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May 1998
Preemptive Epidural Analgesia and Recovery from Radical Prostatectomy: A randomized controlled trial.
Gottschalk A, Smith DS, Jobes DR, Kennedy SK, Lally SE, Noble VE, Grugan KF, Siefert HA, Cheung A, Malkowicz SB, Gutsche BB and Wein AJ; JAMA 1998; 279:1076-82.
[ see abstract below ]
Preempting the memory of pain. (Editorial)
Carr DB; JAMA 1998; 279: 1114-5.
No abstract available
For some time we have heard of the theoretical advantages associated with preemptive analgesia, as well as clinical impressions of the benefits of this approach to pain management. This study is commendable in its relative simplicity but also in the considerable effort required to complete it. In an editorial accompanying this article Dr. Dan Carr reminds us that painful stimuli render the spinal cord highly sensitive for long periods of time following traumatic injury to the periphery, extending beyond the actual stimulus itself. This persistent hyperalgesia is a phenomenon known to be highly preserved throughout the evolutionary process. Preemptive analgesia implies interruption of the afferent neural pathway from injured tissue in the periphery to the spinal cord, or blocking normal intraneuronal responses in the spinal cord following peripheral tissue injury before the actual injury occurs.
These concepts are not new to preclinical neurobiologists nor to seasoned clinicians, having been described in various terms for decades. Actual clinical documentation of the effectiveness of preemptive analgesia in humans, although clearly demonstrable in laboratory settings, has been less than overwhelming. This variability in prior clinical studies was recognized in the present article by Gottschalk et al, suggesting several possible explanations including: incomplete blockage of CNS sensitization, a contribution to central sensitization from inadequately treated postoperative pain, and the potential overriding effect of peripheral nociceptor sensitization by tissue factors released in response to tissue injury.
These authors test in a clinical population whether preemptive epidural analgesia, initiated prior to a major surgical procedure with adequate doses of local anesthetic or opioid, would favorably treat short-and long-term postoperative pain, as well as favorably influence other postoperative outcome variables. They found that administration of specific analgesic regimens through an epidural catheter prior to skin incision is associated with long-term benefits in generally healthy patients undergoing major lower abdominal surgery. They observed a trend, although statistically not significant, toward increased efficacy of bupivicaine treatment, in contrast to fentanyl treatment. Additionally the preemptive analgesic regimens studied were associated with earlier resumption of normal activities than the control patient population.
Now that the advantages of preemptive analgesia have been demonstrated clearly by this notable and commendable study, Dr. Carr adds the voice of pragmatism to the application of these results: "The next phase of clinical research in this intriguing area must address whether and for which patients and procedures preemptive analgesia is achievable in daily practice. Even if it is achievable, economic pressures on medical practice will mandate demonstration that the cost of such efforts is outweighed by savings from reduced length of hospital stay, fewer complications; speedier rehabilitation, and improved patient satisfaction." The pursuit of these considerations will be important for theoretic and very practical reasons.
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Preemptive Epidural Analgesia and Recovery from Radical Prostatectomy: A randomized controlled trial.
(Gottschalk et al)
Context: Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy.
Objective: To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy.
Design and Setting: A block randomized double-blind clinical trial lasting 20 months at a single academic medical center.
Patients: A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia.
Interventions: Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients.
Main Outcome Measures: Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge.
Results: The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks.
Conclusions: Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.
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