Intermittent Perirenal Instillation of Bupivacaine After Tubeless Percutaneous Nephrolithotomy Under Spinal Anesthesia: A Double-Blind,Placebo-Controlled Clinical Trial

Abstract

Background and Purpose:

Pain at the surgery site is a common complaint in patients who experience percutaneous nephrolithotomy (PCNL). The aim of this double-blind, randomized clinical trial is evaluation of the effect of scheduled infusion of bupivacaine on postsurgical pain and narcotic consumption after tubeless PCNL under spinal anesthesia.

Patients and Methods:

Forty patients were randomly divided into two groups. A small caliber fenestrated feeding tube was placed into the nephrostomy tract under direct vision in a manner in which its tip lied close to the renal capsule. The study group received infusion of diluted bupivacaine while physiologic saline was injected in the control group. Each patient was given the same dose every 6 hours until 24 hours after the surgical procedure.

Results:

Mean pethidine injection was significantly lower in the group who underwent bupivacaine instillation (20.5±14.5 vs 3.97±2.4 mg: P=0.009). There was no significant difference between mean visual analogue scale (VAS) score in these two groups after 6 and 12 hours while it was significantly lower after 18 and 24 hours in the patients who had received bupivacaine. Mean time to the first analgesic request was significantly longer in the study group (11.35 vs 6.44 hours: P=0.001).

Conclusion:

Intermittent perirenal instillation of bupivacaine via the nephrostomy tract after PCNL decreases the need for more systemic narcotics and provides acceptable analgesia in the postoperative period.

Introduction

Percutaneous nephrolithotomy (PCNL) is acknowledged as the standard surgical procedure for kidney stones larger than 2 cm.¹ Regarding the widespread and frequent use of PCNL, much effort has been made to reduce patients' pain and discomfort after operation. Narcotics and nonsteroidal anti-inflammatory drugs are the principal medical therapy for postoperative pain relief. Several important side effects, however, such as impairment of kidney function, disturbance of gastrointestinal motility, and respiratory depression limit free utility of systemic analgesics to fully suppress patients' discomfort. This may lead to decline in patient satisfaction and decreased quality of life.²

Several studies have shown that tubeless PCNL is associated with decreased postoperative pain compared with standard PCNL.³ Because the field of surgery and tissue injury includes skin, subcutaneous tissue, muscles, fascia, and renal capsule, instillation or infusion of local anesthetics via the nephrostomy tract seems to have a promising effect on patient discomfort after operation. Some studies have assessed the efficacy and safety of single-dose injection of local anesthetics into the nephrostomy tract after PCNL; nevertheless, the previous studies have not evaluated intermittent and repeated dose of local anesthetics.

Bupivacaine is a relatively safe local anesthetic that is widely used for achieving spinal intrathecal anesthesia and selective nerve block. Its safety and feasibility have made it an appropriate agent for regional pain control.

In this study, a fenestrated small caliber catheter was placed in the nephrostomy tract and adjacent to the renal capsule under direct vision at the end of PCNL. Bupivacaine was injected through the catheter in determined time intervals. The main goal of this study was to evaluate the effect of scheduled doses of local anesthetics on postoperative pain and the need for systemic analgesic intake.

Patients and Methods

Patient selection and study population

This study was conducted between November 2012 and August 2013 in Labbafinejad Medical Center, a tertiary referral hospital for endourology and urolaparoscopy. Considering the 95% confidence interval and 80% power for the study, 40 patients were selected. Primary end point of the study was to compare the need for systemic analgesic intake and postoperative pain (measured by visual analogue scale [VAS]) between the study and control groups. All patients were adults with kidney stones larger than 2 cm who were candidates for PCNL.

All stages of the study were performed under the supervision and approval of the ethical committee of Iranian Urology and Nephrology Research Center. Written informed consent was presented to and taken from all patients before they participated in the study.

Exclusion criteria included patients older than 65 years, known sensitivity or allergy to local anesthetics, obtaining more than one percutaneous access, preoperative cardiac arrhythmias, renal or hepatic failure, and regular narcotic use.

Forty patients were randomized into two groups each containing 20 patients using the block randomization method. In group 1, bupivacaine 0.25% and in group 2 physiologic serum were infused via a small catheter on a regular basis.

All patients underwent routine laboratory tests including complete blood cell count, basic metabolic panel, urine analysis and culture, and coagulation tests. Electrocardiography was performed for all patients before the surgical procedure. Spiral abdominopelvic CT without intravenous contrast media injection or intravenous urography was performed before the operation.

Surgical technique

All operations were performed with the patient under spinal anesthesia using an injection of 0.15 mg/kg bupivacaine 0.5% intrathechally. Then a 5F ureteral catheter was inserted into the ipsilateral ureter via a 19F cystoscope with the patient in the lithotomy position. The rest of the operation was performed with the patient in the prone position, under fluoroscopy guidance. After selecting the favorable lower or middle calix, a 30F Amplatz sheath was inserted using the one-shot dilation technique. A pneumatic lithotripter was used for stone fragmentation, and stone particles were removed by grasper. At the end of the operation single shot antegrade pyelography was performed to assure the continuity of the pyelocaliceal system.

Before withdrawal of the nephroscope from the surgical field, a fenestrated 6F feeding tube was inserted through the working element in a manner in which its tip lay close to the renal capsule. Placement of the feeding tube was performed under direct vision of the nephroscope, and then it the tube was secured with skin suture.

Patients were randomly divided into two equal groups. Considering our previous experience in spinal anesthesia in PCNL in which the patients' first discomfort was seen almost 6 hours after operation, the first dose of bupivacaine or placebo was instilled immediately after surgery and repeated every 6 hours until 24 hours, when the catheter was removed. In group B, 5 mL of bupivacaine 0.25% diluted in physiologic saline and in group N/S (normal saline), 5 mL of physiologic saline were injected each time. The assistant who injected the solution was blinded to the study.

The postoperative pain score was assessed every 6 hours until 24 hours using the VAS. VAS has a score that ranges from 0 to 10 in which 0 means no pain and 10 stands for worst possible pain. If the patient needed systemic analgesics, 0.25 mg/kg of pethidine was injected intravenously.

All patients were discharged 48 hours after operation if there was no problem. All possible side effects were recorded. Patients' vital signs were recorded on a routine basis and after each dose of bupivacaine or placebo instillation. Statistical analysis was performed using SPSS version 19. The t test and the Pearson chi square test were used to compare the variables. A P value lower than 0.05 was considered statistically significant.

Results

All 40 patients who participated in the study completed the study protocol. Basic information about the patients including sex, age, height, weight, and stone characteristics are indicated in Table 1. There were no significant differences between the two groups regarding age, sex, height, and weight (P=0.3, 0.6, 0.3, 0.6, respectively). Mean stone diameters were 39.3 and 38.2 mm in the study and placebo group, respectively, which imply no significant difference (P=0.5).

Table 1.

Patients and Stone Characteristics

	Bupivacaine	Physiologic saline	P value
Sex
Male	13	13	0.619
Female	7	7
Age (years)	39.6±12.1	40.65±10.2	0.338
	(18–64)	(24–60)
Height (cm)	1637.3	169±8.4	0.331
	(155–181)	155–189
Weight	76.6±11.12	75.8±8.7	0.650
	(59–101)	61–91
Stone size	39.3±8.3	38.2±8.6	0.509
	(15–101)	(19–56)
Side
LT	11	10	0.763
RT	9	10
Location
Pelvis	7	4	0.752
Pelvis and calix	7	9
Calix	5	6
Upper ureter	1	1

Mean time to first analgesic request was significantly longer in the study group than in the placebo group. (11.35 vs 6.44 hours: P=0.001). Mean pethidine injection was significantly lower in the patients who underwent bupivacaine instillation (20.5±14.5 vs 3.97±2.4 mg: P=0.009) (Table 2).

Table 2.

Demographic Data About Perioperative Parameters

	Physiologic saline	Bupivacaine	P value
Operative time	70.9 ± 16.6	73.9 ± 18.1	0.095
	(40–130)	(42–125)
Mean time to first analgesic request (hours)	6.44 ± 2.3 (5–8)	11.35 ± 4.2 (9–13)	0.001
Distance from skin to renal capsule (cm)	7.22 ± 1.09 (6–11)	7.95 ± 1.2 (6–11)	0.376
Hospital stay (days)	2.6 ± 0.6	2.65 ± 0.67	0.049
	(2–4)	(2–4)

VAS was assessed every 6 hours. As indicated in Table 3, there was no significant difference between mean VAS scores in the two groups after 6 and 12 hours (P=0.077 and 0.118, respectively). However, The mean VAS scores at 18 and 24 hours after operation, however, were significantly lower in the patients who received bupivacaine (P=0.001 and 0.005, respectively).

Table 3.

Opioid Requirement and Visual Analogue Scale Score During 24 Hours After Operation

	Physiologic saline	Bupivacaine	P value
Opioid requirement (mg)	3.97 ± 24 (15–80)	20.5 ± 14.5 (0–40)	0.009
VAS 6th hour	4.25 ± 1.44	4.2 ± 1	0.077
	2–6	3–6
VAS 12th hour	3.1 ± 1	4.25 ± 1.51	0.118
	(2–5)	(2–7)
VAS 18th hour	3.7 ± 1.41	1.65 ± 0.67	0.001
	(1–6)	(1–3)
VAS 24th hour	3.05 ± 1.23	1.85 ± 0.93	0.005
	(1–5)	(1–3)

No complication was recorded during the hospital stay that could be attributable to bupivacaine or physiologic saline instillation. No significant hemodynamic instability and vital sign disturbances were seen after injection of bupivacaine.

Discussion

Postoperative pain is a manifestation of inflammation because of tissue injury, and its management is a critical component of surgery.⁴ Poorly controlled pain may lead to detrimental physiologic and psychological adverse effects and result in tachycardia, insomnia, and a decrease in alveolar ventilation and patient satisfaction.^5,6 Opioids are the main choice for acute postoperative pain control, but their side effects limit their liberal consumption in an attempt to achieve analgesia after major surgical procedures.

PCNL causes less complication and systemic stress response in comparison with an open stone surgical procedure, but it seems that this procedure is not completely well tolerated.⁷ Previously, placement of a nephrostomy catheter at the end of PCNL is thought to be an integral part of standard PCNL, but some modifications such as using a small pigtail catheter instead of a large-bore catheter and tubeless PCNL have been made to reduce patient discomfort and minimize hospital stay.^8,9

Maheshwari and colleagues¹⁰ in a prospective study compared the effect of using a smaller catheter as a nephrostomy tube on reducing urinary leak, hospital stay, and analgesic use. They concluded that using a small pigtail catheter instead of a 28F nephrostomy tube causes less urinary leak and consequently less hospital stay. Patients had less pain and needed less analgesic support. Ni and associates¹¹ assessed the safety and efficacy of tubeless PCNL compared with standard or small-bore PCNL in a meta-analysis of randomized, controlled trials. After searching 13 eligible studies, they reported that patients undergoing tubeless PCNL needs significantly less analgesia relative to those undergoing standard and small-bore PCNL.

Opioid analgesics that were once considered the standard choice for the management of acute postoperative pain are being replaced by multimodal analgesia. Using this approach, analgesia could be achieved by recruiting synergistic effects of different drugs that act at the central and peripheral nervous systems and it may be associated with fewer side effects relative to high-dose, single-agent analgesia.¹² Infiltration of the surgical site with local anesthetics seems to be a promising method of pain reduction. Haleblian and coworkers¹³ have reported the impact of subcutaneous infiltration of bupivacaine after PCNL in 22 patients. They showed no significant reduction in subjective pain score, but they have claimed that a trend toward less narcotic consumption was observed.

Jonnavithula and colleagues,¹⁴ who were aware of the results that had been presented by the Haleblian and associates¹³ study, extended the site of instillation. They have assessed the effect of peritubal infiltration of bupivacaine from the skin incision to the renal capsule. In their study, 40 patients who were candidates for PCNL were divided randomly to receive a single dose of bupivacaine or placebo. Pain scores and analgesic requirement in the first 24 hours were significantly lower in the group of patients who had received bupivacaine (P<0.005) Likewise, another randomized clinical trial that was performed by Parikh and coworkers¹⁵ showed the same results using bupivacaine.

Kirac and associates¹⁶ evaluated the impact of infiltration of 20 mL bupivacaine 0.25% in the nephrostomy tract in tubeless and standard PCNL. The conclusion of this study was that peritubal infiltration of bupivacaine reduces VAS scores for pain, 6, 12, and 24 hours after operation (P<0.05). This study also revealed that tubeless PCNL would result in less postsurgical discomfort than standard PCNL. To our knowledge, continuous or scheduled infiltration of local anesthetics has not been used for reduction of pain after PCNL. Continuous infusion of local anesthetics into the surgical field may reduce pain by inhibition of afferent signals from peripheral nerve fibers and attenuation of the inflammatory response.¹⁷

It is logical concept that single bolus administration of a local anesthetic has a limited effect because of its short duration of action. Repeated administration through a catheter positioned in the surgical site at the end of the procedure increases the duration of action and may improve the efficacy of local wound infiltration. Local anesthetic wound infusions may have significant benefits in a variety of procedures such as procedures as diverse as open nephrectomy, knee arthroplasty, and inguinal hernia repair.^18
–20

In our study, we selected patients undergoing tubeless PCNL to limit the confounding effect of the nephrostomy tube on patient discomfort. We hypothesized that placement of a small caliber feeding tube (6F) in the nephrostomy tract would not result in a significant increase in postoperative pain. Placement of a small feeding tube enabled us to infuse bupivacaine on determined intervals, and the tube could be removed easily. The surgeon can simply place the feeding tube under direct vision adjacent to the renal capsule; so it would not harm adjacent organs or the pyelocaliceal system. Regarding the concerns related to inadvertent removal or occlusion of the catheter because of the specific surgical site and position of the patient in bed, we used scheduled instillation in certain time intervals instead of continuous infusion of bupivacaine.

Our study supports the idea that infusion of bupivacaine in the PCNL surgical site would reduce the need for narcotics use, thus preventing their unwilling adverse effects. The severity of pain is at its utmost in the first 24 hours after operation, so it would be wise to achieve the synergic effect of various modalities in the first postoperative day to diminish systemic analgesic use. In this study, we observed that bupivacaine infusion resulted in a mean 16.5 mg decrease of pethidine injection per 24 hours. In addition, the mean time to first analgesic request was almost 5 hours later in the study group (11.35 vs 6.44).

Patient pain perception (measured by VAS) was not significantly different betweenthe two groups after the first 6 and 12 hours, which might be because of the residual effect of spinal anesthesia. Nevertheless, it was lower in the study group 18 and 24 hours after operation. Therefore, this effect can be specifically attributed to the timing of infusion of bupivacaine.

The mean VAS score decreased from 4.2 to 1.6 and 1.8, 18 and 24 hours after operation in the study group, respectively; but in the control group it fluctuated from 3.1 to 3.7 and 3.05. This may be from the cumulative effect of bupivacaine in the injured tissue. More clinical trials with a larger study population are needed to justify the results of this study.

Our study is associated with several limitations. The relatively small sample size and application of spinal anesthesia might have a confounding effect on the results of this study. Although we did not observe any critical complication that could be attributed to bupivacaine infiltration, its effect on patients with a history of cardiovascular disease is not yet determined; therefore, it should be applied with caution in this group of patients. It was not the primary end point of this study to evaluate the safety of this approach; thus, if it is to be universally suggested, more multicenter studies with large study groups are needed.

Conclusion

It seems that intermittent perirenal instillation of bupivacaine via the nephrostomy tract after PCNL decreases the need for more systemic narcotics and provides acceptable analgesia in the postoperative period.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

Jones

, Russell

, Kellett

, Wickham

. The changing practice of percutaneous stone surgery. Review of 1000 cases 1981–1988. Br J Urol, 1990; 66:1–5.

White

, Kehlet

. Improving postoperative pain management: What are the unresolved issues?. Anesthesiology, 2010; 112:220–225.

Garofalo

, Pultrone

, Schiavina

, et al. Tubeless procedure reduces hospitalization and pain after percutaneous nephrolithotomy: Results of a multivariable analysis. Urolithiasis, 2013; 41:347–353.

Barden

, Derry

, McQuay

, Moore

. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults. Cochrane Database Syst Rev, 2009; 4:CD007355.

Gousheh

, Nesioonpour

, Javaher Foroosh

, et al. Intravenous paracetamol for postoperative analgesia in laparoscopic cholecystectomy. Anesth Pain Med, 2013; 3:214–218.

Revie

, McKeown

, Wilson

, et al. Randomized clinical trial of local infiltration plus patient-controlled opiate analgesia vs. epidural analgesia following liver resection surgery. HPB (Oxford)., 2012; 14:611–618.

Aghamir

, Mojtahedzadeh

, Meysamie

, et al. Comparison of systemic stress responses between percutaneous nephrolithotomy (PCNL) and open nephrolithotomy. J Endourol, 2008; 22:2495–2500.

Pietrow

, Auge

, Lallas

, et al. Pain after percutaneous nephrolithotomy: Impact of nephrostomy tube size. J Endourol, 2003; 17:411–414.

Agrawal

, Agarwal

. Percutaneous nephrolithotomy: Large tube, small tube, tubeless, or totally tubeless?. Indian J Urol, 2013; 29:219–224.

10.

Maheshwari

, Andankar

, Bansal

. Nephrostomy tube after percutaneous nephrolithotomy: Large-bore or pigtail catheter?. J Endourol, 2000; 14:735–738.

11.

, Qiyin

, Tao

, et al. Tubeless percutaneous nephrolithotomy is associated with less pain and shorter hospitalization compared with standard or small bore drainage: A meta-analysis of randomized, controlled trials. Urology, 2011; 77:1293–1298.

12.

Buvanendran

, Kroin

. Multimodal analgesia for controlling acute postoperative pain. Curr Opin Anaesthesiol, 2009; 22:588–593.

13.

Haleblian

, Sur

, Albala

, Preminger

. Subcutaneous bupivacaine infiltration and postoperative pain perception after percutaneous nephrolithotomy. J Urol, 2007; 178:925–928.

14.

Jonnavithula

, Pisapati

, Durga

, et al. Efficacy of peritubal local anesthetic infiltration in alleviating postoperative pain in percutaneous nephrolithotomy. J Endourol, 2009; 23:857–860.

15.

Parikh

, Shah

, Vora

, et al. Ultrasound guided peritubal infiltration of 0.25% ropivacaine for postoperative pain relief in percutaneous nephrolithotomy. Middle East J Anesthesiol, 2013; 22:149–154.

16.

Kirac

, Tepeler

, Bozkurt

, et al. The efficacy of bupivacaine infiltration on the nephrostomy tract in tubeless and standard percutaneous nephrolithotomy: A prospective, randomized, multicenter study. Urology, 2013; 82:526–531.

17.

Hollmann

, Durieux

. Local anesthetics and the inflammatory response: A new therapeutic indication?. Anesthesiology, 2000; 93:858–875.

18.

Forastiere

, Sofra

, Giannarelli

, et al. Effectiveness of continuous wound infusion of 0.5% ropivacaine by On-Q pain relief system for postoperative pain management after open nephrectomy. Br J Anaesth, 2008; 101:841–847.

19.

Leblanc

, Bellanger

, Rhynes

, Hausmann

. Evaluation of continuous infusion of 0.5% bupivacaine by elastomeric pump for postoperative pain management after open inguinal hernia repair. J Am Coll Surg, 2005; 200:198–202.

20.

Zhang

, Wang

, Lu

, et al. Effect of single-injection versus continuous local infiltration analgesia after total knee arthroplasty: A randomized, double-blind, placebo-controlled study. J Int Med Res, 2011; 39:1369–1380.