Cold saline irrigation, a novel approach, reduces the risk of postoperative urinary tract infection in retrograde intrarenal surgery

doi:10.21203/rs.3.rs-4006506/v1

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Cold saline irrigation, a novel approach, reduces the risk of postoperative urinary tract infection in retrograde intrarenal surgery

https://doi.org/10.21203/rs.3.rs-4006506/v1

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Retrograde intrarenal surgery is a standard treatment for upper urinary tract stones. However, serious postoperative urinary tract infections are frequently experienced. In this study, we hypothesized that vasoconstriction caused by kidney cooling might reduce the risk of bleeding and infection during retrograde intrarenal surgery. We retrospectively analyzed 139 patients who underwent RIRS for the treatment of renal and ureteral stones at the Japanese Red Cross Hadano Hospital in Kanagawa Prefecture. Patients were classified into two groups: the HOT group in which intraoperative irrigation was performed using saline solution heated to 37°C, and the COLD group in which saline solution cooled to 4°C. The incidence of urinary tract infection after surgery was significantly lower in the COLD group (7.4%) than in the HOT group (19.7%). The length of hospital stay was also shorter in the COLD group than in the HOT group. Our results suggest that intraoperative irrigation with cooled saline may reduce the risk of perioperative UTI.

Cold irrigation

intrarenal surgery

lithotripsy

urinary tract infection

Retrograde intrarenal surgery (RIRS) is the standard treatment for upper urinary tract stones. In particular, the ability to directly observe the inside of the urinary tract and irradiate stones with a laser makes it highly effective in treating stones that cannot be treated with conventional methods, such as shock wave lithotripsy, and it has become a widely used procedure worldwide. However, serious postoperative urinary tract infections (UTIs), which sometimes result in sepsis, are frequently experienced.

The exact mechanism by which sepsis occurs in RIRS is not yet understood, but it is assumed to be due to the backflow of bacteria or endotoxins adhering to the urinary tract and stones into the renal vasculature as a result of retrograde manipulation and increased pressure in the renal pelvis.

In this study, we hypothesized that vasoconstriction caused by kidney cooling might reduce the risk of bleeding and infection during RIRS, and we investigated whether or not cooling the saline solution used for irrigation to 4°C would have a favorable outcome for patients undergoing RIRS.

This was a single-center retrospective study. We retrospectively analyzed 139 patients who underwent RIRS for the treatment of renal and ureteral stones at the Japanese Red Cross Hadano Hospital in Kanagawa Prefecture between April 2020 and August 2022. This study was approved by the Institutional Review Board of the Japanese Red Cross Hadano Hospital (approval number R4-09). All surgeons or first assistants in this study were Kasahara, the first author, who already had more than 500 cases of upper urinary tract stone treatment and was familiar with the RIRS techniques.

Patients were classified into two groups: the HOT group (underwent surgery from April 2020 to July 2021), in which intraoperative irrigation was performed using saline solution heated to 37°C, and the COLD group (underwent surgery from August 2021 to August 2022), in which saline solution cooled to 4°C was used. Both groups underwent the same surgical technique, and the equipment used is described below.

Patient characteristics and parameters were recorded, including the age, sex, height, weight, body mass index (BMI), pre-existing medical conditions, antiplatelet or anticoagulant medication, pre- and post-operative estimated glomerular filtration rate (eGFR), stone burden, stone location, history of obstructive pyelonephritis within three months before surgery, and presence of ureteral stents before surgery. The stone burden was the sum of the three largest diameters of each stone measured using computed tomography. All patients underwent RIRS in the lithotomy position, and operation outcomes were evaluated by the operative time, surgical complications, stone-free status, presence of postoperative UTI, hospital stay, and blood laboratory tests (C-reactive protein, white blood cell count, and eGFR) on postoperative day 1. The eGFR was calculated using the Cockcroft-Gault formula.

Surgical procedure

RIRS was performed under general or spinal anesthesia. The endoscope used for surgery was an 8.6- to 9.8-Fr semi-rigid ureteroscope (Olympus, Tokyo, Japan) or a 7.5-Fr flexible ureteroscope (URF P-7; Olympus) or both. The lower ureteral stone was approached using a semi-rigid ureteroscope. For upper ureteral or renal stones, ureteral access sheaths (10/12-Fr or 12/14-Fr RETRACE; Coloplast, Humlebæk, Denmark) were used for stone extraction and intrarenal irrigation.

Saline irrigation was manually adjusted by a first assistant to achieve a flow rate of approximately 0.5-1.0 ml/sec. The first surgeon ensured that the injection volume did not significantly exceed the effluent volume so as not to increase the intrarenal pressure. To prevent body hypothermia, a 12-Fr catheter was placed in the bladder intraoperatively, and all cold saline in the bladder was maintained to avoid retention.

Stone fragmentation or dusting was performed using a Lumenis VersaPulse Holmium YAG laser (Boston Scientific, Marlborough, MA, USA). To prevent tissue damage, the power output was limited to ≤ 20 W. For stone removal, a 1.5-Fr Dormia Tipless Stone Extracter (Coloplast) was used. In all cases, a 6-Fr double- or single-J stent was placed at the end of the procedure. A single-J stent was removed after hospital discharge. The double-J stent was removed within one month.

Thermodynamic test of Holmium YAG laser

As a preliminary experiment for the present study, we conducted thermodynamic experiments to determine the extent to which the holmium laser induced temperature changes in the perfusate (Fig. 1). Fibers of 200 µm were immersed in 40 ml of saline solution, and the holmium laser was continuously operated at 15 W (1.5 J × 10 Hz) and 30 W (1.5 J × 20 Hz) for 120 s. The temperature of the saline solution was initially set at 35°C and 4°C before the start of irradiation, and the temperature change was measured 3 times for each combination, resulting in 12 measurements. The results showed that the temperature of 40 ml of the saline solution increased by approximately 5°C when irradiated with 15 W for 120 s, and by approximately 12°C when irradiated at 30 W (Fig. 2).

Perioperative antibiotics

To prevent postoperative UTI, cefazolin (a first-generation cephalosporin antibiotic agent) was administered intravenously on the day of the operation. When a UTI developed, the antibiotic agents were switched to ceftriaxone or tazobactam/piperacillin, depending on the urine culture and general condition.

Infection criteria

Postoperative UTI was defined as a case in which antimicrobial agents were administered for at least three days after surgery with a fever of ≥ 38.0°C, as well as chills, flank pain, nausea, vomiting, costovertebral angle tenderness, and relevant postoperative blood laboratory test findings.

Stone-free status

Stone-free status was defined as confirmed endoscopic stone-free status at operation or no stones larger than 2 mm on abdominal radiography or computed tomography 1 month postoperatively.

Statistical analyses

Statistical analyses were performed using the Statistical Package for the Social Sciences (IBM, New York, NY, USA). Patient characteristics, operation outcomes, and risk factors for postoperative UTI were analyzed using the Mann–Whitney U test and logistic regression.

Patient characteristics (Table 1)

The mean age of the HOT group was 60.7 years old, with 51 men and 20 women. The mean BMI was 24.94, and the eGFR was 61.5 ml/min. Eleven patients had a history of diabetes mellitus, and no immunosuppressive drugs were administered. A history of pyelonephritis within 3 months before surgery was observed in 23.9% of patients, and the pre-stenting rate was 73.2%.

The mean age of the COLD group was 62.3 years old, with 38 men and 30 women. The mean BMI was 24.89, and the mean eGFR was 54.2 ml/min. Ten patients had a history of diabetes mellitus, and three patients used immunosuppressive drugs. Pyelonephritis within 3 months before surgery was observed in 32.4% of the patients, and the pre-stenting rate was 66.2%.

The mean stone burden was 11.07 mm in the HOT group and 10.11 mm in the COLD group, with no significant differences. The affected side tended to be the left side in the COLD group.

Operation outcomes (Table 2)

The incidence of clinical UTI requiring antibiotics for > 3 days after surgery was significantly lower in the COLD group (7.4%) than in the HOT group (19.7%). The incidence of septic shock was 0% in both groups. The length of hospital stay was also shorter in the COLD group than in the HOT group. The operative time was shorter in the COLD group (40 min) than in the HOT group (52 min). The change in the eGFR was not significantly different between the two groups. No severe complications were associated with the surgical procedures in either group.

Univariate and multivariate analyses were performed to identify the factors that might cause postoperative UTI (Tables 3, Table 4). Based on previous studies, a logistic regression analysis was performed to identify factors strongly influencing postoperative UTI, including a preoperative history of pyelonephritis, sex, age, BMI, stone burden, presence of diabetes, preoperative placement of stents, renal function, diabetes, and presence of oral immunosuppressive drugs (such as steroids).

A history of obstructive pyelonephritis within three months before surgery was the strongest risk factor for postoperative infection. This factor has been noted in many previous studies, and we believe it is the same in our study. Intrarenal irrigation with cooled saline reduced perioperative UTIs. Female sex was also a risk factor.

As RIRS is a widely performed procedure, various methods have been investigated to avoid perioperative complications. In general, the overall complication rate after RIRS has been reported to be 9%-25% [1, 2, 3]. Most of the complications were minor and did not require intervention. However, there are reports of up to a 5% risk of serious urinary sepsis [4, 5]. A history of ureteral perforation, positive preoperative urine culture, and length of operative time were reported to be the most important risk factors for perioperative sepsis [6, 7].

Infectious complications after RIRS can be minimized by using prophylactic antibiotics, limiting operative time, and maintaining low intrarenal pressure [8]. In particular, high intrarenal pressure tends to cause UTI. However, there is currently no way to accurately measure intrarenal pressure [9].

At our hospital, the operative time did not exceed approximately 90 min, and the intraoperative irrigation rate was always manually adjusted by the assistant to be approximately 0.5-1.0 ml/sec. The surgeon also ensured that the irrigation saline was always draining out of the ureteral access sheath to prevent the intrarenal pressure from increasing. Intraoperative contrast was periodically used to ensure the absence of prominent hydronephrosis. Even with adequate perioperative management, there is always a risk of sepsis, and many mild cases of UTI may exist that are not counted in reports.

We have taken the approach of cooling the intraoperative irrigation saline to 4°C to prevent postoperative UTI. It is widely known that tissue cooling generally causes blood vessels to constrict. Consequently, cooling may protect the organs by suppressing inflammation and intracellular metabolism. For example, in the field of urologic surgery, partial nephrectomy is performed by cooling the kidneys to maintain the renal function and control bleeding. Ice is often placed around the kidney to cool it; however, there have also been reports of attempts to cool the kidney with retrograde intrarenal irrigation at some centers. [10, 11]

Postoperative UTI in RIRS is a condition that often results in septic shock caused by the retrograde entry of bacteria and endotoxins from the renal pelvis into the bloodstream as a result of increased intrarenal pressure. Our method is based on the hypothesis that cooling the renal medulla and constricting the blood vessels may inhibit the backflow of toxins into the blood. Our preliminary experiments showed that when 40 ml of 35°C saline was continuously irradiated with a 30 W holmium laser for 120 s, the temperature reached 45°C. If the renal pelvic mucosa is continuously exposed to temperatures above 40°C, vasodilation and thermal damage to the mucosa may occur. However, when cooled saline solution was used, the temperature was maintained below 20°C under similar irradiation conditions. This physical experiment demonstrates that unless adequate perfusion is performed in RIRS, or the temperature of the perfusate is sufficiently low, intraoperative thermal injury to the renal pelvis may occur.

This is the first landmark report on the impact of intraoperative retrograde renal cooling on RIRS, as there have been no reports on this topic. We investigated whether or not cooling the saline used for irrigation to 4°C is desirable for patients undergoing RIRS. Our results suggest that intraoperative irrigation with cooled saline may reduce the risk of perioperative UTI. There was no obvious postoperative renal dysfunction due to cooling.

A limitation of this study is that it is extremely difficult to verify in live human bodies whether or not cooling constricts renal capillaries or suppresses the secretion of inflammatory substances in tissues. Therefore, we believe that further in-depth experiments and verification in animal studies are required. In addition, since this was a retrospective study, and patient parameters varied widely, further validation in randomized prospective studies is necessary.

In retrograde intrarenal surgery, intrarenal irrigation with cooled saline at 4°C has been shown to potentially reduce the risk of perioperative infection.

The authors declare no conflicts of interest in association with the present study.

Author Contribution

RK conceived and designed the experiments. RK performed the surgeries. RK and TK analyzed data. RK and TK wrote the paper. TK, TU, HU, KM supervised the paper.

Acknowledgements:

This paper received no grants.

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Tables 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

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Cold saline irrigation, a novel approach, reduces the risk of postoperative urinary tract infection in retrograde intrarenal surgery

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