Editorial The Evolution of Management of Postoperative Pain The management of postoperative pain has changed dramatically during the past 10 to 12 years. The article by Allaire and associates in this issue of the Mayo Clinic Proceedings (pages 1031 to 1041) reflects the degree of sophistication that has been achieved relative to patient comfort postoperatively. The authors compare two highly technical, recently developed methods for managing acute postsurgical pain: intravenous administration of morphine sulfate by patientcontrolled analgesia (PCA) and epidural infusion of fentanyl citrate to achieve analgesia. Although both techniques provided good relief, statistically significant differences were demonstrated between the groups, the epidural group achieving qualitatively better relief of pain. Accessibility of Drugs.-In analyses of studies of postoperative pain, several issues become evident. Whenever one attempts to compare two techniques such as PCA and epidural analgesia, free access to the analgesic agents must be part of the study design. Many studies unintentionally allow one group to receive more pain medication than the other. Withholding adequate amounts of opiates, intentional or otherwise, can easily bias a study of postoperative pain. In the current study by Allaire and colleagues, the epidural group received approximately 80 )..lglh of fentanyl (1 ug/kg per h). The PCA group received a mean of 1.37 mglh of morphine during the initial 12-hour period, which was gradually decreased to 0.63 mglh for the last 12-hour period. The potency ratio of fentanyl to morphine approaches 100:1. Thus, when morphine-equivalent units are used for comparison, the epidural group received almost 6 times the amount of narcotic as the PCA group. Why would the PCA group self-administer such a small amount of drug? Parker and co-workers! demonstrated that patients administer analgesics to themselves for numerous reasons, including some reasons that are unrelated to achieving relief of pain. Patients also withhold medications from themselves for various reasons-for example, fear of over-
Address reprint requests to Dr. R. L. Rauck, Director, Pain Control Center, Wake Forest University Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1077. MayoClinProc 67:1112-1114,1992
medicating, cultural bias, and stoicism. In a questionnaire given to preoperative patients, Owen and associates' found that most expect some pain postoperatively. If patients are reassured that sufficient medicine will be available and particularly if they can maintain some control (for example, with PCA), their fears are considerably allayed. Patients may choose not to titrate themselves to 0 (that is, no pain) on a scale of 0 to 10 if given the option with PCA. In the current study, the PCA group may have been unable to administer the amount of medicine they desired because of the lockout interval of 10 minutes. These patients could have been given the opportunity to use the PCA machine more frequently by decreasing the lockout interval from 10 to 5 minutes. With this option, more frequent doses might have been used and control of pain might have been more successful. Another possible reason for the variation in doses between the two groups may have been a relative analgesic overdose in the epidural group. Although the arbitrary epidural infusion dosage of 80 )..lglh provided excellent analgesia without side effects, a lower rate of infusion may have maintained similar analgesic results. Control of Intraoperative Factors.-Postoperative patients are a heterogeneous group. In the study by Allaire and colleagues, all patients underwent the same procedureradical retropubic prostatectomy. Some other variables were not well controlled. Intraoperatively, some patients received epidural anesthesia, whereas others received general anesthesia. Although this approach was intentional, the reasons for stratifying the patients in this fashion are somewhat unclear. Other intraoperative events such as intravenous administration of narcotics were not well controlled and would be expected to have effects into the early postoperative period. In addition, the use of local anesthetic agents during the surgical period in some patients with epidural catheters would decrease early postoperative pain and bias the results. All studies of management of postoperative pain should attempt to have standard control of intraoperative events. The tighter the control of preoperative and intraoperative events, the more meaningful the early postoperative data will be. Assessment of Only One Variable.-Because of the heterogeneity of postoperative patients, most immediately postsurgical studies provide the best data when only one issue is addressed. The current study attempts to examine three separate issues: (I) epidural versus systemic routes of administration, (2) comparison of morphine and fentanyl, and
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(3) technique of administration-continuous infusion (epidural group) versus a self-administered model (PCA group). Determining which of these issues accounted for the differences noted-or whether all three issues contributed-is difficult. Any two of these variables could have been controlled, and only one factor could have been the dependent variable. PCA Versus Epidural Analgesia.-The current study attempts to address the question of whether PCA or epidural analgesia can provide better relief of pain in postoperative patients. Within the aforementioned limitations, this article clearly shows epidural analgesia to be superior to PCA for the patient population studied. Qualitatively better results with epidural analgesia have been observed by many clinicians. In a similar comparative postoperative study of orthopedic patients, Loper and co-workers' found epidural analgesia with morphine superior to PCA. Other studies have shown that no advantages exist with fentanyl when administered epidurally versus PCA.4.5 The psychologic advantage of allowing patients some control over their pain medications, at a time (during the early postoperative period) when they have virtually no control over other events surrounding them, cannot be overemphasized. Safety.-Can the administration of potent analgesic drugs by new and sophisticated techniques be considered safe for routine use postoperatively? Epidural analgesia has been shown to cause respiratory depression along with other side effects, including urinary retention, pruritus, and nausea and vomiting.s" Thus, the indications for use of epidural analgesia must be examined for each case, and the indiscriminate application of this technique should be avoided. Nonetheless, a growing body of both clinical and laboratory literature has demonstrated that epidural analgesia in appropriate situations results in substantially less morbidity and mortality in comparison with systemic routes of adminisrration.t'? The overall safety of epidural infusion of narcotics for postoperative pain has been exceptional and compares favorably with systemic techniques. Few investigations have studied the comparative safety of epidural analgesia and PCA. Wheatley and associatesII arbitrarily defined respiratory depression as an oxygen saturation of less than 94% for more than 6 minuteslh. Although this figure may have no clinical correlate, these authors clearly showed that the PCA group had a significantly briefer duration of oxygen saturation less than 94% than did the epidural group. Of importance, postoperative systemic administration of narcotics is not devoid of risks." Deaths have been attributed to intramuscular administration of narcotics postoperatively. During the past decade, epidural infusion of narcotics and intravenous administration of narcotics by PCA have been used extensively in routine postoperative settings, and
EDITORIAL 1113
the result has been an acceptably low risk. This outcome may, in part, reflect a greater vigilance afforded patients with epidural infusion of narcotics or PCA and the dedicated pain-management teams that often monitor their 'analgesic needs. Future Challenges.-What is the future outlook for management of postoperative pain? Developing better analgesic agents remains as one challenge. Narcotics have side effects and are associated with the previously mentioned potential risks. Local anesthesia can produce sympathetic blockade and, potentially, hypotension. Alternative analgesic pathways are being investigated, including the cholinergic and 0. 2 pathways. Representative agents in these classes possess analgesic action without many of the side effects and risks of opiates; however, they have their own sideeffect profile. Until the perfect agent is developed, use of various classes of synergistic drugs in infusion mixtures will facilitate administration of decreased dosages with enhanced analgesia. Therefore, the side effects and potential risks will be less in comparison with administration of any single drug. Tailoring of epidurally administered analgesic agents to meet the individual patient's needs will continue to evolve. Cost.-What is the financial investment associated with these techniques, and can their existence be justified? Epidural analgesia or PCA necessitates special hardware, a procedure for insertion (epidural), drug mixtures, and, preferably, a specific management team. Each of these areas represents a small but actual cost to the patient. The overall cost can be contained if practitioners adhere to reasonable guidelines. Before billing guidelines had been established, some practitioners billed excessively for management of postoperative pain. This practice was unethical and diminished the willingness of third-party payers to reimburse for these expenditures. An active acute pain-management service can be economically successful with modest charges to the patient (less than $IOO/day, total cost). Outcome studies of epidural analgesia have demonstrated a considerable costeffectiveness in high-risk patients.8•9,13 Although similar studies have not been published for PCA, they may be forthcoming, and the excellent relief of pain itself can be considered sufficient reason for use of PCA in many patients. After 6 years in a very busy postoperative pain-management practice, I have never had One patient complain about a bill for management of postsurgical pain. Conclusion.-The routine intramuscular administration of narcotics to control most postoperative pain is no longer standard. Although it will continue to have a role for minor procedures, new techniques such as those described by Allaire and colleagues will provide analgesia for a large portion of the postsurgical patients. Moderate to severe pain cannot be considered beneficial or acceptable during the
Mayo Clin Proc, November 1992, Vol 67
1114 EDITORIAL
postoperative period, and postoperative suffering can now be minimized. Acute pain-management practices have successfully evolved to the benefit of the patient. Refinement of currently available techniques and development of new techniques will continue in the future. Richard L. Rauck, M.D. Pain Control Center Wake Forest University Medical Center Winston-Salem, North Carolina
REFERENCES 1. Parker RK, Holtmann B, White PP: Patient-controlled analgesia: does a concurrent opioid infusion improve pain management after surgery? JAMA 266: 1947-1952, 1991 2. Owen H, McMillan V, Rogowski D: Postoperative pain therapy: a survey of patients' expectations and their experiences. Pain 41:303-307,1990 3. Loper KA, Ready LB, Nessly M, Rapp SE: Epidural morphine provides greater pain relief than patient-controlled intravenous morphine following cholecystectomy. Anesth Analg 69:826-828, 1989 4. Glass PSA, Estok P, Ginsberg B, Goldberg JS, Sladen RN: Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg 74:345-351,1992
5.
Loper KA' Ready LB, Downey M, Sandler AN, Nessly M, Rapp S, Badner N: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 70:72-75, 1990 6. Rawal N, Wattwil M: Respiratory depression after epidural morphine-an experimental and clinical study. Anesth Analg 63:8-14,1984 7. Rawal N, Schott U, Tandon B: Influence of i.v. naloxone infusion on analgesia and untoward effects of epidural morphine (abstract). Anesth Ana1g 64:270, 1985 8. YeagerMP, Glass DD, NeffRK, Brinck-Johnsen T: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729-736, 1987 9. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Patel RV, Ivankovich AD: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696-704, 1991 10. Blomberg S, Emanuelsson H, Kvist H, Lamm C, Ponten J, Waagstein P, Ricksten S-E: Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease. Anesthesiology 73:840-847, 1990 11. Wheatley RG, Somerville ID, Sapsford DJ, Jones JG: Postoperative hypoxaemia: comparison of extradural, i.m. and patient-controlled opioid analgesia. Br J Anaesth 64:267275, 1990 12. Miller RR: Analgesics. In Drug Effects in Hospitalized Patients. Edited by RR Miller, DJ Greenblatt. New York, John Wiley & Sons, 1976, pp 151-152 13. Rawal N, Sjostrand D, Christoffersson E, Dahlstrom B, Arvill A, Rydman H: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583-592, 1984
Address reprint requests to Dr. R. L. Rauck, Director, Pain Control Center, Wake Forest University Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1077. MayoClinProc 67:1112-1114,1992
medicating, cultural bias, and stoicism. In a questionnaire given to preoperative patients, Owen and associates' found that most expect some pain postoperatively. If patients are reassured that sufficient medicine will be available and particularly if they can maintain some control (for example, with PCA), their fears are considerably allayed. Patients may choose not to titrate themselves to 0 (that is, no pain) on a scale of 0 to 10 if given the option with PCA. In the current study, the PCA group may have been unable to administer the amount of medicine they desired because of the lockout interval of 10 minutes. These patients could have been given the opportunity to use the PCA machine more frequently by decreasing the lockout interval from 10 to 5 minutes. With this option, more frequent doses might have been used and control of pain might have been more successful. Another possible reason for the variation in doses between the two groups may have been a relative analgesic overdose in the epidural group. Although the arbitrary epidural infusion dosage of 80 )..lglh provided excellent analgesia without side effects, a lower rate of infusion may have maintained similar analgesic results. Control of Intraoperative Factors.-Postoperative patients are a heterogeneous group. In the study by Allaire and colleagues, all patients underwent the same procedureradical retropubic prostatectomy. Some other variables were not well controlled. Intraoperatively, some patients received epidural anesthesia, whereas others received general anesthesia. Although this approach was intentional, the reasons for stratifying the patients in this fashion are somewhat unclear. Other intraoperative events such as intravenous administration of narcotics were not well controlled and would be expected to have effects into the early postoperative period. In addition, the use of local anesthetic agents during the surgical period in some patients with epidural catheters would decrease early postoperative pain and bias the results. All studies of management of postoperative pain should attempt to have standard control of intraoperative events. The tighter the control of preoperative and intraoperative events, the more meaningful the early postoperative data will be. Assessment of Only One Variable.-Because of the heterogeneity of postoperative patients, most immediately postsurgical studies provide the best data when only one issue is addressed. The current study attempts to examine three separate issues: (I) epidural versus systemic routes of administration, (2) comparison of morphine and fentanyl, and
1112
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(3) technique of administration-continuous infusion (epidural group) versus a self-administered model (PCA group). Determining which of these issues accounted for the differences noted-or whether all three issues contributed-is difficult. Any two of these variables could have been controlled, and only one factor could have been the dependent variable. PCA Versus Epidural Analgesia.-The current study attempts to address the question of whether PCA or epidural analgesia can provide better relief of pain in postoperative patients. Within the aforementioned limitations, this article clearly shows epidural analgesia to be superior to PCA for the patient population studied. Qualitatively better results with epidural analgesia have been observed by many clinicians. In a similar comparative postoperative study of orthopedic patients, Loper and co-workers' found epidural analgesia with morphine superior to PCA. Other studies have shown that no advantages exist with fentanyl when administered epidurally versus PCA.4.5 The psychologic advantage of allowing patients some control over their pain medications, at a time (during the early postoperative period) when they have virtually no control over other events surrounding them, cannot be overemphasized. Safety.-Can the administration of potent analgesic drugs by new and sophisticated techniques be considered safe for routine use postoperatively? Epidural analgesia has been shown to cause respiratory depression along with other side effects, including urinary retention, pruritus, and nausea and vomiting.s" Thus, the indications for use of epidural analgesia must be examined for each case, and the indiscriminate application of this technique should be avoided. Nonetheless, a growing body of both clinical and laboratory literature has demonstrated that epidural analgesia in appropriate situations results in substantially less morbidity and mortality in comparison with systemic routes of adminisrration.t'? The overall safety of epidural infusion of narcotics for postoperative pain has been exceptional and compares favorably with systemic techniques. Few investigations have studied the comparative safety of epidural analgesia and PCA. Wheatley and associatesII arbitrarily defined respiratory depression as an oxygen saturation of less than 94% for more than 6 minuteslh. Although this figure may have no clinical correlate, these authors clearly showed that the PCA group had a significantly briefer duration of oxygen saturation less than 94% than did the epidural group. Of importance, postoperative systemic administration of narcotics is not devoid of risks." Deaths have been attributed to intramuscular administration of narcotics postoperatively. During the past decade, epidural infusion of narcotics and intravenous administration of narcotics by PCA have been used extensively in routine postoperative settings, and
EDITORIAL 1113
the result has been an acceptably low risk. This outcome may, in part, reflect a greater vigilance afforded patients with epidural infusion of narcotics or PCA and the dedicated pain-management teams that often monitor their 'analgesic needs. Future Challenges.-What is the future outlook for management of postoperative pain? Developing better analgesic agents remains as one challenge. Narcotics have side effects and are associated with the previously mentioned potential risks. Local anesthesia can produce sympathetic blockade and, potentially, hypotension. Alternative analgesic pathways are being investigated, including the cholinergic and 0. 2 pathways. Representative agents in these classes possess analgesic action without many of the side effects and risks of opiates; however, they have their own sideeffect profile. Until the perfect agent is developed, use of various classes of synergistic drugs in infusion mixtures will facilitate administration of decreased dosages with enhanced analgesia. Therefore, the side effects and potential risks will be less in comparison with administration of any single drug. Tailoring of epidurally administered analgesic agents to meet the individual patient's needs will continue to evolve. Cost.-What is the financial investment associated with these techniques, and can their existence be justified? Epidural analgesia or PCA necessitates special hardware, a procedure for insertion (epidural), drug mixtures, and, preferably, a specific management team. Each of these areas represents a small but actual cost to the patient. The overall cost can be contained if practitioners adhere to reasonable guidelines. Before billing guidelines had been established, some practitioners billed excessively for management of postoperative pain. This practice was unethical and diminished the willingness of third-party payers to reimburse for these expenditures. An active acute pain-management service can be economically successful with modest charges to the patient (less than $IOO/day, total cost). Outcome studies of epidural analgesia have demonstrated a considerable costeffectiveness in high-risk patients.8•9,13 Although similar studies have not been published for PCA, they may be forthcoming, and the excellent relief of pain itself can be considered sufficient reason for use of PCA in many patients. After 6 years in a very busy postoperative pain-management practice, I have never had One patient complain about a bill for management of postsurgical pain. Conclusion.-The routine intramuscular administration of narcotics to control most postoperative pain is no longer standard. Although it will continue to have a role for minor procedures, new techniques such as those described by Allaire and colleagues will provide analgesia for a large portion of the postsurgical patients. Moderate to severe pain cannot be considered beneficial or acceptable during the
Mayo Clin Proc, November 1992, Vol 67
1114 EDITORIAL
postoperative period, and postoperative suffering can now be minimized. Acute pain-management practices have successfully evolved to the benefit of the patient. Refinement of currently available techniques and development of new techniques will continue in the future. Richard L. Rauck, M.D. Pain Control Center Wake Forest University Medical Center Winston-Salem, North Carolina
REFERENCES 1. Parker RK, Holtmann B, White PP: Patient-controlled analgesia: does a concurrent opioid infusion improve pain management after surgery? JAMA 266: 1947-1952, 1991 2. Owen H, McMillan V, Rogowski D: Postoperative pain therapy: a survey of patients' expectations and their experiences. Pain 41:303-307,1990 3. Loper KA, Ready LB, Nessly M, Rapp SE: Epidural morphine provides greater pain relief than patient-controlled intravenous morphine following cholecystectomy. Anesth Analg 69:826-828, 1989 4. Glass PSA, Estok P, Ginsberg B, Goldberg JS, Sladen RN: Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg 74:345-351,1992
5.
Loper KA' Ready LB, Downey M, Sandler AN, Nessly M, Rapp S, Badner N: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 70:72-75, 1990 6. Rawal N, Wattwil M: Respiratory depression after epidural morphine-an experimental and clinical study. Anesth Analg 63:8-14,1984 7. Rawal N, Schott U, Tandon B: Influence of i.v. naloxone infusion on analgesia and untoward effects of epidural morphine (abstract). Anesth Ana1g 64:270, 1985 8. YeagerMP, Glass DD, NeffRK, Brinck-Johnsen T: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729-736, 1987 9. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Patel RV, Ivankovich AD: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696-704, 1991 10. Blomberg S, Emanuelsson H, Kvist H, Lamm C, Ponten J, Waagstein P, Ricksten S-E: Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease. Anesthesiology 73:840-847, 1990 11. Wheatley RG, Somerville ID, Sapsford DJ, Jones JG: Postoperative hypoxaemia: comparison of extradural, i.m. and patient-controlled opioid analgesia. Br J Anaesth 64:267275, 1990 12. Miller RR: Analgesics. In Drug Effects in Hospitalized Patients. Edited by RR Miller, DJ Greenblatt. New York, John Wiley & Sons, 1976, pp 151-152 13. Rawal N, Sjostrand D, Christoffersson E, Dahlstrom B, Arvill A, Rydman H: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583-592, 1984
