinking bloodstream or non lung type of etiology or pulmonary etiology then daptamycin would be adequate. Right yeah so to the pharmacist yeah that one more thing is because of the pneumonia the daptamycin is not a good choice like yeah patients who have bacteremia lenazulate is not a good pick for the MRSA coverage right usually and if it is that there is a warning about that. Yeah yeah that's correct that's correct and likely what they're finding is that even empirically due to more resistant gram positive bacteria that occasionally you'll actually have daptamycin resistant strains anyway so you end up using lenazulate maybe not first but in some cases because that's all it's sensitive to unfortunately. And again emphasize that you can't use daptamycin for pneumonia. That's correct should not. We'll talk about lysine. Yeah would you prefer IV or PO lenazulate in this situation? Yeah I would initially starting therapy I think the intravenous route due to more so in patients that maybe have gotten large volume resuscitation or you're thinking there's some issue with absorption would probably be would probably be you know preferred. Have I seen people utilize after a few days transition to oral? Yes but I think there were not on the basis of clinical improvement they were just purely on the basis of cost and I don't know if that necessarily is the right thing to do every time for the patient. Good good questions. Any other questions on our antibiotic choice? I'm just wondering that again bactericidal like if we think about vancomycin that idle and when you think about like is about starting a bacterial agent as the initial agent of choice? Ron do you want to address that? Yeah I think then for back where I think there's adequate data to support that outside of that I have not seen and it's likely due to just small numbers in the studies but that it was there just wasn't a pronounced or a clinical difference or statistical rather is there a clinical difference so that there could be but I don't know if we've just observed that yet and it's interesting vancomycin even though it's labeled sidle if you actually take a look and they've done this a lot in the lab and you can even see it clinically but if it's taking you know 48 hours or 72 hours to figure out what a serum level is or to get it and if it's adequate or not then it's not really sidle because you're still waiting that time period whereas the other drug you just initiated started and go. The only caveat I would say at least in the patients that I see oncology patients with neutropenia or stem cell transplant who have no counts we usually start with vancomycin first because of the concern for bone marrow suppression with the nasolids so we generally will start with vancomycin we get levels pretty fast but in some cases that don't respond well then you know we just bite the bullet and switch over but generally we start off with vancomycin as well with all the caveats but in bone marrow suppressed patients neutropenic patients the nasolid can further worsen that problem so. But the pure IDSA ATS guidelines for MRSA pneumonia are starting with nasolid with all the caveats that we talked about. Yeah this excellent discussion and you know antibiotic dosing in the critically ill patient is not an easy thing so we do appreciate the PharmDs and and the boards can't even get into all the different factors that go into you know you the volume of distribution, augmented renal clearance, the protein binding and all that goes into what is the effective dose that you need to give and that's why it is important if you got something you can check a level on at least you can do that and help you understand if they're not improving is it because you're under dosing or you've got the wrong antibiotic. Yep sure how long should you treat this patient with VAP and wait how long should you treat a patient with VAP and good clinical response. So we got three days, 7, 14 or 21. Seven days nice and easy. Long gone are the two-week courses. I'm gonna punt this out to PharmD as well. So if it's a bacteremia associated with it are you 7 or 14? If there's a and we would just call that complicated if you have other sites of infection I would say that would justify and should probably prolong your course slightly. Does it have to necessarily be 14 or more days? Probably not but likely greater than five or seven yep but again associated with good clinical response that's correct. Anybody use a procalcitonin to help you know that they've had enough? One head nods. Okay to the pharmacist like if it is a MRSA pneumonia, VAP with MRSA pneumonia and bacteremia then the whole thing changes right so then you gotta rule out endocarditis and so things could be very different there. So you cannot generalize saying that VAP pneumonia should have a course of seven days. It all depends on the organism right? Absolutely so if you have endocarditis you're in a whole nother you know ballgame but just the pure basic you know VAP with the bacteremia does not necessarily extend your course of antibiotics but if your clinical situation changes then you have to change the duration with that. That's correct and even there's some and you I don't know if you get into it but if it's multi drug-resistant organisms there are there's some literature you know suggesting that seven days is adequate and there's some papers that suggest it's not adequate and there for example if they're immunocompromised you'll likely go greater than five days or seven days and if they're not and they've responded then even multi-drug-resistant the shorter courses are now being supported. Thank you. The lecture online says that seven days unless it's a non-fermenter is that no it still will work. The non-fermenters will have a higher rate of having a recurrence but still the mortality and survival was the same seven versus 14 and actually the study by Shastra and Fagan was 8 versus 15 everybody just shaved one off of that and it was 7 versus 14. The lecture online made a very distinct point that if it was a non-fermenter you should use 14 days I think it was one of the infectious disease specialists that talked about it. George. It mentioned about Pseudomonas and Asimov, it talked about days. I think it was predominantly based off the resistance pattern that could develop. In those cases where there's a very high resistance rate like with Asimov or Pseudomonas, I think I'd put Dr. Parrott in the IP response. They need you. It was recommended that we work along the course of 14 days for institutions with very high resistance rates for gram-negative bacteria such as Asimov or Pseudomonas. Although still with good clinical response I would consider stopping at day 7 if I've gotten the clinical response that I was looking for. I'm surprised nobody seems to use procalcitonin. Is that my own sense from the group? You use it for de-escalation? Any more hands? We use it in the first 48 hours. Not to decide whether you're going to start antibiotics but maybe if you're on it, patient's clinically improving, maybe you're on 2, you want to subtract, maybe de-escalate. Then you get a procalcitonin and if it's low you feel comfortable de-escalating or stopping the antibiotics. Particularly when everything turns out negative. Particularly if all the cultures are negative, correct. Clinically improved, cultures are negative, you say well maybe it wasn't infection after all. And then just as a guide for you, you probably have all seen this, the IDSA-ATS 2016 guidelines. These are the most recent that I'm aware of for HAP and VAP. Just so you can see what are the empiric treatments, which is what we've been talking about. Here's when MRSA is suspected. And as you get into other issues, as far as the pseudomonas that we were just talking about and the vancomycin, lenazolid. Here's the strong recommendations, moderate quality data for vancomycin and lenazolid. As far as HAP and VAP with pseudomonas, antibiotics based on culture and sensitivity data, use monotherapy if not in shock or high risk of death. If you don't know the sensitivity and they're in shock or high risk of death, use combination therapy until you get your data to tell you. Again, it's weak recommendation, very low quality data. And here's for ESBLs, the CREs, and your acinetobacter. And see, I don't know if George mentioned about, here the IDSA talk about treating with polymyxin using inhaled colistin as well. But these are your really multi-drug resistant organisms that are difficult if not impossible to eradicate. And as far as duration, they say VAP seven days, strong recommendation. Again, it's really one study, very low quality data. Recommend de-escalation rather than fixed duration of initial treatment. Procalcitonin in clinical data are better than clinical data alone for deciding on when to discontinue. And don't use the clinical pulmonary infection score to guide discontinuation of antibiotics. Which of the following will help prevent a VAP? Maintain ahead of bed less than 30 degrees, change ventilator tubing every other day, start prophylactic inhaled colistin, or provide daily oral care? Oral care, wonderful. Excellent. And then our cap summary, which basically what we've just been going over, and our HAP-VAP summary. And we're saying treat for seven days with good clinical response. And prevention strategies appear to be effective. But they may need some new studies. We're now going with the infectious ventilator associated complications and the newer definitions of ventilator associated pneumonia. And that concludes our ARDS and pneumonia in the ICU questions. We have a follow-up.

respiratory failure

pneumonia

ICU

management

treatment options

lung protective ventilation

antibiotics