Does High Ventilation Mode Affect the Success Rates of Retrograde Intrarenal Surgery? A Single-Blind Randomized,Prospective,Single-Center Study

Abstract

Purpose:

Retrograde intrarenal surgery (RIRS) has been accepted as a first-line therapeutic option for kidney stones <2 cm. Renal mobility might be a challenging situation for the surgeon targeting the laser, thereby limiting the renal mobility during surgery might affect the surgical success. The main objective of the present trial was to evaluate the effect of two different ventilation modes on the efficacy and safety of RIRS performed under general anesthesia.

Materials and Methods:

The patients undergoing RIRS from January 2023 to April 2023 were prospectively enrolled in the trial. In the standard ventilation (SV) mode, the tidal volume was 8 to 10 mL/kg with respirations per minute being 10–15, whereas in the high ventilation (HV) mode the tidal volume was reduced to 6 to 8 mL/kg with the frequency being increased to 15 to 18 respirations/minute. For the purposes of the trial and the randomization, the anesthesiologist was informed about the ventilation mode used, whereas the surgeon was blinded. The surgical success rates and the observed complications were compared between SV and HV modes.

Results:

A total of 144 patients were enrolled with the mean age 48.78 ± 14.16 years. The mean duration of operation was 62.9 ± 26.3 minutes in the SV group, whereas it was 58.4 ± 20.1 minutes in the HV group (p = 0.031). Fragmentation rate of the stones per minute was higher in the HV group with the difference being statistically significant (p = 0.003). In the preoperative period, while hematuria was seen at higher rates in the HV group, the difference was not statistically significant (p = 0.671). Stone-free rates (Grades A–B–C) and the rates of postoperative complications were comparable between the groups (p = 0.605 and p = 0.676, respectively).

Conclusion:

Using HV mode during the RIRS decreased the operative time and provided the surgeon with the ability to target the laser more effectively. Surgeons might prefer using the HV mode during RIRS in a mobile kidney to reduce their operative time and perform comfortable surgery.

ClinicalTrials.gov:

The trial is registered at ClinicalTrials.gov with the registration number of NCT05792670.

Introduction

With the development of technology and miniaturization of the flexible ureteroscopes, the retrograde intrarenal surgery (RIRS) became a popular technique for the surgical treatment of kidney stones.¹ It is recognized as a preferable therapeutic approach for kidney stones <2 cm. Many studies have demonstrated that several clinical and demographic factors affected the efficacy and safety of RIRS.^2,3 There might still be some other factors affecting surgical success with renal mobility possibly being one of them.

Many techniques including abdominal belt application, periodic apnea technique, low ventilation technique, and high-frequency jet ventilation (HFJV) have been described to decrease renal mobility. However, none of them has gained acceptance as a gold standard method. Kidneys are retroperitoneal organs that may mobilize with respiration.^2,4
–6

Renal mobility is an important parameter for RIRS. Most of the lasers need stone-touch technique for stone dusting and fragmentation; therefore, even millimetric movements might interfere with the effectivity of the laser. Respiration-related renal mobility might also complicate targeting the stone and might lead the surgeon to accidentally fire the laser into the renal tissue, causing redundant hemorrhage and loss of clarity and increasing the risk of complications. Hence, any adjustments performed in the surgical technique to decrease the renal mobility would be of critical importance for the success rates of RIRS.

Many surgeons prefer general anesthesia (GA) during RIRS to minimize the respiration-related renal mobility, but it can also be performed under regional anesthesia.⁷ As the standard mechanical ventilation setting was inadequate to limit the renal mobility, the surgeons have tried to find the most effective ventilation mode to minimize the renal mobility. For this reason, many adjustments on mechanical ventilation including HFJV and apnea techniques have been described.^2,8 However, none of these techniques became popular due to their shortcomings or the risk of ventilation-related complications. This is a topic that must be investigated further to find the most suitable ventilation technique to minimize renal movement without compromising the safety of RIRS.

In our trial, we generated a high ventilation (HV) mode by increasing the frequency of respiration and decreasing the tidal volume and aimed to assess the effect of this mode on the efficacy and safety of RIRS.

Materials and Methods

The present trial was performed upon approval of the local ethics committee (2022.179.10.03). The trial is registered at ClinicalTrials.gov with the registration number of NCT05792670. The sample size for two independent t-tests was estimated using G power-3 analysis software (version 3.1.9.7) with the alpha level of 0.05 and power of 0.90. The patients who had RIRS between January 1, 2022 and April 31, 2023 were prospectively included in the trial.

All trial subjects signed an informed consent form before the surgical procedure. Patients below the age of 18, patients with a known respiratory disease, patients with a renal anomaly, proximal ureteral stone, or stones in multiple locations, and the patients who previously underwent ipsilateral percutaneous nephrolithotomy and/or open renal surgery were excluded from the trial. All operations were carried out by an experienced surgeon at a single center.

For the purposes of standardization of the trial population, subjects who were stent free before the surgery were chosen, and the surgeries were performed using 10–12 ureteral access sheaths with the same-size laser probe (272 nm). Stone dusting procedure was performed <0.8 joule and frequency of 10 by holmium laser (Quanta system 2015, Italy) with the stone fragments being broken into small pieces by using popcorn mode of the laser (1 joule, frequency of 15).

A standard protocol of GA was given to all patients by the same anesthesiologist. A Drager Primus (Germany) mechanic ventilator (MV) was used for GA. The tidal volume and respiration frequency were determined by the MV based on the patient's age and weight with end-tidal carbon dioxide (CO₂) levels of 30 to 35 mm Hg. In the standard ventilation (SV) mode, the tidal volume was 8 to 10 mL/kg with respirations per minute being 10 to 15.

In the HV mode, the tidal volume was reduced to 6 to 8 mL/kg with the frequency being increased to 15 to 18 respirations/minute. No changes were made in the inspiratory–expiratory ratio (1:2), fraction of inspired oxygen, and positive end-expiratory pressure parameters. The ventilation mode of the MV (SV or HV) was determined through a randomization software before the surgery. For the trial and randomization purposes, the anesthesiologist was informed about the ventilation mode, but the surgeons were blinded.

The preoperative assessment consisted of medical history taking; physical examination; laboratory analyses including urinalysis, urine culture, and serum creatinine level; and radiological assessment using noncontrast computed tomography (NCCT). Patients who had a positive urine culture received treatment based on the results of the antibiogram, and all the surgeries were carried out under sterile urine. The clinicodemographic characteristics of the patients including age, gender, body mass index, urine culture status, stone volume, stone density, stone locations, surgical side, American Society of Anesthesiologists Classification, previous history of extracorporeal shock wave lithotripsy (ESL), and presence of Double-J stent were recorded.

The volume of the stones was calculated using the three-dimensional formula described by Sorokin et al.⁹ The surgical technique used was the one defined in our previous trial.¹⁰ Stone-free status was categorized based on postoperative NCCT images into three groups. Grade A indicates no stone in the NCCT images, Grade B indicates the presence of <2 mm residual stones, and Grade C indicates 2.1 to 4 mm residual stones at the postoperative 1st month follow-up visit. The duration of operation was calculated from the beginning of the cryptoscopic evaluation to the insertion of the Double-J stent with the laser time also recorded for analysis. Peri- and postoperative complications were evaluated in accordance with the Clavien–Dindo classification as described in previous papers.¹¹

Statistical analysis

All the obtained data were evaluated using SPSS Statistics, version 25 (IBM, Armonk, NY, USA) software. The Kolmogorov–Smirnov test was used for the evaluation of the distribution of the data. A Chi-square test was performed for the nominal variables in the groups. A t-test was used to analyze the parametric data. As for the nonparametric data, the Mann–Whitney U, Chi-square, and Kruskal–Wallis tests were used.

Results

One hundred forty-four were enrolled in the trial. The mean age of the patient was 48.78 ± 14.16 years. There were 72 patients each in the SV and the HV groups with a mean age of 49.62 ± 13.23 and 47.96 ± 15.09 years, respectively. The demographic and clinical characteristics of the subjects by group are shown in Table 1. Stone-related characteristics including stone density, stone locations, and stone size were found to be similar between the SV and the HV groups (p = 0.286, p = 0.511, and p = 0.641, respectively).

Table 1.

Clinicodemographic and Stone Properties By Standard Ventilation and High Ventilation

	SV, n (%)	HV, n (%)	p
Age (years)	49.62 ± 13.23	47.96 ± 15.09	0.358
Gender
Male	27 (37.5)	24 (33.3)	0.163
Female	45 (62.5)	48 (62.7)
BMI (kg/m²)	29.18 ± 2.61	29.61 ± 2.78	0.618
Side
Right	37 (51.4)	38 (52.8)	0.861
Left	35 (48.6)	34 (47.2)
Presence of ESL
Yes	61 (84.7)	59 (81.9)	0.823
No	11 (15.3)	13 (18.1)
Stone density (HU)	992.55 ± 298.11	1031.912 ± 245.05	0.286
Stone locations
Upper	6 (8.3)	4 (5.5)	0.511
Middle	6 (8.3)	7 (9.7)
Pelvis	35 (48.7)	39 (54.2)	0.641
Lower	25 (34.7)	22 (30.6)	0.105
Stone size (mm³)	989.31 ± 381.37	839.75 ± 353.88
ASA scores	1.92 ± 0.55	2.07 ± 0.68

t-Test, Mann–Whitney U, and Chi-square test were used.

ASA = American Society of Anesthesiologists Classification; BMI = body mass index; ESL = extracorporeal shock wave lithotripsy; HU = Hounsfield units; HV = high ventilation; SV = standard ventilation.

The stone-free rates of the SV and the HV groups were 68.1% and 70.8%, respectively (p = 0.717). The only perioperative complication was nonsignificant hemorrhage, which was observed in 4 (5.5%) subjects in the SV group and 2 (2.7%) subjects in the HV group (p = 0.676). The numbers (percentage) of the postoperative complications in the SV and the HV groups were 9 (12.5%) and 5 (7.0%), respectively (p = 0.398). Most of the complications included Clavien 1 and 2 complications (postoperative fever and flank pain) in both groups (Table 2). There was no Clavien 4 or 5 complication in either group.

Table 2.

Peri- and Postoperative Outcomes By Standard Ventilation and High Ventilation Modes

	SV, n (%)	HV, n (%)	p
Operation time (minutes)	62.96 ± 26.31	58.41 ± 20.14	0.031
Laser shot count	13,990.52 ± 5704.04	14,065.51 ± 4773.71	0.328
Fragmented stone volume (minutes/mm³)	15.65 ± 6.53		0.003
Stone-free rate
Yes
Grade A	46 (63.9)	21.67 ± 8.65	0.717
Grade B 65 (90.2%) 6 (86.1%)	7 (9.7)	48 (66.7)
Grade C	12 (16.7)	6 (8.3)	0.676
No	7 (9.7)	8 (11.1)
Presence of perioperative complication^a
Yes	4 (5.5)	10 (13.9)	0.398
No	68 (94.5)	2 (2.7)
Presence of postoperative complication
Yes	63 (87.5)	70 (97.3)	0.369
No	9 (12.5)	67 (93.0)
Clavien–Dindo classification		5 (7.0)
Grade 1	3 (4.1)	1 (1.4)
Grade 2	5 (6.9)	3 (4.1)
Grade 3a	1 (1.4)	1 (1.4)
Grade 3b	0	0
Grade 4	0	0
Grade 5	0	0
Hospital stays (days)	1 (minimum 1–maximum 9)	1 (minimum 1–maximum 8)

Bold font indicates p value <0.05.

t-Test, Mann–Whitney U, Fisher's exact, and Chi-square tests were used.

The mean duration of operation in the SV group was 62.9 ± 26.3 minutes, whereas it was 58.4 ± 20.1 minutes in the HV group (p = 0.031). To explore the reason for this difference, fragmented stone volume per minute and the mean laser shot counts were compared between the groups. We observed that fragmented stone volume was statistically significantly higher in the HV group, whereas the laser shot count was comparable between the groups. These data showed that the main reason of the difference in operative time was associated with the stone fragmentation part of the RIRS and was independent from the laser shot count (Table 2). The mean laser time in the SV group was 51.78 ± 19.63 minutes, whereas it was 46.58 ± 17.24 minutes in the HV group.

Discussion

Over the last 20 years, flexible ureteroscopy has gained recognition as preferable therapeutic approach for the treatment of upper urinary system stones <2 cm.¹ Although it has been demonstrated to be a safe and effective surgery, several factors might adversely affect the surgical success of RIRS.^12,13 Respiration-related renal mobility might be considered as one of these factors, and we believe that it is an underestimated factor. Previous studies have shown that renal mobility could affect the results of ESL, and less renal mobility might improve the success rates.^14
–16

Renal mobility is also an important variable for RIRS. While several patient-related and surgical factors were evaluated for their effects on the efficacy and safety of RIRS, the data on the association between renal mobility and RIRS were limited. Gadzhiev et al. utilized high-frequency jet ventilation during the RIRS. However, one of the potentially significant drawbacks of this technique is that the anesthetist cannot monitor end-tidal CO₂ and exhaled air volume in HFJV, as this technique requires specialized equipment.⁴

The surgical success and the complication rates of RIRS were similar between the SV and the HV groups. The data showed that, in an experienced hand, the ventilation mode did not affect the efficacy and the safety of RIRS. Nevertheless, the mean duration of operation was statistically significantly lower in the HV group with the laser time being the period which was responsible for this difference. It was observed that the surgeon could perform stone fragmentation in a shorter time in the HV mode compared with the SV mode. This was also confirmed by the significantly higher volume of fragmented stone per minute in the HV group. The data showed that the surgeon was able to use laser more effectively and able to finish the surgery at a shorter time under the HV mode.

In our previous trial, we demonstrated that the renal mobility decreased significantly at HV mode.¹⁰ We believe that the decrease in renal mobility was an important factor for decreasing the laser time. Extreme movement of the renal unit might lead the surgeon to fire the laser to the renal parenchyma, resulting in unexpected hemorrhage. This minor complication might decrease the ureteroscopic vision, thereby complicating the surgery. For this reason, surgeons had to be more cautious during the fragmentation of a stone in a mobile kidney. This would be one of the reasons for increased laser time and prolonged surgery. Using HV mode might be a reasonable solution to decrease renal mobility and comfort the surgeon during RIRS.

Göger et al¹⁶ reported that prolonged operation time was directly correlated with acute kidney injury. The probability of developing acute kidney injury after RIRS was 2.8 times higher in patients with prolonged operative time.¹⁷ Previous studies have shown that prolonged duration of operation was an independent risk factor for urinary sepsis after RIRS.^18,19 Sugihara et al. created a nomogram to predict the adverse events after ureteroscopic lithotripsy. This trial showed that longer duration of operation leads to 1.5- to 4.3 times higher rates of severe adverse events, including intensive care unit, dialysis mechanical ventilation, cardiac support, and mortality.¹⁹ We demonstrated that the duration of operation was statistically significantly shorter in the HV mode.

For this reason, performing RIRS at HV mode reduces the risk of developing possible serious adverse events. Even though we did not observe any difference between the complication and stone-free rates between the HV and the SV modes, there may be statistical differences in a future trial with a larger number of subjects. In the present trial, all operations were performed by an experienced surgeon. In our opinion, this factor is directly related to the reduced rates of complications in both groups. Future studies should evaluate the effect of surgeons' experience on the rate of complications.

The main limitation of the present trial was the limited number of subjects. Nevertheless, the present trial was a prospective trial in which the trial population was calculated by G-power analysis. We believe that the prospective and single-blind nature of the trial were the strengths of our trial. As all the operations were carried out by the same surgeon, there is no inter-surgeon variability or bias.

Conclusion

The use of HV mode during RIRS led to a significant reduction in the duration of operation and potential complications. While no statistically significant difference was detected in complication and stone-free rates between HV and SV modes, the decreased risk of developing crucial complications makes HV mode a preferred option for RIRS. Further research in this area may change the outcome of this trial. Based on our findings, we suggest that surgeons consider incorporating HV mode into their routines for RIRS in the mobile kidney.

Footnotes

Authors' Contributions

Ç.D. and A.Ş. had full access to all the data in the study, and took responsibility for the integrity of the data and the accuracy of the data analysis. Ç.D., C.M.Y., and S.Ş. contributed to study concept and design. H.M.A. assisted with the acquisition of data. A.K., H.A., S.Ş., and A.Ş. performed analysis and interpretation of data. Ç.D. helped with drafting of the article. Ç.D., C.M.Y., and A.Ş. executed critical revision of the article for important intellectual content. C.M.Y. and Ç.D. carried out statistical analysis. H.M.A., A.K., S.Ş., and H.A. contributed to administrative, technical, or material support.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this trial.

Abbreviations Used

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