Does Robot-Assisted Radical Prostatectomy Affect Renal Intravascular Parameters and Glomerular Filtration Rate?

Abstract

Background:

We aimed to investigate the effects of intra-abdominal pressure and steep Trendelenburg position on the intrarenal vascular parameters and estimated glomerular filtration rate (eGFR) in the first 24 hours of robot-assisted radical prostatectomy (RARP) surgery.

Methods:

We prospectively studied 31 men who underwent RARP for prostate cancer in our clinic between September and December 2017. Preoperative color Doppler ultrasonographic (CDUS) measurements of renal intravascular parameters were obtained 24 hours before the operation. Similarly, postoperative CDUS measurements were performed 24 hours after RARP. Preoperative serum creatinine (Cr) level and eGFR were noted. On the postoperative first day, serum Cr levels were checked and eGFR was calculated.

Results:

The mean age of men was 61.9 years, and the mean operation time was 268.5 minutes. No significant differences between preoperative and postoperative intrarenal vascular parameters were observed (P > .05). Serum creatinine was significantly increased (P = .019), but eGFR did not change statistically significant after RARP (P = .144). While the change in the mean resistive index (ΔRI) was affected by intravenous (i.v.) infused fluid volume and renal width; the change in the mean pulsatility index (ΔPI) was only affected by renal width. Also, the change in the mean peak systolic velocity (ΔPSV) was related to age, i.v. infused fluid volume, and renal parenchymal thickness. Finally, the change in the mean end-diastolic velocity (ΔEDV) was related to age and renal width.

Conclusion:

Renal functions and intrarenal vascular parameters return to baseline levels 24 hours after RARP.

Introduction

Radical prostatectomy remains the gold standard surgical treatment for localized prostate cancer.¹ Schuessler et al. performed the first laparoscopic radical prostatectomy as an alternative to open radical prostatectomy in 1992.² With the introduction of the da Vinci robotic surgery system in urology in the early years of this century, Binder and Kramer performed the first robot-assisted radical prostatectomy (RARP) in May 2000.³ RARP provided benefits such as diminished blood loss, reduced postoperative pain, and shorter hospitalization time as well as better oncological and functional outcomes.^4,5 As a matter of fact, 85% of radical prostatectomies in the United States have become robot-assisted, less than a decade after its introduction.⁶

Despite all these advantages, there are some important issues related to the procedure itself. Like every laparoscopic surgery, RARP also requires pneumoperitoneum, usually an intra-abdominal pressure (IAP) between 12 and 15 mmHg. A high IAP combined with a longer operation time in the steep Trendelenburg position increases the risks related to hemodynamic changes. Increased systemic vascular resistance, mean arterial pressure, and filling pressures result in reduced cardiac index.⁷ Hence, the renal and mesenteric arterial flow decrease and impede microcirculation in the related organs.⁸ Therefore, renal cortical perfusion, glomerular filtration rate, and urine output can decrease with high levels of IAP during RARP.^9–11 But altered renal function due to pneumoperitoneum is a multifactorial phenomenon. Baseline volume status, degree of hypercarbia, and individual hemodynamic reserve affect the severity of renal dysfunction, as well as the level of IAP.^12–14 Additional factors are direct compression of the renal parenchyma and renal vein, neurohormonal responses, and increased resistance in renal artery.^15–17

Renal arterial resistance is easily and quickly measured with color Doppler ultrasonography (CDUS), and this method avoids patients' exposure to radiation and contrast material injection. Intrarenal vascular parameters such as resistive index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) are calculated from the blood flow velocities during the cardiac cycle. These parameters are often used to determine and monitor the renal artery resistance.^18,19

In this prospective study, we aimed to investigate the effects of IAP and steep Trendelenburg position on the intrarenal vascular parameters and estimated glomerular filtration rate (eGFR) in the first 24 hours of RARP surgery.

Materials and Methods

After the approval of the local ethics committee was obtained, we prospectively studied 31 men who underwent RARP for prostate cancer in our clinic between September and December 2017. Only patients with an American society of anesthesiologists (ASA) 1–2 scores were included in the study. Written informed consent was taken from all patients.

A standard anesthetic technique was used. Anesthesia was induced with intravenous (i.v.) propofol (1–1.5 mg/kg), fentanil (2 μg/kg), and rocuronium bromide (0.6 mg/kg). Ventilator settings were tidal volume 8–10 mL/kg, inspiratory:expiratory ratio 1:2, inspired O₂ fraction 50% with air, and an inspiratory fresh gas flow of 3 L/minute. Respiratory rate was adjusted to maintain an end-tidal CO₂ (ETCO₂) tension at 35–40 mmHg. Anesthesia was maintained with 1 minimal alveolar concentration end-tidal concentrations of sevoflurane. After induction of anesthesia, a 20-G radial artery catheter was inserted for continuous monitoring of arterial pressure and blood sampling. The mean arterial pressure was maintained within 20% of baseline in all patients. A triple-lumen central venous catheter was inserted into the right internal jugular vein for monitoring central venous pressure (CVP). Pressure transducers were zeroed to the right atrium.

RARP was performed via transperitoneal approach with the da Vinci XI robotic system (Intuitive Surgical, Mountain View, CA). Trocars were placed in the horizontal position, and the IAP was maintained between 12 and 15 mm Hg with insufflation of carbon dioxide, throughout the laparoscopic part of the operation. Then, the patients were positioned in the steep Trendelenburg (45° head-down) position until the robot was undocked. Bilateral pelvic lymphadenectomy was performed in selected patients according to Briganti's nomogram. The pneumoperitoneum was released after the removal of the specimen.

All CDUS measurements were performed by a single experienced radiologist with Toshiba Aplio 500 system (Toshiba Medical Systems Corporation, Otawara, Japan) equipped with a 3.5-MHz convex array transducer. Preoperative gray-scale and CDUS measurements were obtained 24 hours before the operation. Similarly, postoperative CDUS measurements were performed 24 hours after RARP. Diameters of both kidneys and thickness of renal parenchyma were evaluated with conventional gray-scale US followed by CDUS with the calculation of the intrarenal RI, PI, PSV, and EDV values for each kidney. A total of 61 kidneys were evaluated because one patient had a solitary kidney due to nephrectomy.

Preoperative laboratory data included serum creatinine (Cr), eGFR, and hematocrit. eGFR was calculated using the four variables (age, sex, race, and serum creatinine). Perioperative data included operation time, estimated blood loss, amount of administered fluids, and amount of urine output. The operation time was defined as skin-to-skin time. On the postoperative first day, hematocrit and serum Cr levels were checked, and eGFR was calculated.

Statistical analysis

The normality assumptions were controlled by the Shapiro–Wilk test. For the comparison of postoperative and preoperative parameters, paired samples t-test and Wilcoxon signed-rank test were used. Spearman and Pearson correlation coefficient was applied to investigate the correlation between continuous variables. Data are presented as mean ± standard deviation or median (min–max), as appropriate. P values <.05 were considered statistically significant. Statistical analysis was made using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY).

Results

The mean age of men was 61.9 years, and the mean operation time was 268.5 minutes. Patients' demographic data, renal morphological features, and perioperative parameters are summarized in Table 1.

Table 1.

Patients' Demographic Data, Renal Morphological Features, and Perioperative Parameters

Age (years)	61.9 ± 7.8 (51–75)
Operation time (minutes)	268.5 ± 86.7 (105–390)
IV infused fluid volume (mL)	2600 ± 994.7 (500–4000)
Urine output (mL)	540 ± 243.7 (200–1000)
Blood loss (mL)	495 ± 322.4 (50–800)
Renal parenchymal thickness (mm)	14.1 ± 2.1 (11–19)
Renal length (mm)	102.8 ± 9.7 (85–124)
Renal width (mm)	49.5 ± 6.5 (38–59)

Values are given as mean ± SD (range).

SD, standard deviation.

Comparison of preoperative and postoperative values for CDUS findings and P values for each comparison are shown in Table 2. No significant differences between preoperative and postoperative intrarenal vascular parameters were observed (P > .05). Serum creatinine was significantly increased (P = .019), but eGFR did not change statistically significant after RARP (P = .144).

Table 2.

Comparison of Preoperative and Postoperative Values in Intrarenal Vascular Parameters

	Preoperative		Postoperative
	Mean ± SD	Median (min–max)	Mean ± SD	Median (min–max)	P
RI	0.65 ± 0.05	0.64 (0.56–0.73)	0.67 ± 0.08	0.62 (0.58–0.87)	.286^a
PI	1.12 ± 0.24	1.05 (0.65–1.65)	1.2 ± 0.44	1.15 (0.6–2.43)	.348^b
PSV	32.3 ± 7	32.4 (19.2–43.9)	40.9 ± 19.2	38.8 (16–84)	.057^b
EDV	13 ± 4.8	12.1 (7.7–26.8)	14 ± 8.8	10.5 (4.2–37)	.582^a
Serum creatinine (mg/dL)	1.2 ± 0.3	1.1 (1.02–2.03)	1.3 ± 0.4	1.2 (0.86–2.31)	.019^a
eGFR (mL/minute/1.73 m²)	68.5 ± 12.4	70.5 (35–81)	63.9 ± 17.9	63 (30–96)	.144^a

Bold value signifies a significant increase in serum creatinine.

Wilcoxon signed-rank test is used for comparisons.

Paired samples t-test is used for comparisons.

EDV, end-diastolic velocity; PI, pulsatility index; PSV, peak systolic velocity; RI, resistive index; SD, standard deviation.

Correlation between differences in intrarenal vascular parameters and clinical features are given in Table 3. While the change in the mean RI (ΔRI) was affected by i.v. infused fluid volume and renal width; the change in the mean PI (ΔPI) was only affected by renal width. Also, the change in the mean PSV (ΔPSV) was related to age, i.v. infused fluid volume, and renal parenchymal thickness. Finally, the change in the mean EDV (ΔEDV) was related to age and renal width.

Table 3.

Correlation Between Clinical Parameters and Differences in Intrarenal Vascular Parameters

	ΔRI		ΔPI		ΔPSV		ΔEDV
	r	P	r	P	r	P	r	P
Age	0.259	.271	0.114	.631	−0.480	.032	−0.497	.026
Operation time (minutes)	−0.089	.710	0.199	.400	−0.274	.242	−0.259	.269
IV infused fluid volume (mL)	−0.471	.036	0.045	.852	−0.460	.041	−0.046	.846
Urine output	−0.238	.312	0.183	.439	−0.311	.181	−0.087	.714
Blood loss	−0.303	.194	−0.013	.957	−0.382	.097	−0.192	.418
Renal parenchymal thickness (mm)	0.085	.722	0.015	.949	0.590	.006	0.167	.482
Renal length (mm)	0.116	.627	−0.035	.884	−0.189	.424	−0.142	.551
Renal width (mm)	0.583	.007	0.458	.042	−0.149	.530	−0.576	.008

Bold values signify a significant correlation between the change in intrarenal vascular parameters and clinical parameters.

Pearson correlation and Spearman correlation coefficient analysis.

Discussion

RARP has become a commonly used procedure for the treatment of localized prostate cancer since its introduction. Although the robotic system provides a lot of advantages to the surgeon, the need for the steep Trendelenburg position and an IAP between 12 and 15 mm Hg creates some hemodynamic changes. The negative effect of pneumoperitoneum on renal blood flow is well documented in animal models, but in these studies, the animals were horizontally positioned and the clinical significance was unclear.^20,21 Also, some human studies showed decreased urine output and creatinine clearance (CrCl) during the laparoscopic procedures; however, all patients were placed in the horizontal position in these studies.^22,23

During RARP, the combination of an extreme head-down tilt and pneumoperitoneum increases the CVP almost threefold and systemic vascular resistance by 20% compared with the initial values.²⁴ That situation can be more important when prostate cancer patients are thought to be older than 50 years, and nephrosclerosis can reduce the number of functional nephrons by 10% for each 10 years of age after 40 years.²⁵ There are three studies in the literature that researched the renal functions after RARP. In the first study, Ahn et al. have investigated whether CrCl of patients undergoing RARP decreased on the postoperative period and found no reduction in renal function on the postoperative 7th and 30th days.²⁶ They also reported that even in patients with an abnormal CrCl before the surgery, RARP did not induce renal dysfunction. In the second one, Modi et al. have compared the eGFR before and 1 day after surgery. They reported that RARP has no short-term effects on renal function even with an IAP between 15 and 20 mm Hg.²⁷ In the third study, Joo et al. have investigated the acute kidney injury (AKI) rates in RARP and open radical retropubic prostatectomy series and found that the incidence of AKI in RARP as 5.5%, which was significantly lower than the RRP group.²⁸ They used the criteria that define AKI as an increase in serum criteria by 0.3 mg/dL or more within 48 hours or an increase in the serum creatinine by 1.5 times or more within the prior 7 days.

However, these earlier studies analyzed CrCl or eGFR to measure the differences between preoperative and postoperative period but did not use CDUS for the measurement of renal blood flow. CDUS allows painless, rapidly, and noninvasive determination of renal perfusion. The RI and the PI are calculated from the blood flow in intrarenal vessels and reported to correlate with the effective renal plasma flow and the renal vascular resistance.²⁹ It is well known that RI increases in urinary tract obstructions and tubulointerstitial disease of the kidney.^30,31 Also, the parameters calculated as RI and PI have the advantage of being independent of the Doppler angle and that is why this method can be preferred to other invasive tests. In our current study, we used CDUS for analyzing the intrarenal vascular parameters and evaluated the results of sonographic findings and eGFR together. Therefore, we believe that our current results are highly reliable for the evaluation of renal functions after RARP. To the best of our knowledge, our study was the fourth study that investigates the changes in renal parameters after RARP and we found that eGFR and all intrarenal vascular parameters (RI, PI, EDV, and PSV) returned to baseline levels 24 hours after the operation.

Potential limitations of this study should be considered. First of all, it would be more precious if we have investigated the vascular parameters during the operation and showed the differences in Doppler findings. This may be the subject of another study. Second, a larger series may give more valuable data in the future. Third, we included only patients with ASA 1 and 2 physical status classes, and it is unclear if our findings can be extrapolated to more severe patients.

In conclusion, renal functions and intrarenal vascular parameters return to baseline levels 24 hours after RARP.

Footnotes

Acknowledgment

The authors thank Dr. Basak Oguz and appreciate her support for the statistical analysis of this study.

Disclosure Statement

No competing financial interests exist.

References

Heidenreich

, Bellmunt

, Bolla

, Joniau

, Mason

, Matveev

, Zattoni

. EAU guidelines on prostate cancer. Part 1: Screening, diagnosis, and treatment of clinically localised disease. Eur Urol, 2011; 59:61–71.

Schuessler

, Schulam

, Clayman

, Kavoussi

. Laparoscopic radical prostatectomy: Initial short-term experience. Urology, 1997; 50:854–857.

Binder

, Kramer

. Robotically-assisted laparoscopic radical prostatectomy. BJU Int, 2001; 87:408–410.

Menon

, Shrivastava

, Kaul

, Badani

, Fumo

, Bhandari

, Huland

. Vattikuti Institute prostatectomy: Contemporary technique and analysis of results. Eur Urol, 2007; 51:648–658.

Patel

, Palmer

, Coughlin

, Samavedi

. Robot-assisted laparoscopic radical prostatectomy: Perioperative outcomes of 1500 cases. J Endourol, 2008; 22:2299–2306.

Lepor

. Status of radical prostatectomy in 2009: Is there medical evidence to justify the robotic approach?. Rev Urol, 2009; 11:61.

, Nelson

, Wilson

, Kawachi

, Ramin

, Lau

, Crocitto

. Perioperative complications of laparoscopic and robotic assisted laparoscopic radical prostatectomy. J Urol, 2006; 175:541–546.

Johannsen

, Andersen

, Juhl

. The effect of general anaesthesia on the haemodynamic events during laparoscopy with CO₂-insufflation. Acta Anaesthesiol Scand, 1989; 33:132–136.

McDougall

, Monk

, Wolf

, Hicks

, Clayman

, Gardner

, Martin

. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am Coll Surg, 1996; 182:317–328.

10.

Bishara

, Karram

, Khatib

, Ramadan

, Schwartz

, Hoffman

, Abassi

. Impact of pneumoperitoneum on renal perfusion and excretory function: Beneficial effects of nitroglycerine. Surg Endosc, 2009; 23:568–576.

11.

Sass

, Hattori

, Yamamoto

, Kato

, Komatsu

, Matsukawa

, Gotoh

. Direct visualization of renal hemodynamics affected by carbon dioxide–induced pneumoperitoneum. Urology, 2009; 73:311–315.

12.

Kirsch

, Hensle

, Chang

, Kayton

, Olsson

, Sawczuk

. Renal effects of CO₂ insufflation: Oliguria and acute renal dysfunction in a rat pneumoperitoneum model. Urology, 1994; 43:453–459.

13.

Junghans

, Böhm

, Gründel

, Schwenk

, Müller

. Does pneumoperitoneum with different gases, body positions, and intraperitoneal pressures influence renal and hepatic blood flow?. Surgery, 1997; 121:206–211.

14.

London

, Ho

, Neuhaus

, Wolfe

, Rudich

, Perez

. Effect of intravascular volume expansion on renal function during prolonged CO₂ pneumoperitoneum. Ann Surg, 2000; 231:195.

15.

Gudmundsson

, Viste

, Myking

, Bostad

, Grong

, Svanes

. Role of angiotensin II under prolonged increased intraabdominal pressure (IAP) in pigs. Surg Endosc, 2003; 17:1092–1097.

16.

, Saunders

, Gunther

, Wolfe

. Effector of hemodynamics during laparoscopy: CO₂ absorption or intra-abdominal pressure?. J Surg Res, 1995; 59:497–503.

17.

Zacherl

, Thein

, Stangl

, Feussner

, Bock

, Mittlböck

, Siewert

. The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model. Surg Endosc, 2003; 17:1231–1236.

18.

Radermacher

, Chavan

, Bleck

, Vitzthum

, Stoess

, Gebel

, Haller

. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med, 2001; 344:410–417.

19.

Crutchley

, Pearce

, Craven

, Stafford

, Edwards

, Hansen

. Clinical utility of the resistive index in atherosclerotic renovascular disease. J Vasc Surg, 2009; 49:148–155.

20.

Brundell

, Tsopelas

, Chatterton

, Touloumtzoglou

, Hewett

. Experimental study of peritoneal blood flow and insufflation pressure during laparoscopy. BJS, 2002; 89:617–622.

21.

Cısek

, Gobet

, Peters

. Pneumoperitoneum produces reversible renal dysfunction in animals with normal and chronically reduced renal function. J Endourol, 1998; 12:95–100.

22.

Nguyen

, Perez

, Fleming

, Rivers

, Wolfe

. Effect of prolonged pneumoperitoneum on intraoperative urine output during laparoscopic gastric bypass. J Am Coll Surg, 2002; 195:476–483.

23.

Nishio

, Takeda

, Yokoyama

. Changes in urinary output during laparoscopic adrenalectomy. BJU Int, 1999; 83:944–947.

24.

Lestar

, Gunnarsson

, Lagerstrand

, Wiklund

, Odeberg-Wernerman

. Hemodynamic perturbations during robot-assisted laparoscopic radical prostatectomy in 45 Trendelenburg position. Anesth Anal, 2011; 113:1069–1075.

25.

Guyton

, Hall

. Textbook of Medical Physiology. 11th ed. Philadelphia: Elsevier, 2006, pp. 402–415.

26.

Ahn

, Lim

, Chung

, Choi

, Youn

, Lim

. Postoperative renal function in patients is unaltered after robotic-assisted radical prostatectomy. Korean J Anesthesiol, 2011; 60:192–197.

27.

Modi

, Kwon

, Patel

, Dinizo

, Farber

, Zhao

, Kim

. Safety of robot-assisted radical prostatectomy with pneumoperitoneum of 20 mm Hg: A study of 751 patients. J Endourol, 2015; 29:1148–1151.

28.

Joo

, Moon

, Yoon

, Chin

, Hwang

, Kim

. Comparison of acute kidney injury after robot-assisted laparoscopic radical prostatectomy versus retropubic radical prostatectomy: A propensity score matching analysis. Medicine, 2016; 95:e2650.

29.

Petersen

, Petersen

, Ladefoged

, Mehlsen

, Jensen

HAE

. The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic renal failure. Nephrol Dial Transpl, 1995; 10:2060–2064.

30.

Tokgöz

, Tokgöz

, Ünal

, Voyvoda

, Şerifoğlu

. Changes in renal Doppler ultrasonographic parameters in patients managed with rigid ureteroscopy. Acta Radiol, 2013; 54:327–332.

31.

Petersen

, Petersen

, Talleruphuus

, Ladefoged

, Mehlsen

, Jensen

. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure. Nephrol Dial Transplant, 1997; 12:1376–1380.