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PAIN AND QUALITY OF LIFE FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY
0022-5347/98/1605-176 1$03.00/0
THEJOURNAL OF UROLOGY
Vol. 160, 1761-1764, November 1998 Printed in U.S.A.
Copyright 0 1998 by AMERICAN UROLOGICAL ASSOCIATION, INC.
PAIN AND QUALITY OF LIFE FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY JENNIFER A. HAYTHORNTHWAITE, SRINIVASA N. RAJA, BETTY FISHER, STEVEN M. FRANK, CHARLES B. BRENDLER AND YORAM SHIR From the Departments of Psychiatry and Behavioral Sciences, and Anesthesiology and Critical Care Medicine, Johns Hopkins University. Baltimore, Maryland, Department of Urology, University of Chicago, Chicago, Illinois, and Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem, Israel
ABSTRACT
Purpose: We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes. Materials and Methods: A total of 110 patients undergoing radical retropubic prostatectomy were randomly assigned to receive epidural andfor general anesthesia. Patients responded to a questionnaire mailed 3 and 6 months following surgery that assessed prostate symptoms, pain related to surgery, quality of life and mood. Results: No long-term effects of anesthesia were observed. Of the 103 respondents (94%)at 3 months 49%had some pain related to surgery. Although pain was not related to anesthesic technique, patients who had it at 3 months used significantly more pain medication on postoperative day 3. Pain at 3 months was mild, averaging 1.5on a scale of 0 to 10, and associated with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01) and social (p <0.01)functioning. Pain a t 3 months was associated with higher levels of preoperative anxiety (p <0.05).At 6 months 36 of 90 patients (35%)had some pain related to surgery and the impact was similar. Conclusions: Long-term effects of intraoperative anesthesic technique were not apparent. Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life, particularly social functioning. Affective distress, particularly anxiety, before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy. KEY WORDS:pain, quality of life, anesthesia, prostatectomy, follow-up studies
Prostate cancer is the most common cancer in men in the United States1 and a standard surgical treatment is radical retropubic prostatectomy. Quality of life has become an important issue in the surgical treatment of prostate cancer since there are efficacious options other than surgery (radiation and hormonal therapy). Erectile dysfunction following radical retropubic prostatectomy is a frequently cited adverse side effect with the estimated incidence ranging from 31 to 78%.2,3One year after radical retropubic prostatectomy 10% of men have stated that they would avoid surgery to preserve sexual function.4 The impact of sexual difficulties on quality of life remains unclear with some studies demonstrating a n association between sexual difficulties and poor quality of life ratings,3.5 and another large study showing no such association.6 Reports of severe incontinence following radical retropubic prostatectomy range from 162 to 33%.3 A cross-sectional study comparing men at 3 , 6 , 1 2 and 18 months after radical retropubic prostatectomy reported the greatest distress regarding urinary difficulties at 3 months, and significantly less distress with increased time since ~ u r g e r y .Urinary ~ incontinence and voiding difficulties have been consistently associated with decreased quality of While the frequency and impact of sexual and urogenital problems are recognized, similar data are not available to our knowledge on pain following radical retropubic prostatectomy. Recently published data suggest that pain following radical retropubic prostatectomy for prostate cancer is common but mild in the weeks and months following Accepted for publication June 19, 1998.
In an early study of a sample of 24 radical retropubic prostatectomy patients 57% had pelvic pain at 1, 33% a t 3 and 21% at 6 months.9 Pelvic pain 1 month following radical retropubic prostatectomy interfered with walking, work and general enjoyment of life but the impact on these activities decreased with time.9 Interference with sleep was stable, whereas the impact on mood declined by 6 months.9 In a large clinical trial pain scores at 9.5 weeks following surgery were significantly higher in radical prostatectomy patients who did not receive preemptive epidural analgesia.8 In the control group approximately half of the patients (47%) had some pain related to surgery. These preliminary findings suggest the common occurrence of pain following radical retropubic prostatectomy. The impact of pain on quality of life may be as if not more important than sexual and urogenital symptoms. Research on chronic pain not related to cancer suggests that it may have a significant impact on quality of life.10 Peripheral tissue injuries in animals can cause central sensitization that results in behavioral signs of increased pain to noxious and innocuous stimuli.11 Similarly, surgery in humans may lead to central sensitization that prolongs or amplifies postoperative pain. In an earlier study we demonstrated that patients who received epidural anesthesia during radical retropubic prostatectomy required less postoperative analgesia than those receiving general or combined anesthesia.12 In that study neuraxial blockade, through interruption of noxious stimulation to the central nervous system, resulted in preemptive analgesia. Evidence for this finding was a decreased postoperative analgesic requirement,
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PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
suggesting an attenuation of neuronal plasticity leading to central sensitization. Although patients in all 3 anesthetic groups had low postoperative pain scores, the dose of analgesics required to attain these levels differed significantly between the groups beginning on postoperative day 2. In a more recent study epidural bupivacaine or fentanyl administered before anesthesia resulted in lower postsurgical pain during recovery and 9.5 weeks following radical retropubic prostatectomy.8 Despite evidence of early postoperative benefits, the long-term (3 to 6 months) impact of preemptive analgesia on chronic pain following surgical intervention, including radical retropubic prostatectomy, has not been determined. Our study was a longitudinal followup of patients previously enrolled in a clinical trial comparing anesthesia techniques during radical retropubic prostatectomy.12 We determined whether preemptive analgesia results in reduced chronic pain, examined the impact of chronic pain on quality of life and identified psychosocial risk factors for chronic pain following radical retropubic prostatectomy. MATERIALS AND METHODS
A total of 110 men randomized to receive 1 of 3 types of anesthesia in a clinical trial12 were contacted by mail 3 and 6 months following discharge from the hospital. Men eligible for the original clinical trial underwent elective radical retropubic prostatectomy a t the Johns Hopkins Hospital. The only exclusion criteria were medical contraindications for epidural anesthesia or patient refusal to participate. Randomization, and perioperative and postoperative treatment of the patients have been previously described (see figure).12 Anesthesia in all patients included sedation with 2 to 4 mg. intravenous midazolam given on arrival to the operating room followed by an epidural catheter insertion in the L3-4 or L4-5interspaces. Perioperative anesthesic technique varied according t o group assignment. During skin closure all patients received 100 pg. fentanyl epidurally. Postoperative pain management included epidural patient controlled analgesia set to deliver a combination of 5 pg./ml. fentanyl and 0.0625% bupivacaine a t a basal infusion rate of 2 ml. per hour, 4 ml. demand dose and lock out interval of 10 minutes. A scale was designed to measure pain intensity during the previous 2 weeks in the genitals, abdomen, rectum, lower back, area of catheter placement, site of incision, any other site relevant to surgery and globally. Pain in each site was rated on a 0 (none) to 10 (most intense) scale. If there was pain, 8 items from the Multidimensional Pain Inventory Pain Interference Scale were completed.13 Questions were designed to assess the severity of 5 urogenital problems, including loss of bladder control, difficulty with urination, burning with urination, difficulty attaining an erection and loss of sexual interest. Each item was rated on a 6-point scale from 0, none of the time to 5, all of the time. The Short-Form General Health Survey from the Medical Outcomes Study was used to assess quality of life.l4 The scale
includes 20 items that measure physical, social and role functioning (for example work and housework), mental health (for example mood), health perceptions and pain. Items were adapted to cover the previous 3 months for the 3 and &month assessments. Scores range from 1 to 100 with higher scores indicating better health. TO assess mood the depression, anxiety and hostility scales from the Symptom Checklist 90-Revised were included.l5 Each item was rated on a 5-point scale from 0, not at all to 4,extremely. The incidence of pain (score greater than 0) at 3 and 6 months was analyzed as a dichotomous variable. Measures of urogenital symptoms and quality of life were treated as continuous variables, and analyzed by 2-tailed paired Student’s t tests for changes with time, analyses of variance for effects of anesthetic technique, and unpaired Student’s t tests to compare pain-free and pain groups. Multiple linear stepwise regression models were used to examine independent predictors of quality of life indicators. The strength of the prediction model is described as the proportion of variance in the dependent measure (for example quality of life) accounted for by urogenital symptoms and pain predictors. Data were analyzed using computer software. RESULTS
Of the 110 participants enrolled in the original clinical trial 103 (94%)returned the 3-month questionnaire, 90 of whom (87%) responded at 6 months. Of the sample 39 received epidural (38%), 31 general (30%) and 33 combined (32%) anesthesia. The proportions across the 3 groups are similar to those originally reported.12 Changes in quality of life between the 3 and 6-month assessments were examined (table 1).The 90 patients who completed the 6-month assessment demonstrated significant improvement in loss of bladder control (p <0.01), difficulty attaining an erection (p = 0.05), difficulty urinating (p <0.01), overall health perceptions (p <0.01), and physical (p = 0.01) and social (p cO.01) functioning. Efects of anesthetic technique. There were no differences between anesthetic groups in measures of urogenital functioning, quality of life or mood at 3 or 6-month followup. Quality of life results for each group at 3 months are presented in table 2. Pain at 3 and 6 months was not associated with anesthetic technique. Incidence of pain. Of the sample 50 (49%) reported some pain (intensity rating greater than 0) related to radical retropubic prostatectomy a t 3 months. The 3 most common sites of pain were the genitals (53%), abdomen (39%) and site of the incision (34%). Based on a scale of 0 to 10 average total pain severity was 1.5 (standard deviation [SD] 1.9). The majority of patients with pain rated the total pain as 0 (38%) or 1(31%).Of the 50 patients with pain 3 months following surgery 8 (16%) used pain medication, most of which were over-the-counter preparations (for example ibuprofen, acet-
TABLE1. Quality of life measures at 3 and 6 months Mean (SD) ~
3 Mos.
Design of original clinical trial of anesthetic type.l2 N,O, nitrous oxide.
~~
p Value
6 Mos.
Urogenital symptoms (scale 0-5): Loss of bladder control 2.1 (1.4) 1.4(1.43) Burning with urination 0.3 (0.6) 0.2 (0.6) Difficulty urinating 0.6 (1.0) 0.3 (0.8) Difficulty attaining erection 4.6 (1.0) 4.4 (1.1) Decreased sexual interest 1.8 (1.5) 1.8 (1.5) Quality of life (scale 1-100): Overall health 73.2(17.7) 84.6 (16.6) Physical function 80.9(18.6) 86.3 (19.6) Social function 81.6(22.0) 96.3(10.4) Role function 91.6 (19.0) 94.5(16.0) Mental health 82.1 (15.8) 84.1(15.5) * Significant (p <0.05) change between 3 and 6 months.
0.0001*
0.16 0.004% 0.049‘ 0.94 0.0001* 0.012+ 0.0001*
0.14 0.10
PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
TABLE2. Quality of life measures at 3 months by anesthesic technique Mean (SD) General (33pb.) +
Epidural (39pb.)
General (31pts.)
Urogenital symptoms: Loss of bladder control 1.9 (1.2) 2.4 (1.5) 2.2 (1.4) Burning with urination 0.5 (0.8) 0.3 (0.6) 0.2 (0.5) Difficulty urinating 0.7 (1.2) 0.4 (0.8) 0.8 (1.4) Difficulty attaining erection 4.4 (1.2) 4.6 (1.0) 4.7 (0.8) Decreased sexual interest 1.8 (1.6) 1.8 (1.8) 2.1 (1.7) Quality of life: Overall health 70.7 (18.5) 71.5 (17.2) 76.2(15.8) Physical function 80.0 (16.9) 80.8(21.0) 76.3 (22.1) Social function 94.8(12.6) 96.9 (10.3) 97.7 (6.5) Role function 93.8(14.2) 91.0(21.1) 89.2 (19.4) 78.9 (15.9) 84.4(18.0) 83.9 (9.7) Mental health 21.9(29.6) 15.5(23.8) Pain* 18.3 (25.4) There were no significant differences between groups for any urogenital symptom or quality of life indicator. * Pain measured by the Short Form General Health Survey includes pain at any site and pain predating radical retropubic prostatectomy.
~
aminophen). In the pain-free group 5 patients (10%) used pain medications for other conditions. Ratings of interference in daily activities due to pain were low (mean 0.6, SD 1.11, indicating that generally mild pain had virtually no impact on daily activities. Of the 90 patients who returned the 6-month questionnaire 36 (35%)had pain at a site related to surgery. Of these patients 10 had a new onset of pain at a site related to surgery and 26 had continued pain since the 3-month assessment. Impact ofpain. To determine the impact of pain the sample was divided according t o the presence of pain (score greater than 0) at 3 and 6-month followups. Table 3 presents the mean values at 3 months for urogenital symptoms and quality of life scales for the 2 groups. There were no significant group differences in severity of urogenital symptoms. However, patients with pain related to surgery had significantly poorer overall health perceptions (p = 0.02), and poorer physical (p = 0.01) and social (p <0.01)functioning. There were no group differences in mental health or role functioning scales (p >0.10),or effects of pain on mood (p >0.10).Similar effects of pain were observed at 6 months but there were no significant group differences. Multivariate predictors of quality of life, Stepwise linear multiple regression analyses were used to examine the relative contribution of urogenital symptoms and pain in predicting quality of life at 3 and 6 months postoperatively. Age and anesthetic technique were entered first followed by the 5 urogenital symptoms and pain classification variable in predicting each quality of life outcome variable. These exploratory analyses were used to examine the extent to which pain predicted quality of life independent of the effects of urogenTABLE3. Quality of life measures at 3 months by pain group Mean (SD) Pain-Free Group
Pain Group
pValue
Urogenital symptoms: 2.1 (1.5) 2.2 (1.2) 0.73 Loss of bladder control 0.3 (0.6) 0.4 (0.7) 0.47 Burning with urination 0.4 (0.9) 0.8 (1.3) 0.12 Difficulty urinating 4.4 (1.2) 4.7 (0.7) 0.13 Difficulty attaining an erection 1.9 (1.8) 2.0 (1.6) 0.65 Decreased sexual interest Quality of life: Overall health 76.7 (12.3) 68.3(20.5) 0.016* 84.6 (17.1) 73.5 (21.5) 0.005* Physical function 88.4 (17.2) 74.3(23.7) 0.001' Social function 92.7(20.2) 90.0(16.8) 0.48 Role function 84.0 (16.0) 81.0 (14.5) 0.32 Mental health * Significant difference (p <0.05) between pain-free and pain groups.
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ital symptoms already documented in the literature. At 3 months greater difficulty urinating (p = 0.02) and pain (p = 0.04) were associated with lower perceptions of overall health. At 6 months greater difficulty urinating (p = 0.01) and more burning with urination (p = 0.02) predicted poorer health perceptions. Pain alone predicted physical functioning at 3 (p = 0.03) and 6 (p = 0.02) months. At 3 months pain (p = 0.011,greater loss of bladder control (p = 0.01) and difficulty urinating (p = 0.03) predicted poorer social functioning. At 6 months only pain (p = 0.03) predicted poorer social functioning. Decreased sexual interest (p = 0.01) predicted mental health a t 3 months, whereas difficulty urinating (p = 0.01)and burning with urination (p = 0.03) predicted mental health at 6 months. None of the urogenital symptoms or pain predicted role functioning at 3 months, whereas pain at 6 months (p = 0.01) predicted poorer role functioning at 6 months. Predictors of chronic pain. Blood loss during surgery, prostate weight and postoperative pain ratings were comparable for the 2 groups (p >0.05). However, the group with pain at 3 months used significantly larger amounts of patient controlled analgesia on postoperative day 3 (table 41, and retrospectively had a higher level of anxiety (p = 0.05) and tendency for a higher level of depression (p = 0.07) during the week before surgery. These group differences were not a p parent at 6 months. DISCUSSION
Our results demonstrate a high incidence of mild pain followingradical retropubic prostatectomy as 49% of patients had pain at 3 and 36% at 6 months. Although the seventy of pain was mild, pain related to radical retropubic prostatectomy surgery was associated with poorer overall perceived health, and poorer physical and social functioning. As expected from earlier studies urogenital symptoms, including difficulty urinating and loss of bladder control, were predictive of quality of life, whereas sexual functioning was not. The impact of pain on quality of life was comparable to the effects of urogenital symptoms. Type of anesthesia did not impact the incidence of pain or quality of life indicators at either followup. Mective distress, particularly anxiety and possibly depression, at the time of surgery may be associated with chronic pain following radical retropubic prostatectomy. To date few studies have investigated the incidence and impact of pain followingradical retropubic prostatectomy. An earlier study with a considerably smaller sample size demonstrated slightly lower rates of pain9 and a more recent study of a large sample demonstrated comparable rates postoperatively up to 9.5 weeks.8 Neither of these studies directly examined the impact of pain on quality of life. Our findings demonstrate the impact of chronic pain on limitations in physical functioning, such as vigorous and moderate physical activity, walking and bending. Pain, not urogenital sympTABLE4. Risk factors for pain at 3 months Mean (SD) pain Pain-Free Group Group Postop. pt. controlled analgesia requirements (ml.): Day 1 139.91(58.5) 144.51(51.2) Day 2 102.52 (48.4) 108.66(43.5) Day 3 60.80(48.1) 84.6 (49.0) Postop. pain ratings: 1.51 (1.3) 1.58 (1.2) Day 1 0.94 (0.9) 0.77 (0.7) Day 2 0.54 (0.7) 0.72 (0.7) Day 3 Preop. mood ratings: Anxiety 0.27 (0.3) 0.45 (0.6) Depression 0.23 (0.3) 0.37 (0.5) * Significant difference between pain-free and pain group.
pValue
0.69 0.53 0.03' 0.76 0.32 0.24 0.05*
0.07
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PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
toms, predicted physical functioning at 3 and 6 months. Not surprisingly loss of bladder control was associated with poorer social functioning. However, pain predicted poorer social functioning at a similar magnitude in multivariate analyses. Although much of the literature has focused on incontinence and sexual functioning, these data indicate the significance of pain in quality of life following radical retropubic prostatectomy. Due to the mild nature of the pain, it is likely that it escaped medical attention. In fact most patients who were taking pain medications were using over-the-counter preparations. The significant impact of pain on quality of life suggests that physicians need to assess and treat even mild pain following radical retropubic prostatectomy. Whether treatment of this mild pain would improve quality of life, including physical and social functioning, needs to be examined in future studies. Anxiety at the time of surgery was associated with chronic pain following radical retropubic prostatectomy, and depression showed a statistical tendency. These findings must be regarded as preliminary since the ratings were made retrospectively at %month followup. However, patients with pain did not differ from those who were pain-free on ratings of anxiety or depression at 3 months. An intriguing implication of this pattern of tindings suggests that anxiety at the time of surgery may be a risk factor of chronic pain. Similarly, Sall et al concluded that preoperative worry about cancer may be associated with increased risk of postoperative pelvic pain.9 Emotional and cognitive factors appear to be involved in the progression from acute to chronic pain.16 In another surgical model Katz et al reported no association between preoperative anxiety ratings and long-term development of post-thoracotomy pain but their longitudinal analysis was limited to 30 patients.17 Studies using educational or psychological interventions before radical retropubic prostatectomy are needed to examine whether changes in emotional and cognitive factors can reduce the incidence of chronic pain related to surgery. There is considerable interest in determining the influence of perioperative pain, and analgesic and anesthetic management in the prevention of chronic pain. Bach et al observed that patients who received infusions of epidural opioid and local anesthetic for 72 hours before limb amputation had a lower incidence of phantom pain 6 and 12 months after amputation compared to controls treated with conventional analgesics.lS Similar observations have been made in subsequent studies.19 In a recent study Katz et al observed that early postoperative pain in the first 2 days after thoracotomy was a significant predictor of long-term pain 18months aRer surgery.17Although pain ratings were not associated with pain at 3 months in our study, analgesic requirements on postoperative day 3 were higher in the group with pain at 3 months. This difference may reflect more severe andor prolonged postoperative pain, or greater tolerance for postoperative analgesic medication. We previously observed differences in analgesic requirements but not pain ratings in the immediate postoperative period between patients who had epidural versus general or combined anesthesia.'* However, no significant differences in the incidence or severity of pain were observed in the 3 groups 3 and 6 months postoperatively. It is worth noting that postoperatively all patients received epidural patient controlled analgesia and pain was well controlled with pain scores averaging less than 2 on a 10-point verbal rating scale. Hence, aggressive pain management postoperatively may explain the lack of significant influence of the intraoperative anesthetic technique on the incidence of pain or quality of life at 3-month followup. A more recent clinical trial observed lower pain ratings during the immediate postoperative period in radical retropubic prostatectomy patients receiving preemptive epidural bupivacaine or fentanyl relative to controls.xIn addition, patients receiving preemptive treatment with bupivacaine also used less supplemental patient controlled analgesia opioids postoperatively.
In conclusion, intraoperative anesthesic technique did not predict the incidence of pain or quality of life at 3 or 6 months following radical retropubic prostatectomy. There was a high prevalence of generally mild chronic pain following radical retropubic prostatectomy. The impact of pain on quality of life indicators was comparable to that of other common symptoms, such as loss of bladder control. Possible predictors of chronic pain following radical retropubic prostatectomy include mood before surgery and use of pain medications postoperatively. REFERENCES
1. Small, E. J.: Prostate cancer. A current opinion in oncology. CA, 9: 277,1997. 2. Fossa, S. D., Woehre, H., Kurth, K. H., Hetherington, J., Bakke, H., Rustad, D. A. and Skanvik, R.: Influence of urological morbiditv on aualitv of life in patients with prostate cancer. Eur. Ur& suppl., 31: 3, 1997. 3 M.. Neal. D. E., Black, N., Fordham, M., Harrison. _ Emberton. _ M., McBrien, M.'P., Williams, R. E., McPherson, K. and Devlin, H. B.: The effect of prostatectomy on symptom severity and quality of life. Brit. J . Urol., 77: 233, 1996. 4. Braslis, K. G., Santa-Cruz, C., Brickman, A. L. and Soloway, M. S.: Quality of life 12 months after radical prostatectomy. Brit. J. Urol., 7 5 48, 1995. 5. Keoghane, S. R., Doll, H. A,, Lawrence, K. C., Jenkinson, C. P. and Cranston, D. W.: The Oxford Laser Prostate Trial: sexual function data from a randomized controlled clinical trial of contact laser prostatectomy. Eur. Urol., 3 0 424, 1996. 6. Fowler, F. J., Barry, M. J., Lu-Yao, G., Wasson, J., Roman, A. and Wennberg, J.: Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey. Urology, 4 5 1007, 1995. 7. Pedersen, K. V., Carlsson, P., Rahmquist, M. and Varenhorst, E.: Quality of life after radical retropubic prostatectomy for carcinoma of the prostate. Eur. Urol., 2 4 7, 1993. 8. Gottschalk, A,, Smith, D. S., Jobes, D. R., Kennedy, S. K., Lally, S. E., Noble, V. E., Grugan, K. F., Seifert, H. A., Cheung, A,, Malkowicz, S. B., Gutsche, B. B. and Wein, A. J.: Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial. J.A.M.A., 2 7 9 1076, 1998. 9. Sall, M., Madsen, F. A., Rhodes, P. R., Jonler, M., Messing, E. M. and Bruskewitz, R. C.: Pelvic pain following radical retropubic prostatectomy: a prospective study. Urology, 4 9 575, 1997. 10. Banks, S. M. and Kerns, R. D.: Explaining high rates of depression in chronic pain: a diasthesis-stress framework. Psychol. Bull., 1: 95, 1996. 11. Woolf, C. J. and Thompson, S. W.: The induction and maintenance of central sensitizationis dependent on N-methyl-D-asparticacid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain, 44:293, 1991. 12. Shir, Y., Raja, S. N. and Frank, S. M.: The effect of epidural versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing radical prostatectomy. Anesth., 8 0 49, 1994. 13. Kerns, R. D., Turk, D. C. and Rudy, T. E.: The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain, 2 3 345, 1985. 14. Stewart, A. L., Hays, R. D. and Ware, J. E. Jr.: The MOS short-form general health survey: reliability and validity in a patient population. Med. Care, 2 6 724, 1988. 15. Derogatis, L. R.: Symptom checklist-90-R:Administration, Scoring, and Procedures Manual, 3rd ed. Minneapolis, MN: National Computer Systems, Inc., 1994. 16. Dworkin, R. H.: Which individuals with acute pain are most likely to develop a chronic pain syndrome? Pain Forum, 6 127, 1997. 17. Katz, J., Jackson, M., Kavanagh, B. P. and Sandler, A. N.: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin. J . Pain, 1 2 50, 1996. 18. Bach, S., Noreng, M. F. and Tjellden, N. U.: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain, 33: 297, 1988. 19. Dahl, J . B. and Kehlet, H.: The value of pre-emptive analgesia in the treatment of postoperative pain. Brit. J. Anesth., 70: 434, 1993.
THEJOURNAL OF UROLOGY
Vol. 160, 1761-1764, November 1998 Printed in U.S.A.
Copyright 0 1998 by AMERICAN UROLOGICAL ASSOCIATION, INC.
PAIN AND QUALITY OF LIFE FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY JENNIFER A. HAYTHORNTHWAITE, SRINIVASA N. RAJA, BETTY FISHER, STEVEN M. FRANK, CHARLES B. BRENDLER AND YORAM SHIR From the Departments of Psychiatry and Behavioral Sciences, and Anesthesiology and Critical Care Medicine, Johns Hopkins University. Baltimore, Maryland, Department of Urology, University of Chicago, Chicago, Illinois, and Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem, Israel
ABSTRACT
Purpose: We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes. Materials and Methods: A total of 110 patients undergoing radical retropubic prostatectomy were randomly assigned to receive epidural andfor general anesthesia. Patients responded to a questionnaire mailed 3 and 6 months following surgery that assessed prostate symptoms, pain related to surgery, quality of life and mood. Results: No long-term effects of anesthesia were observed. Of the 103 respondents (94%)at 3 months 49%had some pain related to surgery. Although pain was not related to anesthesic technique, patients who had it at 3 months used significantly more pain medication on postoperative day 3. Pain at 3 months was mild, averaging 1.5on a scale of 0 to 10, and associated with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01) and social (p <0.01)functioning. Pain a t 3 months was associated with higher levels of preoperative anxiety (p <0.05).At 6 months 36 of 90 patients (35%)had some pain related to surgery and the impact was similar. Conclusions: Long-term effects of intraoperative anesthesic technique were not apparent. Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life, particularly social functioning. Affective distress, particularly anxiety, before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy. KEY WORDS:pain, quality of life, anesthesia, prostatectomy, follow-up studies
Prostate cancer is the most common cancer in men in the United States1 and a standard surgical treatment is radical retropubic prostatectomy. Quality of life has become an important issue in the surgical treatment of prostate cancer since there are efficacious options other than surgery (radiation and hormonal therapy). Erectile dysfunction following radical retropubic prostatectomy is a frequently cited adverse side effect with the estimated incidence ranging from 31 to 78%.2,3One year after radical retropubic prostatectomy 10% of men have stated that they would avoid surgery to preserve sexual function.4 The impact of sexual difficulties on quality of life remains unclear with some studies demonstrating a n association between sexual difficulties and poor quality of life ratings,3.5 and another large study showing no such association.6 Reports of severe incontinence following radical retropubic prostatectomy range from 162 to 33%.3 A cross-sectional study comparing men at 3 , 6 , 1 2 and 18 months after radical retropubic prostatectomy reported the greatest distress regarding urinary difficulties at 3 months, and significantly less distress with increased time since ~ u r g e r y .Urinary ~ incontinence and voiding difficulties have been consistently associated with decreased quality of While the frequency and impact of sexual and urogenital problems are recognized, similar data are not available to our knowledge on pain following radical retropubic prostatectomy. Recently published data suggest that pain following radical retropubic prostatectomy for prostate cancer is common but mild in the weeks and months following Accepted for publication June 19, 1998.
In an early study of a sample of 24 radical retropubic prostatectomy patients 57% had pelvic pain at 1, 33% a t 3 and 21% at 6 months.9 Pelvic pain 1 month following radical retropubic prostatectomy interfered with walking, work and general enjoyment of life but the impact on these activities decreased with time.9 Interference with sleep was stable, whereas the impact on mood declined by 6 months.9 In a large clinical trial pain scores at 9.5 weeks following surgery were significantly higher in radical prostatectomy patients who did not receive preemptive epidural analgesia.8 In the control group approximately half of the patients (47%) had some pain related to surgery. These preliminary findings suggest the common occurrence of pain following radical retropubic prostatectomy. The impact of pain on quality of life may be as if not more important than sexual and urogenital symptoms. Research on chronic pain not related to cancer suggests that it may have a significant impact on quality of life.10 Peripheral tissue injuries in animals can cause central sensitization that results in behavioral signs of increased pain to noxious and innocuous stimuli.11 Similarly, surgery in humans may lead to central sensitization that prolongs or amplifies postoperative pain. In an earlier study we demonstrated that patients who received epidural anesthesia during radical retropubic prostatectomy required less postoperative analgesia than those receiving general or combined anesthesia.12 In that study neuraxial blockade, through interruption of noxious stimulation to the central nervous system, resulted in preemptive analgesia. Evidence for this finding was a decreased postoperative analgesic requirement,
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PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
suggesting an attenuation of neuronal plasticity leading to central sensitization. Although patients in all 3 anesthetic groups had low postoperative pain scores, the dose of analgesics required to attain these levels differed significantly between the groups beginning on postoperative day 2. In a more recent study epidural bupivacaine or fentanyl administered before anesthesia resulted in lower postsurgical pain during recovery and 9.5 weeks following radical retropubic prostatectomy.8 Despite evidence of early postoperative benefits, the long-term (3 to 6 months) impact of preemptive analgesia on chronic pain following surgical intervention, including radical retropubic prostatectomy, has not been determined. Our study was a longitudinal followup of patients previously enrolled in a clinical trial comparing anesthesia techniques during radical retropubic prostatectomy.12 We determined whether preemptive analgesia results in reduced chronic pain, examined the impact of chronic pain on quality of life and identified psychosocial risk factors for chronic pain following radical retropubic prostatectomy. MATERIALS AND METHODS
A total of 110 men randomized to receive 1 of 3 types of anesthesia in a clinical trial12 were contacted by mail 3 and 6 months following discharge from the hospital. Men eligible for the original clinical trial underwent elective radical retropubic prostatectomy a t the Johns Hopkins Hospital. The only exclusion criteria were medical contraindications for epidural anesthesia or patient refusal to participate. Randomization, and perioperative and postoperative treatment of the patients have been previously described (see figure).12 Anesthesia in all patients included sedation with 2 to 4 mg. intravenous midazolam given on arrival to the operating room followed by an epidural catheter insertion in the L3-4 or L4-5interspaces. Perioperative anesthesic technique varied according t o group assignment. During skin closure all patients received 100 pg. fentanyl epidurally. Postoperative pain management included epidural patient controlled analgesia set to deliver a combination of 5 pg./ml. fentanyl and 0.0625% bupivacaine a t a basal infusion rate of 2 ml. per hour, 4 ml. demand dose and lock out interval of 10 minutes. A scale was designed to measure pain intensity during the previous 2 weeks in the genitals, abdomen, rectum, lower back, area of catheter placement, site of incision, any other site relevant to surgery and globally. Pain in each site was rated on a 0 (none) to 10 (most intense) scale. If there was pain, 8 items from the Multidimensional Pain Inventory Pain Interference Scale were completed.13 Questions were designed to assess the severity of 5 urogenital problems, including loss of bladder control, difficulty with urination, burning with urination, difficulty attaining an erection and loss of sexual interest. Each item was rated on a 6-point scale from 0, none of the time to 5, all of the time. The Short-Form General Health Survey from the Medical Outcomes Study was used to assess quality of life.l4 The scale
includes 20 items that measure physical, social and role functioning (for example work and housework), mental health (for example mood), health perceptions and pain. Items were adapted to cover the previous 3 months for the 3 and &month assessments. Scores range from 1 to 100 with higher scores indicating better health. TO assess mood the depression, anxiety and hostility scales from the Symptom Checklist 90-Revised were included.l5 Each item was rated on a 5-point scale from 0, not at all to 4,extremely. The incidence of pain (score greater than 0) at 3 and 6 months was analyzed as a dichotomous variable. Measures of urogenital symptoms and quality of life were treated as continuous variables, and analyzed by 2-tailed paired Student’s t tests for changes with time, analyses of variance for effects of anesthetic technique, and unpaired Student’s t tests to compare pain-free and pain groups. Multiple linear stepwise regression models were used to examine independent predictors of quality of life indicators. The strength of the prediction model is described as the proportion of variance in the dependent measure (for example quality of life) accounted for by urogenital symptoms and pain predictors. Data were analyzed using computer software. RESULTS
Of the 110 participants enrolled in the original clinical trial 103 (94%)returned the 3-month questionnaire, 90 of whom (87%) responded at 6 months. Of the sample 39 received epidural (38%), 31 general (30%) and 33 combined (32%) anesthesia. The proportions across the 3 groups are similar to those originally reported.12 Changes in quality of life between the 3 and 6-month assessments were examined (table 1).The 90 patients who completed the 6-month assessment demonstrated significant improvement in loss of bladder control (p <0.01), difficulty attaining an erection (p = 0.05), difficulty urinating (p <0.01), overall health perceptions (p <0.01), and physical (p = 0.01) and social (p cO.01) functioning. Efects of anesthetic technique. There were no differences between anesthetic groups in measures of urogenital functioning, quality of life or mood at 3 or 6-month followup. Quality of life results for each group at 3 months are presented in table 2. Pain at 3 and 6 months was not associated with anesthetic technique. Incidence of pain. Of the sample 50 (49%) reported some pain (intensity rating greater than 0) related to radical retropubic prostatectomy a t 3 months. The 3 most common sites of pain were the genitals (53%), abdomen (39%) and site of the incision (34%). Based on a scale of 0 to 10 average total pain severity was 1.5 (standard deviation [SD] 1.9). The majority of patients with pain rated the total pain as 0 (38%) or 1(31%).Of the 50 patients with pain 3 months following surgery 8 (16%) used pain medication, most of which were over-the-counter preparations (for example ibuprofen, acet-
TABLE1. Quality of life measures at 3 and 6 months Mean (SD) ~
3 Mos.
Design of original clinical trial of anesthetic type.l2 N,O, nitrous oxide.
~~
p Value
6 Mos.
Urogenital symptoms (scale 0-5): Loss of bladder control 2.1 (1.4) 1.4(1.43) Burning with urination 0.3 (0.6) 0.2 (0.6) Difficulty urinating 0.6 (1.0) 0.3 (0.8) Difficulty attaining erection 4.6 (1.0) 4.4 (1.1) Decreased sexual interest 1.8 (1.5) 1.8 (1.5) Quality of life (scale 1-100): Overall health 73.2(17.7) 84.6 (16.6) Physical function 80.9(18.6) 86.3 (19.6) Social function 81.6(22.0) 96.3(10.4) Role function 91.6 (19.0) 94.5(16.0) Mental health 82.1 (15.8) 84.1(15.5) * Significant (p <0.05) change between 3 and 6 months.
0.0001*
0.16 0.004% 0.049‘ 0.94 0.0001* 0.012+ 0.0001*
0.14 0.10
PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
TABLE2. Quality of life measures at 3 months by anesthesic technique Mean (SD) General (33pb.) +
Epidural (39pb.)
General (31pts.)
Urogenital symptoms: Loss of bladder control 1.9 (1.2) 2.4 (1.5) 2.2 (1.4) Burning with urination 0.5 (0.8) 0.3 (0.6) 0.2 (0.5) Difficulty urinating 0.7 (1.2) 0.4 (0.8) 0.8 (1.4) Difficulty attaining erection 4.4 (1.2) 4.6 (1.0) 4.7 (0.8) Decreased sexual interest 1.8 (1.6) 1.8 (1.8) 2.1 (1.7) Quality of life: Overall health 70.7 (18.5) 71.5 (17.2) 76.2(15.8) Physical function 80.0 (16.9) 80.8(21.0) 76.3 (22.1) Social function 94.8(12.6) 96.9 (10.3) 97.7 (6.5) Role function 93.8(14.2) 91.0(21.1) 89.2 (19.4) 78.9 (15.9) 84.4(18.0) 83.9 (9.7) Mental health 21.9(29.6) 15.5(23.8) Pain* 18.3 (25.4) There were no significant differences between groups for any urogenital symptom or quality of life indicator. * Pain measured by the Short Form General Health Survey includes pain at any site and pain predating radical retropubic prostatectomy.
~
aminophen). In the pain-free group 5 patients (10%) used pain medications for other conditions. Ratings of interference in daily activities due to pain were low (mean 0.6, SD 1.11, indicating that generally mild pain had virtually no impact on daily activities. Of the 90 patients who returned the 6-month questionnaire 36 (35%)had pain at a site related to surgery. Of these patients 10 had a new onset of pain at a site related to surgery and 26 had continued pain since the 3-month assessment. Impact ofpain. To determine the impact of pain the sample was divided according t o the presence of pain (score greater than 0) at 3 and 6-month followups. Table 3 presents the mean values at 3 months for urogenital symptoms and quality of life scales for the 2 groups. There were no significant group differences in severity of urogenital symptoms. However, patients with pain related to surgery had significantly poorer overall health perceptions (p = 0.02), and poorer physical (p = 0.01) and social (p <0.01)functioning. There were no group differences in mental health or role functioning scales (p >0.10),or effects of pain on mood (p >0.10).Similar effects of pain were observed at 6 months but there were no significant group differences. Multivariate predictors of quality of life, Stepwise linear multiple regression analyses were used to examine the relative contribution of urogenital symptoms and pain in predicting quality of life at 3 and 6 months postoperatively. Age and anesthetic technique were entered first followed by the 5 urogenital symptoms and pain classification variable in predicting each quality of life outcome variable. These exploratory analyses were used to examine the extent to which pain predicted quality of life independent of the effects of urogenTABLE3. Quality of life measures at 3 months by pain group Mean (SD) Pain-Free Group
Pain Group
pValue
Urogenital symptoms: 2.1 (1.5) 2.2 (1.2) 0.73 Loss of bladder control 0.3 (0.6) 0.4 (0.7) 0.47 Burning with urination 0.4 (0.9) 0.8 (1.3) 0.12 Difficulty urinating 4.4 (1.2) 4.7 (0.7) 0.13 Difficulty attaining an erection 1.9 (1.8) 2.0 (1.6) 0.65 Decreased sexual interest Quality of life: Overall health 76.7 (12.3) 68.3(20.5) 0.016* 84.6 (17.1) 73.5 (21.5) 0.005* Physical function 88.4 (17.2) 74.3(23.7) 0.001' Social function 92.7(20.2) 90.0(16.8) 0.48 Role function 84.0 (16.0) 81.0 (14.5) 0.32 Mental health * Significant difference (p <0.05) between pain-free and pain groups.
1763
ital symptoms already documented in the literature. At 3 months greater difficulty urinating (p = 0.02) and pain (p = 0.04) were associated with lower perceptions of overall health. At 6 months greater difficulty urinating (p = 0.01) and more burning with urination (p = 0.02) predicted poorer health perceptions. Pain alone predicted physical functioning at 3 (p = 0.03) and 6 (p = 0.02) months. At 3 months pain (p = 0.011,greater loss of bladder control (p = 0.01) and difficulty urinating (p = 0.03) predicted poorer social functioning. At 6 months only pain (p = 0.03) predicted poorer social functioning. Decreased sexual interest (p = 0.01) predicted mental health a t 3 months, whereas difficulty urinating (p = 0.01)and burning with urination (p = 0.03) predicted mental health at 6 months. None of the urogenital symptoms or pain predicted role functioning at 3 months, whereas pain at 6 months (p = 0.01) predicted poorer role functioning at 6 months. Predictors of chronic pain. Blood loss during surgery, prostate weight and postoperative pain ratings were comparable for the 2 groups (p >0.05). However, the group with pain at 3 months used significantly larger amounts of patient controlled analgesia on postoperative day 3 (table 41, and retrospectively had a higher level of anxiety (p = 0.05) and tendency for a higher level of depression (p = 0.07) during the week before surgery. These group differences were not a p parent at 6 months. DISCUSSION
Our results demonstrate a high incidence of mild pain followingradical retropubic prostatectomy as 49% of patients had pain at 3 and 36% at 6 months. Although the seventy of pain was mild, pain related to radical retropubic prostatectomy surgery was associated with poorer overall perceived health, and poorer physical and social functioning. As expected from earlier studies urogenital symptoms, including difficulty urinating and loss of bladder control, were predictive of quality of life, whereas sexual functioning was not. The impact of pain on quality of life was comparable to the effects of urogenital symptoms. Type of anesthesia did not impact the incidence of pain or quality of life indicators at either followup. Mective distress, particularly anxiety and possibly depression, at the time of surgery may be associated with chronic pain following radical retropubic prostatectomy. To date few studies have investigated the incidence and impact of pain followingradical retropubic prostatectomy. An earlier study with a considerably smaller sample size demonstrated slightly lower rates of pain9 and a more recent study of a large sample demonstrated comparable rates postoperatively up to 9.5 weeks.8 Neither of these studies directly examined the impact of pain on quality of life. Our findings demonstrate the impact of chronic pain on limitations in physical functioning, such as vigorous and moderate physical activity, walking and bending. Pain, not urogenital sympTABLE4. Risk factors for pain at 3 months Mean (SD) pain Pain-Free Group Group Postop. pt. controlled analgesia requirements (ml.): Day 1 139.91(58.5) 144.51(51.2) Day 2 102.52 (48.4) 108.66(43.5) Day 3 60.80(48.1) 84.6 (49.0) Postop. pain ratings: 1.51 (1.3) 1.58 (1.2) Day 1 0.94 (0.9) 0.77 (0.7) Day 2 0.54 (0.7) 0.72 (0.7) Day 3 Preop. mood ratings: Anxiety 0.27 (0.3) 0.45 (0.6) Depression 0.23 (0.3) 0.37 (0.5) * Significant difference between pain-free and pain group.
pValue
0.69 0.53 0.03' 0.76 0.32 0.24 0.05*
0.07
1764
PAIN AND QUALITY OF LIFE AFTER RADICAL RETROPUBIC PROSTATECTOMY
toms, predicted physical functioning at 3 and 6 months. Not surprisingly loss of bladder control was associated with poorer social functioning. However, pain predicted poorer social functioning at a similar magnitude in multivariate analyses. Although much of the literature has focused on incontinence and sexual functioning, these data indicate the significance of pain in quality of life following radical retropubic prostatectomy. Due to the mild nature of the pain, it is likely that it escaped medical attention. In fact most patients who were taking pain medications were using over-the-counter preparations. The significant impact of pain on quality of life suggests that physicians need to assess and treat even mild pain following radical retropubic prostatectomy. Whether treatment of this mild pain would improve quality of life, including physical and social functioning, needs to be examined in future studies. Anxiety at the time of surgery was associated with chronic pain following radical retropubic prostatectomy, and depression showed a statistical tendency. These findings must be regarded as preliminary since the ratings were made retrospectively at %month followup. However, patients with pain did not differ from those who were pain-free on ratings of anxiety or depression at 3 months. An intriguing implication of this pattern of tindings suggests that anxiety at the time of surgery may be a risk factor of chronic pain. Similarly, Sall et al concluded that preoperative worry about cancer may be associated with increased risk of postoperative pelvic pain.9 Emotional and cognitive factors appear to be involved in the progression from acute to chronic pain.16 In another surgical model Katz et al reported no association between preoperative anxiety ratings and long-term development of post-thoracotomy pain but their longitudinal analysis was limited to 30 patients.17 Studies using educational or psychological interventions before radical retropubic prostatectomy are needed to examine whether changes in emotional and cognitive factors can reduce the incidence of chronic pain related to surgery. There is considerable interest in determining the influence of perioperative pain, and analgesic and anesthetic management in the prevention of chronic pain. Bach et al observed that patients who received infusions of epidural opioid and local anesthetic for 72 hours before limb amputation had a lower incidence of phantom pain 6 and 12 months after amputation compared to controls treated with conventional analgesics.lS Similar observations have been made in subsequent studies.19 In a recent study Katz et al observed that early postoperative pain in the first 2 days after thoracotomy was a significant predictor of long-term pain 18months aRer surgery.17Although pain ratings were not associated with pain at 3 months in our study, analgesic requirements on postoperative day 3 were higher in the group with pain at 3 months. This difference may reflect more severe andor prolonged postoperative pain, or greater tolerance for postoperative analgesic medication. We previously observed differences in analgesic requirements but not pain ratings in the immediate postoperative period between patients who had epidural versus general or combined anesthesia.'* However, no significant differences in the incidence or severity of pain were observed in the 3 groups 3 and 6 months postoperatively. It is worth noting that postoperatively all patients received epidural patient controlled analgesia and pain was well controlled with pain scores averaging less than 2 on a 10-point verbal rating scale. Hence, aggressive pain management postoperatively may explain the lack of significant influence of the intraoperative anesthetic technique on the incidence of pain or quality of life at 3-month followup. A more recent clinical trial observed lower pain ratings during the immediate postoperative period in radical retropubic prostatectomy patients receiving preemptive epidural bupivacaine or fentanyl relative to controls.xIn addition, patients receiving preemptive treatment with bupivacaine also used less supplemental patient controlled analgesia opioids postoperatively.
In conclusion, intraoperative anesthesic technique did not predict the incidence of pain or quality of life at 3 or 6 months following radical retropubic prostatectomy. There was a high prevalence of generally mild chronic pain following radical retropubic prostatectomy. The impact of pain on quality of life indicators was comparable to that of other common symptoms, such as loss of bladder control. Possible predictors of chronic pain following radical retropubic prostatectomy include mood before surgery and use of pain medications postoperatively. REFERENCES
1. Small, E. J.: Prostate cancer. A current opinion in oncology. CA, 9: 277,1997. 2. Fossa, S. D., Woehre, H., Kurth, K. H., Hetherington, J., Bakke, H., Rustad, D. A. and Skanvik, R.: Influence of urological morbiditv on aualitv of life in patients with prostate cancer. Eur. Ur& suppl., 31: 3, 1997. 3 M.. Neal. D. E., Black, N., Fordham, M., Harrison. _ Emberton. _ M., McBrien, M.'P., Williams, R. E., McPherson, K. and Devlin, H. B.: The effect of prostatectomy on symptom severity and quality of life. Brit. J . Urol., 77: 233, 1996. 4. Braslis, K. G., Santa-Cruz, C., Brickman, A. L. and Soloway, M. S.: Quality of life 12 months after radical prostatectomy. Brit. J. Urol., 7 5 48, 1995. 5. Keoghane, S. R., Doll, H. A,, Lawrence, K. C., Jenkinson, C. P. and Cranston, D. W.: The Oxford Laser Prostate Trial: sexual function data from a randomized controlled clinical trial of contact laser prostatectomy. Eur. Urol., 3 0 424, 1996. 6. Fowler, F. J., Barry, M. J., Lu-Yao, G., Wasson, J., Roman, A. and Wennberg, J.: Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey. Urology, 4 5 1007, 1995. 7. Pedersen, K. V., Carlsson, P., Rahmquist, M. and Varenhorst, E.: Quality of life after radical retropubic prostatectomy for carcinoma of the prostate. Eur. Urol., 2 4 7, 1993. 8. Gottschalk, A,, Smith, D. S., Jobes, D. R., Kennedy, S. K., Lally, S. E., Noble, V. E., Grugan, K. F., Seifert, H. A., Cheung, A,, Malkowicz, S. B., Gutsche, B. B. and Wein, A. J.: Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial. J.A.M.A., 2 7 9 1076, 1998. 9. Sall, M., Madsen, F. A., Rhodes, P. R., Jonler, M., Messing, E. M. and Bruskewitz, R. C.: Pelvic pain following radical retropubic prostatectomy: a prospective study. Urology, 4 9 575, 1997. 10. Banks, S. M. and Kerns, R. D.: Explaining high rates of depression in chronic pain: a diasthesis-stress framework. Psychol. Bull., 1: 95, 1996. 11. Woolf, C. J. and Thompson, S. W.: The induction and maintenance of central sensitizationis dependent on N-methyl-D-asparticacid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain, 44:293, 1991. 12. Shir, Y., Raja, S. N. and Frank, S. M.: The effect of epidural versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing radical prostatectomy. Anesth., 8 0 49, 1994. 13. Kerns, R. D., Turk, D. C. and Rudy, T. E.: The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain, 2 3 345, 1985. 14. Stewart, A. L., Hays, R. D. and Ware, J. E. Jr.: The MOS short-form general health survey: reliability and validity in a patient population. Med. Care, 2 6 724, 1988. 15. Derogatis, L. R.: Symptom checklist-90-R:Administration, Scoring, and Procedures Manual, 3rd ed. Minneapolis, MN: National Computer Systems, Inc., 1994. 16. Dworkin, R. H.: Which individuals with acute pain are most likely to develop a chronic pain syndrome? Pain Forum, 6 127, 1997. 17. Katz, J., Jackson, M., Kavanagh, B. P. and Sandler, A. N.: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin. J . Pain, 1 2 50, 1996. 18. Bach, S., Noreng, M. F. and Tjellden, N. U.: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain, 33: 297, 1988. 19. Dahl, J . B. and Kehlet, H.: The value of pre-emptive analgesia in the treatment of postoperative pain. Brit. J. Anesth., 70: 434, 1993.