Experts stress individualization of cases, reviewing risk factors for sepsis after ureteroscopy

"We need to try to do as much as we can to limit sepsis, and basing it on the patient's preoperative risk factors can be very helpful," says Naeem Bhojani, MD, FRCSC.

In this interview, Naeem Bhojani, MD, FRCSC, and Ben H. Chew, MD, MSc, FRCSC discuss their abstract, Mortality associated with sepsis post-ureteroscopy among a US-based commercial population,1 which was presented at the 2022 American Urological Association Annual Meeting in New Orleans, Louisiana. Dr. Bhojani is an associate professor of urology, clinical research scholar FRQ-S, and endourologist at the Centre Hospitalier de l'Université de Montréal, Quebec. Dr. Chew is an associate professor of urologic sciences at the University of British Columbia, Vancouver.

Could you discuss the background behind this study?

Bhojani: Dr. Chew and I have been working a lot with looking at infectious complications after ureteroscopy. We did a couple of studies specifically on sepsis after ureteroscopy, because there's not too much in the literature on that subject. We also looked at health care utilization if you end up getting septic vs if you didn't, after ureteroscopy. The first paper was published in the Journal of Endourology.2 The second paper is currently under consideration at the same journal. So then we thought, let's look at something even more severe than sepsis—mortality. There's really not much out there on death after ureteroscopy mainly because it’s considered a very safe procedure and mortality is rare. We looked in a very large data set called the IBM MarketScan data set, which is basically a data set from the United States that includes all patients who have employer insurance, and it goes up to age 65. We looked at all the patients who underwent ureteroscopy, and then we looked at how many of them actually died.

There were some really interesting findings. The first thing we found was that ureteroscopy is a very safe procedure. The risk of death after ureteroscopy is 0.03% if you don't go into sepsis, so a very safe procedure. However, the interesting thing is if you did go into sepsis, that rate goes up to 0.82%. Now, in itself, that seems like not a very high number. But if you look at the hazard ratio, the risk of mortality increases 17 times if you have a septic event, as opposed to just having a normal ureteroscopy with no septic event.

We did another analysis, in which you can separate sepsis into "normal" sepsis vs "severe" sepsis as defined using ICD-9 codes from the data set. When you go into severe sepsis, the rate of death actually increases considerably to 2.5%. If you were to compare non sepsis to severe sepsis, the hazard ratio is almost 50. The bottom line is that sepsis, as we know, is a very dangerous, very morbid condition. It can lead to death. So, you want to try to limit sepsis after ureteroscopy as much as possible. Risk factors that we identified included older age as well as more comorbidities.

Did these findings come as a surprise to you?

Chew: The number, although it's low, is not super surprising. We knew it was going to be sort of low-ish. But the odds ratio of 17.2 of dying if you become septic is certainly alarming.

Bhojani: The numbers are small, which is reassuring. It's the increase in mortality when patients get into sepsis that's interesting, and something that we need to work on. An easy way to reduce mortality would be to reduce sepsis. There's a direct correlation. That's what Dr. Chew and I are trying to figure out now, is how to reduce the risk of sepsis.

What can clinicians do to lower the risk of sepsis in patients undergoing ureteroscopy?

Chew: From our other data, we have shown that risk factors include preoperative stent placement and preoperative positive urine culture, ischemic heart disease, diabetes, older age, and longer procedure times are also risk factors. The way that I've changed my practice is rather than having these guidelines act as blanket statements for everyone undergoing ureteroscopy, I'm taking a more individualized approach. So if patients come in and have been pre-stented for a previous infectious reason—an obstructing stone, for instance—these are patients that may warrant a bit more scrutiny and potentially admission and antibiotics. We need more data on this, but certainly, we know they're at a higher risk of sepsis. So perhaps more antibiotics would help either preoperatively or postoperatively. Currently, the guideline is just to give 1 dose of IV antibiotics at the time of surgery. Dr. Bhojani commented that, if they're very high risk for post ureteroscopy infection, he might give them more IV antibiotics, and then admit them overnight to make sure they don’t spike a fever or become hypotensive/tachycardic .

And then in terms of what we can do, that could be things like shortening our procedure time, because that has been shown to be correlated. Something that we don't know is whether to decrease intra renal pressure. Up until now, we've not really been able to look at renal pressures on a standard basis. But some other studies have shown that there can be increased intrarenal pressure, which can lead to sepsis. We don't know what a safe pressure is. Dr. Bhojani and I are working with Boston Scientific on a new single-use pressure-sensing ureteroscope, which is currently only available at 2 sites in Canada. So now, with each case that we do, we can actually measure the intrarenal pressure. We actually have a prospective study ongoing that will start soon, looking at infectious complications as well as pain and trying to correlate those to intrarenal pressure. All the other studies that have been done have either been done in animals, or in very, very limited human studies with this very cumbersome equipment to measure the pressure inside the kidney. Will it matter? We don't know. But it's something that needs to be studied further.

Bhojani: Just to add on to what Dr. Chew was mentioning, if we can figure out what pressures might lead to a septic event, then maybe we can reduce those pressures, or keep them lower than that threshold. There are a number of ways of reducing intrarenal pressure. One of the simple ways is by using a ureteral access sheath. We actually did this study in a pig model. We showed that when you put in a ureteral access sheath, you decrease those pressures significantly. But it can be as easy as just not using as much pressure on our irrigation, so I think what's really nice and there is data to suggest that higher pressures are associated with infections and sepsis. So now we have a tool to be able to measure those intrarenal pressures, and then hopefully be able to manipulate it in our favor to reduce sepsis, which will, in turn reduce mortality.

What are some take-home messages for the practicing urologist?

Chew: I think one of the take-home messages for the practicing urologist is that we tested 11/13, 12/14, and 13/15 access sheaths, and the pressures were certainly lower in at least a 12/14 and 13/15 sheath. 11/13 lowered it, but not statistically significantly from having no sheath. So putting up a ureteral access sheath will reduce pressure. The next point would be that using gravity irrigation (at 80 cm of water) vs a pressure bag at 150 mmHg, or a pressure bag at 300 mmHg, or a manual filling syringe or a self-filling syringe—those had much higher intrarenal pressures using this pressure sensing ureteroscope. We're just in the midst of submitting the study for publication, but this got presented at AUA this year.

Bhojani: Another take-home message is the importance of individualizing your cases and reviewing risk factors for sepsis after ureteroscopy. We know the rate of sepsis after ureteroscopy is a little bit higher than we thought. But more importantly, ureteroscopy overall is a safe procedure. However, if the patient becomes septic, this increases the rate of mortality. We need to try to do as much as we can to limit sepsis, and basing it on the patient's preoperative risk factors can be very helpful.

Are there other questions that arise out of this research?

Bhojani: That's a great question. The easy one would be, so what if we know that high pressures are associated with sepsis? How do we manipulate it in order to reduce that intrarenal pressure? We always get the urologist saying, "Well, I need to see. I need my irrigation to be able to see well, so I can't reduce it anyway." So how do we manipulate intrarenal pressure to reduce the risk of sepsis but at the same time have enough irrigation to be able to safely treat the kidney stone. We are getting more and more ideas as we do more in human cases.

Chew: I think just looking at pressure, we just don't know where this is going to lead us because it's just such uncharted territory. Dr. Bhojani is already starting to do things differently. He's changing his pressure; if he sees the pressure going up, he's aspirating and emptying the kidney, particularly if patients have had septic episodes. It's another variable that we can try and control that we've never known about before and been able to measure.

Bhojani: We don't know what the cut-offs are, and we also don't know durations. I think that's a big part that we don't know about. Is it the duration that the pressure is elevated above a certain level? Is it the peak that's important or the average pressures? There are a lot of other questions that we need to figure out and parse through. At least now we will have a tool going forward and hopefully our study will be able to shed new light on the role of intrarenal pressure and sepsis and how patients feel after ureteroscopic surgery.

References

1. Bhojani N, Eisner B, Monga M, Paranje R, Cutone B, Chew BH. Mortality associated with sepsis post-ureteroscopy among a US-based commercial population. J Urol. 2022;207(5):e239. doi:10.1097/JU.0000000000002543.17

2. Bhojani N, Miller LE, Bhattacharyya S, Cutone B, Chew BH. Risk factors for urosepsis after ureteroscopy for stone disease: a systematic review with meta-analysis. J Endourol. 2021;35(7):991-1000. doi:10.1089/end.2020.1133