Department of Urology and Department of Anesthesiology, UC Davis Medical Center, Sacramento, California, USA

Correspondence to: C P Evans, Department of Urology, University of California, Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. E-mail: cpevans@ucdavis.edu

We retrospectively analyzed the analgesic efficacy and surgical outcomes of a single preoperative intrathecal long-acting morphine sulfate injection (0.25-0.5 mg) and postoperative intravenous (i.v.) ketorolac in 62 patients who underwent radical retropubic prostatectomy (RRP). Total postoperative analgesic requirement was documented along with assessment of length of hospital stay, pain control and time for resumption of normal activity. Postoperatively, 45% of patients required only nonsteroidal agents (ketorolac), whereas 55% needed a mean of 13.3 mg of supplemental i.v. morphine sulfate. Mean hospital stay was 2.3±0.3 days. Eighty-two per cent of patients felt the length of hospital stay adequate. Ninety-seven per cent of patients were satisfied with anesthesia selected and 95% of patients considered pain control on postoperative days 1 and 2 as effective. All patients resumed to full physical activity by 5.3±0.4 weeks after surgery. We conclude that a single preoperative injection of intrathecal morphine sulfate combined with i.v. ketorolac postoperatively results in effective analgesia, diminished supplemental narcotic requirement and high patient satisfaction during radical retropubic prostatectomy.

Prostate Cancer and Prostatic Diseases (2002) 5, 226-230. doi:10.1038/sj.pcan.4500584

prostatectomy; pain control; intrathecal morphine; analgesia; ketorolac

Introduction

Behar et al¹ and Wang et al² first reported that intrathecal and epidural opioids were effective for acute and severe pain in humans. Despite the early reports regarding the analgesic efficacy of intrathecal morphine,^3,4,5,6,7,8 this regimen failed to gain widespread use. This may be due to an early reported high incidence of respiratory depression and somnolence,⁹ although this was related to the use of large doses of morphine rather than the route of administration. Gwirtz and associates recently reported high patient satisfaction and low incidence of side effects and complications in over 6000 patients.¹⁰ These authors concluded that intrathecal morphine is more cost-effective compared to epidural analgesia. We undertook this study to assess the efficacy of postoperative pain control following radical retropubic prostatectomy (RRP) using intrathecal morphine sulfate at our institution.

We hypothesize that a single preoperative intrathecal injection of long-acting morphine sulfate (MSO4) eliminates the use of an indwelling epidural catheter, greatly reduces postoperative supplemental analgesic requirement and results in high patient satisfaction regarding pain control. The results of our study validate this hypothesis.

Materials and methods

The records of 62 healthy and neurologically intact patients who consecutively underwent RRP at our institution were retrospectively reviewed. The following variables were recorded from the patient hospital chart: length of hospitalization, operative time (time of incision to operation completion time), estimated blood loss (EBL, volume of blood loss recorded by the anesthetist during surgery) and total postoperative analgesia (total dose of narcotics and nonsteroidal anti-inflammatory agents) required. Results are expressed as the mean±s.e.m.

All patients included in the study underwent the same anesthetic technique. After sedation with a small dose of midazolam, the patient's back was prepared with betadine ointment and an intrathecal injection of morphine 0.2-0.5 mg was given at the midline lumbar level using a 25 gauge spinal needle. The dosage selected within this range was at the discretion of the attending anesthesiologist. Positive aspiration of clear cerebrospinal fluid before and after injection was performed to confirm proper needle placement. Following the injection, general anesthesia was induced and the patients were paralyzed, intubated and ventilated for the RRP procedure. Supplementation of the intrathecal dose with long-acting intravenous opioids was avoided.

All surgical procedures were performed by one of two surgeons. The same surgical technique was used in all patients. RRP was performed through a lower midline abdominal incision as previously described.¹¹

Postoperative pain was managed primarily with i.v. ketorolac. The ketorolac was typically administered with one 30 mg dose in the evening on postoperative day zero, or early on postoperative day one, followed by ketorolac 15 mg i.v. every 6 h around the clock for 24 h. Ketorolac was typically discontinued on late postoperative day one or postoperative day two prior to discharge from hospital. Thirty-four (55%) patients required 13.3 mg of supplemental i.v. MSO4 for breakthrough pain. Subsequent pain control was achieved with oral agents such as Vicodin and Tylenol. No indwelling epidural catheters were used for pain control. Patients were discharged only when they were afebrile, demonstrated good oral intake, were satisfied with oral pain control, self-ambulated and were able to manage the urethral catheter.

Patient satisfaction with regards to in-house and post-discharge pain control, anesthesia used, duration of hospitalization, as well as time needed for resumption of normal daily activities following surgery were evaluated by a patient questionnaire (Table 1), similar to previously validated questionnaires.^12,13,14 Each question included five responses from which the single best answer was to be selected.

Results

All 62 patients responded to the questionnaire assessing satisfaction of various pain control issues (Table 1). Chart review tabulated data is summarized in Table 2. Operative time averaged 195±4.7 min, average estimated blood loss was 1047±91 ml and mean length of hospital stay was 2.3±0.3 days. Forty-eight of the 62 patients were discharged on postoperative day two.

Thirty-four patients (55%) required an average total dosage of 13.3 mg of supplemental i.v. narcotics (MSO4). Twenty patients required an average total dosage of 8.8 mg i.v. MSO4 on postoperative day zero, 26 required an average total dosage of 9.8 mg on postoperative day one and seven patients required an average total dosage of 4.6 mg i.v. MSO4 on postoperative day two. Intravenous ketorolac resulted in effective postoperative analgesia in 28 (45%) patients. Supplemental MSO4 were not required in 28 (45%) patients in the recovery room, nor in 28 (45%) patients between discharge from the recovery room and hospital discharge (Table 3). Fourteen patients (23%) did not require any supplemental i.v. MSO4 postoperatively (from operation end-time to hospital discharge).

Patient questionnaire results (Table 4) showed that 82% of the patients felt the number of days spent in the hospital was very appropriate and adequate, with only 11% preferring to stay longer. Of the 48 patients discharged on postoperative day two, only five indicated preference to have extended his length of hospitalization. Ninety-seven per cent of patients were satisfied with the anesthesia selected and only 3% would choose not to undergo surgery if given the chance to make the decision again. Ninety-five per cent of patients considered pain control on postoperative days one and two as effective. Post-discharge pain control was considered effective by 90%, with a reported average of 5.3±0.4 weeks after surgery necessary to resume all normal daily physical activity.

Discussion

In this study, we retrospectively evaluated the pain control, length of hospitalization, and patient satisfaction following a single preoperative intrathecal morphine injection in patients who underwent RRP. It has recently been reported that small-dose intrathecal opioid analgesia is a safe, effective, and comparatively inexpensive modality for acute postoperative pain management in a variety of major surgical procedures.¹⁰

Chart review tabulated data in Table 2 shows an average operative time, EBL, and length of hospital stay (LOS) comparable to reported averages.^14,15,16,17 Forty-eight of the 62 patients were discharged on postoperative day two, though many fit the criteria for hospital discharge on postoperative day one. Our institution follows an established protocol requiring a minimum two-night hospitalization following RRP. We hypothesize that our mean LOS would be lower than reported if patients were allowed hospital discharge on postoperative day one when established discharge criteria were met. However, we recognize that the excellent pain control achieved with intrathecal opioid analgesia and i.v. ketorolac is responsible for potentially earlier hospital discharge and would be lost if patients were switched to oral analgesia on postoperative day one.

Intrathecal morphine acts selectively on opioid receptors in the spinal cord. The technique has been shown to be safe in several studies.^10,18 Common side effects associated with spinal opioids are pruritus (37%) and nausea with or without emesis (25%). Less common side effects include delayed respiratory depression (3%), postdural puncture headache (0.5%) and urinary retention.¹⁹ Delayed respiratory depression (6-12 h after intrathecal injection) is shown to be readily reversible by a small dose of naloxone without exacerbating pain^19,20 and is with smaller doses particularly in the elderly. Only 45% of patients required supplemental opioids in the recovery room or upon the remainder of their hospital stay, averaging a total dosage of 13.3 mg i.v. MSO4 (a relatively low dose). None of the patients in this study developed respiratory depression postoperatively, and none required emergent intubation, the use of naloxone, nor postoperative ventilation. The lower incidence of respiratory depression in our study is also due to the fact that 23% of our patients did not require postoperative narcotics at all. None of the 62 patients in our study had headache or urinary retention.

On postoperative day one, 95% of patients felt their pain was effectively controlled with the combination of one preoperative intrathecal morphine injection and intravenous ketorolac, with the use of MSO4 for breakthrough pain. On day two, 95% of patients were satisfied with their pain management. By postoperative day two, the majority of patients were no longer receiving intravenous ketorolac and pain was primarily managed with oral agents such as Vicodin and Tylenol on an 'as-needed' basis. Upon discharge from hospital 90% of patients reported effective pain control with several patients indicating on their survey that no analgesia was required. Though patients reported that on average 5.3 weeks were needed to resume all normal daily physical activity, we feel that this figure is strongly biased by the treating physician. Ninety-seven per cent of patients reported satisfaction with the type of anesthesia used and only two patients would elect to not undergo the surgery again if given the option. The overall patient satisfaction was well over 90% as assessed by written patient surveys.

Advantages for the use of intrathecal opioids in comparison to epidural analgesia include the technical ease of administration, the simplicity of postoperative management, and the rapid onset of action due to the immediate presence of opioid in the cerebrospinal fluid to act on dorsal horn receptors.²¹ Accurate placement of an epidural is sometimes technically demanding. Watts²² and Gerig et al²³ have reported failure rates of 2 and 4.7%, respectively with epidural analgesia (due primarily to the misplacement of the epidural catheter outside of the epidural space). The failure rate of spinal injection is much lower than that of epidural placement.²⁴ However, Klein et al have reported better outcome with epidural catheters at higher (0.1%) initial dosing of the local anesthetic, use of MSO4 instead of fentanyl for subsequent analgesia and 'opioid sparing' with ketorolac and oral nonsteroidal analgesics, which is known to shorten postoperative ileus.²⁵ Only 2.7% of their patients reported dissatisfaction with analgesia.

In 1998, Gottschalk and associates reported effective analgesia but longer (>5 days) hospitalization with pre-emptive epidural analgesia.²⁶ The average hospitalization in our patients was 2.3 days following a single preoperative intrathecal injection of MSO4, although the patient groups are not comparable.

Another benefit of the intrathecal route is the reduction in costs. Recent changes in healthcare economics have placed cost control at the forefront of medical care and patient management. Gwirtz and associates reported that intrathecal opioids cost less than one third as much as epidural opioids.¹⁰ Although our study does not compare intrathecal morphine with epidural analgesia, based on the current prevailing charges at our institution, intrathecal opioids cost less than one-twentieth as much as the administration and maintenance of epidural opioids over a 3-day period attributable to more expensive administration tray, drug costs, infusion pumps, delivery tubing and follow-up care for epidural analgesia.

In conclusion, a single preoperative injection of intrathecal long-acting morphine sulfate, combined with intravenous ketorolac postoperatively appears to be easy to perform and manage resulting in satisfactory neurological analgesia and high patient satisfaction during RRP. Future prospective, controlled studies focusing on relative hospital costs and length of hospitalization with intrathecal morphine vs other techniques, however, are highly warranted.

1 Behar M et al. Epidural morphine in the treatment of pain. Lancet 1979; 1: 527-529. MEDLINE

2 Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979; 50: 149-151. MEDLINE

3 Kalso E. Effects of intrathecal morphine injected with bupivacaine on pain after orthopaedic surgery. Br J Anaesthiol 1983; 55: 415-422.

4 Nordberg G et al. Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 1984; 60: 448-454. MEDLINE

5 Chadwick HS, Ready LB. Intrathecal and epidural morphine sulfate for postcesarean analgesia: a clinical comparison. Anesthesiology 1988; 67: 137-143.

6 Abboud TK et al. Mini-dose intrathecal morphine for the relief of post-cesarean section pain. Anesth Analg 1988; 67: 137-143. MEDLINE

7 Abouleish E et al. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 1988; 67: 370-374. MEDLINE

8 Kirson LE, Goldman JM, Slover RB. Low-dose intrathecal morphine for postoperative pain control in patients undergoing transurethral resection of the prostate. Anesthesiology 1989; 71: 192-195. MEDLINE

9 Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extradural and intrathecal opiates: report of a nationwide survey in Sweden. Br J Anaesthiol 1982; 54: 479-486.

10 Gwirtz KH et al. The safety and efficacy of intrathecal opioid analgesia for acute postoperative pain: seven years' experience with 5969 surgical patients at Indiana University hospital. Anesth Analg 1999; 88: 599-604. MEDLINE

11 Walsh PC. Radical retropubic prostatectomy. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds) Campbell's Urology 7th edn WB Saunders: Philadelphia, 1998, pp 2565-2588.

12 Fowler FJ Jr et al. Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey. Urology 1995; 45: 1007-1015. MEDLINE

13 Litwin MS, Shpall AI, Dorey F. Patient satisfaction with short stays for radical prostatectomy. Urology 1997; 49: 898-906. MEDLINE

14 Worwag E, Chodak GW. Overnight hospitalization after radical prostatectomy: the impact of two clinical pathways on patient satisfaction, length of hospitalization, and morbidity. Anesth Analg 1998; 87: 62-67. MEDLINE

15 Palmer JS et al. Same day surgery for radical retropubic prostatectomy: is it an attainable goal? Urology 1996; 47: 23-28. MEDLINE

16 Shir Y et al. Intraoperative blood loss during radical retropubic prostatectomy: epidural versus general anesthesia. Urology 1995; 45: 993-999. MEDLINE

17 Eastham JA, Scardino PT. Radical prostatectomy. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds) Campbell's Urology 7th edn WB Saunders: Philadelphia, 1998, pp 2547-2564.

18 Allano C et al. Low dose spinal morphine for postop analgesia on surgical wards. Br J Anethesiol 1999; 82: 189.

19 Chaney M. Side effects of intrathecal and epidural opioids (Review). Can J Anesth 1995; 42: 891-903.

20 Johnson A et al. Influence of postoperative naloxone infusion on respiration and pain relief after intrathecal morphine. Reg Anesth 1988; 13: 146-151.

21 Stoelting RK. Intrathecal morphine: an underused combination for postoperative pain management. Anesth Analg 1989; 68: 707-709. MEDLINE

22 Watts RW. A five-year prospective analysis of the efficacy, safety and morbidity of epidural anaesthesia performed by a general practitioner anaesthetist in an isolated rural hospital. Anaesth Intensive Care 1992; 20: 348-353. MEDLINE

23 Gerig HJ, Kern F. Success and failure rate in peridural anesthesia. A 1-year study. Reg Anaesth 1985; 8: 25-32. MEDLINE

24 Gerancher JC, Liu SS. Complications of neuraxial (spinal/epidural/caudal) anesthesia. In: Benumof JL, Saidman LJ (eds) Anesthesia and Perioperative Complications 2nd edn Mosby: St. Louis, MO, 1999, pp 50-65.

25 Klein EA et al. Maintaining quality of care and patient satisfaction with radical prostatectomy in the era of cost containment. Urology 1996; 48: 269-276. MEDLINE

26 Gottschalk A et al. Preemptive epidural analgesia and recovery from radical prostatectomy. JAMA 1998; 279: 1076-1082. MEDLINE

Table 1 Patient survey questionnaire and answer options

Table 2 Medical record review

Table 3 Supplemental intravenous narcotic use

Table 4 Results of patient survey questionnaire