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Prospective Randomized Trial of Spinal Saddle Block Versus Periprostatic Lignocaine for Anesthesia During Transrectal Prostate Biopsy
Ambulatory and Office Urology Prospective Randomized Trial of Spinal Saddle Block Versus Periprostatic Lignocaine for Anesthesia During Transrectal Prostate Biopsy Anselm Okwudili Obi, Vincent Ugochukwu Okafor, and Paul Ikem Nnodi OBJECTIVE METHODS
RESULTS
CONCLUSIONS
To compare the efficacy and tolerability of spinal saddle block vs periprostatic lignocaine injection for anesthesia during transrectal prostate biopsy. A total of 75 patients were randomized to undergo prostate biopsy in 3 groups (n ⫽ 25). Group 1 had no anesthesia, group 2 had periprostatic lignocaine injection, and group 3 had spinal saddle block. All patients had sextant biopsy. The groups were assessed for pain, level of cooperativeness, willingness to have a repeat biopsy, complication rate, and the duration of the procedure. The mean age in the groups were, respectively, 65.0 (⫾5.7) (group 1), 65.5 (⫾9.3) (group 2), and 68.6 (⫾6.3) (group 3) years. There was no statistical difference between the groups with respect to age, prostate volume, number of biopsies taken, and the prostate-specific antigen. The mean visual analog score in the groups was, respectively, 5.7 (⫾2.3), 4.6 (⫾2.3) and 0.7 (⫾1.6) for groups 1-3. The difference between groups 1 and 2 was not statistically significant (P ⫽ .181), whereas the difference between groups 2 and 3 and groups 1 and 3 was highly statistically significant (P ⫽ .000). There were also highly statistically significant differences in levels of cooperativeness and duration of the procedure between group 3 and groups 1 and 2. The differences between the groups with respect to complication rates and willingness to have a repeat biopsy were not statistically significant. Spinal saddle block was a more effective method of anesthesia than periprostatic lignocaine. It did not sacrifice the current outpatient/day case setting for prostate biopsy. It could be offered routinely to patients undergoing prostate biopsy. UROLOGY 77: 280 –285, 2011. Crown Copyright © 2011 Published by Elsevier Inc.
P
rostate biopsy whether by the transrectal or transperineal route has evolved into the standard procedure for obtaining prostatic tissue for diagnosis of prostate cancer.1,2 Although the procedure is generally performed without any form of anesthesia because it is believed to be not or only mildly uncomfortable,2-4 several studies have shown that up to 19-30% of patients experience moderate to severe pain during prostate biopsy.1,5-7 The need for adequate anesthesia during prostate biopsy cannot be overemphasized. First, a large percentage of patients are biopsied these days based on screen-detected prostate-specific antigen (PSA) values and often repeat biopsies will be indicated in these patients despite initial negative histology. The degree of pain or discomfort felt in this group of patients is an important factor in determining whether they will accept
From the Departments of Urology and Anaesthesia, Federal Medical Centre, Abakaliki, Ebonyi, Nigeria Reprint requests: Dr. Anselm O. Obi, M.B.B.S., F.W.A.C.S., F.I.C.S., Urology Unit, Department of Surgery, Federal Medical Centre, Abakaliki, PMB 102, Abakaliki, Ebonyi State Nigeria. E-mail: [email protected] Submitted: April 29, 2010, accepted (with revisions): July 17, 2010
280
Crown Copyright © 2011 Published by Elsevier Inc. All Rights Reserved
repeat biopsies. Second, there has been a shift in the recent past from the standard sextant biopsy to a 10-12 core biopsy protocol to increase cancer detection rate. This extended biopsy protocol has been shown to be associated with increased pain, discomfort, and anxiety.8,9 Currently, there is no universally accepted method of anesthesia for prostate biopsy as evidenced by the numerous methods that have been tried and published in the literature.10-15 The ideal would be to have adequate analgesia without sacrificing the current day case or outpatient setting for prostate biopsy. Of the methods presently in use, periprostatic lignocaine appears to be the most popular. In this study, we compared the efficacy and tolerability of (low-dose) spinal saddle block vs periprostatic lignocaine injection. Although spinal saddle block is widely used for perineal surgeries, to the best of our knowledge it has never been properly evaluated as a means of anesthesia for prostate biopsy.
PATIENTS AND METHODS The study was carried out from the period January 2007 to December 2009. Seventy-five patients were randomized to un0090-4295/11/$36.00 doi:10.1016/j.urology.2010.07.468
dergo prostate biopsy in 3 different study groups. This number was made up of all eligible patients seen within the study period. Using an effect size of 0.8, a confidence interval of 95%, and a power of 80 returned a total required sample size of 42. Group 1 (n ⫽ 25) underwent biopsy without any form of pain relief. Group 2 (n ⫽ 25) had intrasphincteric and periprostatic lignocaine injection, and group 3 (n ⫽ 25) had spinal saddle block. Patients were allotted to groups using prelabeled envelopes to which the investigator was blinded. The indications for biopsy were a PSA ⬎4.0 ng/mL or a suspicious digital rectal examination (DRE). The DRE was considered suspicious for carcinoma of the prostate if the prostate was hard or nodular or the median sulcus was partially or completely effaced. All patients had an abridged 2-day bowel preparation consisting of low-residue diet, bisacodyl tablets 10 mg b.i.d., tab neomycin 1 g t.i.d., and tab metronidazole 400 mg t.i.d. The patients were administered intravenous ciprofloxacin 400 mg and intravenous metronidazole 500 mg 15 minutes before biopsy. All biopsies were carried out in the left lateral decubitus position using the spring loaded biopsy gun and an 18-G trucut needle. Six to eight cores of prostatic tissue were taken form the apex, midgland, and bases of both halves of the prostate, including any suspicious nodules. All biopsies were done by the consultant urologist. For the periprostatic lignocaine group, the patients were placed in the left lateral decubitus position and the anal sphincter was first infiltrated at 4 equidistant points along its circumference after putting it under a slight stretch. One percent lignocaine (2.5 mL) was injected at the 3, 6, 9, and 12 o’clock points using the needle of an 18-g cannula. This caused paralysis of the anal sphincter and allowed easy access to the prostate for the periprostatic lignocaine injection. The latter was carried out by injecting 2.5 mL of 1% lignocaine each at the base and apex of both sides of the prostate using the same size of needle. The technique for periprostatic lignocaine injection is well described elsewhere.10 The only difference with our technique is that we carried out a digitally-guided injection. We did not have the benefit of ultrasound guidance in administering the injection. Ultrasound guidance ensures that the lignocaine is deposited in the correct plane between the prostate and rectum to avoid intraprostatic injection. Intraprostatic injection would be associated with much resistance during the injection process. Care was taken to avoid intraprostatic injection in this study. Spinal saddle block was achieved in group 3 patients by injecting 0.5 mL, 0.5% bupivacaine in dextrose injection USP (equivalent to 2.5 mg bupivacaine) into the spinal subarachnoid space between L3/L4 vertebrae using a size 21 G spinal needle, with the patient in the sitting position and the spine arched forward (same as for spinal anesthesia). The patient was required to remain seated for up to 5-7 minutes after the injection to enable the bupivacaine to gravitate down and block the saddle region. After this, the patient was positioned in the left lateral decubitus position for biopsy. The patients were noticed to have complete paralysis of the anal sphincter without motor paralysis of the lower limbs. The saddle blocks were induced by an anesthetist. Patients in this group had their blood pressure measured before injection of bupivacaine and after completion of prostate biopsy. They were also assessed for presence or absence of neurological deficits and presence or absence of dizziness or spinal headache. UROLOGY 77 (2), 2011
Other parameters assessed in all the groups of patients were: ●
● ● ● ●
Pain score was assessed immediately after the procedure by a separate blinded observer using the visual analog scale (VAS), where 0 represents no pain at all and 10 represents the worst pain ever felt. 0 1 2 3 4 5 6 7 8 9 10 No pain worst pain Complications were documented immediately after the procedure and at 8 days follow-up in the outpatient department. Duration of the procedure (min) from induction of anesthesia to completion of biopsy was noted. Willingness to have a repeat biopsy was also assessed as a “yes or no” response. Patients cooperativeness during the procedure was assessed as “very cooperative,” “mildly cooperative,” or “uncooperative.” The number of body movements or groans signifying discomfort was used arbitrarily to determine the categories. If there were none at all, the patient was adjudged to be very cooperative. If there were 1-2, the patient was adjudged to be mildly cooperative, and if there were ⱖ3, the patient was classified as uncooperative. This assessment was also done by a separate observer blinded to the method of pain relief.
All patients were observed for 45-90 minutes, during which they were assessed for immediate complications; if there were none that warranted further stay in the hospital, they were discharged home. They were reviewed again after 8 days in the outpatient department for the presence or absence of delayed complications.
Exclusion Criteria We excluded all patients with chronic pain of any etiology, patients with neurological deficits resulting in decreased perineal or rectal sensation, and patients with known allergy to lidocaine or bupivacaine.
Statistical Analysis Statistical analysis was done using the SPSS version 15 statistical package (SPSS, Inc., Chicago, IL). Analysis of variance was performed on all measures with post-hoc analysis using the Bonferroni correction. P value ⬍.05 was considered significant. Effect size calculation was also used to determine significance in view of the sample size.
RESULTS There were 25 patients in each group for a total of 75 patients. The mean age in group 1 was 65.0 (⫾5.7) years. This was not statistically different from the mean ages in the other 2 groups as shown in Table 1. The prostate volume, number of biopsies taken, and PSA values in the 3 groups were also not statistically different (Table 1). Figure 1(A) shows the mean pain scores derived from the VAS for the 3 groups. Group 1 had a mean VAS of 5.7 (⫾2.3), whereas the values for groups 2 and 3 were 4.6 (⫾2.3) and 0.7 (⫾1.6), respectively. The difference in mean VAS between groups 1 and 2 was insignificant (P ⫽ .181), whereas the differences in mean VAS between groups 2 and 3 and groups 1 and 3 were highly statistically significant (P ⫽ .000). The effect size between groups 2 and 3 was greater than 0.8. 281
Table 1. Age, prostate volume, number of biopsies, PSA, and duration of procedure in the 3 treatment groups Reps Patients (n) Age Prostate volume No. of biopsies PSA (ng/ml) Duration of procedure (min)
Group 1 Mean (⫾SD)
Group 2 Mean (⫾SD)
Group 3 Mean (⫾SD)
Group 1 vs 2 P Value
Group 2 vs 3 P Value
Group 1 vs 3 P Value
25 65.0 (⫾5.7) 107.7 (⫾55.3) 6.5 (⫾0.7) 24.2 (⫾29.9) 18.8 (⫾2.7)
25 65.5 (⫾9.3) 113.5 (⫾62.6) 6.3 (⫾0.5) 31.1 (⫾36.4) 21.0 (⫾2.2)
25 68.6 (⫾6.3) 103.8 (⫾44.1) 6.4 (⫾0.7) 43.5 (⫾49.5) 26.8 (⫾2.7)
1.000 1.000 .808 1.000 .008
.429 1.000 1.000 .819 .000
.266 1.000 1.000 .272 .000
Figure 1. VAS scores (A) and level of cooperativeness (B) in the 3 treatment groups.
Figure 1(B) shows the level of cooperativeness between the groups. In group 3, 100% of the patients were very cooperative. However, in group 2, only 4 patients (16%) were very cooperative and the rest (21 (84%)) were mildly cooperative; none was uncooperative. In group 1, 28% were very cooperative, 56% were mildly cooperative, and 16% were uncooperative. The differences between groups 2 and 3 and between groups 1 and 3 were highly statistically significant (P ⫽ .000). However, the difference between groups 1 and 2 was not significant (P ⫽ 1.000). Figure 2(A) shows the complication rates in the groups. The complications noted in all the groups were rectal bleeding, urethral bleeding, hematuria, hematospermia, and urinary tract infection. None of the complications was severe enough to warrant hospital admis282
Figure 2. Histograms showing complication rates (A) and willingness to have a repeat biopsy (B) in the 3 treatment groups.
sion. Details of these will be presented as a separate report later. We assessed only the complication rate in this report. The complication rate in groups 1 and 2 were the same (56%) and this was higher than the complication rate of 24% seen in group 3. However the difference between groups 2 and 3 and groups 1 and 3 were not statistically significant (P ⫽ .067). Figure 2(B) shows the willingness to have a repeat biopsy. Group 3 had the highest number of patients willing to have a repeat biopsy (88%) compared with 72% in groups 1 and 2. The difference between groups 2 and 3 and groups 1 and 3 was not statistically significant (P ⫽ .548). With respect to duration of the procedure, in group 1 the procedure took a mean of 18.8 minutes compared UROLOGY 77 (2), 2011
Table 2. Pain scores in various lidocaine studies Study 16
Nambirajan et al Lee et al12 Kazuaki et Al10 Pareek et al17 Wu et al18 Schostak et al19 Inal et al20
No. of Patients
Method
Pain Score
48 49 99 66 21 44 25
NA 2 mL 1% periprostatic lignocaine Periprostatic injection of 10 mL 1% lignocaine 5 mL, 1% 5 mL, 1% 10 mL, 1% 6 mL
3.0 ⫾ 1.8 4.5 ⫾ 2.6 2.6 ⫾ 1.1 2.7 ⫾ 0.2 2.5 ⫾ 3.0 2.3 3.2 ⫾ 2.1
NA, not available.
with 21.0 minutes in group 2 and 26.8 minutes in group 3. The differences between the groups were statistically significant (P ⬍.05) (Table 1). Blood pressure (BP) changes were assessed only in group 3 patients. Only 3 of the 25 patients in the group had BP changes. This was observed in the systolic BP and ranged between ⫹5 mm Hg to ⫹10 mm Hg, with a mean BP change of 3 mm Hg. None of the group 3 patients complained of dizziness and there were no motor deficits in the lower limbs. Also none of the patients reported spinal headache.
COMMENT Despite claims to the contrary,21 Prostate biopsy has been shown by several studies to be associated with moderate to severe pain.1,5-7 This pain is attributed to ultrasound probe insertion and needle puncture into the prostate.11 This pain needs to be relieved adequately for several reasons. Topmost is the need to guarantee patient comfort. It also affords the operator the liberty to take as many biopsies as are required to increase the chances of making a diagnosis, especially in this era of extended biopsy protocols. Third, it is widely accepted that early detection by screening affords the only chance for cure, especially in patients with a life expectancy of more than 10 years. Several of these screening-based biopsies will need to be repeated because of an initial negative histology result. In a prostate cancer screening study by Djavan et al,22 820 (78%) of a total 1051 patients were negative for cancer at initial biopsy. Of this 820%, 90% were negative for cancer at the second biopsy. In similar prostate cancer screening studies by Catalona et al23 and Brawer et al,24 initial prostate biopsies were positive for cancer in only 22.6% and 30.5% of patients, respectively. Thus, we see that a high percentage of patients will often be required to undergo a repeat biopsy. In this subset of patients, the willingness to accept a repeat biopsy will be determined by the amount of pain and discomfort felt at the initial biopsy. In the study by Irani et al,5 6% of patients judged that the procedure should be carried out under general anesthesia and 19% of patients said they would not agree to undergo it again without some form of anesthesia. Collins et al6 and Clements et al7 similarly found the procedure to be painful in 22% and 30% of their patients, respectively. UROLOGY 77 (2), 2011
Various types of anesthesia have been used for prostate biopsy ranging from periprostatic and intraprostatic lignocaine10,12 to diclofenac suppository,11 intrarectal lignocaine gel,13,14 intrarectal 40% dimethyl sulfoxide,14 and intravenous sedation with propofol.15 The multitude of procedures shows that there is no universally accepted method. Of these procedures, periprostatic lignocaine appears to be the most popular. Pain associated with prostate biopsy arises from the prostatic capsule or stroma, where there is a rich innervation of autonomic fibers. These nerves are derived from the caudal roots of S2-S5 and the sympathetic chain via the presacral and hypogastric neural plexuses.25 Periprostatic lignocaine aims at anesthetizing these nerves. Several studies have shown that periprostatic lignocaine does not completely relieve the pain associated with prostate biopsy, as evidenced by the pain scores from these studies10,12,16-20 (Table 2). In our study, patients in the periprostatic lignocaine group had a relatively high mean VAS of 4.6, which is similar to the VAS of 4.5 obtained by Lee et al.12 The difference in mean VAS in this study between group 2 (VAS 4.6) and group 1 (VAS 5.7) was not statistically significant (P ⫽ .181). Similarly, the prospective, double-blind, placebocontrolled trial of Wu et al of periprostatic lignocaine vs sterile normal saline revealed no significant differences in pain scores between the control and treatment groups.18 Furthermore, concerns about the potential of increased infection and degree of operator variability associated with periprostatic lignocaine injection have been raised.16 Also the administration of periprostatic local anesthesia may result in fibrosis and interfere with nerve sparing radical prostatectomy.26 It has also been noted that local anesthesia may cause a mild stinging sensation when injected into the prostatic vascular pedicle, and incorrect injection in the midline into the external sphincter or urethra is painful.27 In our effort to obviate the obvious shortcomings of periprostatic lignocaine, we experimented with saddle block using only 0.5 mL, 0.5% bupivacaine in dextrose injection USP (2.5 mg bupivacaine). Saddle block has been shown to be nearly the ideal anesthesia technique for anorectal surgery.28 However, traditional saddle block using 0.8 mL or higher doses of bupivacaine causes motor paralyses of the lower limbs and systemic BP changes29,30 that would not be desirable for a day case procedure, such as prostate biopsy. Medhat et al29 have shown that peri283
anal anesthesia could be achieved at lower doses without lower limb motor paralysis. In our modified technique using only 0.5 mL bupivacaine, there was no limb paralysis and no significant blood pressure changes. The patient needs to remain seated for 5-7 minutes after the injection to ensure success of this technique. The pain score from our study was 0.7 for group 3 and this was highly statistically significant compared with a mean pain score of 4.5 for group 2 and 5.7 for group 1. An effect size of ⬎0.8 was observed between group 3 and 2. There was also a willingness to have a repeat biopsy; 88% of the bupivacaine group was willing to return for a repeat biopsy compared with 72% in both groups 1 and 2. The level of cooperativeness was 100% in group 3, whereas in group 2 only 16% were very cooperative and 84% were mildly cooperative. The complication rate was also lower, whereas only 24% of patients in group 3 had complications, the figure was 56% for groups 2 and 3. We believe that the complication rate has a bearing on the level of cooperativeness, which in turn has a bearing on the amount of pain felt during the procedure; the more the patients moved during the procedure the more the likelihood of traumatic complications. The mean duration of the procedure in the 3 groups were, respectively, 18.8 minutes, 21.0 minutes, and 26.8 minutes, for groups 1-3. Although this time differential was found to be statistically significant, the advantages observed in group 3 in terms of reduced pain score, reduced complication rates, increased patient cooperativeness, and willingness to have repeat biopsies far outweigh this. The possible drawbacks of low-dose spinal saddle block include the need for an anesthetist, the additional cost (US $4.0 [excluding anesthetists fees] vs US $2.0 for periprostatic lignocaine injection, per person per procedure). There may also be difficulty in finding the dural space, and there is a theoretical risk of introducing infection into the subarachnoid space (this should never occur if proper aseptic measures are taken.). Also there is the risk of developing postdural headache, although the incidence of the latter decreases with advancing age and should not be a major concern in this category of patients. These drawbacks have to be weighed against the obvious advantage of having definite anesthesia for prostate biopsy without significant hemodynamic or neurological deficits. The procedure is simple and can be easily learned and administered by a nurse anesthetist and even by the urologist in the private setting. In addition, there was no observed increase in postanesthesia care unit time because of the absence of hemodynamic or neurological deficits. The procedure could be adapted easily to the outpatient/office.
CONCLUSIONS This study demonstrates that prostate biopsy without any form of analgesia or anesthesia is associated with signif284
icant pain. It also demonstrates that periprostatic lignocaine does not completely relieve the pain associated with prostate biopsy. In contrast, spinal saddle block achieved highly statistically significant pain relief compared with periprostatic lignocaine. It was also associated with lower complication rates, higher levels of patient cooperativeness, and willingness to return for a repeat biopsy. It proved to be a more effective method of anesthesia and it does not sacrifice the current outpatient/day case setting for prostate biopsy. It could be offered routinely to all patients undergoing prostate biopsy. Acknowledgments. We acknowledge the help of Prof. Ndu Eke of the University of Port Harcourt Teaching Hospital, Nigeria in reading through the manuscript and offering invaluable suggestions and corrections. References 1. Crundwell MC, Cooke PW, Wallace DMA. Patients’ tolerance of transrectal ultrasound– guided prostatic biopsy: an audit of 104 cases. BJU Int. 1999;83:792-795. 2. Coley CM, Barry MJ, Fleming C, et al. Should Medicare provide reimbursement for prostate–specific antigen testing for early detection of prostate cancer?. part 11: Early detection strategies. Urology. 1995;46:125-136. 3. Desmond PM, Clark J, Thompson IM, et al. Morbidity with contemporary prostate biopsy. J Urol. 1993;150:1425-1426. 4. Hammerer P, Huland H. Systematic sextant biopsies in 651 patients referred for prostate evaluation. Urology. 1994;151:99-102. 5. Irani J, Fournier F, Bon D, et al. Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. Br J Urol. 1997;79:608610. 6. Collins GN, Lloyd SN, Hehir M, et al. Multiple transrectal ultrasound– guided prostatic biopsies: true morbidity and patient acceptance. Br J Urol. 1993;71:460-463. 7. Clements R, Aideyan OU, Griffiths GJ, et al. Side effects and patient acceptability of transrectal biopsy of the prostate. Clin Radiol. 1993;47:125-126. 8. Peyromaure M, Ravery V, Messas A, et al. Pain and morbidity of an extensive prostate 10-biopsy protocol; a prospective study in 289 patients. J Urol. 2002;167:218-221. 9. Zisman A, Leibovici D, Kleinsman J, et al. The impact of prostate biopsy on well being; A prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001;165:445. 10. Mutaguchi K, Shinohara K, Akio Matsubara, et al. Local anaesthesia during 10 core biopsy of the prostate: comparison of 2 methods. J Urol. 2005;173:742-745. 11. Haq A, Patel HRH, Habib MR, et al. Diclofenac suppository analgesia for transrectal ultrasound guided biopsies of the prostate: A double blind, Randomized Controlled Trial. J Urol. 2004;171: 1489-1491. 12. Lee HY, Lee HJ, Byun S-S, et al. Effect of intraprostatic Local anaesthesia during transrectal ultrasound guided prostate biopsy: comparison of 3 methods in a randomised, double blind, Placebo Controlled Trial. J Urol. 2007;178:469-472. 13. Naidoo A, Heyns CF, Aziz NA, et al. A prospective, randomized study of periprostatic lignocaine versus intrarectal lignocaine or placebo gel for pain relief during transrectal ultrasound (TRUS) guided needle biopsy of the prostate. African J Urol. 2006;12(2): 65-74. 14. Kravchick S, Peled R, David Ben-Dor, et al. Comparison of different local anaesthesia techniques during TRUS guided biopsies: A prospective pilot study. Urology. 2005;65(1):109-113. 15. Peters JL, Thompson AC, McNicholas TA, et al. Increased patient satisfaction from transrectal ultrasonography and biopsy under sedation. BJU Int. 2001;87:827-830.
UROLOGY 77 (2), 2011
16. Nambirajan T, Woolsey S, Mahendra V, et al. Efficacy and safety of periprostatic local anaesthetic injection in trans-rectal biopsy of the prostate: a prospective randomized study. Surg. 2004;2(4): 221-224. 17. Pareek G, Armenakas NA, Fracchia JA. Periprostatic nerve blockade for transrectal ultrasound guided biopsy of the prostate: a randomized double blind, placebo controlled study. J Urol. 2001; 166(3):894-897. 18. Wu CL, Carter HB, Naquibuddin M, et al. Effect of local anaesthetics on patient recovery after transrectal biopsy. Urology. 2001; 57:925-929. 19. Schostak M, Christopher F, Muller M, et al. Optimizing local anesthesia during 10-core biopsy of the prostate. Urology. 2002; 60(2):253-257. 20. Inal G, Yazici S, Adsan O, et al. Effect of periprostatic nerve blockade before transrectal ultrasound-guided prostate biopsy on patient comfort; a randomized placebo controlled study. Int J Urol. 2004;11(3):148-151. 21. Brawer MK, Chetner MP. Ultrasonography of the prostate and biopsy. In: Walsh PC, Retik AB, Vaughan ED Jr. Jr., et al, eds. Campbell’s Urology; 3 Philadelphia: W. B. Saunders; 1998;chapt 82,PP 2506-2518,1998. 22. Djavan B, Waldert M, Zlotta A, et al. Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies:
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results of a prospective European prostate cancer detection study. J Urol. 2001;166:856-860. William JC, Jerome PR, Frederick RA, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicentre clinical trial of 6,630 men. J Urol. 1994;151:1283-1290. Brawer MK, Chetner MP, Beatie J, et al. Screening for prostatic carcinoma with prostate specific antigen. J Urol. 1992;147:841-845. Nash PA, Jeremy EB, Indudhara R, et al. Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol. 1996;155:607-609. Klein EA, Zippe CD. Editorial: transrectal ultrasound guided prostate biopsy-defining a new standard. J Urol. 2000;163:179. Seymour H, Perry MJ, Lee-Elliot C, et al. Pain after transrectal ultrasonography-guided prostate biopsy: the advantages of periprostatic local anaesthesia. BJU Int. 2001;88:540. Schmittner MD, Schrieber H, Janke A, et al. Randomised clinical trial of perianal surgery performed under spinal saddle block versus total intravenous anaesthesia. Br J Surg. 2010;97(1):12-20. Medhat RW, Emil IM, Jeffery MR, et al. Spinal perianal block: A prospective randomised, double blind comparison with spinal saddle block. Anesth Analg. 2007;104:1594-1596. Tarkkila P, Huhtala J, Tuominen M. Home-readiness after spinal anaesthesia with small doses of hyperbaric. 0.5 % bupivacaine. J Anesth. 1997;52(12):1157-1160.
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RESULTS
CONCLUSIONS
To compare the efficacy and tolerability of spinal saddle block vs periprostatic lignocaine injection for anesthesia during transrectal prostate biopsy. A total of 75 patients were randomized to undergo prostate biopsy in 3 groups (n ⫽ 25). Group 1 had no anesthesia, group 2 had periprostatic lignocaine injection, and group 3 had spinal saddle block. All patients had sextant biopsy. The groups were assessed for pain, level of cooperativeness, willingness to have a repeat biopsy, complication rate, and the duration of the procedure. The mean age in the groups were, respectively, 65.0 (⫾5.7) (group 1), 65.5 (⫾9.3) (group 2), and 68.6 (⫾6.3) (group 3) years. There was no statistical difference between the groups with respect to age, prostate volume, number of biopsies taken, and the prostate-specific antigen. The mean visual analog score in the groups was, respectively, 5.7 (⫾2.3), 4.6 (⫾2.3) and 0.7 (⫾1.6) for groups 1-3. The difference between groups 1 and 2 was not statistically significant (P ⫽ .181), whereas the difference between groups 2 and 3 and groups 1 and 3 was highly statistically significant (P ⫽ .000). There were also highly statistically significant differences in levels of cooperativeness and duration of the procedure between group 3 and groups 1 and 2. The differences between the groups with respect to complication rates and willingness to have a repeat biopsy were not statistically significant. Spinal saddle block was a more effective method of anesthesia than periprostatic lignocaine. It did not sacrifice the current outpatient/day case setting for prostate biopsy. It could be offered routinely to patients undergoing prostate biopsy. UROLOGY 77: 280 –285, 2011. Crown Copyright © 2011 Published by Elsevier Inc.
P
rostate biopsy whether by the transrectal or transperineal route has evolved into the standard procedure for obtaining prostatic tissue for diagnosis of prostate cancer.1,2 Although the procedure is generally performed without any form of anesthesia because it is believed to be not or only mildly uncomfortable,2-4 several studies have shown that up to 19-30% of patients experience moderate to severe pain during prostate biopsy.1,5-7 The need for adequate anesthesia during prostate biopsy cannot be overemphasized. First, a large percentage of patients are biopsied these days based on screen-detected prostate-specific antigen (PSA) values and often repeat biopsies will be indicated in these patients despite initial negative histology. The degree of pain or discomfort felt in this group of patients is an important factor in determining whether they will accept
From the Departments of Urology and Anaesthesia, Federal Medical Centre, Abakaliki, Ebonyi, Nigeria Reprint requests: Dr. Anselm O. Obi, M.B.B.S., F.W.A.C.S., F.I.C.S., Urology Unit, Department of Surgery, Federal Medical Centre, Abakaliki, PMB 102, Abakaliki, Ebonyi State Nigeria. E-mail: [email protected] Submitted: April 29, 2010, accepted (with revisions): July 17, 2010
280
Crown Copyright © 2011 Published by Elsevier Inc. All Rights Reserved
repeat biopsies. Second, there has been a shift in the recent past from the standard sextant biopsy to a 10-12 core biopsy protocol to increase cancer detection rate. This extended biopsy protocol has been shown to be associated with increased pain, discomfort, and anxiety.8,9 Currently, there is no universally accepted method of anesthesia for prostate biopsy as evidenced by the numerous methods that have been tried and published in the literature.10-15 The ideal would be to have adequate analgesia without sacrificing the current day case or outpatient setting for prostate biopsy. Of the methods presently in use, periprostatic lignocaine appears to be the most popular. In this study, we compared the efficacy and tolerability of (low-dose) spinal saddle block vs periprostatic lignocaine injection. Although spinal saddle block is widely used for perineal surgeries, to the best of our knowledge it has never been properly evaluated as a means of anesthesia for prostate biopsy.
PATIENTS AND METHODS The study was carried out from the period January 2007 to December 2009. Seventy-five patients were randomized to un0090-4295/11/$36.00 doi:10.1016/j.urology.2010.07.468
dergo prostate biopsy in 3 different study groups. This number was made up of all eligible patients seen within the study period. Using an effect size of 0.8, a confidence interval of 95%, and a power of 80 returned a total required sample size of 42. Group 1 (n ⫽ 25) underwent biopsy without any form of pain relief. Group 2 (n ⫽ 25) had intrasphincteric and periprostatic lignocaine injection, and group 3 (n ⫽ 25) had spinal saddle block. Patients were allotted to groups using prelabeled envelopes to which the investigator was blinded. The indications for biopsy were a PSA ⬎4.0 ng/mL or a suspicious digital rectal examination (DRE). The DRE was considered suspicious for carcinoma of the prostate if the prostate was hard or nodular or the median sulcus was partially or completely effaced. All patients had an abridged 2-day bowel preparation consisting of low-residue diet, bisacodyl tablets 10 mg b.i.d., tab neomycin 1 g t.i.d., and tab metronidazole 400 mg t.i.d. The patients were administered intravenous ciprofloxacin 400 mg and intravenous metronidazole 500 mg 15 minutes before biopsy. All biopsies were carried out in the left lateral decubitus position using the spring loaded biopsy gun and an 18-G trucut needle. Six to eight cores of prostatic tissue were taken form the apex, midgland, and bases of both halves of the prostate, including any suspicious nodules. All biopsies were done by the consultant urologist. For the periprostatic lignocaine group, the patients were placed in the left lateral decubitus position and the anal sphincter was first infiltrated at 4 equidistant points along its circumference after putting it under a slight stretch. One percent lignocaine (2.5 mL) was injected at the 3, 6, 9, and 12 o’clock points using the needle of an 18-g cannula. This caused paralysis of the anal sphincter and allowed easy access to the prostate for the periprostatic lignocaine injection. The latter was carried out by injecting 2.5 mL of 1% lignocaine each at the base and apex of both sides of the prostate using the same size of needle. The technique for periprostatic lignocaine injection is well described elsewhere.10 The only difference with our technique is that we carried out a digitally-guided injection. We did not have the benefit of ultrasound guidance in administering the injection. Ultrasound guidance ensures that the lignocaine is deposited in the correct plane between the prostate and rectum to avoid intraprostatic injection. Intraprostatic injection would be associated with much resistance during the injection process. Care was taken to avoid intraprostatic injection in this study. Spinal saddle block was achieved in group 3 patients by injecting 0.5 mL, 0.5% bupivacaine in dextrose injection USP (equivalent to 2.5 mg bupivacaine) into the spinal subarachnoid space between L3/L4 vertebrae using a size 21 G spinal needle, with the patient in the sitting position and the spine arched forward (same as for spinal anesthesia). The patient was required to remain seated for up to 5-7 minutes after the injection to enable the bupivacaine to gravitate down and block the saddle region. After this, the patient was positioned in the left lateral decubitus position for biopsy. The patients were noticed to have complete paralysis of the anal sphincter without motor paralysis of the lower limbs. The saddle blocks were induced by an anesthetist. Patients in this group had their blood pressure measured before injection of bupivacaine and after completion of prostate biopsy. They were also assessed for presence or absence of neurological deficits and presence or absence of dizziness or spinal headache. UROLOGY 77 (2), 2011
Other parameters assessed in all the groups of patients were: ●
● ● ● ●
Pain score was assessed immediately after the procedure by a separate blinded observer using the visual analog scale (VAS), where 0 represents no pain at all and 10 represents the worst pain ever felt. 0 1 2 3 4 5 6 7 8 9 10 No pain worst pain Complications were documented immediately after the procedure and at 8 days follow-up in the outpatient department. Duration of the procedure (min) from induction of anesthesia to completion of biopsy was noted. Willingness to have a repeat biopsy was also assessed as a “yes or no” response. Patients cooperativeness during the procedure was assessed as “very cooperative,” “mildly cooperative,” or “uncooperative.” The number of body movements or groans signifying discomfort was used arbitrarily to determine the categories. If there were none at all, the patient was adjudged to be very cooperative. If there were 1-2, the patient was adjudged to be mildly cooperative, and if there were ⱖ3, the patient was classified as uncooperative. This assessment was also done by a separate observer blinded to the method of pain relief.
All patients were observed for 45-90 minutes, during which they were assessed for immediate complications; if there were none that warranted further stay in the hospital, they were discharged home. They were reviewed again after 8 days in the outpatient department for the presence or absence of delayed complications.
Exclusion Criteria We excluded all patients with chronic pain of any etiology, patients with neurological deficits resulting in decreased perineal or rectal sensation, and patients with known allergy to lidocaine or bupivacaine.
Statistical Analysis Statistical analysis was done using the SPSS version 15 statistical package (SPSS, Inc., Chicago, IL). Analysis of variance was performed on all measures with post-hoc analysis using the Bonferroni correction. P value ⬍.05 was considered significant. Effect size calculation was also used to determine significance in view of the sample size.
RESULTS There were 25 patients in each group for a total of 75 patients. The mean age in group 1 was 65.0 (⫾5.7) years. This was not statistically different from the mean ages in the other 2 groups as shown in Table 1. The prostate volume, number of biopsies taken, and PSA values in the 3 groups were also not statistically different (Table 1). Figure 1(A) shows the mean pain scores derived from the VAS for the 3 groups. Group 1 had a mean VAS of 5.7 (⫾2.3), whereas the values for groups 2 and 3 were 4.6 (⫾2.3) and 0.7 (⫾1.6), respectively. The difference in mean VAS between groups 1 and 2 was insignificant (P ⫽ .181), whereas the differences in mean VAS between groups 2 and 3 and groups 1 and 3 were highly statistically significant (P ⫽ .000). The effect size between groups 2 and 3 was greater than 0.8. 281
Table 1. Age, prostate volume, number of biopsies, PSA, and duration of procedure in the 3 treatment groups Reps Patients (n) Age Prostate volume No. of biopsies PSA (ng/ml) Duration of procedure (min)
Group 1 Mean (⫾SD)
Group 2 Mean (⫾SD)
Group 3 Mean (⫾SD)
Group 1 vs 2 P Value
Group 2 vs 3 P Value
Group 1 vs 3 P Value
25 65.0 (⫾5.7) 107.7 (⫾55.3) 6.5 (⫾0.7) 24.2 (⫾29.9) 18.8 (⫾2.7)
25 65.5 (⫾9.3) 113.5 (⫾62.6) 6.3 (⫾0.5) 31.1 (⫾36.4) 21.0 (⫾2.2)
25 68.6 (⫾6.3) 103.8 (⫾44.1) 6.4 (⫾0.7) 43.5 (⫾49.5) 26.8 (⫾2.7)
1.000 1.000 .808 1.000 .008
.429 1.000 1.000 .819 .000
.266 1.000 1.000 .272 .000
Figure 1. VAS scores (A) and level of cooperativeness (B) in the 3 treatment groups.
Figure 1(B) shows the level of cooperativeness between the groups. In group 3, 100% of the patients were very cooperative. However, in group 2, only 4 patients (16%) were very cooperative and the rest (21 (84%)) were mildly cooperative; none was uncooperative. In group 1, 28% were very cooperative, 56% were mildly cooperative, and 16% were uncooperative. The differences between groups 2 and 3 and between groups 1 and 3 were highly statistically significant (P ⫽ .000). However, the difference between groups 1 and 2 was not significant (P ⫽ 1.000). Figure 2(A) shows the complication rates in the groups. The complications noted in all the groups were rectal bleeding, urethral bleeding, hematuria, hematospermia, and urinary tract infection. None of the complications was severe enough to warrant hospital admis282
Figure 2. Histograms showing complication rates (A) and willingness to have a repeat biopsy (B) in the 3 treatment groups.
sion. Details of these will be presented as a separate report later. We assessed only the complication rate in this report. The complication rate in groups 1 and 2 were the same (56%) and this was higher than the complication rate of 24% seen in group 3. However the difference between groups 2 and 3 and groups 1 and 3 were not statistically significant (P ⫽ .067). Figure 2(B) shows the willingness to have a repeat biopsy. Group 3 had the highest number of patients willing to have a repeat biopsy (88%) compared with 72% in groups 1 and 2. The difference between groups 2 and 3 and groups 1 and 3 was not statistically significant (P ⫽ .548). With respect to duration of the procedure, in group 1 the procedure took a mean of 18.8 minutes compared UROLOGY 77 (2), 2011
Table 2. Pain scores in various lidocaine studies Study 16
Nambirajan et al Lee et al12 Kazuaki et Al10 Pareek et al17 Wu et al18 Schostak et al19 Inal et al20
No. of Patients
Method
Pain Score
48 49 99 66 21 44 25
NA 2 mL 1% periprostatic lignocaine Periprostatic injection of 10 mL 1% lignocaine 5 mL, 1% 5 mL, 1% 10 mL, 1% 6 mL
3.0 ⫾ 1.8 4.5 ⫾ 2.6 2.6 ⫾ 1.1 2.7 ⫾ 0.2 2.5 ⫾ 3.0 2.3 3.2 ⫾ 2.1
NA, not available.
with 21.0 minutes in group 2 and 26.8 minutes in group 3. The differences between the groups were statistically significant (P ⬍.05) (Table 1). Blood pressure (BP) changes were assessed only in group 3 patients. Only 3 of the 25 patients in the group had BP changes. This was observed in the systolic BP and ranged between ⫹5 mm Hg to ⫹10 mm Hg, with a mean BP change of 3 mm Hg. None of the group 3 patients complained of dizziness and there were no motor deficits in the lower limbs. Also none of the patients reported spinal headache.
COMMENT Despite claims to the contrary,21 Prostate biopsy has been shown by several studies to be associated with moderate to severe pain.1,5-7 This pain is attributed to ultrasound probe insertion and needle puncture into the prostate.11 This pain needs to be relieved adequately for several reasons. Topmost is the need to guarantee patient comfort. It also affords the operator the liberty to take as many biopsies as are required to increase the chances of making a diagnosis, especially in this era of extended biopsy protocols. Third, it is widely accepted that early detection by screening affords the only chance for cure, especially in patients with a life expectancy of more than 10 years. Several of these screening-based biopsies will need to be repeated because of an initial negative histology result. In a prostate cancer screening study by Djavan et al,22 820 (78%) of a total 1051 patients were negative for cancer at initial biopsy. Of this 820%, 90% were negative for cancer at the second biopsy. In similar prostate cancer screening studies by Catalona et al23 and Brawer et al,24 initial prostate biopsies were positive for cancer in only 22.6% and 30.5% of patients, respectively. Thus, we see that a high percentage of patients will often be required to undergo a repeat biopsy. In this subset of patients, the willingness to accept a repeat biopsy will be determined by the amount of pain and discomfort felt at the initial biopsy. In the study by Irani et al,5 6% of patients judged that the procedure should be carried out under general anesthesia and 19% of patients said they would not agree to undergo it again without some form of anesthesia. Collins et al6 and Clements et al7 similarly found the procedure to be painful in 22% and 30% of their patients, respectively. UROLOGY 77 (2), 2011
Various types of anesthesia have been used for prostate biopsy ranging from periprostatic and intraprostatic lignocaine10,12 to diclofenac suppository,11 intrarectal lignocaine gel,13,14 intrarectal 40% dimethyl sulfoxide,14 and intravenous sedation with propofol.15 The multitude of procedures shows that there is no universally accepted method. Of these procedures, periprostatic lignocaine appears to be the most popular. Pain associated with prostate biopsy arises from the prostatic capsule or stroma, where there is a rich innervation of autonomic fibers. These nerves are derived from the caudal roots of S2-S5 and the sympathetic chain via the presacral and hypogastric neural plexuses.25 Periprostatic lignocaine aims at anesthetizing these nerves. Several studies have shown that periprostatic lignocaine does not completely relieve the pain associated with prostate biopsy, as evidenced by the pain scores from these studies10,12,16-20 (Table 2). In our study, patients in the periprostatic lignocaine group had a relatively high mean VAS of 4.6, which is similar to the VAS of 4.5 obtained by Lee et al.12 The difference in mean VAS in this study between group 2 (VAS 4.6) and group 1 (VAS 5.7) was not statistically significant (P ⫽ .181). Similarly, the prospective, double-blind, placebocontrolled trial of Wu et al of periprostatic lignocaine vs sterile normal saline revealed no significant differences in pain scores between the control and treatment groups.18 Furthermore, concerns about the potential of increased infection and degree of operator variability associated with periprostatic lignocaine injection have been raised.16 Also the administration of periprostatic local anesthesia may result in fibrosis and interfere with nerve sparing radical prostatectomy.26 It has also been noted that local anesthesia may cause a mild stinging sensation when injected into the prostatic vascular pedicle, and incorrect injection in the midline into the external sphincter or urethra is painful.27 In our effort to obviate the obvious shortcomings of periprostatic lignocaine, we experimented with saddle block using only 0.5 mL, 0.5% bupivacaine in dextrose injection USP (2.5 mg bupivacaine). Saddle block has been shown to be nearly the ideal anesthesia technique for anorectal surgery.28 However, traditional saddle block using 0.8 mL or higher doses of bupivacaine causes motor paralyses of the lower limbs and systemic BP changes29,30 that would not be desirable for a day case procedure, such as prostate biopsy. Medhat et al29 have shown that peri283
anal anesthesia could be achieved at lower doses without lower limb motor paralysis. In our modified technique using only 0.5 mL bupivacaine, there was no limb paralysis and no significant blood pressure changes. The patient needs to remain seated for 5-7 minutes after the injection to ensure success of this technique. The pain score from our study was 0.7 for group 3 and this was highly statistically significant compared with a mean pain score of 4.5 for group 2 and 5.7 for group 1. An effect size of ⬎0.8 was observed between group 3 and 2. There was also a willingness to have a repeat biopsy; 88% of the bupivacaine group was willing to return for a repeat biopsy compared with 72% in both groups 1 and 2. The level of cooperativeness was 100% in group 3, whereas in group 2 only 16% were very cooperative and 84% were mildly cooperative. The complication rate was also lower, whereas only 24% of patients in group 3 had complications, the figure was 56% for groups 2 and 3. We believe that the complication rate has a bearing on the level of cooperativeness, which in turn has a bearing on the amount of pain felt during the procedure; the more the patients moved during the procedure the more the likelihood of traumatic complications. The mean duration of the procedure in the 3 groups were, respectively, 18.8 minutes, 21.0 minutes, and 26.8 minutes, for groups 1-3. Although this time differential was found to be statistically significant, the advantages observed in group 3 in terms of reduced pain score, reduced complication rates, increased patient cooperativeness, and willingness to have repeat biopsies far outweigh this. The possible drawbacks of low-dose spinal saddle block include the need for an anesthetist, the additional cost (US $4.0 [excluding anesthetists fees] vs US $2.0 for periprostatic lignocaine injection, per person per procedure). There may also be difficulty in finding the dural space, and there is a theoretical risk of introducing infection into the subarachnoid space (this should never occur if proper aseptic measures are taken.). Also there is the risk of developing postdural headache, although the incidence of the latter decreases with advancing age and should not be a major concern in this category of patients. These drawbacks have to be weighed against the obvious advantage of having definite anesthesia for prostate biopsy without significant hemodynamic or neurological deficits. The procedure is simple and can be easily learned and administered by a nurse anesthetist and even by the urologist in the private setting. In addition, there was no observed increase in postanesthesia care unit time because of the absence of hemodynamic or neurological deficits. The procedure could be adapted easily to the outpatient/office.
CONCLUSIONS This study demonstrates that prostate biopsy without any form of analgesia or anesthesia is associated with signif284
icant pain. It also demonstrates that periprostatic lignocaine does not completely relieve the pain associated with prostate biopsy. In contrast, spinal saddle block achieved highly statistically significant pain relief compared with periprostatic lignocaine. It was also associated with lower complication rates, higher levels of patient cooperativeness, and willingness to return for a repeat biopsy. It proved to be a more effective method of anesthesia and it does not sacrifice the current outpatient/day case setting for prostate biopsy. It could be offered routinely to all patients undergoing prostate biopsy. Acknowledgments. We acknowledge the help of Prof. Ndu Eke of the University of Port Harcourt Teaching Hospital, Nigeria in reading through the manuscript and offering invaluable suggestions and corrections. References 1. Crundwell MC, Cooke PW, Wallace DMA. Patients’ tolerance of transrectal ultrasound– guided prostatic biopsy: an audit of 104 cases. BJU Int. 1999;83:792-795. 2. Coley CM, Barry MJ, Fleming C, et al. Should Medicare provide reimbursement for prostate–specific antigen testing for early detection of prostate cancer?. part 11: Early detection strategies. Urology. 1995;46:125-136. 3. Desmond PM, Clark J, Thompson IM, et al. Morbidity with contemporary prostate biopsy. J Urol. 1993;150:1425-1426. 4. Hammerer P, Huland H. Systematic sextant biopsies in 651 patients referred for prostate evaluation. Urology. 1994;151:99-102. 5. Irani J, Fournier F, Bon D, et al. Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. Br J Urol. 1997;79:608610. 6. Collins GN, Lloyd SN, Hehir M, et al. Multiple transrectal ultrasound– guided prostatic biopsies: true morbidity and patient acceptance. Br J Urol. 1993;71:460-463. 7. Clements R, Aideyan OU, Griffiths GJ, et al. Side effects and patient acceptability of transrectal biopsy of the prostate. Clin Radiol. 1993;47:125-126. 8. Peyromaure M, Ravery V, Messas A, et al. Pain and morbidity of an extensive prostate 10-biopsy protocol; a prospective study in 289 patients. J Urol. 2002;167:218-221. 9. Zisman A, Leibovici D, Kleinsman J, et al. The impact of prostate biopsy on well being; A prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001;165:445. 10. Mutaguchi K, Shinohara K, Akio Matsubara, et al. Local anaesthesia during 10 core biopsy of the prostate: comparison of 2 methods. J Urol. 2005;173:742-745. 11. Haq A, Patel HRH, Habib MR, et al. Diclofenac suppository analgesia for transrectal ultrasound guided biopsies of the prostate: A double blind, Randomized Controlled Trial. J Urol. 2004;171: 1489-1491. 12. Lee HY, Lee HJ, Byun S-S, et al. Effect of intraprostatic Local anaesthesia during transrectal ultrasound guided prostate biopsy: comparison of 3 methods in a randomised, double blind, Placebo Controlled Trial. J Urol. 2007;178:469-472. 13. Naidoo A, Heyns CF, Aziz NA, et al. A prospective, randomized study of periprostatic lignocaine versus intrarectal lignocaine or placebo gel for pain relief during transrectal ultrasound (TRUS) guided needle biopsy of the prostate. African J Urol. 2006;12(2): 65-74. 14. Kravchick S, Peled R, David Ben-Dor, et al. Comparison of different local anaesthesia techniques during TRUS guided biopsies: A prospective pilot study. Urology. 2005;65(1):109-113. 15. Peters JL, Thompson AC, McNicholas TA, et al. Increased patient satisfaction from transrectal ultrasonography and biopsy under sedation. BJU Int. 2001;87:827-830.
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