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What if one of the most common escalation strategies for acute heart failure doesn’t actually improve outcomes? Internal medicine physicians Benjamin P. Geisler, Jeffrey L. Greenwald, and Kathy May Tran, editors of 50 Studies Every Hospitalist Should Know, join the show to break down what the DOSE trial really tells us about managing diuretics on the wards. Based on their KevinMD article “Managing acute heart failure: evidence from the DOSE trial,” they explain why continuous furosemide infusions showed no clinical advantage over intermittent boluses for decongestion, and what that means for your daily practice. You will hear how headline-driven medicine can mislead clinicians, why knowing who was excluded from a trial matters as much as the results, and how evidence-based medicine teaching is evolving in the age of AI. Whether you are a hospitalist, a trainee on the wards, or a primary care physician managing heart failure transitions, this episode will sharpen how you read and apply the studies that shape patient care.

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome Benjamin Geisler, Jeff Greenwald, and Kathy May Tran. All of them are internal medicine physicians. They’re the editors of 50 Studies Every Hospitalist Should Know. There’s an excerpt from that book on KevinMD talking about managing acute heart failure, evidence from the DOSE trial.

We’re going to talk about the DOSE trial and then zoom out and talk more about the book in general. Everybody, thank you so much for joining me and welcome to the show.

Benjamin Geisler: Thanks for having us.

Jeff Greenwald: Thanks for having us.

Kevin Pho: All right, so Jeff, we’re going to start with you. As we talked offline, you were an attending when I was a resident 24 years ago back in Boston Medical Center. So it’s wonderful to see you again on KevinMD. Neither of us have aged in that 24 years, don’t worry.

Jeff Greenwald: Exactly. I look exactly the same.

Kevin Pho: So for those who aren’t familiar with the DOSE trial specifically, tell us exactly what that is and why it’s so impactful to your life as a hospitalist.

Jeff Greenwald: Well, so first, thanks for having us again, Kevin. This is one of those trials that, as a teaching hospitalist, comes up all the time as we’re trying to decide on the diuretic plans for our patients with heart failure, and how you think about the dose of a loop diuretic that you’re going to use, the intervals, whether we should be using it as a bolus or whether we should put them on a drip to continuously diurese them, how that fits into the mechanics and pharmacokinetics of patients’ responsiveness to diuretics. All these questions come up all the time. It’s a super practical study to have the background on.

They randomized about 300 patients. So it’s not a huge trial by cardiology standards. That’s almost tiny. But they randomized patients to get either intermittent boluses of furosemide or a continuous drip, with the theory that we can achieve higher levels more consistently, keep patients above the diuretic threshold by using a drip, and maybe that has a real advantage. They were looking for measures of decongestion as their outcomes and clinical improvements as their outcomes.

This relatively small trial began to show fairly quickly that it wasn’t clear that in fact a drip was better than a bolus. And we often see when we get recommendations from our colleagues in cardiology around heart failure management, there are often still people who use drips for patients who are having somewhat refractory heart failure. It’s helpful to go back and understand that in this trial, actually there was no difference. Now, one could interpret that as, therefore, don’t use drips. Or you could interpret it as, we understand that everybody’s a little bit different, and these are aggregated data. So there might be someone who responds more to a bolus than a drip or vice versa. It’s a little hard to know, but the overall sentiment from this study is it didn’t matter.

This almost biblical adherence to keeping people above a diuretic threshold may in fact, despite its physiologic sense, not actually make a clinical difference. We like this DOSE trial because, A, it comes up when we’re teaching our trainees all the time, when we’re managing our heart failure patients, pretty commonly when we’re interacting with our colleagues in cardiology who may say, put them on a drip. We know that in fact from the data, and it’s one trial with 300 patients, it didn’t actually impact clinical outcomes like decongestion and clinical improvements.

Kevin Pho: So, Kathy, as you reflect on the DOSE trial, what was clinical practice like before the trial? And maybe give an example of how the DOSE trial kind of affected things after it became so prominent.

Kathy May Tran: Yeah. So I think one thing that’s really important to point out, what Jeff highlighted, is the variability in medicine and the variability in interpretation of these trials is so specific. We have to look at our specific patients. And so thinking about what our patient needs, also their setting, in the hospital and outside the hospital, negotiating shared decision-making with the patient. All of this is really important to what we decide to do.

Kevin Pho: So for people who aren’t on the hospital wards dealing with heart failure, just give us a typical case that you would see the DOSE trial influence your decision or not.

Jeff Greenwald: Sure. So we commonly admit patients with congestive heart failure symptoms where they have pulmonary edema, leg swelling, things like that. We are often in the position of giving them IV diuretics with loop diuretics. We often start with once-a-day diuretics and may add twice-a-day diuretics. We may add medications that will augment their diuresis, like thiazides or other drugs like that. But there’s a subset of patients for whom that’s not enough, and we just can’t get them to decongest adequately. So we’ll often bring in our cardiologist, and sometimes they recommend trying a drip.

The reason we often use the once-daily version or the twice-daily version as a bolus is because it’s easy. It doesn’t take a huge amount of nursing time. You don’t have to put it on a pump. So practically speaking, these are easy things to do. Whereas putting them on a drip, there’s more monitoring, there’s more equipment. So we often end up believing that we’re going to put in this extra effort and get a better bang for the buck from our patient’s response.

What’s important about the DOSE trial is that actually isn’t generally the case. You can achieve the same diuretic impact by giving high doses of diuresis. In this study, they also looked at higher and lower doses, and clearly higher doses achieved a better diuretic effect than lower doses. But the benefit of the continuous drip was not there. We see this all the time when we have patients who are becoming more diuretic refractory, are requiring higher and higher doses. The mental leap of trying to go to, let’s start a continuous infusion, we now understand after the DOSE trial may be unfounded.

Kevin Pho: And I could also imagine that the transition from a bolus IV dose, transitioning to a PO dose, transitioning to outpatient when they see primary care like me, it’s a little bit easier than going from a continuous drip, right?

Jeff Greenwald: Absolutely. Absolutely.

Kevin Pho: So this study came from the book that all three of you edited, 50 Studies Every Hospitalist Should Know. So Ben, tell us more about this book. Tell us about the audience and tell us about some of the criteria of the studies that you included in this book.

Benjamin Geisler: Yeah, so there’s this book series, 50 Studies Every Doctor Should Know, and there was a volume in the series, 50 Studies Every Internist Should Know, which contains a lot of relevant studies for hospitalists. But there’s also some studies that, as you might appreciate, are more applicable to the outpatient setting. I think you, PCP Kevin.

So we selected studies that are really more of interest to the hospitalists, and we took over from two other editors, Pri and Cha. They came up with the idea. They had recruited me as a contributor, as a chapter author, and then they asked us to take over. I share an interest with Jeff in evidence-based medicine. We were very lucky to recruit Kathy, who has editorial experience, and we three became the new editors of this book.

Kevin Pho: So Ben, there’s so many studies that come out, obviously. So what makes a study so important that you have to include it in a book like this? How do you measure the impact of a study?

Benjamin Geisler: Yeah, that’s a really good question. So the original criteria were that the study had to be cited quite often, but there are really often-cited studies in the hospital that are not cited much in the literature and vice versa. So we took that list from the original editors and we modified it. We consulted with other EBM-interested folks. For example, the person who wrote our forward, Tony Brew. And we generally restricted the study, so a little bit older.

For example, we had a really interesting study on urine electrolytes from the seventies that we took out. We didn’t really want to include studies that hadn’t stood the test of time yet, say last five or 10 years. So we have sort of 10- to 30-year-old studies that are really, as Jeff said, come up all the time on the wards.

Kevin Pho: So Kathy, give us your perspective in terms of your experience as an editor of this book. Tell us about maybe some other impactful studies that have changed hospitalist practice. Just share your experience in terms of editing this book.

Kathy May Tran: First of all, it was really hard to choose the 50 studies every hospitalist should know. That was a lot of the fun of it, figuring out what actually informs how we practice medicine and how we care for the patients in front of us. I think that a lot of the way that we approached this book was out of an interest in how we practice medicine, how we care for the patients in front of us, but also how we teach and how we learn. How do we take those foundational trials and make them accessible and clinically relevant and actually usable on rounds?

I’m on the resident teaching service right now, and I bet when you were Jeff’s student at BMC, maybe this book could have been helpful there as a reference too. The book goes through 50 studies that we should know, but it also helps us think and have a perspective on how we should approach our practice and every patient, and how we can actually use the medical literature, can use the evidence, to make thoughtful decisions.

Kevin Pho: So, Kathy, just to follow up on that, I have to say, probably the last time I saw Jeff on the wards, that was the last time I stepped into a hospital ward to take care of patients. I’ve been in the office for the last 20-plus years. Kathy, tell us about the evolution of medical training, about how you guys teach evidence-based medicine to the students and the residents. How has that changed over the years?

Kathy May Tran: Yeah. Well, we’re all living history. So would love to hear Ben and Jeff’s, and even your thoughts on this too. I think that how medical education changes not only with time and history and the evidence we have available, but also stage of training too. For example, when I was first starting out in medicine, the headlines are what you need to know when you don’t yet know what you need to know or what there is to know. As we grow from medical students to residents, to early physicians, to seasoned physicians, then we’re thinking about those studies a little bit more.

We realize that headlines are just headlines. There’s actually a lot of nuances into how a study is created, what the patient population the study examines, the results that are discovered, and most importantly, the questions that are left. So I think that as we go through our stage of training, that really changes.

Similarly, on the wards too. I think that very, very fortuitously, our generation now is asking really hard questions. It’s not just what should I do, it’s what should I do for this patient? And it’s not just what should I do for this patient, it’s why am I doing this for this patient? And is this the best thing? I think that kind of curiosity and inquisitiveness in this generation really pushes us to become better physicians, and it makes them better physicians too.

Kevin Pho: Jeff, I’d love to hear your perspective about the evolution of how you teach medical students and residents over the years about evidence-based studies.

Jeff Greenwald: Yeah, so I totally agree with everything Kathy said. I’ll tell you a little story. After I finished my residency in the late nineties, I went to England and I had the opportunity to work under David Sackett, who was really one of the founders of evidence-based medicine. He was doing a professorship year at Oxford, where I was spending a year doing inpatient medicine. It was really the first time where this concept of, analyze, you know, studies have been out for hundreds of years, but analyzing how does that study impact your care, that was new. That really didn’t percolate through a lot of my training. We did what we did because it was biblically told to us, rather than there was a lot of discussion of evidence.

So from there, evolving through the leadership of people like Dr. David Sackett and his followers and other people who have really championed this cause of evidence-based medicine, you flash forward and then you have access to things like UpToDate and other references that really talk about, what are the newest studies that talk about what you should do? And today, of course, we have things like Open Evidence or other really good resources for giving us the why questions for this patient, as Kathy pointed out.

I think that the trick here is mitigating the tendency to go for the headline. The classic and most important example that I’ve seen of that in the last several years was when the BRIDGE trial came out, which was a trial randomizing stopping versus not stopping anticoagulation and bridging it in the perioperative space. When this study was published, it was splashed everywhere, both in the medical and in the public press, that basically said, don’t bridge, don’t bridge.

Well, the problem, having had the opportunity to dig through that trial, is that a lot of the patients that were included in that trial were low risk for bleeding, going for low-risk procedures. In the hospital, when I have a patient going for a colectomy or a brain surgery or a hip replacement, they were represented in only about 10 or 12 percent of the population of that trial. And people who had high bleeding risks or high clotting risks, those were a small percent in that trial. So the no-bridging thing that came out and splashed across the popular press was a classic example of, if you don’t dig into a trial and understand who they represent, you’re going to miss it. That is not an accurate read of that trial.

So the beauty is, our residents, because as Kathy pointed out, are eager to understand a little bit of the why, not just the what questions, and now they have access to these great resources that can dig into, is this right for my patient at this moment? Hopefully we won’t get tripped up by just the headline only of, don’t bridge.

Kevin Pho: Ben, as you continue to edit future editions of this book, tell us about the type of challenges that you anticipate facing as you go forward. What do you have to look forward to as you continue to evaluate evidence-based medicine and new studies as it relates to hospital medicine?

Benjamin Geisler: Yeah, I tend to see three challenges, or one that is actually from the past. When David Sackett and others came up with evidence-based medicine, they actually envisioned it as a bedside tool. They went around with cards with the studies, and maybe they had a little bit more time to talk about the evidence. On the other hand, nowadays you can just pull a study up in seconds on your phone, and you can talk about it.

The second was mentioned already: AI. Will EBM literacy become more or less important in an AI-assisted clinical environment? You could argue maybe it’s going to become more important, because even if AI can surface the guideline recommendation really fast, maybe you need to understand the underlying evidence base that that recommendation is based on. Or maybe not. Maybe we’re going to be all de-skilled and AI will explain the evidence to us, but we still have to apply it to each individual patient. As Jeff said, it’s not just important to know who was in the trial, but also who wasn’t in the trial.

And then thirdly, new studies come out all the time, and I think the challenge is not just access, it’s the synthesis. We need to find tools that make us see the evidence in its breadth, but also see what’s really relevant to us. We need to find the relevant studies for us in that growing number of studies that come out every week.

Kevin Pho: We’re talking about Benjamin Geisler, Jeff Greenwald, Kathy May Tran. They’re all internal medicine physicians, and they’re editors of the book, 50 Studies Every Hospitalist Should Know. Now, I’m just going to end by asking each of you just to share some short take-home messages with the KevinMD audience. Ben, we’ll start with you, then Kathy, then we’ll end with Jeff. Ben, why don’t you go.

Benjamin Geisler: My takeaway from editing a book or doing research broadly in general is, it can really also aid individual clinical practice. You see some deeper aspects of certain things, but you can really bring them back to the patient. If you are curious, if you ask why, it’s both good for yourself or your own development, and it’s also good for your patients.

Kevin Pho: Kathy, your take-home messages.

Kathy May Tran: I think my take-home message would be, if you can critically evaluate a study and understand how it applies or doesn’t apply to your patient, then you’re practicing medicine and you’re teaching medicine to yourself and to others at a higher level.

Kevin Pho: And Jeff, we’ll end with you. Your take-home messages.

Jeff Greenwald: Thanks again. I agree with those points. What I would add is that the medical literature is overwhelming. There is no way to keep up with it. There is no way reasonably to know every study. So I think part of the responsibility of practicing clinicians is to, A, kind of build up a portfolio of the studies that you’re going to come across every day in practice, and to invest in learning something about those. And B, knowing how to ask the questions that allow you to assess whether studies are out there that will help your patient and your clinical question in that moment. And when there isn’t, and you’re really in the zone of clinical expertise, to be able to tease out those differences.

Kevin Pho: Everybody, thank you so much for sharing your perspective and insight. Thanks again for coming on the show.