Thank you. Thank you, Christina. Okay. Welcome everyone to sunny Phoenix. I'm from Philadelphia where it's always sunny and bad things happen. And I do have a dad jokes t-shirt. I was given that this year. Okay, good. So this talk has a new title compared to what's in the program, severe acidemia and hypoxemia and kidney and respiratory failure and unholy alliance of organ badness and intensivist perspective on the excessive use of colons. Okay. Here are my disclosures. I don't think anything super exciting, except as you may know from the title, I am not a nephrologist. Okay. So kidney and respiratory failure. I think this is your basic nightmare and it happens frequently. And here's a rough outline of the talk, but I will highlight that most of the time I'm going to spend focusing on this first bullet point, severe acidemia, when and in whom is it a problem? And should we use sodium bicarbonate? That's going to be the principle focus of the talk, because that's what I'm thinking about a lot as an intensivist. Now, hypercapnia and hypoxemia, I definitely think about that a lot in these particular patients, but I don't think going through every last detail of, okay, here's how let's manage the vent and whatnot is going to be helpful to this learned crowd. So I will go over some of the basics to put that in, uh, in context and the limits that may push me towards engaging the nephrologist, fighting multi-organ failure instead of each other. Okay. So I'll go through, uh, four common acidemia scenarios and treatments, and then we're going to mostly focus on one of them. Imagine a 55 year old male with septic shock. Here's what the blood gas looks like. pH of 7.15. PCO2 is low at 15. Uh, oxygen is 95 and the bicarb is five. Lactic acid is high. Anion gap is high. This patient gets antimicrobials, IV fluid, pressors. I'm summarizing here. Um, 33 year old female with DKA, same look in blood gas. Lactic acid is 2.4, not too high. Anion gap is high. We're giving this patient insulin and IV fluid. 78 year old female with diarrhea. Blood gas looks the same. Lactic acid is two. Anion gap is normal. We're giving this patient IV sodium bicarbonate. And here's a 65 year old male. Blood gas does not look the same. 7.15, so the pH is low. But in this case, the PCO2 is quite elevated. And we're going to give this patient non-invasive ventilation. So now we add kidney and respiratory failure. And I'm acknowledging here that the middle two scenarios, that doesn't happen a lot. And even the one all the way over on the right, patient with COPD, that's not like, yeah, all the time that happens. But in the scenario on the left, it's like, I feel like this is every day in the intensive care unit. We've got the patient whose serum creatinine goes way up, urine output drops significantly, they become hypoxemic and dyspneic, and they get intubated. So let's go briefly into detail just on this patient and think through what questions we may be asking. So again, you have the blood gas and some of the data over on the left-hand side and the things that we've already done. Here you can see that the patient has widespread pulmonary opacities. You can take a look at what we're doing on the vent here. The patient's being ventilated at a rate of 36, has, I will tell you, low tidal volume ventilation, 6 cc per kilo, is on 60% FiO2, is on a PEEP of 7.5. And here's what the blood gas looks like now. So what you can see is the pH is still in a I'm not super enthusiastic about it zone. The PCO2 is now up to 35, not surprisingly, with that chest x-ray. PaO2 is also down. The lactic acid is coming down. Serum creatinine does not look great. We're not peeing well. We're on a reasonable amount of vasopressor. So then summarizing a few things I'm thinking about, are there things that I can do with the ventilator to help this patient? Are there additional things? And that's the top box. Then are there additional things that, hmm, maybe I should be doing, whether because there's an evidence base or I think physiologically that may help me out of what I think may be a pickle? Because I will be honest with you, I'm a little nervous about the pH of 7.16. We'll go through that. And then, of course, there's the question of whether I should use sodium bicarbonate in this patient. And so here's where we focus on acidemia. I want to now take a step back and think through what kind of data do we have? What do we know about the physiology? What is going to inform us about when does acidemia matter? And then what we should do about it. So homeostatic mechanisms tightly regulate blood pH. Hopefully this is not controversial. A pH of 3.7 is bad, okay? If you didn't know that before, you heard it here first. Do not let that happen to your patient. But I think we all agree that's probably bad for cells. It's not going to go well. But less clear is what cutoff do you need to get to at which there's a direct toxic effect of the pH? And is it dependent on the type of acidemia? And will giving base raise the pH? And will it improve outcomes? And I included this graph on the right-hand side just to remind everyone that sort of between 7.2 and 7.5, there's a roughly linear association of the change in pH with the change in hydrogen ion concentration. But when you start getting down below 7.2, you fall off that curve a little. And getting down to 7.1 and 7.0, now you're going from a normal, you know, a concentration of 40. Now you're all the way up at 100, 6.9. You're at 120. So we're really talking about pretty high hydrogen ion concentrations, which is what we presume, but don't know for sure, would be the potential toxic effect. So what do we think we know about the effects of acidemia? It's complicated. And I encourage us all to think, you know what, I kind of think this is simple, but no, it's not simple. And then when I think I've figured it out, no, I haven't figured it out. Because every time I read one of the reviews of physiology on this, I'm like, oh yeah, oh, I didn't know that that happened in lactic acidosis or that sort of unusual thing that could happen with the bicarbonate buffer system. So it's complicated, but we have some animal data that show a cardiac depressant effect once the pH gets below 7.1 or 7.2, certainly below 7.1, a predisposition to arrhythmias, hypotension, resistance to vasopressors, and phenoconstriction. A decreased sensorium is quite common. And then reduced hepatic blood flow and insulin resistance has been demonstrated. There can be different effects on the hemoglobin oxygen dissociation curve. So acutely, you can see in the blue on the right, the pH drops, and it right shifts, and it has the effect of offloading oxygen into the tissues. However, if you wait 12, 24, 36 hours, there is a change in 2,3-DPG, which ends up causing a left shift of this curve and worsened oxygenation of the tissues. Regarding cell injury, acidemia can increase injury via multiple mechanisms, but has also been demonstrated to decrease reperfusion injury. And with the lungs, in asthma, acidemia is metabolic acidosis is shown to decrease the effectiveness of beta agonists, but hypercapnia and even metabolic acidosis in bench studies have been shown to decrease lung injury when exposed to a precipitant of acute lung injury. Okay, so then we get to the, well, the pH is low, so you just give them some bicarb and everything will be fine. So here we go. We have our blood gas again, this patient is still on pressers and whatnot, and here's a very basic model of what's going on with the bicarbonate buffer system in the blood and interstitium, and then separately within the cells. So we take this sodium bicarbonate, we add it in, there's some more bicarb, it combines with the hydrogen, and then it goes through this very complicated system to produce CO2 and water, and then the CO2 is just breathed off by the lungs. So we're totally fine. We got rid of that, right? We got rid of the acid and here we go. This is ideally what we have on the other side. We gave bicarb and then at least the numbers look prettier. Okay, well, are there some negative effects? Are there some concerns? So you give this bicarb and here we go. Now you're combining this stuff within the blood and interstitium, but what happens if that CO2, instead of being ventilated off, then goes intracellularly? And in fact, the CO2 more rapidly will diffuse into the cells than the bicarb. Bicarb will ultimately go into the cells, but particularly with rapid administration of bicarb, there's a concern that you will rapidly produce CO2 that will rapidly go into the cells. And actually, as you can see with the arrows here, you then have more CO2 in the cells and you go the opposite direction and you create acid. So that is the way in which one can have a paradoxical worsened intracellular acidosis by dosing bicarb. And then of course there are other potential effects. You can cause hypocalcemia, you can cause hypokalemia, hypernatremia, hypervolemia. These things are not necessarily good in our patients. You can left shift the hemoglobin oxygen dissociation curve if you rapidly raise the pH. And then sodium bicarb has even been shown to increase lactic acid production. Okay. This is a great study from 1991. Does sodium bicarbonate improve shock? I think many of us have heard of this study. Many of us have looked at this study. It was a crossover RCT. And the question was, if we have patients with really bad lactic acidosis in the setting of septic shock, does giving them bicarb do anything for us in terms of the arterial pH, the bicarb level, the PCO2? And what does it do to hemodynamics? And what they found in the crossover, so basically they gave them bicarb, they randomized them to bicarb first and then sodium chloride. Not surprisingly, it did raise the arterial pH and the bicarb and the PCO2 level as expected because of the equation. But there was no difference in the effect on the parameters of wedge pressure, arterial pressure, and cardiac output. There were some limitations to this study. Only half of the 14 patients had a pH less than 7.2. It was a single bolus. It was about 3 amps of bicarb that they gave, only 30 minutes of follow-up, and nearly all the patients died. So this was kind of a select population. And I think it's hard to totally extrapolate that, especially if you say, hey, we're going to infuse bicarb into a patient. So what do we do? That I know of, this is still the only survey that's been done. It was specifically to look at intensivists and nephrologists. Do you give base? And for most, it was bicarbonate. Back when they did this survey, Pham was still on the market, and so that was considered as well. And I don't know if anybody's surprised by this, but here we go. For lactic acidosis, 86% of nephrologists said that they gave base, 67% of critical care physicians. 60% of nephrologists said that they gave base for ketoacidosis. Interesting to me, 28% of critical care physicians. And what were the thresholds that people used? So among the nephrologists, less than 7.2, right? That was the, OK, once you get less than that, that's when I'm giving it. For the critical care physicians, it was spread a little bit more evenly among the 7.0 to 7.2 range. None of this is evidence-based. This is just, what are you doing? I'd be interested to see what these numbers would look like today. This was published in 2006. So then I'm sure most of us are familiar with the Bicar ICU study. This probably represents the main semi-large study that looked at infusing bicarb and looked at outcomes. It was an open label RCT in 389 patients. It was stratified by those who had AKI stage 2 to 3 at entry. That was about half the patients in the study. The patients were sick. 80% were ventilated on vasopressors. The median lactic acid level was about 5 to 6. 80% of the patients had a lactic acid level greater than or equal to 2. And they were focused on patients with metabolic acidosis, as highlighted by the inclusion criteria here. And the intervention was sodium bicarb 4.2%. This was hypertonic, so about 3 times isotonic. And the goal pH was 7.3. And what I can tell you is most of this was given in the first day of the study, even though it was technically a study out through day 28. The primary outcome was day 28 mortality or day 7 organ failure. These are some things separated out. Here's the acute RRT. And you can see that the rate of acute RRT in the control group was much higher than in the bicarbonate group. And then 28-day mortality did not differ overall. But in the subgroup that had AKI stage 2 to 3 at randomization, there was a difference favoring the bicarbonate group. These were secondary outcomes, though. So the aftermath of bicarb ICU. There was no statistically significant difference in the primary outcome. People who are Bayesian can go back and you can take a look at this if you would like. The sodium bicarb was associated with metabolic alkalosis, hypernatremia, hypocalcemia, the things that we expected. The patients got similar volume, but there was a higher sodium load in the bicarb group. And of course, it was an open-label study. And whether knowing the patient was on bicarb, did that impact the RRT decisions? We don't know. Everyone should know that the bicarb ICU 2 trial is recruiting, I believe. This is going to be focused on patients who have AKI stage 2 to 3. So they want to try and take that group and say, how much do these patients benefit? Let's go for a higher number and let's try and answer a question about mortality as definitively as they can. That's the primary outcome. And then there's a SOTABIC RCT that ANZICS is running. This is designed a little bit differently. Patients on vasopressors, metabolic acidosis with a pH less than 7.3, and they're going to use 8.4% sodium bicarb. It will be a blinded study or is a blinded study. And they're looking at make 30. Okay, my brief comments on the ventilator. So going back to this portion here, this is just what I'm thinking through. When I get this patient and I'm like, I am concerned about the pH here. I would like not, in particular, I'm concerned that the pH of 716 is going to turn into a pH of 6.9. So have I maxed out the respiratory rate? And at the same time, I'm thinking I need to minimize the auto PEEP. And to do that, I potentially reduce the inspiratory time as long as the pressures can handle it. Have I optimized PEEP? Did I make sure I went back to the ARMA PEEP FIO2 table? Have I assessed for PEEP responsiveness in this patient that could improve VQ matching and may get me more out of my ventilation? Is the patient a candidate for prone positioning? As we know, for some of those patients, the blood gas will improve. And should I consider neuromuscular blockade, which I mostly think of in this setting to reduce CO2 production? Should I use a diuretic? It depends on the fluid status of the patient. I'm going to leave it at that. But what do I want to avoid? High tidal volumes outside of acute rescue. I want to avoid hypotension related to increased intrathoracic pressure. And I'd like to avoid long-term effects of some of my therapies, excessive sedation, neuromuscular blockade. And we run into a post-resuscitative positive fluid balance. You resuscitate them, and then it's like, what are we doing now? They're not peeing. And you're giving them all these medications and whatnot. And this is what is pushing me towards needing to engage with or getting, I should say this for Christina, since we are colleagues, getting to engage with my nephrologist colleague. Now, do I give bicarbonate for respiratory acidosis? Here's what I'm concerned is going to happen. You already can't excrete the CO2. And as we showed before, that may just go into the cells and result in an intracellular acidosis. Certainly, it's going to be a lot less effective if I can't ventilate the CO2. So I mean, this is one of the bad things that happens in Philadelphia. That's me with my now great friend Dan Nagoyanu. We're just having a nice consultation. And so in my last two slides here, what do I think I'm getting out of the nephrologist and renal replacement therapy? And then I'm going to defer a lot of this to my fellow speakers. I hope to avoid hypervolemia, hypernatremia, and hypocalcemia, get more durable, though sometimes temporary alkalinization, which may give me time. Like, I know that dialysis and bicarb are not the answer to lactic acidosis. But I might need a little bit of time to work on the lactic acidosis. But there are still limitations, as I know, intracellular acidosis, hypotension on the machine. And we really don't have fantastic data for this. So when do I engage a nephrologist to discuss renal replacement therapy? Septic shock with lactic acidosis, early. DKA and hyperchloremic acidosis, if there's significant kidney dysfunction and volume overload, or I think the patient is not going to breathe it off. Primary respiratory acidosis, I'm really just focused, is there kidney dysfunction? I'm not trying to treat one with the other. And then if the patient has a complicated acid-base status, they could benefit from a discussion. So I will leave with these take-home points. Simultaneous kidney and respiratory failure greatly increase the complexity of acidemia and hypoxemia management. Acidemia has negative and some positive physiologic effects, likely varying by type of acidemia and clinical context. The decision to use sodium bicarb is complicated and varies among practitioners and has limited outcomes data. And as I shared, at least my thoughts as to what I do. And then really, I do call the nephrologists a lot. I think in these patients, kidney replacement therapy ends up oftentimes being a must. Thanks very much.

acidemia

sodium bicarbonate

organ failure

ICU management

collaborative care