INTRARECTAL LIDOCAINE DURING TRANSRECTAL PROSTATE BIOPSY: RESULTS OF A PROSPECTIVE DOUBLE-BLIND RANDOMIZED TRIAL

0022-5347/01/1666-2178/0 THE JOURNAL OF UROLOGY® Copyright © 2001 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 166, 2178 –2180, December 2001 Printed in U.S.A.

INTRARECTAL LIDOCAINE DURING TRANSRECTAL PROSTATE BIOPSY: RESULTS OF A PROSPECTIVE DOUBLE-BLIND RANDOMIZED TRIAL SAM S. CHANG,* GREGORY ALBERTS, NANCY WELLS, JOSEPH A. SMITH, JR.† MICHAEL S. COOKSON‡

AND

From the Departments of Urologic Surgery and Patient Care Services, Vanderbilt University Medical Center, Nashville, Tennessee

ABSTRACT

Purpose: Recent reports have indicated the benefit of anesthesia during prostate biopsy. To assess this finding objectively we performed a prospective randomized double-blind study to compare patient pain with and without local anesthesia during transrectal ultrasound guided prostate biopsies. Materials and Methods: Between August 2000 and March 2001, 108 men undergoing transrectal ultrasound guided biopsy of the prostate were randomized in double-blind fashion to receive intrarectal 2% lidocaine gel or intrarectal lubricant alone. No patient received preprocedure narcotics or sedation. Pain associated with biopsy was determined using a horizontal linear visual analog pain scale. Pain scores in the 2 treatment groups were compared and possible predictors of increased pain were examined. Results: The 2 groups were similar in demographic characteristics. There was no significant difference in pain score in the 2% lidocaine and lubricant alone groups (28.3 versus 28.9 mm., p ⫽ 0.88). Previous biopsy, time since previous biopsy, physician, number of biopsies and prostate volume did not correlate with pain score, while age correlated negatively with the score (r ⫽ ⫺0.27, p ⫽ 0.005). A single complication involving a vasovagal episode resolved spontaneously. Conclusions: Intrarectal lidocaine gel provides no significant therapeutic or analgesic benefit compared with lubricant alone for transrectal ultrasound guided biopsy of the prostate. In younger patients more discomfort is associated with this procedure. KEY WORDS: prostate, biopsy, lidocaine, pain

Transrectal ultrasound biopsy of the prostate is the most common method of evaluating and diagnosing prostate cancer. Currently urologists perform most of these procedures in the clinic without patient analgesia. Recently various forms of anesthesia, including lidocaine injection1–3 and intrarectal lidocaine gel,2, 4 have been reported as effective ways to decrease patient pain during transrectal ultrasound guided prostate biopsy. However, in these studies subjective measures of pain were used and/or physicians were not blinded to the type of anesthesia. In addition, to our knowledge patient characteristics such as age or previous biopsies that may affect the patient level of pain perception have not been previously examined. In a double-blind randomized prospective trial we compared the pain scores of intrarectal 2% lidocaine gel versus lubricant gel alone and evaluated the anesthetic effectiveness of lidocaine. We also evaluated patient characteristics that may impact the degree of pain. MATERIALS AND METHODS

During an 8-month period 108 men underwent transrectal ultrasound biopsy of the prostate. Indications for biopsy included elevated serum prostate specific antigen, abnormal digital rectal examination and/or a history of high grade prostatic intraepithelial neoplasia. Patients currently on any

oral narcotic medication were excluded from study to avoid interference with pain evaluation. After a history was obtained and physical examination was done patients were randomly assigned to a group that received 10 cc 2% lidocaine gel or 10 cc lubricant gel intrarectally. Patients were placed in the lateral decubitus position with the knees and hips flexed. Lubricant only or 2% lidocaine gel was carefully instilled into the rectal vault for 10 minutes. A 7 MHz. ultrasound probe was used to examine and measure the whole prostate. Routinely, at least 8 biopsy cores were obtained from the prostate with an automatic spring loaded biopsy gun and 20 gauge needle. Additional samples were obtained when areas of concern were noted on ultrasound and/or biopsy was suboptimal. Before biopsy and for 2 days afterward patients received oral quinolone antibiotics. Within 2 minutes of procedure completion patients were asked to grade the pain associated with the ultrasound/biopsy experience on a horizontal visual analog pain scale (fig. 1). Each patient was questioned during followup regarding complications 10 to 15 days after transrectal ultrasound biopsy. Any complications were recorded. The chi-square and Student t tests as well as Pearson’s r analysis were performed to compare groups using commercially available software with p ⬍0.05 considered significant. The study was

Accepted for publication July 27, 2001. * Financial interest and/or other relationship with TAP Pharmaceuticals, Amgen, Ilex, Schering, Intracel and Shire. † Financial interest and/or other relationship with Glaxo, Praeces, Astra-Zeneca, TAP Pharmaceuticals, Abbott Laboratories, Anthina and Pharmacia. ‡ Financial interest and/or other relationship with TAP Pharmaceuticals, Schering Plough, Intracel, Praecis and Abbott Laboratories. 2178

FIG. 1. Horizontal visual analog pain scale used

INTRARECTAL LIDOCAINE FOR PROSTATE BIOPSY

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powered at 0.8 to detect a 10 mm. difference in the pain score with an effect size of 0.51. RESULTS

A total of 108 men 53 to 84 years old (mean age plus or minus standard deviation 69 ⫾ 6.01, median 68) met study inclusion criteria, including 93 (77%) who underwent initial biopsy and 25 who had undergone 1 to 3 previous biopsies 2 to 166 months before the study procedure. We obtained 8 to 13 biopsies per case. Digital rectal examination was normal in 92 men (85%). Pathological findings were normal in 76 cases (70%), 17 (16%) involved malignancy and 15 (14%) involved high grade prostatic intraepithelial neoplasia. Prostate volume was 18 to 73.6 cc (mean 28.8 ⫾ 13.42, median 24). Two physicians performed the biopsies. Of the patients 52 and 56 were randomized to receive lubricating lubricant gel and 2% lidocaine gel, respectively, before biopsy. No significant differences were noted on chi-square analysis in the 2 groups based on physician performing biopsy, history of biopsy (yes/no), normal/abnormal digital rectal examination or pathological results. The groups were similar in terms of age, number of biopsies and prostate volume (see table). Student’s t test revealed no significant difference in the level of pain reported (t (106) ⫽ 0.15, p ⫽ 0.88). Mean pain scores and variability were similar in patients randomized to lubricant alone and 2% lidocaine gel (28.9 ⫾ 20.9 and 28.3 ⫾ 18.9 mm., respectively, fig. 2). Pearson’s r was used to assess the correlation of pain with interval level variables. No significant correlation was observed of pain with the number of biopsies obtained, history of biopsy, time since the previous biopsy or prostate volume. Pain negatively correlated with age (r ⫽ ⫺0.27, p ⫽ 0.005), indicating a higher level of pain at younger ages. A single patient in the lidocaine group had a brief vasovagal episode while still on the biopsy table, which resolved spontaneously within several minutes and without sequelae. No other adverse events were associated with biopsy in either treatment group. A followup telephone call at 2 weeks confirmed no other complications. DISCUSSION

Transrectal ultrasound and biopsy of the prostate have been commonly performed in the office setting for more than 10 years and yet no standard anesthetic protocol has been established. At our institution intravenous sedation and/or lidocaine injection is not commonly administered, nor do we administer intrarectal lidocaine gel since there is no consensus on its effectiveness. Like others, we have observed that patients tolerate the procedure well without anesthesia.5, 6 In this prospective double-blind study we identified no significant difference in the pain score for lidocaine gel and lubricant gel alone.

Patient characteristics and pain scores Lubricant Gel No. pts. Av. age No. previous biopsy: Yes No Mean serum PSA (ng./ml.): No. digital rectal examination: Normal Abnormal Mean No. biopsies No. pathological findings: Neg. Pos. Mean prostate vol. (gm.) Mean pain score (mm.)

Lidocaine

52 68

56 69.4

14 38 3.8

11 45 3.9

44 8 9.96

48 8 10

36 15 27.5 28.9

40 11 30 28.3

p Value 0.23 0.49 ⬎0.1 1 0.71 0.49 0.34 0.88

FIG. 2. Pain score comparison in lubricant (KY) only and 2% lidocaine gel groups.

It is commonly accepted that the visual analog scale is the best instrument for assessing pain intensity. It is independent of language after instruction, provides a sensitive measure and enables statistical comparison.7, 8 The mean pain score in the lidocaine and lubricant only groups (28.3 versus 28.9 mm.) would be considered mild if used for analysis of postoperative analgesia, while a score of greater than 50 mm. would be considered moderate to severe.9 Although the finding was not statistically different, more patients in the lidocaine group had a pain score of greater than 50 compared with the lubricant gel group (10 of 55 or 17.9% versus 6 of 52 or 11.5%). Desgrandchamps et al also did not note that patients who received lubricant alone were more likely to have moderate or severe pain.4 Although our number of patients was modest, our cohort size compares favorably with that in previous studies. Our study was powered to ascertain a 10 mm. difference in the visual analog scale, which is a slight difference considering that others have previously determined that a 20 mm. difference is the minimum statistical value correlating with clinical significance.10 Thus, despite small sample size it is statistically unlikely that chance alone explains the lack of benefit from intrarectal 2% lidocaine. Recently Issa et al from Emory University recommended the routine administration of 2% lidocaine gel due to a significant difference in the median pain score compared with placebo jelly.2 Our conclusions differ, perhaps for several reasons. A key difference was the type of pain scale used. Instead of a 10-point linear visual analog scale we used a linear scale without numbers that avoids limiting the discriminating ability of a numbered scale. Scott and Huskisson believed that numbers superimposed on a visual analog scale interfere with the distribution of results.8 Also, our study was double-blind. No physician bias influenced the determination of anesthetic efficacy or lack of efficacy of either treatment modality. Furthermore, Issa et al excluded patients with a history of biopsy, which represents an important population that continues to increase.3 In fact, in our series regardless of the time since biopsy, that group did not have a significantly different pain experience when given intrarectal lidocaine or lubricant gel at repeat biopsy. Recent data imply that increasing the number of biopsies does not necessarily increase the pain associated with the procedure.11 Although in our study 8 to 13 biopsies were

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INTRARECTAL LIDOCAINE FOR PROSTATE BIOPSY

done, we also noted no correlation of the number of biopsies with the pain score, nor did we detect a correlation of physician, prostate volume, prostate specific antigen, clinical examination or pathological findings with the score. However, we determined that age independently had a significant effect on pain perception. Younger patients had significantly more pain than older patients regardless of 2% lidocaine gel or lubricant alone (p ⫽ 0.005). Therefore, younger patients are likely to benefit from some type of anesthesia. Due to the number of patients in our study we did not statistically determine a specific age cutoff for those with more pain. As an increasing number of biopsies are performed, identifying effective anesthesia becomes more important. Others have advocated intraprostatic block by injection with anesthetic agents such as lidocaine.1, 3 However, the pain decreasing capability of intraprostatic or periprostatic injection has not been universally confirmed.12 In addition, injection must be done after placing the transrectal ultrasound probe without anesthetic and many patients complain that this discomfort is worse than needle biopsy. Thus, at this point the most effective anesthesia during prostate biopsy remains unclear and requires more study. Our findings do not support the use of intrarectal lidocaine gel as an anesthesia during transrectal ultrasound guided biopsy. It did not show any benefit in our patients and only adds cost to this procedure compared with lubricant gel only. Our data confirm that this procedure can be done safely in the clinical setting. A single patient had a vasovagal episode with bradycardia (pulse 52 beats per minute) and hypotension (87/50 mm. Hg) but did not lose consciousness and recovered completely within minutes. There were no complications, such as sepsis, urinary retention, significant bleeding or clot retention, within 2 weeks after biopsy. CONCLUSIONS

Transrectal ultrasound and standard biopsy of the prostate can be safely and effectively performed in the clinical setting. Compared with lubricant gel alone intrarectal 2% lidocaine gel offers no anesthetic benefit to patients. Younger patients experience significantly more pain during transrectal ultra-

sound guided biopsy. Further studies are needed to identify the most effective strategy for decreasing pain in all patients who undergo this procedure. REFERENCES

1. Nash, P. A., Bruce, J. E., Indudhara, R. et al: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol, 155: 607, 1996 2. Issa, M. M., Bux, S., Chun, T. et al: A randomized prospective trial of intrarectal lidocaine for pain control during transrectal prostate biopsy: the Emory University experience. J Urol, 164: 397, 2000 3. Soloway, M. S. and Obek, C.: Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol, 163: 172, 2000 4. Desgrandchamps, F., Meria, P., Irani, J. et al: The rectal administration of lidocaine gel and tolerance of transrectal ultrasonagraphy-guided biopsy of the prostate. BJU Int, 83: 1007, 1999 5. Clements, R., Aideyan, O. U., Griffiths, G. J. et al: Side effects and patient acceptability of transrectal biopsy of the prostate. Clin Radiol, 47: 125, 1993 6. Irani, J., Fournier, F., Bon, D. et al: Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. Br J Urol, 79: 608, 1997 7. Herr, K. A. and Mobily, P. R.: Comparison of selected pain assessment tools for use with the elderly. Appl Nursing Res, 6: 39, 1993 8. Scott, J. and Huskisson, E. C.: Graphic representation of pain. Pain, 2: 175, 1976 9. Slappendel, R., Weber, E. W., Bugter, M. L. et al: The intensity of preoperative pain is directly correlated with the amount of morphine needed for postoperative analgesia. Anesth Analg, 88: 146, 1999 10. Farrar, J. T., Portenoy, R. K., Berlin, J. A. et al: Defining the clinically important differences in pain outcome measures. Pain, 88: 287, 2000 11. Naughton, C. K., Ornstein, D. K., Smith, D. S. et al: Pain and morbidity of transrectal ultrasound guided prostate biopsy: a prospective randomized trial of 6 versus 12 cores. J Urol, 163: 168, 2000 12. Wu, C. L., Carter, H. B., Naqibuddin, M. et al: Effect of local anesthetics on patient recovery after transrectal biopsy. Urology, 57: 925, 2001