Efficacy of Levobupivacaine Infiltration to Nephrosthomy Tract in Combination with Intravenous Paracetamol on Postoperative Analgesia in Percutaneous Nephrolithotomy Patients

Introduction

S ince the first successfully planned and completed cases by Fernstrom and Johansson ¹ in 1976, percutaneous nephrolithotomy (PCNL) has evolved and become the most preferred surgical intervention for kidney stones. Although it has the advantage of being less invasive compared with open techniques, it is still not without complications.

Placing a nephrostomy catheter after PCNL is a standard of postoperative care. It enables sufficient urinary drainage during the healing process, prevents bleeding through the renal parenchyma, and provides a tract for second-look procedures. It can be the cause of postoperative discomfort and pain, however. To decrease postoperative discomfort and pain related to the nephrostomy tube, tubeless PCNL was introduced, and recent studies with tubeless PCNL have demonstrated decreased postoperative pain. ^{2 –4} The tubeless PCNL procedure, however, can only be performed in selected cases, and nephrostomy still stands as the standard of care for the majority of patients. Therefore, an attempt to establish an effective post-PCNL pain management protocol was needed. ⁵

Despite the progression in the knowledge of the pathophysiology and management of pain, most patients still have insufficient postoperative analgesic medication. This insufficiency results in delayed mobilization, associated new onset morbidities, and increased treatment costs. ⁶ Opioid and nonopioid analgesics and local anesthetics are the preferred agents for postoperative pain management. ⁷ Although the opioid analgesics are the most effective agents, their side effects limit their use with the effective optimum dosage. ⁸ Therefore, “balanced” or “multimodal” protocols that combine opioids with nonsteroidal anti-inflammatory or local anesthetics were developed to increase the quality of analgesia and decrease the mentioned undesired effects related to opioids. ^7,9,10

In this study, we aimed to evaluate the efficacy of intraoperative local anesthetic infiltration in combination with intravenous paracetamol infusion on postoperative pain management in patients who underwent PCNL. We performed this evaluation in terms of assessment of quality of pain management and the amount of systemic opioid needed.

Patients and Methods

Sixty adult patients who underwent PCNL between April 2007 and April 2009 were included in the study. The design of the study was discussed and approved by the local ethics committee, and informed consent was obtained from all patients before entry to the study. In all patients, PCNL was performed through a single subcostal access. Patients with severe cardiopulmonary disease, previous renal stone surgery, positive urinary culture, abnormal hepatic and renal function tests, and allergy to local anesthetics were excluded to minimize the possible drug metabolism related effects. To make similar surgical groups, operative time longer than 2 hours, surgery via more than one access, necessity of an access at a different level from the infiltration site, massive bleeding necessitating blood transfusion, neighboring organ or urinary system injury were used as other exclusion criteria.

All patients were preoperatively evaluated with complete blood cell count, serum chemistry, coagulation profile, serologic tests for hepatitis and human immunodeficiency virus, urinalysis, and urine culture. Imaging tests included intravenous urography or nonenhanced spiral CT. Sixty patients were consecutively randomized into three treatment groups.

In the first group (group SP), 20 mL saline was infiltrated through the whole (cutaneous, subcutaneous, and muscle layers) nephrostomy tract intraoperatively, and this was followed by intravenous paracetamol (4 × 1 g, within 100 mL saline) infusion postoperatively. In the second group (group LP), 20 mL of 0.25% levobupivacaine infiltration to the nephrostomy tract in a similar manner was followed by postoperative intravenous paracetamol (4 × 1 g, within 100 mL saline) infusion. In the third group (group LS), 20 mL of 0.25% levobupivacaine infiltration to the nephrostomy tract in a similar manner was followed by intravenous saline infusion postoperatively. The infiltration of saline or levobupivacaine was performed just before the puncture of the PCNL tract.

All operations were performed under general anesthesia with a standard approach. Intravenous infusions (saline or paracetamol) were performed 30 minutes before the end of the operation and four times a day in 100 mL saline. In the postoperative period, pain status of the patients was evaluated in the recovery unit at 6 and 24 hours by using the visual analogue scale (VAS: 0, no pain to 10, unbearable pain) by another doctor who was blinded to the study. For patients who had VAS ≥ 3 despite the medication, depending on their demands, meperidine (1 mg/kg intramuscularly) was given as on additional “rescue” analgesic. In all patients, after 24 hours postoperative, kidneys-ureters-bladder radiography was performed for possible residual stones. The patients were followed up with a 20F nephrostomy in place. The nephrostomy tube was withdrawn at the third postoperative day if hematuria or fever was not present. Patients were observed for urinary leakage from the nephrostomy site or pain after nephrostomy withdrawal for 6 to 12 hours. None of the patients was sent to home with an internal or external stent. Before discharge from the hospital, satisfaction from postoperative analgesia management was assessed by a 5 point satisfaction scale (0, poor, to 4, excellent).

Patients were also evaluated regarding the possible postoperative complications and opioid or medication related side effects (nausea, vomiting, sedation, respiratory depression, fatigue, pruritus, hypotension, tachycardia), if present. The time to first mobilization (period between the transfer of the patient to his or her bed and first standing and walking in the room with or without help) and postoperative hospital stay were recorded.

The statistical analysis was performed using SPSS 13.0 (SPSS, Chicago, IL). The chi-square test was used for analysis of proportions, evaluation of means was performed by the Mann-Whitney test, one-way analysis of variance test, and Kruskal-Wallis test where appropriate. A P value < 0.05 was considered to be statistically significant.

Results

Overall, 30 patients were female and 30 were male. The right kidney was operated in 35 patients and the left in 25. The only complication was urinary tract infection caused by extended spectrum beta lactamase (+) Escherichia coli in one patient. Groups were similar regarding gender distribution, operated side, and complication rates. Opioid medication was needed in 11 (55%), 4 (20%), and 17 (85%) of patients in groups SP, LP, and LS, respectively. None of the patients experienced opioid-related severe side effects, such as respiratory depression or excessive sedation. Some patients, however, experienced different symptoms that might be attributed to the medications (Table 1). Although the frequency of complications seemed to be lower in group LP, the statistically significant difference was present only between groups LS and LP in terms of nausea-vomiting and dizziness (chi-square test, P < 0.05).

Head to head comparisons were made between the three groups regarding the VAS scores at 6 and 24 hours, needed opioid analgesic dosage and number of injections, satisfaction scale, mobilization time, and postoperative hospital stay. The comparison between groups SP and LS revealed no significant difference. The LP vs SP and LP vs LS comparisons revealed that the LP group was advantageous over the SP and LS groups in all parameters mentioned above, except the postoperative hospital stay. The results are given in Table 2.

Discussion

After surgical tissue trauma, inflammatory and pain mediators are released. These mediators induce the production of cytokines, adhesion molecules, and coagulation factors. This “stress response” increases the metabolic rate, results in water retention, and triggers the “fight or flight” reaction. The process at last causes postsurgical pain and morbidities, particularly in patients with preexisting cardiovascular and pulmonary diseases. ¹¹ The resultant pain inevitably causes severe postoperative disturbances and decreases quality of life. In the era of advanced pharmacology and technology, insufficient postoperative pain management is unacceptable. Patients still have pain, however. Postoperative pain is the most significant cause of preoperative anxiety and has a strong impact on the recovery period and daily life at home. ^12,13

The most important factors that increase postoperative pain and morbidity in patients who undergo PCNL are the width of the tract and the presence of a nephrostomy catheter. In this respect, tubeless PCNL has been described with an attempt to decrease postoperative pain and hospital stay. The initial study of Belman and associates ¹⁴ showed the possibility of urinary drainage and healing over an internal ureteral stent without complications. Then, several studies confirmed those findings in selected cases that do not require more than one access, do not last more than 2 hours, and do not have significant bleeding or suspicion of residual fragments. These studies showed decreased postoperative hospital stay, analgesic requirement, health costs, and shortening of the recovery period. ^{2 –4,15} Moreover, Rana and Mithani ¹⁶ reported their experience with tubeless PCNL. Regardless of the size, burden, number of the stones, the degree of obstruction, and anatomic variations of the kidney in more than 100 patients, they showed the feasibility of omission of a nephrostomy tube after PCNL while retaining an externalized ureteral catheter for 16 to 20 hours, irrespective of the stone characteristics.

The width of the nephrostomy catheter was one of the investigated possible factors for postoperative pain. Pietrow and colleagues ¹⁷ compared a 22F nephrostomy catheter and a 10F pigtail catheter in terms of postoperative pain. They found that patients with the 10F pigtail catheter had lower VAS scores and decreased opioid need. Another study compared an 8.3F pigtail nephrostomy catheter and an 8.2F nephroureteral stent. ¹⁸ These authors also reported decreased VAS scores and analgesic need in the pigtail group. Although the difference was significant for VAS scores (P = 0.004), the difference regarding the analgesic need did not reach statistical significance (P = 0.06). They concluded that the differences in VAS scores could be related to the ureteral and vesical irritation of the nephroureteral stent. Two recent studies from Turkey also reported decreased postoperative analgesic need and hospital stay in patients undergoing tubeless PCNL. ^3,4

The efficacy of postoperative local anesthetic infiltration to the incision site has been reported in the general surgery and gynecology literature. In the systematic review of Moiniche and coworkers, ¹⁹ pain scores, time to first analgesic demand, and total analgesic need were compared in patients in whom the incision site was infiltrated with local anesthetic after cholecystectomy, abdominal hysterectomy, inguinal hernia, and various abdominal surgeries. They showed that local anesthetic to the incision site yielded effective analgesia for a 2 to 7 hour period only for inguinal hernia operations. The effective postoperative analgesia could not be achieved for other types of surgeries.

Among the percutaneous stone surgery literature, however, there are a few articles that focus on postoperative pain management. In one of these studies, although statistical significance was not present, a trend toward decreased postoperative narcotic use was seen in patients who received subcutaneous bupivacaine administration around the nephrostomy tube tract. ²⁰ In another study oo 40 patients by Jonnavithula and colleagues, ⁵ the efficacy of peritubal infiltration of bupivacaine from the renal capsule to the skin along the nephrostomy tract on postoperative pain was evaluated. The authors concluded that peritubal infiltration of 0.25% bupivacaine solution resulted in a significant decrease in the pain scores and analgesic need.

Insufficient pain management may cause hypertension, tachycardia, increased cardiac load, superficial respiration, and depression of cough. This can cause difficulty in excretion of pulmonary secretions and increase the risk of pulmonary infections. In addition, insufficient pain management prolongs the hospitalization period, which also increases the costs. In the study of Ugras and associates, ²¹ the effect of local anesthetic infiltration on postoperative pain status and pulmonary functions was assessed. The authors infiltrated 30 mL of either 0.02% ropivacaine or saline into the renal puncture site, nephrostomy tract, and skin. Patients received parenteral metamizol (500 mg/dose) on demand. The results of this study showed that the combination of ropivacaine instillation with metamizol decreased pain and analgesic use and improved peak expiratory flow more than use of metamizol alone.

Preemptive analgesia is a concept that has come into practice after the understanding of peripheral and central sensitization mechanisms. It aims to produce a suppression before neural hypersensitization occurs. ²² In this respect, local anesthetics or nonsteroidal analgesics are given intraoperatively to delay postoperative pain perception and decrease postoperative analgesic consumption. ²² The effect of levobupivacaine starts at 5 to 7 minutes, and the maximum effect is achieved at 20 to 25 minutes. The duration of the neural blockage may last up to 6 hours. ²³ Although the duration of the local anesthetic effect is about 6 hours, when used in combination with nonsteroidal analgesics, an additive effect might occur because of delayed and decreased pain perception from the preemptive application. Therefore, the effect on pain management may last beyond the duration of neural blockage. This can be an explanation for the lower VAS scores in group LP at both postoperative 6 and 24 hours. This lower pain status may be the factor for shorter time to mobility in this group. In addition, the higher frequency and dosage of opioid requirement in groups SP and LS may be the cause of the relatively higher incidence of side effects, such as nausea and dizziness, which might also be a contributing factor for the longer time to mobility in these groups.

Our study is the first to show the efficacy of a combination of local anesthetic (levobupivacaine) infiltration and parenteral paracetamol infusion on postoperative pain management. Our choice of local anesthetic was levobupivacaine, because it has some advantages over the others. Levobupivacaine belongs to the aminoamide group of local anesthetics. It blocks the voltage gated sodium channels in peripheral nerves as the other local anesthetics do. ²³ Its potency with respect to sensorial and motor blockage is equivalent to that of bupivacaine. Its duration of sensorial blockage was shown to be longer than bupivacaine, which was attributed to its intrinsic vasoconstrictor effect. It blocks lesser amounts of inactive sodium channels and therefore has less cardiovascular toxic effects than bupivacaine. ²⁴ Levobupivacaine has a more potent and long-lasting sensorial and motor blockage than ropivacaine. There are no significant differences regarding the cardiovascular side effects between the two agents. Because of its lower blocking effect on inactive ion channels, however, levobupivacaine has a lesser depressive and convulsogenic effect on the central nervous system. ²⁴

In our study, intravenous paracetamol infusion was applied 30 minutes before the end of the operation. This proved a painless recovery from anesthesia. The routine four times a day application of intravenous paracetamol has been effective for the early postoperative period and decreased the opioid need. We achieved a better postoperative pain status and patient satisfaction with this combination strategy. As a preliminary study, we excluded patients with cardiac and pulmonary comorbidities and the pediatric patient group. These results of our study are encouraging, and the efficacy in these patient groups may be investigated with further studies.

Conclusion

According to the results of our study, levobupivacaine infiltration through the nephrostomy tract in combination with intravenous paracetamol infusion was shown to be safe and efficacious as an analgesia method after PCNL. The results of our study may be a subject of a further study on postoperative pain management in patients with cardiac and respiratory comorbidities and the pediatric patient group.