Dr. Chew and Dr. Bhojani highlight their findings on sepsis rates post ureteroscopy

Naeem Bhojani, MD

In this interview, Naeem Bhojani, MD, and Ben H. Chew, MD, MSc, FRCSC, discuss their recent studies, “Inpatient, ICU Admissions & Readmissions Associated with Sepsis Post Ureteroscopy among a US-Based Commercial Population” and “Yearly Trends in Sepsis and Mortality After Ureteroscopy,” which were presented at the World Congress of Endourology in San Diego, California.^1,2 Bhojani is an associate professor in the division of urological surgery and a clinical researcher at the University of Montreal, and Chew is an associate professor in the department of urological sciences at the University of British Columbia and a scientist at the Stone Centre at Vancouver General Hospital.

Ben H. Chew, MD, MSc, FRCSC

Please describe the background for these studies.

Bhojani: Ben and I have done a number of studies looking at infectious complications—mainly sepsis—after ureteroscopy, and we decided it would be interesting to look at one of the most feared complications after ureteroscopy, and that's mortality. We had access to a very large data set—the IBM MarketScan data set—which basically includes all individuals and dates with employer insurance, up to the age of 65. We used that database to look at patients who underwent ureteroscopy, and then looked at all-cause inpatient mortality after ureteroscopy or within 30 days of ureteroscopy.

Chew: It stemmed from a meta-analysis that we did. This looked at just over 5000 patients. What we found from that was the sepsis rate was about 5%, and we wanted to verify that. When we looked in this large IBM MarketScan database³, the actual percentage was 5.48%, and this was just over 105,000 ureteroscopies. So we verified that, and we found that 5.4% of patients had sepsis. We thought it was kind of high, but in asking around, that is probably a real number. Putting that in perspective, it's about 1 out of every 20 patients that will get this complication. Then we wanted to look further in this dataset, because they have more about the mortality as well.

Bhojani: Looking at that same data set and looking at mortality, when patients went into sepsis, their risk of mortality increased significantly. What we found is that ureteroscopy is a very safe procedure. If you don't have a septic event, your risk of all-cause inpatient mortality—so that's not just due to ureteroscopy—all-cause was .03%, so extremely low. Very reassuring. However, if you have a septic event, this increases to 0.3%. That's a hazard ratio of 17. It increases significantly if you have a septic event. Because it's a retrospective study with ICD-9 coding analysis, we also had patients who went into severe sepsis after ureteroscopy, and those patients did even worse, with a mortality rate of 2.5%.

Chew: To clarify that, all septic patients was 0.27%. But we can look at the sepsis as just regular sepsis, and then very severe sepsis, which is the very ill patients who go to ICU and require pressure support intubation, those kinds of things. So certainly, those patients did a lot worse. It was 2.5% mortality for them, vs 0.3% for those with regular sepsis.

Bhojani: I think that another great point from Ben is the ICU admissions. They tripled when you had a severe septic event. If you didn't have a septic event, then you didn't do so bad. You might be hospitalized for a day or 2, but that was quite low, and it was rare that you would go to the ICU. But if you had a septic event, you would go to the ICUthree-fourths of the time. The idea of sepsis after ureteroscopy is important and is one of the main determinants of patients going to the ICU or even possibly having mortality.

Were any of your notable findings surprising to you and your coauthors?

Bhojani: I think what was most surprising was the all-cause inpatient mortality when you have a septic event. If you have a severe septic event, it goes up to 2.5%. That's really significant for a procedure that most people think is extremely safe, and it is a safe procedure, but I think the key here is the sepsis. What do you think, Ben? I mean, 2.5% is quite high.

Chew: Thankfully, that number is low overall, but if you had a 2.5% chance of dying from a procedure, I think we would all consider that very high. So thankfully, the severe sepsis is quite rare, but of those people, you have a 2.5% chance of dying. We know that it's not a kidney stone that will kill people; we know that it's an accompanying infection that may do it. One of the other things that was not totally surprising to us was that when we looked at the cost analysis of a regular ureteroscopy, it costs somewhere around $17,000. Then when you have regular sepsis, the average cost to the health care system is about $43,000. If you have severe sepsis, it goes up to $68,000. So not only is the mortality higher, but it's a huge cost to the health care system as well.

Bhojani: The other thing I thought was interesting was inpatient hospitalization after ureteroscopy. For me, the majority of my patients go home the same day of the procedure. In this study, we found that almost 18% of patients remain in hospital. It wasn't necessarily associated with ureteroscopy, but 18% stayed in hospital, whether it was they had some sort of cardiac event, or an infection, or pain, or the stent was bothering them. But still, I thought that was quite high.

Chew: Yes, that's a little surprising, too. This is the United States where the day procedure is generally the case. Other places around the world; in Europe, for instance, some need to be admitted overnight, sometimes for billing purposes. Other times, that's just what their culture is. But this is a bit high for that—we're at 18% with non-septic. However, the interesting part is that with sepsis, 75% of those patients were directly admitted. They became septic immediately; essentially, right on the day of admission. So, 75% were admitted right on the day of surgery, but if you were readmitted afterwards, like if you went home within 30 days, that was about 12%. So about 12% of them were readmitted with sepsis, and then 15% with severe sepsis. So just because you're going home doesn't mean everything is OK. Certainly, there is a good rate of being readmitted, particularly for sepsis.

Bhojani: When we look at our last abstract, we found that the septic rate after ureteroscopy is increasing over the time period we looked at; it was over a 5-year period. So not only, as we've shown, does sepsis cost a lot of money and is very morbid and can lead to mortality, but it's increasing.

Chew: I want to just go over those numbers. In 2015, the sepsis rate was 4.7%, followed by 5.1%, 5.7%, 6%, and then 6.6% in 2019. Each of those years had roughly about 110,000, ureteroscopies. The mortality did start to go up a little bit, it was .7% in 2015, 1.3%, and then sort of coming down to 0.8%, followed by 0.5%, and then 0.2% in 2019. It's not like there were more ureteroscopies done during those cases. It was all very similar, around 110,000 to 115,000 ureteroscopies, but certainly the rate of sepsis is getting higher. I can't really explain it. What do you hypothesize about that, Naaem?

Bhojani: The only thing I can think of is antibiotic resistance. We have more and more bugs that are resistant. So maybe we're not treating patients adequately preoperatively possibly, but it is definitely concerning.

Chew: Especially knowing that when you do become septic, your rate of mortality does get a bit higher, which we showed in 2016 when it went up to 1.3% with a 30-day inpatient mortality.

Bhojani: The nice thing is that if you look at the mortality over that 5-year period, it didn't go up significantly. Sepsis is going up, but not mortality. Even when they become septic, at least we're able to control it enough that mortality rate remains relatively stable.

Chew: And the last one we have in 2019 was only 0.2%. So certainly, it's gone down from initially in 2015. It's probably just better medical care overall and improvements everywhere.

What are some steps that you have taken in your own clinical practice to mitigate the risk of sepsis post-URS?

Chew: I think following the guidelines, which have been studied and are well looked at in each of our systems. Looking at antibiotic nomograms, following those. I'm not giving more antibiotics. In fact, I feel like the guidelines now have a lot more antibiotic stewardship. A lot of people say, “Well, why not get more antibiotics?” It induces resistance, and we also miss some of the patients that get a lot of antibiotic complications as well as Clostridioides difficile colitis and other things. But it really is the resistance that I'm worried about. A lot of the studies show that the one single dose for uncomplicated ureteroscopy is absolutely fine, no need for pre-operative antibiotics, no need for postoperative antibiotics. It's just that one single dose. The one thing we are making sure of is that we do get a sterile urine culture and that we're treating any preoperative cultures effectively.

The other thing is trying to make sure that our systems and our techniques are good. There are some data coming out that have not been in the literature yet. It's not from us, but from Tom Chi, MD, at the University of California, San Francisco. He’ll be looking at some of the data. One of the questions will be: Is using a single-use ureteroscope going to reduce the amount of urinary tract infections following ureteroscopy, rather than using reusable scopes? So, there's going to be data coming out with that. I think it'll be very interesting to look at. The other thing that Naeem and I are very interested in looking at is something that is very poorly studied so far, because we don't really have a tool to measure it, and that's intrarenal pressure.

Bhojani: Yes, if you look at the studies we've done and how we've looked at a number of risk factors for sepsis after ureteroscopy, we've identified patients who are at risk of sepsis. We know that females, older-aged patients, patients with comorbidities, patients with a stent, patients with preoperative positive urine cultures, these are patients who are at risk of sepsis after ureteroscopy. The question is, how do we reduce the risk in these patients? As Ben mentioned, intrarenal pressure has been associated with systemic inflammatory response syndrome (SIRS). We have a nice study coming out, a porcine model study⁴ from Dr. Eisner's group, showing that when you increase your intrarenal pressure, you can increase sepsis postoperatively. As Ben mentioned, intrarenal pressure is a hot topic. I feel it is associated with postoperative infections, but we still need to discover what the cutoffs are. Specifically, I think it'll be important in those patients who have risk factors for sepsis after ureteroscopy.

Chew: There's been a lot of preclinical studies or studies where patients have a nephrostomy tube, for instance, and you can measure what their pressures are. So, there are a few things that are out there, but very small. It's difficult to measure a patient's intrarenal pressure. In terms of the Eisner study you're talking about, he did a couple of studies. One of them was to use irrigation with E. Coli in it—this is in an animal model, preclinical—and did a low-pressure irrigation and a high-pressure irrigation. In the high-pressure irrigation model, all those animals had bacteria showing up in their urine as well as in their blood. The low-pressure, below 40, so there's 37 mm of mercury, they did not show it in the blood, but they all did have positive urine culture. So that was good, direct evidence. He also showed that fluid absorption was higher to infusing ethanol into the irrigant system in a porcine model and showing that the higher pressures you had, if you were at 75 mm of mercury, or 150 mm of mercury of irrigation pressure, that those systems absorbed a lot more fluid than if you were lower at, say, 37 mm of mercury. So, we have pressure in a preclinical model. There are some spotty human data. How would people measure pressure?

Bhojani: With the previous studies, it was either a nephrostomy tube in place or adding a second wire that can measure pressure. So it's more equipment in the renal system and the collecting system. That's probably one of the main reasons we don't have too much information on intrarenal pressure. Fortunately, going forward, we should be able to measure pressures easier and get more data.

Chew: There is a new product, a new scope that's only available in Canada. It's not available in the US yet, but it's a new single-use ureteroscope that can sense intrarenal pressure. We're able to sense pressure in every case we have now. I think we're at the infancy, but now at least we have a tool where we can measure the pressure. Then we can be able to determine if we are going to be able to correlate that with some of these potential complications like pain and sepsis. Furthermore, we need to figure out what that actual threshold is. What is the pressure that sets it off and then triggers off all these other complications? We're just kind of at the new frontier there.

What would you say is the take-home message for practicing urologists?

Chew: I think just to be aware. We all believe that sepsis and certainly mortality is quite low in ureteroscopy. The sepsis will potentially increase that mortality rate. We always think it's very low, but I guarantee we've all had a patient; it's 1 out of 20 patients that will get a septic event. This is a major burden on the health care system, and obviously, not a fun experience for each of the patients. We need to look at antibiotic stewardship, our techniques, and also, from Naaem and I's standpoint in terms of looking at new frontiers of research, looking at things such as the intrarenal pressure, which we don't know anything about right now, but we'll hopefully know more in the future.

Bhojani: That's a great answer. The only thing I would add is that you need to evaluate your patient. Each patient is different, each patient has different risk factors. In those patients who are at risk of sepsis, you want to be careful, and you want to make sure that you prepare them well and that they understand the risks associated with the intervention. Hopefully, with our new tool, we'll be able to figure out what the cutoffs are and which patients we need to be even more careful with.

References

1. Chew BH, Eisner B, Bhojani N, et al.MP10-10: Inpatient, ICU admissions & readmissions associated with sepsis post ureteroscopy among a US-based commercial population. 39th World Congress of Endourology. Published online September 29, 2022. doi.org/10.1089/end.2022.36001.abstracts

2. N Bhojani, B Eisner, M Monga, et al. MP10-12: Yearly trends in sepsis and mortality after ureteroscopy. 39th World Congress of Endourology. Published online September 29, 2022. doi.org/10.1089/end.2022.36001.abstracts

3. Bhojani N, Eisner B, Monga M, et al. MP10-11: Mortality following ureteroscopy in a large US-based commercial database. 39th World Congress of Endourology. Published online September 29, 2022. doi.org/10.1089/end.2022.36001.abstracts

4. Kottooran C, Twum-Ampofo J, Lee J, et al. Evaluation of fluid absorption during flexible ureteroscopy in an in vivo porcine model. PubMed. Published online July 21, 2022. doi.org/10.1111/bju.15858