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Is Periprostatic Local Anesthesia For Transrectal Ultrasound Guided Prostate Biopsy Associated With Increased Infectious Or Hemorrhagic Complications? A Prospective Randomized Trial
0022-5347/02/1682-0558/0 THE JOURNAL OF UROLOGY® Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 168, 558 –561, August 2002 Printed in U.S.A.
IS PERIPROSTATIC LOCAL ANESTHESIA FOR TRANSRECTAL ULTRASOUND GUIDED PROSTATE BIOPSY ASSOCIATED WITH INCREASED INFECTIOUS OR HEMORRHAGIC COMPLICATIONS? A PROSPECTIVE RANDOMIZED TRIAL ¨ BEK, BU ¨ LENT O ¨ NAL, BURAK O ¨ ZKAN, ALI U. O ¨ NDER, VELI YALC CAN O ¸ IN
AND
VURAL SOLOK
From the Department of Urology, University of Istanbul Cerrahpasa School of Medicine, Istanbul, Turkey
ABSTRACT
Purpose: Periprostatic local anesthesia for prostate biopsy requires 2 or more extra needle punctures and injection of the local anesthetic through the highly colonized rectum. To our knowledge we report the first prospective randomized trial to assess the infectious or hemorrhagic complications associated with this method. Materials and Methods: A total of 100 consecutive patients with sterile urine cultures underwent transrectal ultrasound guided prostate biopsy. They were randomized to receive a periprostatic nerve block or no anesthesia. Patients were evaluated for the amount of rectal and urethral bleeding, and symptoms and signs of infection after biopsy. Results: The amount of urethral bleeding was slight and similar in the 2 groups. Rectal bleeding was significantly less in the patients who received anesthesia. High fever (greater than 37.8C) was more frequent in the nerve block group and 2 patients in this group required rehospitalization. Bacteriuria in post-biopsy urine cultures was significantly more common in the anesthesia group. Conclusions: Our results suggest that periprostatic local anesthesia for prostate biopsy does not increase the risk of urethral bleeding. It is associated with a decreased incidence of rectal bleeding, presumably due to decreased patient discomfort. The incidence of bacteriuria was significantly higher in the anesthesia group. High fever and hospitalization due to infectious complications were also more common in the local anesthesia group, although not statistically significant. Prospective randomized trials seem warranted to determine the optimum antibiotic prophylaxis regimen in patients undergoing biopsy with a periprostatic nerve block. KEY WORDS: prostate, biopsy, anesthesia and analgesia, infection, hemorrhage
Prostate cancer continues to be the second most common cancer in men.1 Prostate biopsy is the mainstay of tissue diagnosis of adenocarcinoma of the prostate. Enhanced awareness of the importance of the early diagnosis of prostate cancer has led to a dramatic increase in the number of prostate biopsies. More than 500,000 prostate biopsies are performed yearly in the United States alone. Classical sextant biopsies have been largely replaced with 8, 10 and even 12 or more biopsy cores per patient. Not infrequently when the suspicion for cancer persists, patients undergo repeat biopsies despite negative histological findings. There has been recent enthusiasm about administering periprostatic local anesthesia during transrectal ultrasound guided prostate biopsy in an effort to render the procedure more comfortable for the patient.2–7 Several studies have proved that local anesthesia significantly decreases pain and patient discomfort.2–9 Applying local anesthesia requires 2 to 8 extra needle punctures depending on the method.2, 3, 6 More importantly lidocaine is injected into the periprostatic area through the rectum, which is known to be highly colonized by bacteria. We speculated that extra punctures and transrectal injection may be associated with higher infectious and/or bleeding complications associated with the procedure. To our knowledge none of the studies published to date has specifically been designed to address this issue. We report the results of the first prospective randomized trial assessing the incidence of morbidity associated with periprostatic local anAccepted for publication March 28, 2002.
esthesia during transrectal ultrasound guided prostate biopsy. MATERIAL AND METHODS
A total of 104 consecutive patients underwent transrectal ultrasound guided prostate biopsy between October 2000 and April 2001. The indications for biopsy were abnormal digital rectal examination and/or elevated serum prostate specific antigen (PSA). Three patients underwent repeat biopsies. All study participants read and signed an informed consent form. Before biopsy urine cultures were sterile for patient inclusion into the study. Bleeding diathesis and/or anticoagulant treatment, history of sulfa allergies, active anal and rectal conditions such as hemorrhoids, anal fissure or stricture were study exclusion criteria. Patients were randomized to receive a periprostatic nerve block or no anesthesia. Bowel cleansing with a self-administered Fleet’s enema was performed the night before the procedure. Antibiotic coverage with 160 mg. trimethoprim-800 mg. sulfamethoxasole twice daily was initiated the night before biopsy at 9 p.m. Patients received the antibiotic dose 1 hour before the procedure on the day of the biopsy and it continued for 2 days. Biopsies were performed with the patient in the left lateral decubitus position using a Sono Line 1 ultrasound machine (Siemens, Erlangen, Germany), a biplanar 7.5 MHz. transrectal probe and an automated biopty gun with 18 gauge biopsy needles. After the transrectal probe was introduced into the rectum periprostatic lidocaine infiltration was performed in the local anesthesia group. Local anesthesia con-
558
MORBIDITY OF PERIPROSTATIC ANESTHESIA FOR PROSTATE BIOPSY
sisted of 5 cc 2% lidocaine infiltration, that is 2.5 cc. to each side of the prostate. With the ultrasound probe in the sagittal view injection was done within the neurovascular bundle at the base of the prostate just lateral to the junction between prostate and seminal vesicle using a 7-inch 22 gauge spinal biopsy needle. Infiltration was done on each side of the prostate for a total of 2 punctures. The prostate was then viewed in transverse and sagittal section to delineate any hypoechoic areas and determine prostate volume. This maneuver allowed 2 to 3 minutes for the anesthetic effect to settle. We then obtained 10 core biopsies, including 5 from each side of the prostate, in all patients. Patient demographics were noted. Vital signs, including blood pressure and heart rate, were determined before and after biopsy. At the end of the procedure the patients completed a linear pain scale with responses ranging from 0 —no discomfort to 5—the most severe ever experienced. The amount of rectal bleeding was determined on a scale of 1—none (a few drops of blood) to mild, 2—moderate (5 to 10 cc of blood) and 3—severe or prolonged bleeding (greater than 10 cc of blood, observation and/or hematochezia for a few days). Urethral bleeding was scored as 1 and its absence was scored as 0. Urethral and rectal bleeding was evaluated by the same 2 urologists. Clinical symptoms and signs of infection, such as fever, chills, epididymitis and acute prostatitis, were monitored for a week and noted. Patients recorded oral body temperature twice daily for 1 week. Oral body temperature in the range of 36.5C to 37.8C was considered low grade fever, while above 37.8C (100F) it was considered high fever. Complications necessitating rehospitalization during the 2-week postbiopsy period were defined as serious. Urine cultures were obtained 5 days after the procedure. Potential side effects associated with the systematic absorption of lidocaine, such as dizziness, visual disturbance, tinnitus and respiratory distress, were assessed. Statistical analysis was performed using the chi-square, Fisher’s exact and Mann-Whitney U tests. RESULTS
Urine cultures were positive before prostate biopsy in 4 patients, who were excluded from analysis. Thus, 100 men were enrolled in the study. Each group was well matched regarding patient demographics, digital rectal examination findings, serum PSA and prostate volume (table 1). The mean pain score was 0.98 in the local anesthesia group and 1.56 in the control arm (Mann Whitney U test p ⫽ 0.02). Hence, the periprostatic nerve blockade decreased pain and patient discomfort significantly. The amount of urethral bleeding was almost negligible and similar in the 2 groups. Urethral bleeding was not detected in 45 (90%) and 46 (92%) patients in the anesthesia and control arms, respectively (Fisher’s exact test p ⫽ 0.5, table 2). The amount of rectal bleeding was significantly less in the local anesthesia group (chi-square test 6.77, p ⫽ 0.034, table 2). It was none to mild (a score 1) in 29 men (58%) in the anesthesia group compared with 17 controls (34%). Body temperature was above normal at (greater than 36.5C) in 10 patients in the local anesthesia group compared with 9 in the control group within the week after biopsy (chi-square test 0.06, p ⫽ 0.798). However, when
TABLE 1. Patient demographics No. pts. Median age Median PSA (ng./ml.) No. abnormal digital rectal examination Median prostate vol. (cc)
Anesthesia
Controls
50 67 8.9 25
50 63 7.2 20
48
56
559
stratified for fever above and below 37.8C (100F), high fever was more frequent in the local group (5 versus 1 patients, Fisher’s exact test p ⫽ 0.102). After biopsy positive urine cultures were significantly more common in the local anesthesia group (11 versus 3 patients, chi-square test 0.02, table 3). Escherichia coli was the most frequently identified organism. It was detected in 9 and 2 patients in the anesthesia and control arms, respectively. Pseudomonas aeroginosa grew in the urine of a patient in the control group, while Klebsiella pneumonia and Proteus mirabilis were identified in 1 each in the periprostatic block group. Rehospitalization within 72 hours was required in 2 cases due to high fever. They were managed by the administration of intravenous fluids and third generation cephalosporins. These 2 patients had undergone biopsy with local anesthesia. Nevertheless, statistical analysis failed to achieve significance regarding hospitalization in the 2 groups (Fisher’s exact test p ⫽ 0.247). A change in vital signs, allergic reaction to lidocaine, dizziness, visual disturbance, tinnitus, respiratory distress, urinary or clot retention was not observed in any patient. DISCUSSION
Administering some type of local anesthesia during transrectal ultrasound guided prostate biopsies has recently gained popularity as a quality of life issue. Intravenous sedation, intrarectal lidocaine gel and periprostatic nerve blockade with lidocaine infiltration have been used in an effort to render the procedure more comfortable for the patient.2–9 All 3 methods have proved superior to biopsy without anesthesia regarding pain control and increased patient comfort. We believe that periprostatic nerve blockade is being increasingly adapted among urologists worldwide and it may become the gold standard in the near future. Before any procedure can be accepted as a standard associated morbidity must be explored. Studies published to date have shown no increased or serious morbidity related to the procedure.2– 6 However, none was specifically designed to assess morbidity associated with the method. Dizziness, visual disturbance, tinnitus and respiratory distress are potential side effects associated with the systematic absorption of lidocaine that were not observed in the current study, confirming published data.4 We emphasize the importance of syringe aspiration before injection to avoid inadvertent entry into the vascular system. This maneuver should minimize the risk of systemic absorption. An increase in the number of cores per biopsy was reportedly associated with an increased incidence of hematochezia.10 Periprostatic lidocaine infiltration requires at least 2 and up to 8 extra needle punctures depending on physician choice.2, 3, 6 Thus, we hypothesized that extra punctures could lead to increased rectal bleeding. However, the results of the study proved our assumption wrong. Interestingly the amount of rectal bleeding was not more, but rather less after administering local anesthesia. In the single prospective study of the risks and complications of transrectal ultrasound guided prostate needle biopsy with a thorough review of the literature Rodriguez and Terris reported that the amount of discomfort was proportional to the amount of rectal bleeding at biopsy (r ⫽ 0.25, p ⫽ 0.008).11 Thus, we explain the smaller amount of rectal bleeding in the local anesthesia group by improved patient comfort. Consequently decreased rectal bleeding seems to be another advantage of local anesthesia. Whether infiltrating lidocaine at more than 2 sites would influence the results must be explored in future trials. Pareek et al addressed the issue of potential increased bleeding (hematuria, hematospermia or blood via the rec-
560
MORBIDITY OF PERIPROSTATIC ANESTHESIA FOR PROSTATE BIOPSY TABLE 2. Urethral and rectal bleeding in the 2 groups
Urethral bleeding: No Yes Rectal bleeding: None–mild Moderate Severe–prolonged
No. Anesthesia (%)
No. Controls (%)
p Value
45 (90) 5 (10)
46 (92) 4 (8)
0.5 (Fisher’s exact test)
29 (58) 18 (36) 3 (6)
17 (34) 31 (62) 2 (4)
0.034 (chi-square test)
TABLE 3. Infectious complications in the 2 groups No. Anesthesia (%) Serious clinical infection Fever: Less than 37.8C Greater than 37.8C Bacteriuria
No. Controls (%)
p Value
2 (4) 5 (10) 5 (10) 11 (22)
tum) after a periprostatic nerve block and reported no difference.4 However, the control group involved placebo, in that patients received saline injection. Hence, the only difference in the 2 groups was the content of injected material, whereas the number of needle punctures was equal. Therefore, a difference in hemorrhagic complications would have been unlikely. The number of biopsies was standardized at 10 cores per patient in our study in an effort to prevent bias. In addition, urethral and rectal bleeding evaluations were performed by the same 2 urologists to obviate interobserver variability. The amount of urethral bleeding was similar and slight in the 2 groups. This result was not unexpected since lidocaine infiltration is done at a region far from the urethra. In addition, because biopsy sites have moved lateral with time, urethral bleeding should be much less of a problem. Another important aspect of our study was the investigation of whether periprostatic local anesthesia was associated with a higher incidence of infectious complications. Periprostatic nerve block involves infiltration of a soluble substance through the highly colonized rectum into a highly vascular space. Again it is performed by extra needle punctures. A direct correlation of the number of biopsies with fever and chills was reported.11 Moreover, in our experience one might need to apply some pressure during injection. Therefore, we hypothesized that periprostatic lidocaine infiltration may be associated with a higher risk of infection compared with performing biopsy without anesthesia. In fact, we observed a higher incidence of infectious complications in the local anesthesia group. The incidence of bacteriuria was significantly higher in the nerve block group (11 versus 3 patients). The 2 patients who required hospitalization underwent biopsy with lidocaine infiltration. High fever (greater than 100F) was observed in 5 patients in the local anesthesia group compared with 1 control. Nevertheless, neither the difference in fever nor hospitalization in the groups achieved statistical significance. A larger number of patients may have resulted in a significant difference in clinical infectious complications in addition to a difference in the rate of bacteriuria. Recently Leibovici et al noted septicemia in 2 of 90 patients who underwent biopsy with periprostatic infiltration.7 Although their results reinforce our finding that periprostatic lidocaine infiltration may be associated with a higher rate of infectious complications, comparison with those without a nerve block was not possible since all patients received a nerve block. Leibovici et al did not provide information on antibiotic prophylaxis. Although antibiotic coverage with prostate biopsies is given almost universally, there remains a lack of prospective randomized trials to support this practice. Quinolones, gentamycin, trimethoprim/sulfamethozasole and metronidazole
0.247 (Fisher’s exact test) 8 (16) 1 (2) 3 (6)
0.37 (chi-square test) 0.102 (Fisher’s exact test) 0.02 (chi-square test)
are generally given alone or in various combinations.2– 6, 8, 11 Others could argue that quinolones have better penetration into prostatic tissue and, thus, would be preferable in the setting of prostatic biopsy. We preferred trimethoprim/sulfamethozasole in this study since it is cost-effective and was equivalent to fluoroquinolone in the only prospective randomized trial of antibiotics and prostate biopsy.12 Using different antibiotics may have affected our results. However, importantly the 2 groups received the same antibiotic coverage in the current series and the nerve blockade group was associated with more frequent bacteriuria and a tendency toward higher clinical infection. Thus, biopsy with periprostatic infiltration seems to place patients in higher risk for infectious complications. Hence, there appears to be a need for prospective randomized trials to establish the optimum antibiotic prophylaxis and coverage in men undergoing prostate biopsy with a periprostatic nerve block. CONCLUSIONS
Based on the results of this study periprostatic local anesthesia for prostate biopsy does not increase the risk of urethral bleeding. It is associated with a decreased incidence of rectal bleeding, probably due to alleviated patient discomfort. The incidence of bacteriuria after biopsy was significantly higher in the nerve block group. Although high fever and hospitalization due to infectious complications were more common in the local anesthesia group, the higher bacteriuria rate did not translate into a significantly higher incidence of clinical signs and symptoms of infection. Prospective randomized trials seem warranted to determine the optimum antibiotic prophylaxis regimen in patients undergoing prostate biopsy with a nerve block. REFERENCES
1. Greenlee, R. T., Murray, T., Bolden, S. and Wingo, P. A.: Cancer statistics, 2000. CA Cancer J Clin, 50: 7, 2000 2. Nash, P. A., Bruce, J. E., Indudhara, R. and Shinohara, K.: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol, 155: 607, 1996 ¨ 3. Soloway, M. S. and Obek, C.: Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol, 163: 172, 2000 4. Pareek, G., Armenakas, N. A. and Fracchia, J. A.: Periprostatic nerve blockade for transrectal ultrasound guided biopsy of the prostate: a randomized double-blind, placebo controlled study. J Urol, 166: 894, 2001 5. Alavi, A. S., Soloway, M. S., Vaidya, A., Lynne, C. M. and Gheiler, E. L.: Local anesthesia for ultrasound guided prostate biopsy: a prospective randomized trial comparing 2 methods. J Urol, 166: 1343, 2001 6. Vaidya, A. and Soloway, M. S.: Periprostatic local anesthesia
MORBIDITY OF PERIPROSTATIC ANESTHESIA FOR PROSTATE BIOPSY before ultrasound-guided prostate biopsy: an update of the Miami experience. Eur Urol, 40: 135, 2001 7. Leibovici, D., Zisman, A., Siegel, Y. I., Sella, A., Kleinmann, J. and Lindner, A.: Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study. J Urol, 167: 563, 2001 8. Issa, M. M., Bux, S., Chun, T., Petros, J. A., Labadia, A. J., Anastasia, K. 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 9. Peters, J. L., Thompson, A. C., McNicholas, T. A., Hines, J. E., Hanbury, D. C. and Boustead, G. B.: Increased patient satisfaction from transrectal ultrasonography and biopsy under
561
sedation. Br J Urol, 87: 827, 2001 10. Naughton, C. K., Ornstein, D. K., Smith, D. S. and Catalona, W. J.: Pain and morbidity of transrectal ultrasound guided prostate biopsy: a prospective randomized trial of 6 versus 12 cores. J Urol, 163: 168, 2000 11. Rodriguez, L. V. and Terris, M. K.: Risks and complications of transrectal ultrasound guided prostate needle biopsy: a prospective study and review of the literature. J Urol, 160: 2115, 1998 12. Isen, K., Kupeli, B., Sinik, Z., Sozen, S. and Bozkirli, I.: Antibiotic prophylaxis for transrectal biopsy of the prostate: a prospective randomized study of the prophylactic use of single dose oral fluoroquinolone versus trimethoprim-sulfamethoxasole. Int Urol Nephrol, 31: 491, 1999
Vol. 168, 558 –561, August 2002 Printed in U.S.A.
IS PERIPROSTATIC LOCAL ANESTHESIA FOR TRANSRECTAL ULTRASOUND GUIDED PROSTATE BIOPSY ASSOCIATED WITH INCREASED INFECTIOUS OR HEMORRHAGIC COMPLICATIONS? A PROSPECTIVE RANDOMIZED TRIAL ¨ BEK, BU ¨ LENT O ¨ NAL, BURAK O ¨ ZKAN, ALI U. O ¨ NDER, VELI YALC CAN O ¸ IN
AND
VURAL SOLOK
From the Department of Urology, University of Istanbul Cerrahpasa School of Medicine, Istanbul, Turkey
ABSTRACT
Purpose: Periprostatic local anesthesia for prostate biopsy requires 2 or more extra needle punctures and injection of the local anesthetic through the highly colonized rectum. To our knowledge we report the first prospective randomized trial to assess the infectious or hemorrhagic complications associated with this method. Materials and Methods: A total of 100 consecutive patients with sterile urine cultures underwent transrectal ultrasound guided prostate biopsy. They were randomized to receive a periprostatic nerve block or no anesthesia. Patients were evaluated for the amount of rectal and urethral bleeding, and symptoms and signs of infection after biopsy. Results: The amount of urethral bleeding was slight and similar in the 2 groups. Rectal bleeding was significantly less in the patients who received anesthesia. High fever (greater than 37.8C) was more frequent in the nerve block group and 2 patients in this group required rehospitalization. Bacteriuria in post-biopsy urine cultures was significantly more common in the anesthesia group. Conclusions: Our results suggest that periprostatic local anesthesia for prostate biopsy does not increase the risk of urethral bleeding. It is associated with a decreased incidence of rectal bleeding, presumably due to decreased patient discomfort. The incidence of bacteriuria was significantly higher in the anesthesia group. High fever and hospitalization due to infectious complications were also more common in the local anesthesia group, although not statistically significant. Prospective randomized trials seem warranted to determine the optimum antibiotic prophylaxis regimen in patients undergoing biopsy with a periprostatic nerve block. KEY WORDS: prostate, biopsy, anesthesia and analgesia, infection, hemorrhage
Prostate cancer continues to be the second most common cancer in men.1 Prostate biopsy is the mainstay of tissue diagnosis of adenocarcinoma of the prostate. Enhanced awareness of the importance of the early diagnosis of prostate cancer has led to a dramatic increase in the number of prostate biopsies. More than 500,000 prostate biopsies are performed yearly in the United States alone. Classical sextant biopsies have been largely replaced with 8, 10 and even 12 or more biopsy cores per patient. Not infrequently when the suspicion for cancer persists, patients undergo repeat biopsies despite negative histological findings. There has been recent enthusiasm about administering periprostatic local anesthesia during transrectal ultrasound guided prostate biopsy in an effort to render the procedure more comfortable for the patient.2–7 Several studies have proved that local anesthesia significantly decreases pain and patient discomfort.2–9 Applying local anesthesia requires 2 to 8 extra needle punctures depending on the method.2, 3, 6 More importantly lidocaine is injected into the periprostatic area through the rectum, which is known to be highly colonized by bacteria. We speculated that extra punctures and transrectal injection may be associated with higher infectious and/or bleeding complications associated with the procedure. To our knowledge none of the studies published to date has specifically been designed to address this issue. We report the results of the first prospective randomized trial assessing the incidence of morbidity associated with periprostatic local anAccepted for publication March 28, 2002.
esthesia during transrectal ultrasound guided prostate biopsy. MATERIAL AND METHODS
A total of 104 consecutive patients underwent transrectal ultrasound guided prostate biopsy between October 2000 and April 2001. The indications for biopsy were abnormal digital rectal examination and/or elevated serum prostate specific antigen (PSA). Three patients underwent repeat biopsies. All study participants read and signed an informed consent form. Before biopsy urine cultures were sterile for patient inclusion into the study. Bleeding diathesis and/or anticoagulant treatment, history of sulfa allergies, active anal and rectal conditions such as hemorrhoids, anal fissure or stricture were study exclusion criteria. Patients were randomized to receive a periprostatic nerve block or no anesthesia. Bowel cleansing with a self-administered Fleet’s enema was performed the night before the procedure. Antibiotic coverage with 160 mg. trimethoprim-800 mg. sulfamethoxasole twice daily was initiated the night before biopsy at 9 p.m. Patients received the antibiotic dose 1 hour before the procedure on the day of the biopsy and it continued for 2 days. Biopsies were performed with the patient in the left lateral decubitus position using a Sono Line 1 ultrasound machine (Siemens, Erlangen, Germany), a biplanar 7.5 MHz. transrectal probe and an automated biopty gun with 18 gauge biopsy needles. After the transrectal probe was introduced into the rectum periprostatic lidocaine infiltration was performed in the local anesthesia group. Local anesthesia con-
558
MORBIDITY OF PERIPROSTATIC ANESTHESIA FOR PROSTATE BIOPSY
sisted of 5 cc 2% lidocaine infiltration, that is 2.5 cc. to each side of the prostate. With the ultrasound probe in the sagittal view injection was done within the neurovascular bundle at the base of the prostate just lateral to the junction between prostate and seminal vesicle using a 7-inch 22 gauge spinal biopsy needle. Infiltration was done on each side of the prostate for a total of 2 punctures. The prostate was then viewed in transverse and sagittal section to delineate any hypoechoic areas and determine prostate volume. This maneuver allowed 2 to 3 minutes for the anesthetic effect to settle. We then obtained 10 core biopsies, including 5 from each side of the prostate, in all patients. Patient demographics were noted. Vital signs, including blood pressure and heart rate, were determined before and after biopsy. At the end of the procedure the patients completed a linear pain scale with responses ranging from 0 —no discomfort to 5—the most severe ever experienced. The amount of rectal bleeding was determined on a scale of 1—none (a few drops of blood) to mild, 2—moderate (5 to 10 cc of blood) and 3—severe or prolonged bleeding (greater than 10 cc of blood, observation and/or hematochezia for a few days). Urethral bleeding was scored as 1 and its absence was scored as 0. Urethral and rectal bleeding was evaluated by the same 2 urologists. Clinical symptoms and signs of infection, such as fever, chills, epididymitis and acute prostatitis, were monitored for a week and noted. Patients recorded oral body temperature twice daily for 1 week. Oral body temperature in the range of 36.5C to 37.8C was considered low grade fever, while above 37.8C (100F) it was considered high fever. Complications necessitating rehospitalization during the 2-week postbiopsy period were defined as serious. Urine cultures were obtained 5 days after the procedure. Potential side effects associated with the systematic absorption of lidocaine, such as dizziness, visual disturbance, tinnitus and respiratory distress, were assessed. Statistical analysis was performed using the chi-square, Fisher’s exact and Mann-Whitney U tests. RESULTS
Urine cultures were positive before prostate biopsy in 4 patients, who were excluded from analysis. Thus, 100 men were enrolled in the study. Each group was well matched regarding patient demographics, digital rectal examination findings, serum PSA and prostate volume (table 1). The mean pain score was 0.98 in the local anesthesia group and 1.56 in the control arm (Mann Whitney U test p ⫽ 0.02). Hence, the periprostatic nerve blockade decreased pain and patient discomfort significantly. The amount of urethral bleeding was almost negligible and similar in the 2 groups. Urethral bleeding was not detected in 45 (90%) and 46 (92%) patients in the anesthesia and control arms, respectively (Fisher’s exact test p ⫽ 0.5, table 2). The amount of rectal bleeding was significantly less in the local anesthesia group (chi-square test 6.77, p ⫽ 0.034, table 2). It was none to mild (a score 1) in 29 men (58%) in the anesthesia group compared with 17 controls (34%). Body temperature was above normal at (greater than 36.5C) in 10 patients in the local anesthesia group compared with 9 in the control group within the week after biopsy (chi-square test 0.06, p ⫽ 0.798). However, when
TABLE 1. Patient demographics No. pts. Median age Median PSA (ng./ml.) No. abnormal digital rectal examination Median prostate vol. (cc)
Anesthesia
Controls
50 67 8.9 25
50 63 7.2 20
48
56
559
stratified for fever above and below 37.8C (100F), high fever was more frequent in the local group (5 versus 1 patients, Fisher’s exact test p ⫽ 0.102). After biopsy positive urine cultures were significantly more common in the local anesthesia group (11 versus 3 patients, chi-square test 0.02, table 3). Escherichia coli was the most frequently identified organism. It was detected in 9 and 2 patients in the anesthesia and control arms, respectively. Pseudomonas aeroginosa grew in the urine of a patient in the control group, while Klebsiella pneumonia and Proteus mirabilis were identified in 1 each in the periprostatic block group. Rehospitalization within 72 hours was required in 2 cases due to high fever. They were managed by the administration of intravenous fluids and third generation cephalosporins. These 2 patients had undergone biopsy with local anesthesia. Nevertheless, statistical analysis failed to achieve significance regarding hospitalization in the 2 groups (Fisher’s exact test p ⫽ 0.247). A change in vital signs, allergic reaction to lidocaine, dizziness, visual disturbance, tinnitus, respiratory distress, urinary or clot retention was not observed in any patient. DISCUSSION
Administering some type of local anesthesia during transrectal ultrasound guided prostate biopsies has recently gained popularity as a quality of life issue. Intravenous sedation, intrarectal lidocaine gel and periprostatic nerve blockade with lidocaine infiltration have been used in an effort to render the procedure more comfortable for the patient.2–9 All 3 methods have proved superior to biopsy without anesthesia regarding pain control and increased patient comfort. We believe that periprostatic nerve blockade is being increasingly adapted among urologists worldwide and it may become the gold standard in the near future. Before any procedure can be accepted as a standard associated morbidity must be explored. Studies published to date have shown no increased or serious morbidity related to the procedure.2– 6 However, none was specifically designed to assess morbidity associated with the method. Dizziness, visual disturbance, tinnitus and respiratory distress are potential side effects associated with the systematic absorption of lidocaine that were not observed in the current study, confirming published data.4 We emphasize the importance of syringe aspiration before injection to avoid inadvertent entry into the vascular system. This maneuver should minimize the risk of systemic absorption. An increase in the number of cores per biopsy was reportedly associated with an increased incidence of hematochezia.10 Periprostatic lidocaine infiltration requires at least 2 and up to 8 extra needle punctures depending on physician choice.2, 3, 6 Thus, we hypothesized that extra punctures could lead to increased rectal bleeding. However, the results of the study proved our assumption wrong. Interestingly the amount of rectal bleeding was not more, but rather less after administering local anesthesia. In the single prospective study of the risks and complications of transrectal ultrasound guided prostate needle biopsy with a thorough review of the literature Rodriguez and Terris reported that the amount of discomfort was proportional to the amount of rectal bleeding at biopsy (r ⫽ 0.25, p ⫽ 0.008).11 Thus, we explain the smaller amount of rectal bleeding in the local anesthesia group by improved patient comfort. Consequently decreased rectal bleeding seems to be another advantage of local anesthesia. Whether infiltrating lidocaine at more than 2 sites would influence the results must be explored in future trials. Pareek et al addressed the issue of potential increased bleeding (hematuria, hematospermia or blood via the rec-
560
MORBIDITY OF PERIPROSTATIC ANESTHESIA FOR PROSTATE BIOPSY TABLE 2. Urethral and rectal bleeding in the 2 groups
Urethral bleeding: No Yes Rectal bleeding: None–mild Moderate Severe–prolonged
No. Anesthesia (%)
No. Controls (%)
p Value
45 (90) 5 (10)
46 (92) 4 (8)
0.5 (Fisher’s exact test)
29 (58) 18 (36) 3 (6)
17 (34) 31 (62) 2 (4)
0.034 (chi-square test)
TABLE 3. Infectious complications in the 2 groups No. Anesthesia (%) Serious clinical infection Fever: Less than 37.8C Greater than 37.8C Bacteriuria
No. Controls (%)
p Value
2 (4) 5 (10) 5 (10) 11 (22)
tum) after a periprostatic nerve block and reported no difference.4 However, the control group involved placebo, in that patients received saline injection. Hence, the only difference in the 2 groups was the content of injected material, whereas the number of needle punctures was equal. Therefore, a difference in hemorrhagic complications would have been unlikely. The number of biopsies was standardized at 10 cores per patient in our study in an effort to prevent bias. In addition, urethral and rectal bleeding evaluations were performed by the same 2 urologists to obviate interobserver variability. The amount of urethral bleeding was similar and slight in the 2 groups. This result was not unexpected since lidocaine infiltration is done at a region far from the urethra. In addition, because biopsy sites have moved lateral with time, urethral bleeding should be much less of a problem. Another important aspect of our study was the investigation of whether periprostatic local anesthesia was associated with a higher incidence of infectious complications. Periprostatic nerve block involves infiltration of a soluble substance through the highly colonized rectum into a highly vascular space. Again it is performed by extra needle punctures. A direct correlation of the number of biopsies with fever and chills was reported.11 Moreover, in our experience one might need to apply some pressure during injection. Therefore, we hypothesized that periprostatic lidocaine infiltration may be associated with a higher risk of infection compared with performing biopsy without anesthesia. In fact, we observed a higher incidence of infectious complications in the local anesthesia group. The incidence of bacteriuria was significantly higher in the nerve block group (11 versus 3 patients). The 2 patients who required hospitalization underwent biopsy with lidocaine infiltration. High fever (greater than 100F) was observed in 5 patients in the local anesthesia group compared with 1 control. Nevertheless, neither the difference in fever nor hospitalization in the groups achieved statistical significance. A larger number of patients may have resulted in a significant difference in clinical infectious complications in addition to a difference in the rate of bacteriuria. Recently Leibovici et al noted septicemia in 2 of 90 patients who underwent biopsy with periprostatic infiltration.7 Although their results reinforce our finding that periprostatic lidocaine infiltration may be associated with a higher rate of infectious complications, comparison with those without a nerve block was not possible since all patients received a nerve block. Leibovici et al did not provide information on antibiotic prophylaxis. Although antibiotic coverage with prostate biopsies is given almost universally, there remains a lack of prospective randomized trials to support this practice. Quinolones, gentamycin, trimethoprim/sulfamethozasole and metronidazole
0.247 (Fisher’s exact test) 8 (16) 1 (2) 3 (6)
0.37 (chi-square test) 0.102 (Fisher’s exact test) 0.02 (chi-square test)
are generally given alone or in various combinations.2– 6, 8, 11 Others could argue that quinolones have better penetration into prostatic tissue and, thus, would be preferable in the setting of prostatic biopsy. We preferred trimethoprim/sulfamethozasole in this study since it is cost-effective and was equivalent to fluoroquinolone in the only prospective randomized trial of antibiotics and prostate biopsy.12 Using different antibiotics may have affected our results. However, importantly the 2 groups received the same antibiotic coverage in the current series and the nerve blockade group was associated with more frequent bacteriuria and a tendency toward higher clinical infection. Thus, biopsy with periprostatic infiltration seems to place patients in higher risk for infectious complications. Hence, there appears to be a need for prospective randomized trials to establish the optimum antibiotic prophylaxis and coverage in men undergoing prostate biopsy with a periprostatic nerve block. CONCLUSIONS
Based on the results of this study periprostatic local anesthesia for prostate biopsy does not increase the risk of urethral bleeding. It is associated with a decreased incidence of rectal bleeding, probably due to alleviated patient discomfort. The incidence of bacteriuria after biopsy was significantly higher in the nerve block group. Although high fever and hospitalization due to infectious complications were more common in the local anesthesia group, the higher bacteriuria rate did not translate into a significantly higher incidence of clinical signs and symptoms of infection. Prospective randomized trials seem warranted to determine the optimum antibiotic prophylaxis regimen in patients undergoing prostate biopsy with a nerve block. REFERENCES
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