Combination of Low-Dose Epidural Morphine and Intramuscular Diclofenac Sodium in Postcesarean Analgesia Hsiao-Lun Sun, m, Chi-Chen Wu, Martin S. Mok, MD
MB,
Min-Shung Lin,
MB,
Ching-Feng Chang,
MB,
and
Departments of Anesthesiology and Family Medicine, Cathay General Hospital, Taipei, Taiwan, Republic of China and Department of Anesthesiology, University of Southern California, Los Angeles, California
Epidural morphine is used for postcesarean analgesia, and nonsteroidal antiinflammatory drugs are frequently administered to relieve uterine cramps after vaginal delivery. To assess the efficacy of a combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia, a double-blind, randomized study was conducted. Epidural anesthesia was given to 120 parturients who were randomly allocated into four treatment groups: group A received normal saline solution, 10 mL epidurally and 3 mL intramuscularly (IM); group B received 10 mL of epidural saline solution and 75 mg (3 mL) of diclofenac IM; group C received 2 mg of morphine in 10 mL of epidural saline solution and 3 mL of saline solution IM; and group D received 2 mg of morphine in 10 mL of epidural saline solution and 75 mg of diclofenac IM. Epidural injections were given after delivery of the placenta, and IM injections were given on arrival in the recovery room. Verbal analogue pain scores were recorded at 2, 4, 8, 12, 18, and 24 h after epidural injection.
C
ontrol of postoperative pain with epidural opioids has become common practice, particularly after cesarean delivery (1-5). A low dose of 2 mg of epidural morphine has been found to be effective in inducing analgesia after lower abdominal surgery (6) but inadequate in a considerable proportion of patients after cesarean section (2,6,7). The difference is noteworthy. Patients after cesarean section suffer from two kinds of acute pain: wound pain and spasmodic uterine contraction pain; however, only a few studies related to postcesarean analgesia have ever addressed this issue (6,8,9). In the past 10 yr, a number of reports (10-14) demonstrating the analgesic efficacy of parenteral nonsteroidal antiinThis study was conducted at Cathay General Hospital, Taipei, Taiwan, Republic of China. Accepted for publication March 6, 1992. Address correspondenceto Hsiao-Lun Sun, MB, Department of Anesthesiology, Cathay General Hospital, 280, Section 4, Jen-Ai Road Taipei, Taiwan, Republic of China.
64
Anesth Analg 1992;75:M
Subjective scores of overall pain relief were also recorded at 24 h. Results showed that scores of overall pain relief were significantly better in group D compared with group A, B, or C (P < 0.05). Groups A and B required more supplemental meperidine than groups C and D. None of the subjects in group D requested supplemental analgesia. Compared with the other three groups, group D experienced a better analgesic effect for both wound pain and uterine cramping pain from 4 to 18 h (P C 0.05). Incidence of nausea or vomiting, or both, and pruritus occurred more frequently in groups C and D compared with group A or B (P < 0.05).No bradypnea was observed during the study period. Diclofenac alone was not effective in postcesarean analgesia. We conclude that combining low-dose (2 mg) epidural morphine and IM diclofenac enhances analgesic efficacy in the treatment of both wound pain and uterine cramps after cesarean section. (Anesth Analg 1992;75:64-8)
flammatory drugs (NSAIDs) alone or in combination with opioids for various types of acute pain have been presented. The NSAIDs have also been used to relieve uterine cramps after vaginal delivery (8,9,15,16). Therefore, much interest has been generated in finding the means of potentiating the analgesic effect of low-dose epidural morphine without accentuating the adverse effects. In this study, we evaluated the effect of 75 mg of intramuscular (Ih4) diclofenac sodium, 2 mg of epidural morphine, and the combination of these two regimens in postcesarean analgesia to see whether the combination could be clinically more effective than either drug alone.
Methods A double-blind, randomized study was approved by the Human Subjects Committee of our hospital and conducted from November 1990 to February 1991. One hundred twenty parturients of ASA physical 01992 by the International Anesthesia Research Sodety O003-2999/92/$5.00
ANESM ANALG 1!392;75:64-8
status I or I1 about to undergo elective cesarean section were enrolled in the study. Informed consent was obtained from all of them, and a verbal analogue pain score (0, no pain; 10, the worst pain) was explained before induction of anesthesia. After hydration with 750 mL of lactated Ringefs solution, an epidural catheter was inserted through a Portex minipack 16G Tuohy needle at the L2-3 or L3-4 interspace and the tip advanced 3-S an cephalad. Sensory anesthesia (determinedby pinprick) extending to the T-4 dermatome was achieved with 2% lidocaine with freshly added epinepluine 1:200,000. After delivery, 10 U of oxytocin and 0.2 mg of ergonovine were administered intravenously. The parturients were allocated at random into one of four treatment groups: group A received 10 mL of epidural and 3 mL of IM normal saline solution; group B received 10 mL of epidural normal &e solution and 75 mg (3mL) of IM diclofenac; group C received 2 mg of epidural morphine in 10 mL of n o d saline solution and 3 mL of IM normal saline solution; and group D received 2 mg of epidural morphine in 10 mL of normal saline solution and 75 mg (3 mL) of IM diclofenac. Epidural injections were given after delivery of the placenta and the IM injections on arrival in the recovery room. Epidural catheters were removed after surgery. All drugs were given in a double-blind manner. After a 2-h stay in the recovery room, patients were sent to the obstetric ward. An Ohmeda Biox 3760 pulse oximeter was used continuously during the study period, and hemoglobin oxygen saturation was recorded every 3 h or at any time it declined to 12 breaths/ min during the study period, and the hemoglobin
Nausedvomiting Pruritus" Bleeding Bradypnea
Group A (n = 29)
Group B (n = 29)
Group C (n = 29)
3 0 1
6 1 1
0
0
10 27 1 0
12
30 0 0
oxygen saturation was >90% in all patients. Pruritus was the most frequent side effect in the present study, especially in patients who received morphine treatment; however, the condition was mild in most of the patients, and only one patient needed diphenhydramine (30 mg IM) management.
We observed higher pain scores and the need for additional analgesia in the 2-mg epidural morphine regimen, compared with the drug combination regimen. This is compatible with previous reports that dthough 2 mg of epidural morphine is effective for pain relief after lower abdominal surgery, it is not as effective in postcesarean analgesia (2,6,7). The finding that the combination of epidural morphine and [M diclofenac was superior to epidural morphine done in analgesic quality and duration during the
ANESTH ANALG 1992;7564-8
P18-h period indicates that diclofenac contributes to additional relief of both wound pain and uterine contraction pain. The efficacy of 2 mg of epidural morphine in postcesarean analgesia was enhanced by the addition of diclofenac. Niv et al. (6) reported spasmodic uterine cramps in a postcesarean section group given 2 mg of epidural morphine. They were subsequently treated with single doses of IM dipyrone. Bloomfield et al. (8,9,15) and Sunshine et al. (16) compared various oral NSAIDs in the treatment of postpartum pain after vaginal delivery and found that NSAIDs were superior to codeine and placebo in relieving uterine cramps. In our study, patients given IM diclofenac consumed less meperidine and had lower pain scores compared with the placebo group. This finding is consistent with other studies (10-12) that indicated that NSAIDs have an opioid-sparing effect. We also observed that diclofenac was more effective in relieving uterine contraction pain than wound pain, indicating the contribution of NSAIDs to the relief of uterine cramps, as shown in other studies (8,9,15,16). Although better than placebo, IM diclofenac alone was not as effective as 2 mg of epidural morphine with regard to relieving both wound pain and uterine contraction pain. The results demonstrated that the 75-mg dose of diclofenac alone was not adequate in postcesarean analgesia. Prostaglandins have been recognized as important mediators in enhancing postpartum uterine contractile activity (17). Prostaglandins are closely related to dysmenorrhea and are probably the cause of postpartum uterine pain. The NSAIDs were thought to exert their analgesic effect by the inhibition of prostaglandin synthesis, thus reducing both wound pain and uterine contraction pain after cesarean section. In addition to the welldocumented peripheral mechanism, a central antinociceptive action of NSAIDs has been demonstrated in both animals (18,19) and humans (20). Diclofenac sodium, a potent prostaglandin synthetase inhibitor, has been shown to possess antiinflammatory, antiedema, antipyretic, and analgesic properties (21,22). Martini et al. (23) also demonstrated increased levels of peripheral Mndorphin after diclofenac treatment and proposed its contribution to analgesia. In the present study, we identified the advantages of each analgesic component ([a] the spinal analgesia of epidural morphine; [b] the peripheral inhibition of prostaglandin synthesis and the nonopioid supraspinal noaceptive reflex inhibition property of NSAIDs) in providing enhanced postcesarean analgesia. Most of the patients receiving combination analgesia were satisfied with the pain control, and there was no difference among the other three groups with regard to overall pain relief. Our results showed that
OBSTETRIC ANESTHESIA SUN ET AL. LOW-DOSE EPIDURAL MORPHINE AND IM DICLOFENAC
67
approximately %%Iof the patients receiving the combination of 2 mg of epidural morphine and IM diclofenac experienced excellent to good pain relief. Analgesia resulted from the combination of drugs with different mechanisms, especially the contribution of NSAIDs to uterine cramp pain relief. In view of the high level of effectiveness and average incidence of side effects, postcesarean pain may be relieved by the combination of 2 mg of epidural morphine and J M diclofenac without potentiating other side effects. The risk of postpartum hemorrhage related to NSAIDs should be taken into consideration. Three patients were found to have abnormal amounts of lochia because of poor uterine contraction; only one of them received diclofenac injection. Diclofenac can prolong bleeding time and reduce platelet aggregation (24,E); however, diclofenac-induced postoperative bleeding is rare in clinical practice (10,24,25). Furthermore, in studies reported by Bloomfield et al. (8,9,15) and Sunshine et al. (16), NSAIDs have been used effectively for relieving postpartum uterine cramps and postepisiotomy pain without significant side effects. In conclusion, diclofenac sodium alone is not adequate for postcesarean analgesia. Although effective in relieving most wound pain, 2 mg of epidural morphine is not fully effective in relieving uterine contraction pain. The combination of low-dose (2 mg) epidural morphine and 75 mg of IM diclofenac sodium enhances the analgesic effect in the treatment of both wound pain and uterine cramps after cesarean section. The authors thank Chi-Tse Lee, MPH, Social Medicine Department, National Yang Ming Medical College, for study design consultation and statisticalassistance.
References 1. Youngstrom PC, Cowan RI, Sutheimer C, Eastwood DW, Yu JCM. Pain relief and plasma concentrations from epidural and intramuscular morphine in postcesarean patients. Anesthesiology 1982;57404-9. 2. Rosen MA,Hughes SC,Shnider SM, et al. Epidural morphine for the relief of postoperative pain after cesarean delivery. Anesth Analg 1983;62&72. 3. Chadwidc Hs,Ready LB. Intrathed and epidural morphine sulfate for postcesarean analgesia-a clinical comparison. Anesthesiology 1988;68:-9. 4. Harrison DM, Sinatra R, Morgese L, Chung JH. Epidural narcotic and patient-controlled analgesia for postcesarean section pain relief. Anesthesiology 1988,68:454-7. 5. Douglas MJ, McMorland GH, Janzen JA. Influence of bupivacaine as an adjuvant to epidural morphine for analgesia after cesarean section. Anesth Analg 1988;67113&11. 6. Niv D, Rudidc V, Chayen MS, David MP. Variations in the
68
OBSTETRIC ANESTHESIA SUN ET AL. LOW-DOSE EPIDURAL MORPHINE AND IM DICLOFENAC
effect of epidural morphine in gynecological and obstetric patients. Acta Obstet Gynecol Scand 1983;62:455-9. 7. Coombs DW, Danielson DR, Pagaue MG, Rippe E. Epidurally administered morphine for postcesarean analgesia. Surg Gynecol Obstet 1982;154:3&8. 8. Bloomfield SS, Cissel GB, Mitchell J, Barden TP. Analgesic sensitivity of two postpartum pain models. Pain 1986;27171-9. 9. Bloomfield SS, Barden TI', Mitchell J. Naproxen, aspirin and codein in postpartum uterine pain. Clin Pharmacol Ther 1977; 21:414-21. 10. Hodsman NBA, Burns J, Blyth A, Kenny GNC, McArdle CS, Rotman H. The morphine sparing effects of diclofenac sodium following abdominal surgery. Anaesthesia 1987;42:1005-8. 11. Gillies GWA, Kenny GNC, Bullingham RES, McArdle CS. The morphine sparing effect of ketorolac tromethamine: a study of a new, parenteral non-steroidal anti-inflammatoryagent after abdominal surgery. Anaesthesia 1987;42:727-31. 12. Carlborg I, Lindoff C, Hellman A. Didofenac versus pethidine in the treatment of pain after hysterectomy. Eur J Anaesthesiol 1987;4241-7. 13. Kantor TG. Use of diclofenac in analgesia. Am J Med 1986; 8O(Suppl4b):64-9. 14. Schulze S, Roikjaer 0, Hasselstrram L, Jensen NH,Kehlet H. Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. Surgery 1988;103321-7. 15. Bloomfield SS, Cissel GB, Mitchell J, Barden TP.Codeine and aspirin analgesia in postpartum uterine cramps: qualitative aspects of quantitative assessments. Clin Pharmacol Ther 1983;34:488-95. 16. Sunshine A, Zighelboim I, Olson NZ, Sarrazin CD,Laska E. A
ANESTH ANALG 1992;75364-8
comparative oral analgesic study of indoprofen, aspirin, and placebo in postpartum pain. J Clin Pharmacol 1985;25:374-80. 17. Anderson KE, Forman A, Ulmsten U. Pharmacology of labor. Clin Obstet Gynecol 1983;2656-77. 18. Ferreira SH, Lorenzetti BB, CorrPa FMA. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol 1978;53:3W. 19. Attal N, Kayser V, Eschalier A, Benoist JM, Guilbaud G. Behavioural and electrophysiological evidence for an analgesic effect of a non-steroidal anti-inflammatory agent, sodium diclofenac. Pain 1988;35341-8. 20. Willer JC, Broucker TD, Bussel B, Agnes RB, Harrewyn JM. Central analgesic effect of ketoprofen in humans: electrophysiological evidence for a supraspinal mechanism in a doubleblind and cross-over study. Pain 1989;38:1-7. 21. Maier R, Manass6 R, Riesterer L, Pericin C, Ruegg M, Ziel R. The pharmacology of didofenac sodium (Voltarol). Rheumatol Rehab 1979;17(Suppl2):11-21. 22. Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1988;35:244-85. 23. Martini A, Bondiolotti GP, Biol D, et al. Diclofenac increases beta-endorphin plasma concentrations. J Int Med Res 1984;12: 925. 24. Rorarius M, Miralles J, Bare GA, Palomaki E. Diclofenac versus indomethacin given as intravenous infusions: their effect on haemodynamics and bleeding time and side-effects in healthy subjects. Ann Clin Res 1985;17306-9. 25. Power I, Chambers WA, Greer IA, Ramage D, Simon E. Platelet function after intramuscular diclofenac. Anaesthesia 1990;45:916-9.
MB,
Min-Shung Lin,
MB,
Ching-Feng Chang,
MB,
and
Departments of Anesthesiology and Family Medicine, Cathay General Hospital, Taipei, Taiwan, Republic of China and Department of Anesthesiology, University of Southern California, Los Angeles, California
Epidural morphine is used for postcesarean analgesia, and nonsteroidal antiinflammatory drugs are frequently administered to relieve uterine cramps after vaginal delivery. To assess the efficacy of a combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia, a double-blind, randomized study was conducted. Epidural anesthesia was given to 120 parturients who were randomly allocated into four treatment groups: group A received normal saline solution, 10 mL epidurally and 3 mL intramuscularly (IM); group B received 10 mL of epidural saline solution and 75 mg (3 mL) of diclofenac IM; group C received 2 mg of morphine in 10 mL of epidural saline solution and 3 mL of saline solution IM; and group D received 2 mg of morphine in 10 mL of epidural saline solution and 75 mg of diclofenac IM. Epidural injections were given after delivery of the placenta, and IM injections were given on arrival in the recovery room. Verbal analogue pain scores were recorded at 2, 4, 8, 12, 18, and 24 h after epidural injection.
C
ontrol of postoperative pain with epidural opioids has become common practice, particularly after cesarean delivery (1-5). A low dose of 2 mg of epidural morphine has been found to be effective in inducing analgesia after lower abdominal surgery (6) but inadequate in a considerable proportion of patients after cesarean section (2,6,7). The difference is noteworthy. Patients after cesarean section suffer from two kinds of acute pain: wound pain and spasmodic uterine contraction pain; however, only a few studies related to postcesarean analgesia have ever addressed this issue (6,8,9). In the past 10 yr, a number of reports (10-14) demonstrating the analgesic efficacy of parenteral nonsteroidal antiinThis study was conducted at Cathay General Hospital, Taipei, Taiwan, Republic of China. Accepted for publication March 6, 1992. Address correspondenceto Hsiao-Lun Sun, MB, Department of Anesthesiology, Cathay General Hospital, 280, Section 4, Jen-Ai Road Taipei, Taiwan, Republic of China.
64
Anesth Analg 1992;75:M
Subjective scores of overall pain relief were also recorded at 24 h. Results showed that scores of overall pain relief were significantly better in group D compared with group A, B, or C (P < 0.05). Groups A and B required more supplemental meperidine than groups C and D. None of the subjects in group D requested supplemental analgesia. Compared with the other three groups, group D experienced a better analgesic effect for both wound pain and uterine cramping pain from 4 to 18 h (P C 0.05). Incidence of nausea or vomiting, or both, and pruritus occurred more frequently in groups C and D compared with group A or B (P < 0.05).No bradypnea was observed during the study period. Diclofenac alone was not effective in postcesarean analgesia. We conclude that combining low-dose (2 mg) epidural morphine and IM diclofenac enhances analgesic efficacy in the treatment of both wound pain and uterine cramps after cesarean section. (Anesth Analg 1992;75:64-8)
flammatory drugs (NSAIDs) alone or in combination with opioids for various types of acute pain have been presented. The NSAIDs have also been used to relieve uterine cramps after vaginal delivery (8,9,15,16). Therefore, much interest has been generated in finding the means of potentiating the analgesic effect of low-dose epidural morphine without accentuating the adverse effects. In this study, we evaluated the effect of 75 mg of intramuscular (Ih4) diclofenac sodium, 2 mg of epidural morphine, and the combination of these two regimens in postcesarean analgesia to see whether the combination could be clinically more effective than either drug alone.
Methods A double-blind, randomized study was approved by the Human Subjects Committee of our hospital and conducted from November 1990 to February 1991. One hundred twenty parturients of ASA physical 01992 by the International Anesthesia Research Sodety O003-2999/92/$5.00
ANESM ANALG 1!392;75:64-8
status I or I1 about to undergo elective cesarean section were enrolled in the study. Informed consent was obtained from all of them, and a verbal analogue pain score (0, no pain; 10, the worst pain) was explained before induction of anesthesia. After hydration with 750 mL of lactated Ringefs solution, an epidural catheter was inserted through a Portex minipack 16G Tuohy needle at the L2-3 or L3-4 interspace and the tip advanced 3-S an cephalad. Sensory anesthesia (determinedby pinprick) extending to the T-4 dermatome was achieved with 2% lidocaine with freshly added epinepluine 1:200,000. After delivery, 10 U of oxytocin and 0.2 mg of ergonovine were administered intravenously. The parturients were allocated at random into one of four treatment groups: group A received 10 mL of epidural and 3 mL of IM normal saline solution; group B received 10 mL of epidural normal &e solution and 75 mg (3mL) of IM diclofenac; group C received 2 mg of epidural morphine in 10 mL of n o d saline solution and 3 mL of IM normal saline solution; and group D received 2 mg of epidural morphine in 10 mL of normal saline solution and 75 mg (3 mL) of IM diclofenac. Epidural injections were given after delivery of the placenta and the IM injections on arrival in the recovery room. Epidural catheters were removed after surgery. All drugs were given in a double-blind manner. After a 2-h stay in the recovery room, patients were sent to the obstetric ward. An Ohmeda Biox 3760 pulse oximeter was used continuously during the study period, and hemoglobin oxygen saturation was recorded every 3 h or at any time it declined to 12 breaths/ min during the study period, and the hemoglobin
Nausedvomiting Pruritus" Bleeding Bradypnea
Group A (n = 29)
Group B (n = 29)
Group C (n = 29)
3 0 1
6 1 1
0
0
10 27 1 0
12
30 0 0
oxygen saturation was >90% in all patients. Pruritus was the most frequent side effect in the present study, especially in patients who received morphine treatment; however, the condition was mild in most of the patients, and only one patient needed diphenhydramine (30 mg IM) management.
We observed higher pain scores and the need for additional analgesia in the 2-mg epidural morphine regimen, compared with the drug combination regimen. This is compatible with previous reports that dthough 2 mg of epidural morphine is effective for pain relief after lower abdominal surgery, it is not as effective in postcesarean analgesia (2,6,7). The finding that the combination of epidural morphine and [M diclofenac was superior to epidural morphine done in analgesic quality and duration during the
ANESTH ANALG 1992;7564-8
P18-h period indicates that diclofenac contributes to additional relief of both wound pain and uterine contraction pain. The efficacy of 2 mg of epidural morphine in postcesarean analgesia was enhanced by the addition of diclofenac. Niv et al. (6) reported spasmodic uterine cramps in a postcesarean section group given 2 mg of epidural morphine. They were subsequently treated with single doses of IM dipyrone. Bloomfield et al. (8,9,15) and Sunshine et al. (16) compared various oral NSAIDs in the treatment of postpartum pain after vaginal delivery and found that NSAIDs were superior to codeine and placebo in relieving uterine cramps. In our study, patients given IM diclofenac consumed less meperidine and had lower pain scores compared with the placebo group. This finding is consistent with other studies (10-12) that indicated that NSAIDs have an opioid-sparing effect. We also observed that diclofenac was more effective in relieving uterine contraction pain than wound pain, indicating the contribution of NSAIDs to the relief of uterine cramps, as shown in other studies (8,9,15,16). Although better than placebo, IM diclofenac alone was not as effective as 2 mg of epidural morphine with regard to relieving both wound pain and uterine contraction pain. The results demonstrated that the 75-mg dose of diclofenac alone was not adequate in postcesarean analgesia. Prostaglandins have been recognized as important mediators in enhancing postpartum uterine contractile activity (17). Prostaglandins are closely related to dysmenorrhea and are probably the cause of postpartum uterine pain. The NSAIDs were thought to exert their analgesic effect by the inhibition of prostaglandin synthesis, thus reducing both wound pain and uterine contraction pain after cesarean section. In addition to the welldocumented peripheral mechanism, a central antinociceptive action of NSAIDs has been demonstrated in both animals (18,19) and humans (20). Diclofenac sodium, a potent prostaglandin synthetase inhibitor, has been shown to possess antiinflammatory, antiedema, antipyretic, and analgesic properties (21,22). Martini et al. (23) also demonstrated increased levels of peripheral Mndorphin after diclofenac treatment and proposed its contribution to analgesia. In the present study, we identified the advantages of each analgesic component ([a] the spinal analgesia of epidural morphine; [b] the peripheral inhibition of prostaglandin synthesis and the nonopioid supraspinal noaceptive reflex inhibition property of NSAIDs) in providing enhanced postcesarean analgesia. Most of the patients receiving combination analgesia were satisfied with the pain control, and there was no difference among the other three groups with regard to overall pain relief. Our results showed that
OBSTETRIC ANESTHESIA SUN ET AL. LOW-DOSE EPIDURAL MORPHINE AND IM DICLOFENAC
67
approximately %%Iof the patients receiving the combination of 2 mg of epidural morphine and IM diclofenac experienced excellent to good pain relief. Analgesia resulted from the combination of drugs with different mechanisms, especially the contribution of NSAIDs to uterine cramp pain relief. In view of the high level of effectiveness and average incidence of side effects, postcesarean pain may be relieved by the combination of 2 mg of epidural morphine and J M diclofenac without potentiating other side effects. The risk of postpartum hemorrhage related to NSAIDs should be taken into consideration. Three patients were found to have abnormal amounts of lochia because of poor uterine contraction; only one of them received diclofenac injection. Diclofenac can prolong bleeding time and reduce platelet aggregation (24,E); however, diclofenac-induced postoperative bleeding is rare in clinical practice (10,24,25). Furthermore, in studies reported by Bloomfield et al. (8,9,15) and Sunshine et al. (16), NSAIDs have been used effectively for relieving postpartum uterine cramps and postepisiotomy pain without significant side effects. In conclusion, diclofenac sodium alone is not adequate for postcesarean analgesia. Although effective in relieving most wound pain, 2 mg of epidural morphine is not fully effective in relieving uterine contraction pain. The combination of low-dose (2 mg) epidural morphine and 75 mg of IM diclofenac sodium enhances the analgesic effect in the treatment of both wound pain and uterine cramps after cesarean section. The authors thank Chi-Tse Lee, MPH, Social Medicine Department, National Yang Ming Medical College, for study design consultation and statisticalassistance.
References 1. Youngstrom PC, Cowan RI, Sutheimer C, Eastwood DW, Yu JCM. Pain relief and plasma concentrations from epidural and intramuscular morphine in postcesarean patients. Anesthesiology 1982;57404-9. 2. Rosen MA,Hughes SC,Shnider SM, et al. Epidural morphine for the relief of postoperative pain after cesarean delivery. Anesth Analg 1983;62&72. 3. Chadwidc Hs,Ready LB. Intrathed and epidural morphine sulfate for postcesarean analgesia-a clinical comparison. Anesthesiology 1988;68:-9. 4. Harrison DM, Sinatra R, Morgese L, Chung JH. Epidural narcotic and patient-controlled analgesia for postcesarean section pain relief. Anesthesiology 1988,68:454-7. 5. Douglas MJ, McMorland GH, Janzen JA. Influence of bupivacaine as an adjuvant to epidural morphine for analgesia after cesarean section. Anesth Analg 1988;67113&11. 6. Niv D, Rudidc V, Chayen MS, David MP. Variations in the
68
OBSTETRIC ANESTHESIA SUN ET AL. LOW-DOSE EPIDURAL MORPHINE AND IM DICLOFENAC
effect of epidural morphine in gynecological and obstetric patients. Acta Obstet Gynecol Scand 1983;62:455-9. 7. Coombs DW, Danielson DR, Pagaue MG, Rippe E. Epidurally administered morphine for postcesarean analgesia. Surg Gynecol Obstet 1982;154:3&8. 8. Bloomfield SS, Cissel GB, Mitchell J, Barden TP. Analgesic sensitivity of two postpartum pain models. Pain 1986;27171-9. 9. Bloomfield SS, Barden TI', Mitchell J. Naproxen, aspirin and codein in postpartum uterine pain. Clin Pharmacol Ther 1977; 21:414-21. 10. Hodsman NBA, Burns J, Blyth A, Kenny GNC, McArdle CS, Rotman H. The morphine sparing effects of diclofenac sodium following abdominal surgery. Anaesthesia 1987;42:1005-8. 11. Gillies GWA, Kenny GNC, Bullingham RES, McArdle CS. The morphine sparing effect of ketorolac tromethamine: a study of a new, parenteral non-steroidal anti-inflammatoryagent after abdominal surgery. Anaesthesia 1987;42:727-31. 12. Carlborg I, Lindoff C, Hellman A. Didofenac versus pethidine in the treatment of pain after hysterectomy. Eur J Anaesthesiol 1987;4241-7. 13. Kantor TG. Use of diclofenac in analgesia. Am J Med 1986; 8O(Suppl4b):64-9. 14. Schulze S, Roikjaer 0, Hasselstrram L, Jensen NH,Kehlet H. Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. Surgery 1988;103321-7. 15. Bloomfield SS, Cissel GB, Mitchell J, Barden TP.Codeine and aspirin analgesia in postpartum uterine cramps: qualitative aspects of quantitative assessments. Clin Pharmacol Ther 1983;34:488-95. 16. Sunshine A, Zighelboim I, Olson NZ, Sarrazin CD,Laska E. A
ANESTH ANALG 1992;75364-8
comparative oral analgesic study of indoprofen, aspirin, and placebo in postpartum pain. J Clin Pharmacol 1985;25:374-80. 17. Anderson KE, Forman A, Ulmsten U. Pharmacology of labor. Clin Obstet Gynecol 1983;2656-77. 18. Ferreira SH, Lorenzetti BB, CorrPa FMA. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol 1978;53:3W. 19. Attal N, Kayser V, Eschalier A, Benoist JM, Guilbaud G. Behavioural and electrophysiological evidence for an analgesic effect of a non-steroidal anti-inflammatory agent, sodium diclofenac. Pain 1988;35341-8. 20. Willer JC, Broucker TD, Bussel B, Agnes RB, Harrewyn JM. Central analgesic effect of ketoprofen in humans: electrophysiological evidence for a supraspinal mechanism in a doubleblind and cross-over study. Pain 1989;38:1-7. 21. Maier R, Manass6 R, Riesterer L, Pericin C, Ruegg M, Ziel R. The pharmacology of didofenac sodium (Voltarol). Rheumatol Rehab 1979;17(Suppl2):11-21. 22. Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1988;35:244-85. 23. Martini A, Bondiolotti GP, Biol D, et al. Diclofenac increases beta-endorphin plasma concentrations. J Int Med Res 1984;12: 925. 24. Rorarius M, Miralles J, Bare GA, Palomaki E. Diclofenac versus indomethacin given as intravenous infusions: their effect on haemodynamics and bleeding time and side-effects in healthy subjects. Ann Clin Res 1985;17306-9. 25. Power I, Chambers WA, Greer IA, Ramage D, Simon E. Platelet function after intramuscular diclofenac. Anaesthesia 1990;45:916-9.
