Peritubal Infiltration of Fentanyl Compared to Dexmedetomidine with Ropivacaine in Percutaneous Nephrolithotomy: A Randomized Comparative Analysis.

CONTEXT: Dexmedetomidine has been found as an effective adjuvant in various nerve blocks. Despite several studies on dexmedetomidine with ropivacaine, there is no study on comparing with fentanyl in peritubal infiltration in percutaneous nephrolithotomy (PCNL). AIMS: The aim of this study was to compare the effect of the addition of dexmedetomidine or fentanyl in peritubal local anesthetic infiltration on pain scores and analgesic consumption in patients who underwent PCNL. SETTINGS AND
DESIGN: This was a prospective, randomized, double-blind, tertiary care center-based study. SUBJECTS AND METHODS: A total of 60 American Society of Anesthesiologists Class I, II, and III patients were selected and randomly divided into two groups: Group RF ropivacaine and fentanyl (n = 30) and Group RD ropivacaine and dexmedetomidine (n = 30). Balanced general anesthesia was given. After completion of the surgery, peritubal infiltration was given at 6 and 12 O'clock positions under fluoroscopic guidance. Postoperative pain was assessed using the visual analog scale and dynamic visual analog scale rating 0-10 for initial 48 h. Postoperative sedation was assessed using five-point sedation score. Time to first rescue analgesic, number of doses of tramadol, and total consumption of tramadol required in 48 h were noted. STATISTICAL ANALYSIS USED: Descriptive data were expressed in mean and standard deviation for between-group comparisons; the Chi-square and Fisher's exact tests were used for categorical variables, whereas t-test and Mann-Whitney U-test were used to compare continuous variables between two groups.
RESULTS: Duration of analgesia in group RD (12.87 ± 3.85) is more prolonged than group RF (8.13 ± 3.28) h. Total dose of rescue analgesia required in 48 h in group RF was higher as compared to group RD.
CONCLUSIONS: Addition of dexmedetomidine to ropivacaine is more effective than fentanyl in terms of prolongation of analgesic efficacy of local anesthetic in peritubal block along with short-lived mild sedation.

INTRODUCTION

To alleviate the pain due to percutaneous nephrolithotomy (PCNL) surgery and nephrostomy tube, high-dose analgesics are required, but the use of analgesics in patients with decreased renal function has certain challenges.[1] Skin infiltration around the incision, thoracic paravertebral block, can be used for postoperative pain relief.[2] Some studies have shown that the infiltration of local anesthetic along the nephrostomy tube tract from the skin up to renal capsule in patient undergoing conventional PCNL is effective.[3]

Additives are commonly used with local anesthetics for its synergistic effect.[4] In this study, we aimed to compare the analgesic efficacy of fentanyl and dexmedetomidine to ropivacaine in peritubal infiltration.

SUBJECTS AND METHODS

This prospective randomized comparative study was performed in a tertiary care center. Institutional Ethical Committee clearance was obtained before and registered in CTRI with registration number CTRI/2018/06/014619. Informed consent was obtained in written from the patients. The study included a total of 60 American Society of Anesthesiologists (ASA) Class I, II, and III patients who were scheduled for percutaneous nephrolithotomy. Exclusion criteria included patients requiring supracostal puncture or more than one puncture or patients having excessive intraoperative bleeding and stone size >3 cm.

Patients were enrolled sequentially and randomized by computer-generated block size. Each block had three patients. They were divided in two equal groups randomly, Group ropivacaine and fentanyl (RF) or fentanyl group (0.2% ropivacaine with 0.5 μg/kg fentanyl) and Group ropivacaine and dexmedetomidine (RD) or dexmedetomidine group (0.2% ropivacaine with 0.5 μg/kg dexmedetomidine), of 30 patients each. Preoperatively, detailed history was obtained and routine investigations were done.

The procedure was performed under general anesthesia assisted with mechanical ventilation. Anesthesia was induced with 2 μg/kg fentanyl, 1% propofol in titrated dose, and 0.5 mg/kg atracurium. An appropriate-sized cuffed endotracheal tube was used for tracheal intubation. Standard ASA monitoring included electrocardiogram, pulse oximetry, capnography, and core temperature. Anesthesia was maintained with isoflurane (0.4%–0.8%) in N2O and O2 mixture, and intermittent atracurium boluses were administered according to train-of-four responses. Fentanyl 1 μg/kg will be administered if required based on hemodynamic parameters. After the completion of procedure, a routine nephrostogram was performed, and the nephrostomy tube was clamped.

Retained contrast in the tube helped to guide the needle during peritubal infiltration. A 20G spinal needle was introduced under fluoroscopic guidance at 12 O’clock position to the nephrostomy tube up to the renal capsule [Figure 1]. The study drug was then injected along the tissue planes while withdrawing the needle slowly. Similarly, the drug was infiltrated at 6 O’clock position [Figure 2]. At each site, 10 ml of 0.2% ropivacaine along with 0.5 μg/kg fentanyl in group RF and 10 ml of 0.2% ropivacaine along with 0.5 μg/kg dexmedetomidine in group RD were infiltrated along renal capsule, muscle, subcutaneous tissue, and skin maintaining aseptic conditions. The patients were shifted to the postanesthesia care unit for further care after extubation.

Figure 1

20G spinal needle at 12 O’clock position to the nephrostomy tube under fluoroscopic guidance

Figure 2

20G spinal needle at 6 O’clock position to the nephrostomy tube under fluoroscopic guidance

Postoperatively, visual analog scale (VAS) (0–10) was used for assessment of pain at rest and dynamic VAS (DVAS) (0–10) was used during coughing and deep breathing, by an independent observer who was blinded to the study drug infiltrated. VAS is presented as a 10-cm horizontal line that represents as a continuum between the two ends of scale with the left end (0 cm) as “no pain” and the right end (10 cm) as “worst imaginable pain.”[5] Patients were asked to mark a point on the line that best represented their pain. VAS numerical value was measured as the distance in cm. From the starting point (0 cm) to the patient's mark, pain was checked out at 0 h, every hour for the next 2 h, every 2 h for the next 4 h, and every 6 h till 48 h. Intravenous tramadol 1 mg/kg was given when VAS or DVAS was ≥4, as a rescue analgesic up to 48 h. The total dose of tramadol was restricted to 400 mg in 48 h. Peritubal block duration was considered as the time from infiltration to the first demand for rescue analgesic. The total requirement of tramadol within 48 h and any side effects such as nausea, vomiting, and sedation was observed. Sedation score (1–5) was used for assessment of sedation (from 1 – completely awake to 5 – asleep and not responsive to any stimulus).

Statistical analysis

Statistical analysis was performed using SPSS version 18.0.CHICAGO: SPSS Inc. for Windows program. Descriptive data were expressed in mean and standard deviation for between-group comparisons; the Chi-square and Fisher's exact tests were used for categorical variables, whereas t-test and Mann–Whitney U-test were used to compare continuous variables between the two groups. P < 0.05 was considered statistically significant.

Sample size

Required sample size for each study group was estimated with the help of OpenEpi software (version 3) based on a similar study by Parikh et al., where mean duration of analgesia of 13.7 h (95% confidence interval [CI]: 12.4–15.02) for one group and 10.7 h (95% CI: 9.72–11.78) for another group.[6] It was estimated as minimum sample size of 23 each, at 0.05 significance level with 90% power. Thirty patients were recruited in each group in our study.

RESULTS

Sixty-eight patients were enrolled in the study. Eight patients were excluded due to not fulfilling inclusion criteria. A total of 60 patients scheduled for PCNL were randomized. There were no dropouts [Figure 3]. Basic details were comparable in both the groups [Table 1]. VAS and DVAS were significantly high in fentanyl group in first 24 h with the exclusion at 0 min and 18 h postoperatively. Furthermore, VAS and DVAS were comparable in the next 24 h postoperatively [Table 2 and Figures 4,5].

Figure 3

Consort flow diagram

Table 1

Demographic data

Characteristics	Group of patients		P
	Group 1 (RF) (n=30)	Group 2 (RD) (n=30)
Age (years)	38.57±13.39	37.87±9.27	0.815
Gender (male:female)	20:10	18:12	0.592
ASA (I:II:III)	12:17:01	14:15:01	0.870
Weight	68.8±4.9	67±5.6	0.17
Duration of surgery	98.50±14.51	99.00±14.76	0.895

ASA=American Society of Anesthesiologists

Table 2

Postoperative visual analog scale and dynamic visual analog scale score

Time	Mean±SD
	Postoperative VAS		Postoperative DVAS
	Group 1 (RF)	Group 2 (RD)	Group 1 (RF)	Group 2 (RD)
0 min	0.17±0.379	0.10±0.305	0.17±0.38	0.10±0.30
1 h	1.43±0.50	0.33±0.55*	1.43±0.50	0.33±0.55*
2 h	2.10±0.30	1.20±0.61*	2.10±0.30	1.20±0.61*
4 h	2.93±0.69	1.77±0.93*	2.93±0.69	2.03±1.09*
6 h	4.20±1.21	2.07±0.45*	4.47±1.33	2.50±0.63*
12 h	4.90±1.58	4.10±0.88*	4.97±1.61	4.27±1.05*
18 h	3.53±0.82	3.97±1.43	3.73±0.87	4.03±1.47
24 h	3.90±0.84	2.97±0.99*	4.07±0.83	3.13±1.17*
30 h	3.20±0.89	3.17±0.91	3.23±0.97	3.23±1.01
36 h	3.90±1.06	3.67±0.99	3.90±1.06	3.83±0.83
42 h	3.10±0.76	2.73±0.94	3.17±0.87	2.73±0.94
48 h	2.07±0.36	2.23±0.57	2.07±0.36	2.23±0.57

*Significant. VAS=Visual analog scale, DVAS=Dynamic visual analog scale, SD=Standard deviation

Figure 4

Mean values of visual analog scale according to groups

Figure 5

Mean values of dynamic visual analog scale according to groups

Total number of dose of rescue analgesia in 48 h was significantly higher in fentanyl group (4.30 ± 0.70) as compared to dexmedetomidine (3.20 ± 0.61). Total number of dose of rescue analgesia in the first 24 h was significantly higher in fentanyl group (2.90 ± 0.61) as compared to dexmedetomidine (1.73 ± 0.69), whereas total dose of rescue analgesia in the next 24 h was comparable in both the groups. Time of requirement of the first rescue analgesic was 8.13 ± 3.28 h in fentanyl group, whereas it was 12.87 ± 3.85 h in dexmedetomidine group, which was significantly longer in dexmedetomidine group [Table 3]. Sedation was significantly higher in the group RD in the first 2 h postoperative [Table 4], with maximum sedation score of 3. There was no incidence of bradycardia or hypotension found in dexmedetomidine group [Figure 6].

Table 3

Doses of rescue analgesia according to groups

Parameter	Group of patients		P
	Group 1 (RF) (n=30)	Group 2 (RD) (n=30)
Dose of rescue analgesia in 24 h	2.90±0.61	1.73±0.69	0.000*
Dose of rescue analgesia in 24-48 h	1.40±0.49	1.47±0.51	0.610
Total doses of rescue analgesia in 48 h	4.30±0.70	3.20±0.61	0.000*
Time of first rescue analgesia (h)	8.13±3.28	12.87±3.85	0.000*

*Significant

Table 4

Comparison of sedation score between two groups

Time	Group of patients, mean±SD		P
	Group 1 (RF)	Group 2 (RD)
0 min	1.00±0.00	1.00±0.00	-**
30 min	1.57±0.50	2.00±0.69	0.008*
1 h	1.33±0.48	1.77±0.73	0.009*
2 h	1.00±0.00	1.17±0.38	0.019*
4 h	1.00±0.00	1.00±0.00	-**
6 h	1.00±0.00	1.00±0.00	-**
12 h	1.00±0.00	1.00±0.00	-**
18 h	1.00±0.00	1.00±0.00	-**
24 h	1.00±0.00	1.00±0.00	-**

*Significant, **T cannot be computed because the SD of both groups are 0. SD=Standard deviations

Figure 6

Postoperative hemodynamic trends in the two groups

DISCUSSION

Nephrostomy tube is generally placed after the completion of PCNL to provide adequate drainage, hemostasis, and as access for second-look procedure. Various studies are done aiming to decrease the pain and discomfort due to nephrostomy tube. Furthermore, tubeless PCNL has been advocated by some authors, decreasing pain, and analgesic requirement.[7] However, there are some limitations for tubeless PCNL, such as perforation, excess bleeding, or complex stones.

A further alternative to lessen postoperative pain is to reduce the size of the nephrostomy tube. Small size (8–12 Fr) nephrostomy tube has been used in patients with uneventful PCNL or in those patients in whom percutaneous access may be required for succeeding calculus manipulation. While for procedures with significant bleeding, prolong duration, large complex or infected calculi, or major perforations, conventional nephrostomy tube with large bore may be required.

The pain and discomfort after PCNL may be caused by local inflammatory reaction produced by nephrostomy tube. Local anesthetics can inhibit inflammatory response by suppressing some phases of inflammation and local sensitizing response by blocking inflammation-induced neuronal pathways.[8]

It is demonstrated by Jonnavithula et al., where bupivacaine infiltration was given beside the nephrostomy tube under fluoroscope, resulting in prolonged duration of analgesia and lower pain scores in bupivacaine group compared to the control group.[9] In our study, we used 0.2% ropivacaine because of its better pharmacokinetic profile than bupivacaine.

Kaushal-Deep et al. used 0.2% ropivacaine as intraincisional infiltration and intraperitoneal instillation in postlaproscopic cholecystectomy. It showed that low concentration (0.2%) provides adequate postoperative analgesia and emphasized that large amount of drug is unjustified.[10]

In this study, we aimed to assess analgesic efficacy of dexmedetomidine and fentanyl when added to ropivacaine in peritubal infiltration. There is no such study in literature comparing the analgesic efficacy of dexmedetomidine and fentanyl in peritubal infiltration.

In a study by Parikh et al., it was concluded that the use of morphine as additive to local anesthetic for peritubal infiltration extended the analgesic duration significantly, and the time of requirement of the first rescue analgesics is also significantly prolonged.[11] In our study, we used fentanyl instead of morphine due to its less histamine-releasing property.

Fentanyl has been used as an adjunct to local anesthetics during regional or peripheral nerve blocks and has resulted in prolongation of analgesic duration.[12] Mechanism of fentanyl in prolongation of analgesia may be due to the existence of peripheral functional opioid receptors, but this existence in peripheral tissue is still doubtful.[13] A less likely mechanism of action is local anesthetic action of fentanyl. Local anesthetic properties of opioids have been discussed in earlier studies.[14]

Murugan et al. used dexmedetomidine along with ropivacaine as nephrostomy tract block in tubeless PCNL.[15] The total analgesic requirement was significantly lower than the control group, whereas the first analgesic dose time was prolonged (10 h). Major limitation of the study was that it used placebo as control group. Murphy et al.[16] and Brummett et al.[17] reported in their studies on administration of dexmedetomidine as an adjuvant that the mechanism of analgesic properties of dexmedetomidine is still not clear and may be multifactorial. Possible mechanisms explained by Lee et al. showed that dexmedetomidine induces vasoconstriction through an action on α2 receptors, or it produces analgesia peripherally by reducing norepinephrine release and increasing the potassium conduction in C- and A-delta neurons responsible for passage of pain stimulus, whereas it produces sedation and analgesia centrally by acting on locus coeruleus and dorsal root ganglia thereby inhibiting the release of substance P in nociceptive pathway.[18]

The analgesic supplementary effects of dexmedetomidine in this study confirm the conclusion of other investigators.

The present study also confirms the better analgesic-sparing effect of dexmedetomidine than fentanyl as demonstrated in the previous studies when used as an adjuvant to bupivacaine in supraclavicular nerve block[19] and wound infiltration in abdominal hysterectomy.[20]

On the other hand, we observed mild sedation in both the groups with maximum sedation score of 3 in RD group which was short lived. This was in fact well tolerated. There was no difference between the groups in terms of nausea or postoperative bleeding episode. Major limitation of this study is its being single-centered design.

CONCLUSIONS

Peritubal block is simple, easy to perform, and effective method for postoperative analgesia in PCNL procedures. Addition of dexmedetomidine to local anesthetic ropivacaine for peritubal block significantly prolonged the duration of postoperative analgesia as compared to fentanyl. Furthermore, total consumption of rescue analgesia is significantly less in initial 24 h when dexmedetomidine is used as additive as compared to fentanyl in peritubal block in PCNL surgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.