Ambulatory and Office Urology

A Prospective, Randomized Controlled

Study Comparing Lidocaine and
Tramadol in Periprostatic Nerve
Blockage for Transrectal
Ultrasound-guided Prostate Biopsy
Ilker Seçkiner, Haluk Sen, Sakıp Erturhan, and Faruk Yağcı
OBJECTIVES To assess the efficacy of tramadol and lidocaine in reducing pain using the periprostatic nerve
block technique with a spinal needle, guided by transrectal ultrasound (TRUS) before the biopsy
application.
METHODS Of the 112 eligible candidates who were asked to participate in the study, 90 agreed and provided
informed consent. These 90 men were randomized into 3 groups. Group 1 (n ⫽ 30) received
lidocaine, group 2 (n ⫽ 29) received tramadol, and group 3 (n ⫽ 31) received saline solution.
Within 10 minutes of biopsy procedure completion, the patients were presented with visual pain
scales and asked to rate the pain. The patients also asked whether they would be to return for
this procedure if it became medically necessary.
RESULTS The postprocedural mean pain scores of lidocaine, tramadol, and placebo groups were found to
be 1.73, 2.89, and 4.32, respectively. The mean pain scores were significantly lower in both the
lidocaine and the tramadol groups compared with the placebo group (P ⬍.001). In addition,
statistically significant differences were found among the 3 groups regarding how willing they
would be to return for the procedure if necessary.
CONCLUSIONS In this study, we showed that the local anesthetic effect of tramadol in decreasing pain in
periprostatic nerve block during TRUS-guided biopsy. The use of tramadol for pain relief in
transrectal ultrasound-guided prostate biopsy is a practical, effective, and comfortable method
compared with the results of the control group. UROLOGY 78: 257–260, 2011. © 2011 Elsevier
Inc.

P
rostate biopsy accompanied by transrectal ultra-
sonography (TRUS) has been accepted as the gold
standard for the diagnosis of prostate cancer. Al-
though the procedure is performed without any anes-
thetic methods in many centers, many patients have
been reported to have ailments worthy of record.1,2 How-
ever, there have been numerous studies concerning the
efficiency of different methods, the foremost of which is
periprostatic local anesthetic infiltration; periprostatic
lidocaine injection and intrarectal lidocaine gel instilla-
tion are among these. Factors such as age of the patient
and the performance of a former biopsy besides insertion
and movements of the ultrasonographic probe into the
rectum were reported to affect the amount of the pain
experienced.3,4
Few studies have investigated the local anesthetic ef-
fect of tramadol. Antonucci5 and Sarihasan et al6 have
shown that 100 mg tramadol as adjunct to brachial plexus
anesthesia exerts a beneficial effect. In addition, Robaux
et al7 suggested that tramadol can be added to 1.5%
mepivacaine for brachial plexus block.
In this study, we administered lidocaine, prevalently
used before prostate biopsy, and tramadol, an analogue of
codeine with central effect, in periprostatic nerve block-
age; and we evaluated the efficacy of lidocaine and tra-
madol for pain reduction.

MATERIAL AND METHODS

From the Department of Urology, University of Gaziantep, Gaziantep, Turkey
Reprint requests: Ilker-Seçkiner, M.D., Associate Professor of Urology University of
Gaziantep, School of Medicine, Department of Urology, 27310 Gaziantep, Turkey.
E-mail: iseckiner@yahoo.com
Submitted: January 24, 2011, accepted (with revisions): March 8, 2011
Our institutional review board approved this prospective,
randomized, double-blind, controlled trial. Patients present-
ing to our outpatient clinic between March 2009 and August
2009 were eligible for study inclusion. All patients were

© 2011 Elsevier Inc. 0090-4295/11/$36.00 257

All Rights Reserved doi:10.1016/j.urology.2011.03.010
Table 1. Patient characteristics and demographics
Group Group Group P
1 (Lidocaine) 2 (Tramadol) 3 (Placebo) Value
No. of patients 30 29 31
Mean age ⫾ SEM 67.16 ⫾ 1.46 67.2 ⫾ 1.6 66.8 ⫾ 1.2 .98
No. abnormal DREs 22 18 23 .863
Mean serum PSA ⫾ SEM (ng/mL) 23.1 ⫾ 5.2 19.8 ⫾ 4.6 15.0 ⫾ 3.4 .424
Average number of prostate biopsies (mean ⫾ SEM) 7.7 ⫾ 0.3 7.6 ⫾ 0.4 7.3 ⫾ 0.3 .882
SEM ⫽ standard error of the mean; DRE ⫽ digital rectal examination.

evaluated by medical history, physical examination, and

measurement of free and total prostate-specific antigen
(PSA) ARCHITECT i2000, (Abbott Laboratories, Abbott
Park, IL). The indication for TRUS-guided prostate biopsy
was PSA ⬎4.0 ng/mL and/or abnormal digital rectal exam-
ination results. Inclusion criteria were all patients who were
eligible for prostate biopsy and willing to provide informed
consent. Patients who had received selective serotonin re-
uptake inhibitors, tricyclic antidepressants or other tricyclic
compounds, opioids, monoamine oxidase inhibitors, or neu-
roleptics within the previous 3 months and history of epi-
lepsy or any other seizure disorder were excluded from the
study.
Before the biopsy procedure, all patients were informed about
the kind of procedure they would undergo and its possible
complications. Of the 112 eligible candidates who were asked to Figure 1. Pain scores after biopsy according to the groups.
participate in the study, 90 agreed and provided informed
consent. These 90 men were randomized into 3 groups using a
blocked randomization plan. Group 1 (n ⫽ 30) received 2.5 mL
tistical program. The statistical analyses were performed with
2% lidocaine, group 2 (n ⫽ 29) received 2.5 mL 25 mg trama-
Kruskal-Wallis and chi-square tests.
dol, and group 3 (n ⫽ 31) received 2.5 mL saline solution. Any
anticoagulation or aspirin therapy regimens were discontinued
7 days before the biopsy procedure.
Treatment with a daily dose of ciprofloxacin 500 mg twice
RESULTS
daily was planned to start one day before the procedure and Ninety patients aged 40 – 85 years (mean age, 67.06 ⫾
continued until the fifth day after biopsy. Two rectal tubes of 7.7) underwent prostate biopsies for elevated PSA of 19.3
enema were administered 2 hours before the biopsy. Biopsies ⫾ 13.5, with the interval of 1–100 ng/mL. Patient pop-
were performed using an end-firing 7.5-MHz biplane transrectal ulation according to grouping, the mean patient age,
probe attached to the ultrasonography device (Hitachi, Medical values of serum PSA levels, and value of abnormal digital
Co., Tokyo, Japan) and with a fully automatic biopsy instru- rectal examination findings of the total 90 patients in-
ment. The patients were placed in a left lateral decubitus cluded in the study are found in Table 1.
position during the procedure. The postprocedural mean (⫾SD) pain scores of the
The medications were prepared in 10-mL syringes and the
lidocaine, tramadol, and placebo groups were found to be
volume and color of the solutions were the same for the 3
groups. Thus, the physician responsible for the procedure was
1.73 (⫾ 1.23), 2.89 (⫾ 1.63), and 4.32 (⫾ 1.94), respec-
unaware of the group to which the patient belonged. Injections tively. The mean pain scores were significantly lower in
were done within the neurovascular bundle at the base of the both the lidocaine and the tramadol groups compared
prostate, just lateral to the junction between the prostate and with the placebo group (P ⬍.001). We also found that
seminal vesicle in the sagittal plane on both sides using a mean pain score in the lidocaine group was significantly
22-gauge spinal needle through the ultrasound probe. Biopsy lower compared with the tramadol group (P ⬍.05). Dis-
was performed five minutes after the injection. tribution of mean pain scores according to the groups is
Within 10 minutes of biopsy procedure completion, the displayed in Figure 1.
patients were presented with visual pain scales and asked to rate In addition, statistically significant differences were
their pain. The scale was a linear, 10-point visual analog pain found among the 3 groups concerning how willing they
scale (VAS). The patients also asked whether they would need
would be to return for the procedure if necessary. When
to return for this procedure if it became medically necessary.
Their answers were recorded according to the groups.
the positive responses to rebiopsy were compared among
Before the trial was initiated, it was determined that 28 the groups, there was a statistically significant difference
patients would need to be enrolled in each study arm to detect in the lidocaine group from the placebo group (P ⬍.05);
a decrease in the pain score of 1.0 at a standard deviation of 1.2, however, no significance was found in the tramadol-
a significance of 5%, and a power of 86%. Pain scores among administered group (P ⬎.05) (Fig. 2).
the groups were compared using a commercially available sta- A critical status did not develop with respect to com-

258 UROLOGY 78 (2), 2011


Figure 2. Responses to the question “If medically neces-
sary, how willing would you be to return for this procedure?”
plications. Three quadrants of biopsies were taken only
from a patient in the placebo group because he was not
able to tolerate the procedure and developed vasovagal
syncope. One patient from each group was diagnosed
with high fever and successfully treated with intravenous
antibiotics.
COMMENT
Prostate cancer is the most common form of urological
cancer among men. The biopsy procedure without any
form of analgesia or anesthesia for prostate cancer diag-
nosis causes pain or discomfort.1,8 Pain perception ap-
pears especially with the movement of the probe during
insertion into the anal canal. When there is no patient
adaptation, obtaining the required amount of specimens
from the correct site becomes more difficult. Various
forms of anesthesia, such as periprostatic lidocaine injec-
tion and intrarectal gel have been used to increase pa-
tient adaptation.3,9,10
In our study, we assessed the efficacy of tramadol and
lidocaine in reducing pain using the periprostatic nerve
block technique with a spinal needle, guided by TRUS
before the biopsy application to the predetermined pa-
tients who had an increase in PSA level or abnormal
digital rectal examination. We used a VAS to demon-
strate the effects of the analgesic agents and to ask the
patient to accurately rate their current pain. To our
knowledge, this is the first study to use tramadol as a local
anesthetic agent during TRUS-guided prostate biopsy.
Initially, it was thought that tramadol produced its
antinoceptive and analgesic effects through spinal and
supraspinal sites rather than via a local anesthetic action.
However, several clinical studies have shown that it
might have peripheral local anesthetic-type proper-
ties.11-13 By direct tramadol application to the sciatic
nerve in rats, it was proven that tramadol exerts a local
anesthetic-type effect on peripheral nerves.14 In the pres-
ent study, tramadol had a local anesthetic action similar
to that of lidocaine.
UROLOGY 78 (2), 2011
The pain experienced during prostate biopsy is trans-
mitted through the autonomic nerve fibers, crossing the
prostatic pedicle in the neighborhood of the seminal
vesicles and innervating the prostate. The anesthetic
agent will reduce the pain experienced during the bi-
opsy.15,16 Nash and colleagues described periprostatic
nerve block technique for the first time and reported that
the anesthesia group who received periprostatic nerve
block experienced less pain than the group without an-
esthesia.8 With a group of 50 patients, Soloway and Öbek
described a new technique of periprostatic nerve block
into the middle and apex of the prostate by the injection
of 5 mL of 1% lidocaine into the junction of the prostate
and seminal vesicle under TRUS guidance. All patients
reported a decrease in pain during the procedure and no
important complication was observed except in 1 patient.
The investigators emphasized anesthesia or analgesic re-
quirement during the biopsy procedure.17 Alavi et al
compared periprostatic local anesthesia with 1% lido-
caine with intrarectal 2% lidocaine gel before prostate
biopsy, and consequently reported that TRUS-guided
periprostatic nerve blockade was more successful.9
Repetitive TRUS-guided prostate biopsy was reported
as a risk factor in reducing patient tolerance for biopsy
procedure.18,19 In the current study, all patients were
asked whether they would permit a repeat biopsy if it
became medically necessary. The positive responses
given by lidocaine and tramadol groups, who especially
had lower pain scores, were found to be significant
(P ⬍.05).
Mallick et al compared the pain scores of 2 groups of
patients who were administered intrarectal gel and
periprostatic blockage during anesthesia, during the bi-
opsies and 30 minutes after. They found statistically
significantly lower pain score values, especially during the
anesthesia procedure and 30 minutes after anesthesia, in
the intrarectal gel group; however, they determined lower
pain score values in the periprostatic blockage group,
especially during the biopsy procedure. In conclusion,
they suggested intrarectal gel administration with peripros-
tatic blockage. No serious anesthesia-related complications
were noted in any of the patients. Persistent hematuria
(2%) and hematospermia (1%) were reported in patients
of both groups who were reassessed after 3 weeks.20 Ra-
gavan et al compared periprostatic lidocaine infiltration
during TRUS-guided prostate biopsy and the addition of
diclofenac sodium suppository 40 minutes before the pro-
cedure, and the methods were used together. Except in
the diclofenac sodium–administered group, a statistically
significant decrease in pain was detected in 2 other
groups during the biopsy. However, no difference be-
tween pain scores experienced an hour and a day after the
procedure was observed owing to the presence of the
probe in the rectum. Infectious or hemorrhagic compli-
cations were also found at similar rates between the
groups.21 Öbek et al divided the patients into 4 groups in
another study: control, periprostatic nerve blockage, in-
259
trarectal lidocaine gel plus periprostatic nerve block and
tramadol, and centrally acting codeine analog. They
demonstrated that the analgesic- or anesthesia-adminis-
tered group was superior to the nonadministered group.
They simultaneously reported that it provided the best
analgesia together with the intrarectal gel at the peripros-
tatic block.22 However, using tramadol in periprostatic
nerve block, we observed its pain-decreasing effect and
deduced that tramadol was at least as effective as lido-
caine in providing patient comfort by decreasing pain.
CONCLUSIONS
Although there was not an exact consensus of opinion on
a standard method, periprostatic nerve block has been
accepted as a gold standard regarding decreased pain and
increased patient comfort. This method is an easily ap-
plicable and minimally invasive method with a high rate
of patient admissibility. In this study, we showed the local
anesthetic effect of tramadol in decreasing pain in
periprostatic nerve block during TRUS-guided biopsy.
We propose that tramadol can be used as an alternative
drug to lidocaine in periprostatic nerve block during
TRUS-guided biopsy.
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UROLOGY 78 (2), 2011