EGS BTK_Episode8

Welcome, everyone, to our eighth episode on emergency general surgery. I'm Jordan Nada, and as always, I'm joined by Ashley Nadler, Marika Sevigny, and Graham Scalawong Gross. Hi. Hello. Hi, everyone. You know, Jordan, I was thinking about it the other day, and we've managed to do seven episodes on emergency general surgery, and not once have we mentioned the humble appendix.

Oh, yeah, that's a bit weird, as appendicitis is probably one of the most common problems we deal with as emergency general surgeons. I don't know, guys. Like, what's there to talk about? The resident calls you at 2 a. m. You're only really hearing every third or fourth word, but then they say that magic appendicitis word, and you just book the case.

Yeah, so, not so fast, Graham. So there's been more and more discussion recently on whether or not we can delay appendectomy until the morning. Come on, Jordan. Didn't you watch cartoons growing up? That thing is a ticking time bomb. You need to get it out ASAP. Well, actually,

Graham, Jordan's right. In fact, today we're gonna review two recent randomized controlled trials.

First, delayed versus early laparoscopic appendectomy, or delay, for adult patients with acute appendicitis, a randomized controlled trial by Patel et al. And the second, role of preoperative in hospital delay on appendiceal perforation while awaiting appendectomy, or PERFECT, a Nordic pragmatic open label multi central non inferiority randomized controlled trial by Jalava et al.

Ooh, sounds fun. I refuse to review trials that don't have cool acronyms. Yeah, I I appreciated it when they tell you exactly how they structured the trial right there in the title. Although I have to say, I appreciate when the acronym actually fits the words in the title, but I digress. I'm still confused.

So you guys are telling me that at 2 a. m. I don't need to call in the OR team, argue with anesthesia about whether the case needs to go,

complain about the overnight laparoscopic equipment, finish the case at 4 a. m. only to struggle to stay awake through clinic the next day? That's exactly what these trials are saying, but of course, we will let our listeners ultimately decide if these trials give them enough evidence to delay these cases.

Excellent. Let's get started. The first paper we're going to review is for the delay trial published in Annals of Surgery. Okay. This paper is near and dear to our hearts, as it was done by amazing Canadian colleagues at Queen's University, the University of Ottawa, and Western University. I love how much academic contribution to emergency general surgery there is out of Canada.

Yeah, me too. And this is an excellent trial. It's not only relevant to patient outcomes, but to surgeon wellness and hospital resource use. It's relevant to all our listeners, but can be of particular interest in a publicly funded system like Canada. So we all know that there are potential risks of operating at night, like fatigue and subsequent increases in complications.

And any operations that we can avoid overnight, that's, that's going to benefit surgeons and likely the whole health care system. So to me, it makes perfect sense that they did this randomized control, non inferiority study to see if delaying operative to see if delaying operating affected patient outcomes.

Exactly, Graham. They enrolled patients in two groups. The delayed appendectomy or intervention group, the surgery taking place after 6 o'clock in the morning, following a decision to operate. Great. To the immediate appendectomy or control group with surgery taking place between 8 p. m. and 4 a. m. and within 6 hours of a decision to operate.

It is important to note that they only included stable, non septic appendicitis patients. All of the patients had the diagnosis confirmed with ultrasound or CT scan. Perforated appendicitis identified on imaging was included if they met the other criteria for stability. And all patients had standard post operative care.

So their primary outcome here was a 30 day composite

post operative complication rate. So they included mortality, readmission to hospital, emergency department visits, percutaneous drain insertion, re operation, prolonged hospital stay over seven days, and any other system based post operative complication.

So they set an a priori non inferiority margin at 15%. This was based on some of their previous work. So essentially, in order to conclude that delaying surgery was non inferior, they had to see a less than 15 percent increased risk of complications in the delayed group. Thanks for explaining that, Jordan.

You know, I always find it tricky to interpret non inferiority studies because we're so used to studies that prove superiority. By setting a minimal clinical important difference in their margin, it does help us to be conservative in the estimate of the difference and reduce bias in a non inferiority trial.

We'll talk a bit more about specific bias in non inferiority trials. When we get to their analysis, but let's start with their enrollment and results. They randomized the total of 127 patients with 59 in the delayed

group and 68 in the immediate group. Two patients crossed over to the control and eight to the intervention, respectively.

They did both intention to treat and per protocol analysis. So obviously patients and surgeons couldn't be blinded in this study, but the data was analyzed in a blinded fashion. The study was just shy of meeting its power calculation at 91 percent of intended enrollment because one of the hospital sites in the study lost access to reliable emergency general surgery operative time due to surgical backlog from the pandemic.

So while this might damper the effect size, the results are still quite noteworthy and should be strongly considered. In the intention to treat analysis, they found a 30 day complication rate of 10 percent in the delayed group and 22 percent in the immediate group, with a p less than 0. 001 for a test of non inferiority.

The risk difference is minus 12%, actually in favour of the delayed group in this case. Yeah, I mean, that's, that's just really so surprising. The delayed group

actually seems to trend towards fewer complications. They also did not have an increase in perforated appendixes in that group. So maybe not operating overnight isn't such a bad thing and can benefit surgeons without harming our patients.

Yeah, that's great. In the per protocol analysis, they actually found that the delayed group met criteria for being not only non inferior, but actually superior. It's essential that they did both of these analyses here. While intention to treat analysis generally reduces bias in superior, superiority studies, it can actually increase bias in non inferiority studies.

When patients cross over in a non inferiority study, the outcomes for the groups are potentially more similar, which may lead to conclude that the study is non inferior when it may not be. But by doing both analyses and finding that they have similar conclusions, it helps us be more confident that the results are real and not just due to chance.

So all in all, I think we can feel pretty optimistic about these results and what's great is that they represent real world experience

and resources. So I think we can feel comfortable improving surgeon well being and night resource allocation without putting patients at risk. Yeah, and that's all great.

But unfortunately, there are some there's some butts. We don't know what patients thought of the delay in surgery in terms of their satisfaction or quality of life. So we do have to make sure the delays are acceptable to both surgeons and our patients. We also need to know that reliable daytime emergency surgery, operative time is available as this approach really hinges on that resource being available.

Yeah, and as we all know, that can be a pretty big if at centres that are constantly scrambling for operative time. So I think that's a really important consideration in taking these into account. Alright, and that brings us to our second paper, The Perfect Trial. That was published in Lancet in 2023.

So this is another RCT, but coming out of a group from Finland and Norway. Alright, another non inferiority study. So, I think we can assume that a lot of our assumptions about this kind of still apply. This group compared appendectomies in adults within

8 hours versus 24 hours at three hospitals, two of which were in Finland and one in Norway.

That's right, Graham. Although it was a similar study designed at its heart, the details of the study are a bit different. They didn't limit this to radiographically confirmed patients. Believe it or not, some people were still willing to trust their exam and clinical acumen alone. Oh, wow. I mean, and even if they did trust their assessments, they thankfully standardized the clinical diagnosis aspect by using an adult appendicitis score cutoff.

They also excluded patients with complicated appendicitis and went as far as to recommend imaging for any patients with more than three days of symptoms. Yeah, I think it's important to realize that the lack of uniform imaging findings preoperatively means that their inclusion of only, quote, uncomplicated appendicitis becomes a little bit more complex.

Of course, patients had to be stable, but they also excluded patients with suspicion of complications, including a high CRP or if they're febrile. So it's important to keep that in mind because this might change how this

applies to patients. That's a really great point. It's so important to know exactly what patients these studies apply to.

I also noticed that like our last study, the treating teams and patients weren't blinded to the interventions. And what really struck me as interesting because it's so much different than our local practice where we treat everyone with antibiotics with appendicitis, but they actually allocated patients in each group to antibiotics or no antibiotics.

Yeah, that's really interesting and raises some good questions about the evidence or luck thereof that sometimes drives local practices. For their endpoint, they looked at complicated appendicitis identified in the operating room, which they defined as AAST grades 3 to 5 perforated appendicitis. They also evaluated several secondary endpoints, including length of stay, surgical site infections, positive blood cultures any postoperative complications and patient rated pain.

And that brings us nicely to what everyone is waiting for, those sweet, sweet results. In the end, 1,

803 patients were included in the attention to treat analysis with 907 early and 896 delayed appendectomies. The breakdown of patient characteristics is pretty similar with a median age of 35 in each group.

And most patients had imaging beforehand, but about half of each group had antibiotics. And it looks like they had a pretty good separation of groups based on the exposure with the early group having a median 6 hour time to operation compared to 14 hour in the delayed group. But there's definitely some overlap between the two that could potentially blunt the findings.

So a quarter of patients in the delayed group actually had surgery within 8 hours. Yeah, so taking it with a bit of a grain of salt since there's some overlap between the groups, but there was no difference in the rate of perforation with 8 percent of the early operation and 9 percent of the delayed having a perforated appendectomy or appendix in the operating room.

The rest of the secondary outcomes were pretty similar, and if you were worried that patients were too similar to show non inferiority,

their secondary per protocol analysis again didn't show any differences between the two groups. So all in all, that's pretty reassuring. Yeah, right. You are, Graham. In the end, I think we have another solid non inferiority trial showing that some delay in operative management, like waiting until the morning, is probably not harmful to patients.

All right, so I think we're all pretty thrilled to hear the results of these studies, because there is nothing more I dread than getting out of bed, my warm, sweet bed, at 3 a. m. for a straightforward appendix. For sure. But you also have to work somewhere where there's daytime operating time to accommodate whoever comes in at night.

And that really strengthens the argument for dedicated emergency surgery triage OR time during the day. Yeah, for sure, Ashley. And it's also great to be able to reassure patients that their appendix is highly unlikely to explode in the hours that they are waiting for that pesky organ to come out. So I think it's time for a game to apply our newfound knowledge.

All right, game

on. Let's bring it on. Hey, can we call this one do the appy or take a nappy? Incredible, yes. Yeah, I'll actually be mad if we call it anything else now. All right. Yeah, the necessary. So as our appointed Game Master, I will provide the scenarios and each of you will comment. Do you operate now or admit?

Turn on that white noise machine and rest up to get it done in the morning. All right, let's do it, but I don't think they'll let me have a white noise machine in the call room anymore. You can download an app and put it on your phone. It's called Fan Noise. It's incredible. Now we know who's paying you.

Go ahead with the game. Let's do it. All right, friends, case one. 34 year old male presenting with three days of migratory abdominal pain, elevated CRP, white count 18. Initially was febrile to 38. 3 in the emergency department. He had a CT scan which shows appendicitis with a fecal api or nappy. Dr. Nadler.

He

sounds pretty sick for somebody with appendicitis. So I actually wouldn't wait till the morning. I would just do it overnight. What do you think, Jordan? Yeah, it's a tough one. That's a tough one. So, you know, he's got a, he's got a fever, but I don't hear anything here about his stability. So, you know, assuming that he settles with a little bit of pain control, getting started on antibiotics I think as long as he's human dynamically normal, I'm okay with the nappy.

What about you, Graham? Are you pulling yourself out of bed for this? Yeah, I'm a little on the fence too. You know, I was leaning towards taking out the appendix and, you know, wondering if you know, I was being too influenced by you who, you know, who seems to be in cahoots with big white noise.

But I think I'll, I think I'll hold off. I think I'll treat this patient with antibiotics. Yeah, I think, you know, I was a little bit leading with this, but I think he actually meets the criteria for the patients included in the studies for having delayed operative management or delayed till the morning.

So I don't

usually comment, but I think I would wait because I like for the elevated CRP. Oh, that's a good point. Okay. Okay. But most cases of appendicitis will have some elevated CRP. So I think it would actually read to this. All right. Okay. Let's try another one. Case two, 29 year old female, 18 weeks pregnant, presenting with two days of right lower quadrant pain, nausea and vomiting.

Afebrile, mildly tachycardic with a heart rate of 115, but blood pressure is normal. She had an MRI that confirms a distended appendix to a centimeter with fat stranding and a small volume of free fluid. All right, Graham, appy or nappy? You know, this is a subject that I'm really passionate about. This patient's getting an appy in my hands and and I I hope to just plug that there's a paper by our group coming out all about pregnant patients and emergency general surgery hopefully coming out soon.

Amazing. Okay. And what about you, Dr. Nadler? Yeah, I agree.

Neither of these studies included pregnant patients. I don't think we should take a risk and they should have their appendix out as soon as we can get it done overnight. Dr. Nada, any disagreement here? No, 100 percent agree. And I think a big thing to remember here is that there, I would say there's probably some increased risk of fetal loss with prolonged intra abdominal sepsis.

So I'd be worried about waiting for an extended period of time to remove this. So I would do an Appy in the middle of the night for this lady. Okay, great. I think we're all in agreement on this case. Case 3 is a 90 year old female, generally in good health, living alone with some supports, presents with perforated appendicitis without an obvious abscess.

Her vital signs are stable and her white count is 11.

Yeah. So, I mean, we have a lady who is pretty advanced in age, sounds like this is freely perforated. So we're not really going to have a good non operative option here. It doesn't, you know, you're not describing a walled off abscess I can drain or anything like that. I promise I'm not just

rambling to buy myself time.

All that taken together, I think that she probably doesn't have you know, enough ability to deal with a substantial complication. I would just move towards doing her API. This is one that would get me out of bed. Okay. Dr. Nadler. Yeah, I mean, I agree with what Jordan said, but I review the imaging, get a sense of how long her symptoms have been.

Is this an operation that we should be doing? Or is this a non operative patient in terms of if there's any evidence of phlegmon or it's not within her goals of care? If she is. So if she's not. Unwell. We would do it overnight, but there is potentially a role for not operating if we find any kind of other concerns on her imaging, but hard to tell what the information again.

Okay. Anything else you'd like to add Graham? No, I'm leaning towards taking out the appendix overnight in this patient, especially if she's in good health, but I appreciate the comments made by my colleagues. Okay, great. Okay, so last case for the

win, 46 year old male as child B cirrhotic with umbilical vein recannulization and ascites presenting with fever and abdominal pain for five days.

His white count is elevated at 14 and CT scan shows perforated appendicitis with possible phlegmonous changes. It's febrile to 39, tachycardic to 120 and needed a bolus in the ED for brief hypotension. Who wants to go first? Any takers? I first asked my resident how they calculated the child B cirrhosis, because this sounds pretty advanced.

But this is not a patient I'd be taking to the operating room. I would treat them with antibiotics. I would have a hard time having a nappy after after hearing this story, because I'm very worried about this patient but we wouldn't be going to the operating room. Anything to add, Dr. Nadler?

This sounds like every patient you see at Sunnybrook. Yeah no I'm, I mean, I'm quite concerned about this patient. I mean, it's difficult because of, like, generally, if we see flagmentous changes. We are

trying not to operate or we're trying for non operative management but this patient's quite sick So it's hard to tell if it's the actual appendicitis that's making them this sick or it's their lower ability to kind of tolerate any Infection, so I would have a very brief trial of antibiotics But if they really were continuing to get worse, I probably would end up at the OR with this patient despite the risk What do you think, Jordan?

Yeah, I think great points made by both of my colleagues here. This is a tough case. I would lean towards non operative in this or care in this patient if possible, but again, you know, this is not somebody to go back to sleep on. I'd be, you know, resuscitating this patient, ensuring that they that their human dynamics completely normalized and that they're safe for a trial of non operative management.

But if your hand gets forced for sure you may end up in the operating room with this patient But given their high perioperative risk, I would try to treat them non operatively. Okay. Okay So the winner of our game, Appy or

Nappy, I think will be Dr. Nadler, because I think out of all of us here, she's probably the single person who's had to get out of bed the most times in her life as an acute care surgeon.

So in respect to all of the middle of the night appies she's had to do up until now, I'm calling Dr. Nadler the winner. Thanks. Clearly I lean on the more operative side than the other two, but thanks for that. All right. Well, thank you all for listening today. We hope you found this episode educational and entertaining.

And we look forward to the next one with everyone listening and dominate the day.