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COMBINED “PERIPROSTATIC AND PERIAPICAL” LOCALANESTHESIA IS NOT SUPERIOR TO “PERIPROSTATIC”

ANESTHESIA ALONE IN REDUCING PAIN DURING Tru-CutPROSTATE BIOPSY

IBRAHIM CEVIK, OZDAL DILLIOGLUGIL, AMNON ZISMAN, AND ATIF AKDAS

ABSTRACTbjectives. To evaluate, in a prospective study, the benefit of adding local periapical prostatic anesthesia

o routine periprostatic infiltration to the prostate-seminal vesicle junction in a randomized fashion. Trans-ectal ultrasound-guided biopsy is the reference standard in the diagnosis of prostate cancer. Although wellolerated by most patients, it can be associated with discomfort.ethods. A total of 120 consecutive evaluable patients with an elevated total prostate-specific antigen

tPSA) level, increased tPSA velocity, and/or abnormal digital rectal examination findings were enrolled. Theatients were randomized into two groups. Group 1 received periprostatic infiltration of 6 mL 1% lidocaine.roup 2 received periprostatic and apical infiltration: 4 mL 1% lidocaine at the prostate-seminal vesicle

unction and 2-mL infiltration at the prostatic apex 15 minutes before transrectal ultrasound-guided biopsy.ain was assessed using a 10-point modified visual analog scale.esults. The mean patient age was 63.7 � 1.2 years and 64.2 � 1.1 years, the mean tPSA level was 12.1 �.5 ng/mL and 13.6 � 2.7 ng/mL, the mean biopsy duration was 6.2 � 2.5 minutes and 6.1 � 2.2 minutes,nd the mean visual analog scale pain score was 1.26 � 0.1 and 1.23 � 0.1 for groups 1 and 2, respectively.o statistically significant difference was observed with respect to age, tPSA level, mean biopsy duration, orain score between the two groups.onclusions. Periprostatic lidocaine infiltration provides local anesthesia that results in improved visualnalog scale pain scores. Additional apical infiltration did not improve patient discomfort further. However,omparative evidence has indicated that increasing the time elapsed between the anesthetic infiltration andhe biopsy procedure may further improve pain control. UROLOGY 68: 1215–1219, 2006. © 2006 Elseviernc.

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ransrectal ultrasound (TRUS)-guided biopsyis an essential step in the diagnosis of prostate

ancer. TRUS-guided Tru-Cut biopsy has becomehe reference standard because of its effectivenessn cancer diagnosis, as well as a low rate of associ-ted side effects. When performed without anes-hesia, it is well tolerated by most patients but canause a wide range of pain perceptions from mild

rom the Department of Urology, Urotip Diagnosis Center, Istan-ul, Turkey; Department of Urology, Kocaeli University School ofedicine, Kocaeli, Turkey; and Department of Urology, Assafarofeh’ Medical Center, Tel Aviv University Sackler School ofedicine, Tel Aviv, IsraelReprint requests: Ibrahım Cevık, M.D., Department of Urol-

gy, Urotip Diagnosis Center, Bagdat cad. No. 448/1 Suadiye,stanbul, Turkey. E-mail: cevik@rancomp.com

Submitted: February 25, 2006, accepted (with revisions): Au-

tust 11, 2006

2006 ELSEVIER INC.LL RIGHTS RESERVED

iscomfort to severe pain, as shown by differenttudies.1,2 This can be easily explained by varyingain thresholds and varying rectoanal abnormali-ies. A number of studies have reported on the ben-fit of local anesthesia. Although the techniqueshat do not involve injectable anesthetics are in-ffective in diminishing discomfort,3 peripros-atic infiltration with local anesthesia reducesain effectively.4In this prospective study, we evaluated the ben-

fit of adding periapical 1% lidocaine infiltration inddition to routine periprostatic lidocaine infiltra-ion to the prostate-seminal vesicle junction.

MATERIAL AND METHODS

Prostate biopsy was indicated in patients with an elevated

otal prostate-specific antigen (tPSA), increased tPSA velocity,

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nd/or abnormal digital rectal examination findings. In pa-ients with a history of prostate cancer in one or two first-egree relatives, prostate biopsy was performed even when thePSA level was lower (2.5 to 4.0 ng/mL).

Patients were enrolled in the study from January 2003 toarch 2005. The exclusion criteria were a history of anal

ssure or stricture, any neurologic disease, or concomitant usef pain relief medicine or drug addiction. A total of 145 pa-ients were evaluated for eligibility. Fifteen patients were ex-luded because they met the exclusion criteria, two had anllergy history for lidocaine, and four declined to provide writ-en informed consent. Thus, randomization with numberedontainers was terminated on the inclusion of 124 patients.our patients could not be included in the final evaluationecause of cooperation deficiency, resulting in 120 patients.his study was not double-blinded because of the natural se-uence of the procedures (single site or double-site injection).lacebo controls were not used because numerous previoustudies have clearly demonstrated the superiority of injectionnesthesia.5,6 Double-blinding was deemed unnecessary be-ause the investigator (who also performed the injections andiopsies) did not have any influence on the determination ofhe key evaluation factor: the pain score.

Patients were randomized into two groups according to localnesthesia application using numbered containers. Group 1periprostatic infiltration only) received a total of 6 mL of 1%idocaine solution (3 mL on each side). Group 2 (periprostaticnd apical infiltration) received 4 mL of 1% lidocaine solution2 mL on each side) at the prostate-seminal vesicle junctionnd 2 mL (1 mL on each side) in the region of the prostaticpex. Infiltration was done transrectally through the workinghannel of the ultrasound probe using the outer sheath of an8-gauge Tru-Cut needle directed to the prostate-seminal vesicleunction. Fifteen minutes after infiltration, the biopsy was done.

The two groups were not different with respect to patientge, mean tPSA level, or mean biopsy duration (Table I). Theiopsy duration was defined as the period that elapsed be-ween the sampling of the first and last biopsy cores. One gram

TABLE I. Comparison between study groupsharacteristic Group 1 Group 2 P Value

atient age (yr) 0.750*Mean 63.7 64.2Range 50–87 48–83

PSA (ng/mL) 0.620*Mean 12.1 13.6Range 2.2–63.0 2.5–156.0iopsy duration (min) 0.850*Mean 6.2 6.1Range 5.0–11.0 5.0–10.0

atients with CaP (n) 35 (58) 21 (35) 0.010†AS pain score 0.860*Mean 1.26 1.23Range 0–3 0–3o. with VAS pain

score (%)0 13 (21.6) 8 (13.3) 0.340†1 24 (40) 36 (60) 0.045†2 16 (26.6) 10 (16.6) 0.270†3 7 (11.6) 6 (10) 1.000†

EY: tPSA � total prostate-specific antigen; CaP � prostate cancer; VAS � visualnalog scale.ata in parentheses are percentages.Student’s t test.Chi-square test.

f ceftriaxone was administered intramuscularly 30 minutes (

216

efore the biopsy followed by 400 mg/day of oral ofloxacineor an additional 48 hours.

The biopsy was performed in an outpatient setting, with theatient in the left lateral decubitus position. All biopsies wereerformed using the B&K Hawk ultrasound scanner with anndosonic multiplane 7.5-MHz transducer. The biopsy coresere taken using an automated spring-loaded 18-gauge nee-le. A total of 12 biopsy cores were obtained from all patientsn a systematic fashion.7 All patients were monitored for ap-roximately 15 minutes after the procedure, during whichhey graded the level of pain on a 10-point modified visualnalog scale (VAS), as previously reported.8

Patients were followed up for 1 month postoperatively, andll complications were recorded, including rectal bleeding,ematuria, urinary retention, vasovagal reaction, fever, hema-ospermia, and urinary tract infection.

Statistical analyses were performed using a computerizedoftware package (STATA, College Station, Tex). The cate-orical variables between the two groups were analyzedsing the chi-square test. The Student t test was used toompare the continuous variables between the two groups,nd the Kruskal-Wallis test was used for continuous andrdinal variables among more than two groups.

RESULTS

During the study period, 120 patients were en-olled: 60 each into groups 1 and 2. Table I details theistologic type and mean VAS pain scores. Althoughrostate cancer was more prevalent in group 1, apicalancer was more prevalent in group 2. Apical canceras present in 27 (77%) of 35 patients in group 1

nd 22 (81%) of 27 patients in group 2. However,he mean pain VAS score was not significantly dif-erent between groups 1 and 2. A malignant histo-ogic finding was not associated with increasedain (data not shown). No patient had a VAS paincore of 5 or more in either of these two groups.Table II details the results according to subcat-

gorization into different age groups within groupsand 2. Although no statistically significant differ-

nce was found in group 2 with respect to the meanAS pain score, this difference was significant inroup 1. Patients younger than 60 years old re-orted significantly more painful experience thanid older patients. When the mean VAS pain scores

TABLE II. Mean VAS score distributionamong age categories by study group

ean VASain Scorerange)

Age (yr)

<60 60–70 >70P

Value

roup 1 1.92 (0–3) 1.23 (0–2) 1.22 (0–2) 0.020(n � 24) (n � 19) (n � 17)

roup 2 1.72 (0–3) 1.43 (0–2) 1.21 (0–2) 0.358(n � 17) (n � 27) (n � 16)

value† 0.496 0.389 0.972

EY: VAS � visual analog scale.Kruskal-Wallis test.Student’s t test.

Student’s t test) in matched age categories in

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roup 1 were compared with those in group 2, notatistically significant difference was noted (youngerhan 60, 60 to 70, and older than 70 years) betweenhe two groups (Table II).

Minor and transient complications were observedn both groups. The complication rates did not dif-er between the two study groups (Table III). Weid not observe a single event of septicemia withhe antibiotic prophylaxis used.

COMMENT

TRUS-guided Tru-Cut prostate biopsy has stoodhe test of time in terms of effective cancer diagnosisnd acceptably low rates of side effects.9,10 Althoughell tolerated, it is associated with considerable painhen performed without anesthesia.9–13 Therefore,

ocal anesthesia is given by many physicians. Al-hough lidocaine (either in gel suspension [2%] or annjectable preparation [1%]) has generally beensed,7,14,15 other anesthetics, such as injectable arti-aine,6 have also been used, although rarely.Periprostatic nerve block with direct infiltration

f a local anesthetic agent does improve pain per-eption.5,6 In a previous study, we demonstratedhat intraanal and perianal lidocaine gel applica-ion did not improve the discomfort felt, and weeported a mean VAS score of around 4.8. As haslso been reported in another study, more than0% of our patients had moderate to intolerableain (VAS score of 5 or greater), stressing the needor effective anesthesia for transrectal biopsy.8 VAScores in the range of 3.29 to 4.59 have been re-orted when only intrarectal gel was applied.6owever, when periprostatic injectable local anes-

hesia was administered, the mean VAS scores de-reased dramatically to 0.76 to 1.85.5,6,14 Thesendings have clearly shown that periprostatic lido-aine infiltration is effective in providing analgesiauring Tru-Cut TRUS-guided prostate biopsy.As for the site and amount of anesthetic infiltra-

ion, a study using a placebo and six groups ofscalating doses of 1% lidocaine (2.5, 5, and 10L) infiltration revealed that the best pain reliefas obtained with 10 mL of lidocaine infiltrated

TABLE III. Complications of TRUS-guidedbiopsy

omplication Group 1 Group 2 P Value*

ematuria 18 (30) 17 (28.3) 0.824ematospermia 17 (28.3) 20 (33.3) 0.820lood in stool 13 (21.6) 15 (25) 0.575ever 0 (0) 0 (0) 1.000

EY: TRUS � transrectal ultrasound.ata presented as numbers of patients, with percentages in parentheses.Chi-square test.

olely at the neurovascular bundle region (single r

ROLOGY 68 (6), 2006

ite) or to the neurovascular bundle and apical re-ions (double site). The total delivered dose of li-ocaine was 10 mL and was unchanged in thetudy groups. In their six study groups, the trend ofmean VAS score reduction with increased anes-

hetic administered was steady, but no significantdditive pain relief was achieved when the totalose was equally divided to include additional peri-pical infiltration. Therefore, they recommended sin-le-site, 10-mL infiltration in the region of the neuro-ascular bundle.16

Various infiltration sites have been studied, in-luding the apex only,15,17 bilateral neurovascularundle regions only (defined variously as basolat-ral, posterolateral, periprostatic nerve plexus,rostate-vesicular junction injections),6,18,19 apexnd neurovascular bundle,15,16 three locationsbase, mid, and apex) posterolaterally,4 and lateralo the tip of the seminal vesicles.20 The prostaticapsule has been shown to involve rich autonomicnnervations conveying visceral pain to the spinalord through fibers that run with the vascularedicles21 and culminate in the inferior hypogas-ric plexus. Therefore, infiltration of the neurovas-ular bundle region seems essential for effectivenesthesia. However, apical infiltration alone haslso been reported to provide significant pain re-ief.15,17 In one study, pain relief with apical infil-ration alone was reported to be superior to infil-ration at the neurovascular bundle region.15

lthough it is difficult to rationalize, these investi-ators also suggested that apical injection reducedain perception in the areas near the prostatic baseegion by a retrograde effect.15

A recent study by Mutaguchi et al.,22 using a non-alidated tool that included a six-level question-aire, showed better pain control with intrapros-atic infiltration than with traditional periprostaticnjection. Thus, it would probably be better to per-orm more studies using an actual VAS and record-ng the method and intraprostatic injection site toonfidently compare the results within these newtudies with other published traditional peripros-atic injection studies using identical evaluationeasures.Investigators usually begin the prostate biopsy

pproximately 3 minutes after infiltration of therostate with 10 mL of local anesthetic (1% lido-aine) at the neurovascular bundle region,17,19

ith resultant mean VAS scores of 2.419 and 1.44.16

owever, in the present study, we waited for 15inutes after infiltration and were able to obtain a

etter mean VAS score of 1.26 (Table II), with al-ost one half the volume (6 mL) of lidocaine. WithmL of lidocaine infiltrated only at the neurovas-

ular bundle region, our VAS score was more than0% better than that (1.26 versus 2.76) previously

eported.16 We attribute this marked improvement

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o the interval between injection and biopsy.herefore, we recommend an approximately 15-inute delay between the local anesthetic infiltra-

ion and the actual prostate biopsy.Many investigators believe that a younger patient

ge predisposes to increased pain perception. In theuropean Prostate Cancer Detection Study, Djavant al.23 found significantly increased pain percep-ion during prostate biopsy in patients youngerhan 60 years when using no anesthesia. However,hen patients received local anesthesia, Kaver etl.24 found no difference in pain perception amonghree age groups (younger than 60, 60 to 70, andlder than 70 years). In our present and previoustudies,5 we obtained similar results, with patientsounger than 60 years reporting significantlyreater VAS scores. However, this statistically sig-ificant difference did not translate into a mean-

ngful clinical experience because the mean VAScore for all age groups was less than 2 in the lo-ally anesthetized patients. The explanation maye that younger patients experience prostate bi-psy as a more painful experience unless locallynesthetized.The prostate cancer diagnosis was significantly

ower (35% versus 58%) in group 2. According tohe study population characteristics, no discrimi-ation or selection bias was present in the tworoups. It might be possible that periapical infiltra-ion technically interfered with sampling, resultingn a lower yield of cancer detection. However, thisas not the case, because apical cancer was notore prevalent in group 1 (77%) compared with

roup 2 (81%).One study limitation was that periapical infiltra-

ion was not added to a fixed amount of peribasalidocaine infiltration. However, in the study byzden et al.,16 in which periapical injections were

dded to a fixed amount of peribasal injections, thenvestigators also failed to show any difference inain improvement.

CONCLUSIONS

Periprostatic infiltration with local anesthesiarovides better pain control that results in lowerain scores. Additional apical infiltration did noturther improve analgesia. However, evidence ob-ained by comparing the VAS scores in other stud-es with those of the present study has indicatedhat increasing the interval between anesthetic in-ltration and the biopsy procedure may further im-rove pain control.

ACKNOWLEDGMENT. To the staff of our department, Muallaurel, Miray Bayraktaroglu, and Erol Mut, for their kind ef-

orts and help, for which we are most grateful. 1

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REFERENCES1. Issa MM, Bux S, Chun T, et al: A randomized prospec-

ive trial of intrarectal lidocaine for pain control during trans-ectal prostate biopsy: the Emory University experience. J Urol64: 397–399, 2000.

2. Irani J, Fournier F, Bon D, et al: Patient tolerance ofransrectal ultrasound guided biopsy of the prostate. Br J Urol9: 608–610, 1997.

3. Desgrandchamps F, Meria P, Irani J, et al: The rectaldministration of lidocaine gel and tolerance of transrectalltrasonography-guided biopsy of the prostate: a prospectiveandomized placebo controlled study. Br J Urol 83: 1007–009, 1999.

4. Leibovici D, Zisman A, Siegel YI, et al: Local anesthesia forrostate biopsy by periprostatic lidocaine injection: a double-lind placebo controlled study. J Urol 167: 563–565, 2002.

5. Ozveri H, Cevik I, Dillioglugil O, et al: Transrectaleriprostatic lidocaine injection anesthesia for transrectalrostate biopsy: a prospective study. Prostate Cancer Prostaticis 6: 311–314, 2003.

6. von Knobloch R, Weber J, Varga Z, et al: Bilateral fineeedle administered local anesthetic nerve block for pain con-rol during TRUS-guided multi-core prostate biopsy: a pro-pective randomized trial. Eur Urol 41: 508–514, 2002.

7. Naughton CK, Miller DC, Mager DE, et al: A prospec-ive randomized trial comparing 6 versus 12 prostate biopsyores: impact on cancer detection. J Urol 164: 388–392, 2000.

8. Cevik I, Ozveri H, Dillioglugil O, et al: Lack of effect ofntrarectal lidocaine for pain control during transrectal pros-ate biopsy: a randomized prospective study. Eur Urol 42:17–220, 2002.

9. Collins GN, Lloyd SN, Hehir M, et al: Multiple trans-ectal ultrasound guided prostatic biopsies: true morbiditynd patient acceptance. Br J Urol 71: 460–463, 1993.

10. Clements R, Aideyan OU, Griffiths GJ, et al: Side effectsnd patient acceptability of transrectal biopsy of the prostate.lin Radiol 47: 125–126, 1993.11. Revell SI, Robinson JO, Rosen M, et al: The reliability oflinear analogue for evaluating pain. Anesthesia 31: 1191–

198, 1976.12. Scott J, and Huskisson EC: Graphic representation of

ain. Pain 2: 175–184, 1976.13. Issa MM, Ritenour C, Greenberger M, et al: The pros-

ate block for outpatient prostate surgery. World Urol 16:78–383, 1998.14. Berger AP, Frauscher F, Halpern EJ, et al: Peripros-

atic administration of local anesthesia during transrectalltrasound guided biopsy of the prostate: a randomized,ouble blind, placebo controlled study. Urology 61: 585–88, 2003.15. Schostak M, Christoph F, Müller M, et al: Optimizing

ocal anesthesia during 10-core biopsy of the prostate. Urology0: 253–257, 2002.16. Ozden E, Yaman O, Gögüs Ç, et al: The optimum doses

f and injection locations for periprostatic nerve blockade forransrectal ultrasound guided biopsy of the prostate: a pro-pective, randomized, placebo controlled study. J Urol 170:319–2322, 2003.17. Seymour H, Perry MJA, Lee-Eliot C, et al: Pain after trans-

ectal ultrasonography-guided prostate biopsy: the advantages oferiprostatic local anesthesia. BJU Int 88: 540–544, 2001.18. Addla SK, Adeyoju AAB, Wemyss-Holden GD, et al:

ocal anesthetic for transrectal ultrasound guided prostate bi-psy: a randomized, double blind, placebo controlled study.ur Urol 43: 441–443, 2003.19. Alavi AS, Soloway MS, Vaidya A, et al: Local anesthe-

ia for ultrasound guided prostate biopsy: a prospective,andomized trial comparing 2 methods. J Urol 166: 1343–

345, 2001.

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20. Wu CL, Carter HB, Naqibuddin M, et al: Effect of localnesthetics on patient recovery after transrectal biopsy. Urol-gy 57: 925–929, 2001.21. Hollabaugh RS Jr, Dmochowski RR, and Steiner MS: Neu-

oanatomy of male rhabdosphincter. Urology 49: 426–434, 1997.22. Mutaguchi K, Shinohara K, Matsubara A, et al: Local

nesthesia during 10 core biopsy of the prostate: comparison

f two methods. J Urol 173: 742–745, 2005. 4

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23. Djavan B, Waldert M, Zlotta A, et al: Safety and mor-idity of first and repeat transrectal ultrasound guided pros-ate needle biopsies: results of a prospective European prostateancer detection study. J Urol 166: 856–860, 2001.

24. Kaver I, Mabjeesh NJ, and Matzkin H: Randomized pro-pective study of periprostatic local anesthesia during trans-ectal ultrasound-guided prostate biopsy. Urology 59: 403–

08, 2002.

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