- Email: [email protected]
traumatologic surgery
CURRENT THERAPEUTIC RESEARCH ® VOL. 55, NO. 12, DECEMBER 1994
EVALUATION OF PIROXICAM AND PIRITRAMIDE IN THE MANAGEMENT OF PAIN AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY DANIELWELRAEDS Center of Traumatology and Rehabilitation, Brugmann University Hospital, Brussels, Belgium
ABSTRACT A randomized, open-label, comparative study was undertaken to assess the analgesic efficacy of piroxicam and piritramide in 57 inpatients who underwent orthopedic/traumatologic surgery. They received either piroxicam 40 mg or piritramide 20 mg in a single intramuscular (IM) dose after surgery and a second IM dose the next morning. Supplemental analgesic medication (usually paracetamol) was given at the patient's request during the postoperative period. Up to 3 days after surgery, both drugs were highly effective, relieved the pain significantly ( P < 0.001), and were rated statistically equivalent on three pain scales. No difference was detected between the two groups regarding the need for supplemental analgesic medication, except on day 2, when 36% of the piritramide-treated patients requested supplemental analgesics versus 8% of piroxicam-treated patients. A low incidence of mainly mild side effects was reported with both medications. Results confirm those of short-term postoperative/posttraumatologic and other pain studies in which piroxicam provided good analgesia and was well tolerated. The two agents studied provided comparable and significant pain relief after orthopedic/ traumatologic surgery. INTRODUCTION
Postoperative pain is an inherent drawback of surgery t h a t can be detrimental to the normal course of postoperative cure. 1 Centrally acting analgesic agents and injectable nonsteroidal a n t i - i n f l a m m a t o r y a g e n t s (NSAIDs) have been used to control postoperative pain. NSAIDs have been shown to be effective against pain, reducing the need for opiate agents following general surgery. 2 Piroxicam* is the first well-studied oxicam. It has a high potency and long e l i m i n a t i o n half-life, which m a k e once-daily dosing possible. 3'4 Piroxicam was studied as an analgesic agent following various types of surgical procedures, including oral surgery, 5-7 orthopedic surgery, s - l ° and gynecologic surgery. 11 Generally, those studies compared oral piroxiAddress correspondence to: D. Welraeds, MD, C.T.R., HSpital Brugmann, place A. Van Gehuchten 4, t020-Brussels, Belgium. Received for publication on July 5, 1994. Printed in the U.S.A. Reproduction in whole or part is not permitted. *Trademark: Feldene ® (Pfizer Inc., New York, New York).
1509
0011-393x/94/$3.50
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
cam with other oral agents and with placebo; however, often only a single administration was involved and observation lasted only a few hours. To the best of our knowledge, a study has never been done to compare the efficacy of injectable piroxicam with an injectable opiate such as piritramide on postoperative orthopedic/traumatologic pain over a longer period of time. Hence, this study focused on the duration and intensity of pain in the postoperative days using short-term therapy of either piroxicam or piritramide, a conventional therapeutic agent. PATIENTS
AND METHODS
Fifty-seven male and female inpatients between the ages of 16 and 75 years who had undergone orthopedic or traumatologic surgery and who were expected to remain hospitalized for at least 3 days were admitted to the study. Oral informed consent, in accordance with the revised Declaration of Helsinki (Hong Kong, 1990) was obtained from all participants. Consent was provided by a parent or guardian for patients under legal age. Patients with a history of drug allergy or gastrointestinal or other serious diseases were excluded, as were lactating women and women who were pregnant or who were of childbearing potential. Patients with concomitant conditions that could interfere with the assessment of pain were also excluded from the study. Similarly, medications that could interfere with pain assessment were not allowed. The dose of any allowed drug had to be kept stable for at least 2 weeks. In this open-label, comparative evaluation, patients were randomly assigned to receive either piroxicam or piritramide. For reasons of comparability, both groups were given the same treatment regimen. Each patient was followed up for a minimum of 3 days and received an intramuscular (IM) injection of piroxicam 40 mg (two vials) or piritramide 20 mg after surgery and a second injection the next morning (8 AM). A supplemental analgesic medication (a short-acting, nonnarcotic analgesic, usually paracetamol) was given at the patient's request but could not be given in the 3 hours preceding the next clinical assessment. Patients were followed up for 3 days after the operation. A medical history and physical examination were done at inclusion (day - 1 or day 0), and assessments were made on day 0 (the evening of surgery) and at 2 PM on days 1, 2, and 3. Assessments included pain evaluation since the end of surgery (day 0) or since the last visit (days 1 to 3), the need for supplemental analgesics given at the patient's request, and adverse reactions. Pain was rated as follows: • visual analog pain intensity score ( V A S ) - - t h e patient was asked to m a r k the maximal pain intensity since the end of surgery/last visit on a horizontal bar: between the left end = no pain and the right end = unbearable pain; 1510
D. WELRAEDS
• verbal categorical pain intensity score--the investigator asked the patient to evaluate the pain at the time of the visit using a four-point rating scale: 0 = no pain, 1 = slight pain, 2 = moderate pain, 3 = severe pain; • pain relief score--the investigator asked the patient to evaluate the overall pain relief since the end of surgery/last visit using a five-point rating scale: 0 = no relief, 1 = slight relief, 2 = moderate relief, 3 = marked relief, 4 = complete relief of pain; • overall assessment ofpain relief--at the time of the last visit, a global impression of efficacy and tolerability was made by the investigator: excellent, good, fair, poor; • totalpain duration--the total number of days the patient experienced pain requiring a supplemental analgesic medication; and • supplemental analgesia--the amount of drug given at patients' request was noted at each visit between the end of surgery and day 1 assessment, and at 24-hour intervals from day 1 to day 3.
Statistical Analysis All statistical tests were two-sided and were carried out at the 5% level of significance (~ = 0.05). In comparing patient characteristics between the two t r e a t m e n t groups, the Mann-Whitney test and the unpaired t test were used to evaluate continuous variables--age, body weight, and overall tolerability. The chi-square test and Fisher's exact test were used to evaluate discrete variables--sex, concurrent conditions, and concomitant medications. A repeated measures analysis of variance (MANOVA) was used to evaluate the VAS score. The chi-square test, Fisher's exact test, and Mann-Whitney test were used to evaluate the other efficacy par a m e t e r s - v e r b a l categorical pain intensity score, pain relief score, overall assessment of pain relief, total duration of pain, and number of patients requiring supplemental analgesic medication. RESULTS
The surgical procedures performed on the study patients were common orthopedic/traumatologic operations, mostly on the lower limbs, occasionally involving use of a tourniquet (Table I). Of the 57 patients included in the study, 7 (4 patients in the piroxicam group and 3 patients in the piritramide group) could not be evaluated for efficacy for the following reasons: use of prohibited medication, use of inappropriate dosage of the study medication, and patient's inability to cooperate (cranial trauma). Tolerability of the study drug was analyzed for all 57 patients. 1511
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
Table I. Summary of surgical procedures (N = 57).
Removal of osteosynthesismaterial Ankle procedures (collateralligament reconstruction) Osteosynthesis Stump reconstruction Tendon or muscle sutures Operation on hallux valgus Tibial osteotomy/Maquetprocedure Releasecarpal tunnel Boot resection Foot tenotomy Miscellaneous
10 8 4 7 3 2 5 1 2 2 13
Of the 50 patients included in the efficacy analysis, 27 were men and 23 were women. The ages of this subset ranged from 16 to 74 years. The distribution of patients by sex, age, and body weight was similar for the two groups, as were the presence of concomitant conditions and the use of other medications (mostly cardiovascular). Five patients (1 in the piroxicam group and 4 in the piritramide group) included in the efficacy analysis were withdrawn before t h e end of the 3-day follow-up period because of therapeutic failure. Pain Assessment The intensity of the pain as assessed by the patients on the VAS is shown in Figure 1 for both treatment groups on each evaluation day. A significant pain reduction was seen within both groups when the pain assessments on the first day were compared with the assessments on the next 3 days (MANOVA, effect of time P < 0.001). No statistically significant difference was found when comparing the two t r e a t m e n t groups (MANOVA, interaction treatment by time P = 0.406). A higher (but not statistically significantly different) pain score was noted in the piroxicam group than in the piritramide group on the evening of the operation (mean -+ SD score, 3.57 -+ 3.09 vs 2.88 +- 2.60, respectively). This probably occurred because more patients responded early to piritramide treatment than to piroxicam treatment administered just after surgery and before the first pain assessment, which was made the evening after surgery. The rate of pain reduction was slightly higher in the piroxicam group, compared with the piritramide group, between day 0 and day 1. The verbal categorical pain intensity scale is based on the pain described by the patients at the time of the evaluation visits. On the evening of surgery (day 0), 80% and 88% of the patients were still experiencing slight, moderate, or severe pain in the piroxicam and piritramide groups, respectively, notwithstanding the fact that the first dose of both drugs was given a few hours before the first assessment (Figure 2). On days 1 to 3, no 1512
D. WELRAEDS
3.5 3 2,5
Piroxicam g r o u p
_~__
o (,9
(n = 25)
2 Piritramide g r o u p I
(n = 25)
1.5 1
0.5 0 Day 0
-t Day 1
I
I
Day 2
Day 3
Figure 1. Pain intensity score as assessed by the patients using a visual analog scale.
significant differences (Mann-Whitney test, P > 0.05) were detected between the two groups, although more patients seemed to respond to piroxicam than to piritramide. This difference was most pronounced on day 2. In light of the slight difference in the verbal categorical pain intensity scores on day 0 between the two groups, the pain relief scale provided a complementary method of pain evaluation. Similar trends for pain since the end of surgery or since the last visit were seen on both scales. Using the pain relief score, a slightly greater number of patients had pain relief in the piroxicam group than in the piritramide group (32% vs 24%, respec90 8070 c-
.e
60-
's
50-
4--'
[~]Piroxicam group (n = 25)
40-
[ ] Piritramide group (n = 251
,o 3020 10 O-
Day 0 Day 1 Day 2 Day 3 Figure 2. Percentage of patients with pain on each observation day. 1513
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
tively); however, no statistically significant differences could be detected (Mann-Whitney test, P > 0.05) between the two treatments when comparing them at each assessment day. This is in accordance with the VAS data. At the time of the last visit, our impression was one of global efficacy (Figure 3). The piroxicam-treated patients showed a statistically significant (Mann-Whitney test, P = 0.0003) improvement in pain relief over the piritramide-treated patients. The responses of 88% of the patients in the piroxicam group were rated as excellent or good compared with 52% in the piritramide group. The total number of days that patients experienced pain requiring supplemental analgesic medication was similar in the two groups (MannWhitney test, P = 0.359), although more patients needed 2 or 3 days of supplemental analgesic medication in the piritramide group than in the piroxicam group. No supplemental analgesics were needed in 52% and 44% of the patients in the piroxicam and piritramide groups, respectively. The number of patients requesting a supplemental analgesic on each day was similar in both groups (Figure 4), except on day 2, when 36% of the piritramide-treated patients asked for supplemental analgesia, compared with 8% of the piroxicam-treated patients (chi-square with Yates correction, P = 0.048).
Tolerability The tolerability of the two study drugs was evaluated in all 57 patients. Table II summarizes the data on adverse effects. Six patients (2 in the piroxicam group and 4 in the piritramide group) experienced adverse effects, all of which were mild and were thought to be related to therapy. Overall evaluation of treatment tolerance was rated excellent or good 6050.
40-
"5
30-
!
1
[ ] Piroxicam group (n = 25) / /
IWPiritramide group (n = 25) 1
~ 20Q.
10
o
|
Excellent
Good
Fair
Poor
Figure 3. Overall impression of efficacy. 1514
D. WELRAEDS
40 35 30
13.
"5
25 20 [ ] Piroxicam group (n = 25)
+.,
15 o_
[ ] Piritramide group (n = 25)
10 5 ODay 0
Day 1
Day 2
Day 3
Figure 4. Percentage of patients requiring supplemental analgesic medication at each assessment day.
in 96.6% of the patients in the piroxicam group and 85.7% of the patients in the piritramide group (Mann-Whitney test, P = 0.0029) (Figure 5). DISCUSSION AND CONCLUSION
Postoperative pain may be inhibited peripherally at the starting point by using NSAIDs, which inhibit prostaglandin synthesis, 7 or at the central level by centrally acting analgesic agents, such as the opiates. The efficacy of NSAIDs, especially the injectable form, in relieving perioperative pain has been investigated in a number of studies. 2'9'11 In the present study, the actions of two successive IM injections of either piroxicam or piritramide on postoperative pain over 3 days were compared. The study protocol provided for the administration of a mild, short-acting pain reliever as needed in addition to piroxicam and piritramide. The two study drugs proved comparable overall. The pain score on the Table II. Adverse effects of therapy.
Vomiting Nausea Headache Dizziness Lack of appetite No. (%) of patients with adverse reactions
1515
Piroxicam (n = 29)
Piritramide (n = 28)
--1 1 -2 (7)
3 2 --1 4 (14)
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
9080 'E 70-
#_ 60 "5 50-
1
(D
[ ] Piroxicam group (n = 25) L
40-
o~ Q_
|
i P i r i t r a m i d e group (n = 25)1
30 20 100Excellent
Good
Fair
Poor
Figure 5. Overall impression of drug tolerability.
night after surgery was higher for piroxicam than for piritramide (Figure 1). Thus piritramide appears to have a faster onset of action. However, this should be balanced against the longer-lasting action of piroxicam. On day 2, 8% of the piroxicam-treated patients versus 36% of the piritramidetreated patients requested supplemental analgesia. The extended action of piroxicam probably results from its long elimination half-life, which has been widely reported. 3'4 This potential benefit, although not systematically evaluated in the study, is an appreciable asset in a nursing-intensive institution such as ours. Global evaluation at the end of the study showed piroxicam to be significantly (P = 0.003) more effective and better tolerated than piritramide. However, since this was an open-label study, this finding probably only indicates a trend, while reflecting a high degree of overall satisfaction with piroxicam. Global tolerability was rated excellent or good by 96.6% of the piroxicam-treated patients compared with 85.7% of the piritramide group. Nausea and vomiting, commonly reported with opiate agents, were noted in 4 (14%) of the piritramide-treated patients and in none of the piroxicamtreated patients, whereas one patient in the piroxicam group experienced headache and another reported dizziness. Unavoidable ethical and methodologic constraints justified the concomitant use of supplemental analgesia. Only on one day did the statistical analysis show a difference in analgesic requirements between the two groups. However, interference of these analgesics, particularly with respect to the time of their administration, with our results cannot be ruled out. Throughout the 3 postoperative days, residual pain was present in the majority of patients. Our experience suggests, though, the beneficial effect 1516
D. WELRAEDS
of combining an opiate agent, which provides rapid onset of pain relief, and an NSAID, which ensures more durable relief. However, these empirical findings need confirmation by means of large controlled studies. In conclusion, the two agents studied here provided comparable and significant pain relief after orthopedic/traumatologic surgery.
Acknowledgments The author wishes to thank D.I.C.E. (rue Eugene Toussaint 56, B-1090 Brussels) for the statistical review and Dr. Ph. Vandeven (Pfizer S.A., Brussels, Belgium) for the logistics of the study. This study was supported in part by Pfizer S.A. References:
1. Devine A. Empowering the patient to control post-operative pain. B r J Theatre Nurs. 1993;3(3):11-22, 29-30. 2. Mather LE, Kehlet H, Haljamae H, et al. Do the pharmacodynamics of the nonsteroidal anti-inflammatory drugs suggest a role in the management of postoperative pain? Drugs. 1992;44(Suppl 5):1-13. 3. Hutchinson GL, Crofts SL, Gray IG. Preoperative piroxicam for postoperative analgesia in dental surgery. B r J Anaesth. 1990;65:500-503. 4. Desjardins PJ. Analgesic efficacy of piroxicam in postoperative dental pain. A m J Med. 1988;84(Suppl 5A):35-41. 5. Sunshine A, Marrero I, McCormick DH, et al. The analgesic efficacy of piroxicam, aspirin and placebo in postoperative oral surgery pain. Clin Pharmacol Ther. 1985;39:232. Abstract. 6. Olson N, Sunshine A, Marrero I, et al. Piroxicam, aspirin and placebo in dental pain. Clin Pharmacol Ther. 1987;41:162. Abstract. 7. Melzack R, Bentley KC, Jeans ME. Piroxicam versus acetaminophen and placebo for the relief of postoperative dental pain. Curr Ther Res. 1985;37:1134-1140. 8. Breivik H, Stenseth R, Apalseth K, et al. Piroxicam, acetylsalicylic acid and placebo for postoperative pain. Acta Anaesthesiol Scand. 1984;28:37-39. 9. Serpell MG, Thomson MF. Comparison of piroxicam with placebo in the management of pain after total hip replacement. B r J Anaesth. 1989;63:354-356. 10. Martens M. Piroxicam treatment for postoperative pain of orthopedic surgery: A doubleblind comparative study. Curr Ther Res. 1991;49:750-763. 11. Sunshine A, Roure C, Colon A, et al. Analgesic efficacy of piroxicam in the treatment of postoperative pain. A m J Med. 1988;84(Suppl 5A):16-22.
1517
EVALUATION OF PIROXICAM AND PIRITRAMIDE IN THE MANAGEMENT OF PAIN AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY DANIELWELRAEDS Center of Traumatology and Rehabilitation, Brugmann University Hospital, Brussels, Belgium
ABSTRACT A randomized, open-label, comparative study was undertaken to assess the analgesic efficacy of piroxicam and piritramide in 57 inpatients who underwent orthopedic/traumatologic surgery. They received either piroxicam 40 mg or piritramide 20 mg in a single intramuscular (IM) dose after surgery and a second IM dose the next morning. Supplemental analgesic medication (usually paracetamol) was given at the patient's request during the postoperative period. Up to 3 days after surgery, both drugs were highly effective, relieved the pain significantly ( P < 0.001), and were rated statistically equivalent on three pain scales. No difference was detected between the two groups regarding the need for supplemental analgesic medication, except on day 2, when 36% of the piritramide-treated patients requested supplemental analgesics versus 8% of piroxicam-treated patients. A low incidence of mainly mild side effects was reported with both medications. Results confirm those of short-term postoperative/posttraumatologic and other pain studies in which piroxicam provided good analgesia and was well tolerated. The two agents studied provided comparable and significant pain relief after orthopedic/ traumatologic surgery. INTRODUCTION
Postoperative pain is an inherent drawback of surgery t h a t can be detrimental to the normal course of postoperative cure. 1 Centrally acting analgesic agents and injectable nonsteroidal a n t i - i n f l a m m a t o r y a g e n t s (NSAIDs) have been used to control postoperative pain. NSAIDs have been shown to be effective against pain, reducing the need for opiate agents following general surgery. 2 Piroxicam* is the first well-studied oxicam. It has a high potency and long e l i m i n a t i o n half-life, which m a k e once-daily dosing possible. 3'4 Piroxicam was studied as an analgesic agent following various types of surgical procedures, including oral surgery, 5-7 orthopedic surgery, s - l ° and gynecologic surgery. 11 Generally, those studies compared oral piroxiAddress correspondence to: D. Welraeds, MD, C.T.R., HSpital Brugmann, place A. Van Gehuchten 4, t020-Brussels, Belgium. Received for publication on July 5, 1994. Printed in the U.S.A. Reproduction in whole or part is not permitted. *Trademark: Feldene ® (Pfizer Inc., New York, New York).
1509
0011-393x/94/$3.50
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
cam with other oral agents and with placebo; however, often only a single administration was involved and observation lasted only a few hours. To the best of our knowledge, a study has never been done to compare the efficacy of injectable piroxicam with an injectable opiate such as piritramide on postoperative orthopedic/traumatologic pain over a longer period of time. Hence, this study focused on the duration and intensity of pain in the postoperative days using short-term therapy of either piroxicam or piritramide, a conventional therapeutic agent. PATIENTS
AND METHODS
Fifty-seven male and female inpatients between the ages of 16 and 75 years who had undergone orthopedic or traumatologic surgery and who were expected to remain hospitalized for at least 3 days were admitted to the study. Oral informed consent, in accordance with the revised Declaration of Helsinki (Hong Kong, 1990) was obtained from all participants. Consent was provided by a parent or guardian for patients under legal age. Patients with a history of drug allergy or gastrointestinal or other serious diseases were excluded, as were lactating women and women who were pregnant or who were of childbearing potential. Patients with concomitant conditions that could interfere with the assessment of pain were also excluded from the study. Similarly, medications that could interfere with pain assessment were not allowed. The dose of any allowed drug had to be kept stable for at least 2 weeks. In this open-label, comparative evaluation, patients were randomly assigned to receive either piroxicam or piritramide. For reasons of comparability, both groups were given the same treatment regimen. Each patient was followed up for a minimum of 3 days and received an intramuscular (IM) injection of piroxicam 40 mg (two vials) or piritramide 20 mg after surgery and a second injection the next morning (8 AM). A supplemental analgesic medication (a short-acting, nonnarcotic analgesic, usually paracetamol) was given at the patient's request but could not be given in the 3 hours preceding the next clinical assessment. Patients were followed up for 3 days after the operation. A medical history and physical examination were done at inclusion (day - 1 or day 0), and assessments were made on day 0 (the evening of surgery) and at 2 PM on days 1, 2, and 3. Assessments included pain evaluation since the end of surgery (day 0) or since the last visit (days 1 to 3), the need for supplemental analgesics given at the patient's request, and adverse reactions. Pain was rated as follows: • visual analog pain intensity score ( V A S ) - - t h e patient was asked to m a r k the maximal pain intensity since the end of surgery/last visit on a horizontal bar: between the left end = no pain and the right end = unbearable pain; 1510
D. WELRAEDS
• verbal categorical pain intensity score--the investigator asked the patient to evaluate the pain at the time of the visit using a four-point rating scale: 0 = no pain, 1 = slight pain, 2 = moderate pain, 3 = severe pain; • pain relief score--the investigator asked the patient to evaluate the overall pain relief since the end of surgery/last visit using a five-point rating scale: 0 = no relief, 1 = slight relief, 2 = moderate relief, 3 = marked relief, 4 = complete relief of pain; • overall assessment ofpain relief--at the time of the last visit, a global impression of efficacy and tolerability was made by the investigator: excellent, good, fair, poor; • totalpain duration--the total number of days the patient experienced pain requiring a supplemental analgesic medication; and • supplemental analgesia--the amount of drug given at patients' request was noted at each visit between the end of surgery and day 1 assessment, and at 24-hour intervals from day 1 to day 3.
Statistical Analysis All statistical tests were two-sided and were carried out at the 5% level of significance (~ = 0.05). In comparing patient characteristics between the two t r e a t m e n t groups, the Mann-Whitney test and the unpaired t test were used to evaluate continuous variables--age, body weight, and overall tolerability. The chi-square test and Fisher's exact test were used to evaluate discrete variables--sex, concurrent conditions, and concomitant medications. A repeated measures analysis of variance (MANOVA) was used to evaluate the VAS score. The chi-square test, Fisher's exact test, and Mann-Whitney test were used to evaluate the other efficacy par a m e t e r s - v e r b a l categorical pain intensity score, pain relief score, overall assessment of pain relief, total duration of pain, and number of patients requiring supplemental analgesic medication. RESULTS
The surgical procedures performed on the study patients were common orthopedic/traumatologic operations, mostly on the lower limbs, occasionally involving use of a tourniquet (Table I). Of the 57 patients included in the study, 7 (4 patients in the piroxicam group and 3 patients in the piritramide group) could not be evaluated for efficacy for the following reasons: use of prohibited medication, use of inappropriate dosage of the study medication, and patient's inability to cooperate (cranial trauma). Tolerability of the study drug was analyzed for all 57 patients. 1511
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
Table I. Summary of surgical procedures (N = 57).
Removal of osteosynthesismaterial Ankle procedures (collateralligament reconstruction) Osteosynthesis Stump reconstruction Tendon or muscle sutures Operation on hallux valgus Tibial osteotomy/Maquetprocedure Releasecarpal tunnel Boot resection Foot tenotomy Miscellaneous
10 8 4 7 3 2 5 1 2 2 13
Of the 50 patients included in the efficacy analysis, 27 were men and 23 were women. The ages of this subset ranged from 16 to 74 years. The distribution of patients by sex, age, and body weight was similar for the two groups, as were the presence of concomitant conditions and the use of other medications (mostly cardiovascular). Five patients (1 in the piroxicam group and 4 in the piritramide group) included in the efficacy analysis were withdrawn before t h e end of the 3-day follow-up period because of therapeutic failure. Pain Assessment The intensity of the pain as assessed by the patients on the VAS is shown in Figure 1 for both treatment groups on each evaluation day. A significant pain reduction was seen within both groups when the pain assessments on the first day were compared with the assessments on the next 3 days (MANOVA, effect of time P < 0.001). No statistically significant difference was found when comparing the two t r e a t m e n t groups (MANOVA, interaction treatment by time P = 0.406). A higher (but not statistically significantly different) pain score was noted in the piroxicam group than in the piritramide group on the evening of the operation (mean -+ SD score, 3.57 -+ 3.09 vs 2.88 +- 2.60, respectively). This probably occurred because more patients responded early to piritramide treatment than to piroxicam treatment administered just after surgery and before the first pain assessment, which was made the evening after surgery. The rate of pain reduction was slightly higher in the piroxicam group, compared with the piritramide group, between day 0 and day 1. The verbal categorical pain intensity scale is based on the pain described by the patients at the time of the evaluation visits. On the evening of surgery (day 0), 80% and 88% of the patients were still experiencing slight, moderate, or severe pain in the piroxicam and piritramide groups, respectively, notwithstanding the fact that the first dose of both drugs was given a few hours before the first assessment (Figure 2). On days 1 to 3, no 1512
D. WELRAEDS
3.5 3 2,5
Piroxicam g r o u p
_~__
o (,9
(n = 25)
2 Piritramide g r o u p I
(n = 25)
1.5 1
0.5 0 Day 0
-t Day 1
I
I
Day 2
Day 3
Figure 1. Pain intensity score as assessed by the patients using a visual analog scale.
significant differences (Mann-Whitney test, P > 0.05) were detected between the two groups, although more patients seemed to respond to piroxicam than to piritramide. This difference was most pronounced on day 2. In light of the slight difference in the verbal categorical pain intensity scores on day 0 between the two groups, the pain relief scale provided a complementary method of pain evaluation. Similar trends for pain since the end of surgery or since the last visit were seen on both scales. Using the pain relief score, a slightly greater number of patients had pain relief in the piroxicam group than in the piritramide group (32% vs 24%, respec90 8070 c-
.e
60-
's
50-
4--'
[~]Piroxicam group (n = 25)
40-
[ ] Piritramide group (n = 251
,o 3020 10 O-
Day 0 Day 1 Day 2 Day 3 Figure 2. Percentage of patients with pain on each observation day. 1513
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
tively); however, no statistically significant differences could be detected (Mann-Whitney test, P > 0.05) between the two treatments when comparing them at each assessment day. This is in accordance with the VAS data. At the time of the last visit, our impression was one of global efficacy (Figure 3). The piroxicam-treated patients showed a statistically significant (Mann-Whitney test, P = 0.0003) improvement in pain relief over the piritramide-treated patients. The responses of 88% of the patients in the piroxicam group were rated as excellent or good compared with 52% in the piritramide group. The total number of days that patients experienced pain requiring supplemental analgesic medication was similar in the two groups (MannWhitney test, P = 0.359), although more patients needed 2 or 3 days of supplemental analgesic medication in the piritramide group than in the piroxicam group. No supplemental analgesics were needed in 52% and 44% of the patients in the piroxicam and piritramide groups, respectively. The number of patients requesting a supplemental analgesic on each day was similar in both groups (Figure 4), except on day 2, when 36% of the piritramide-treated patients asked for supplemental analgesia, compared with 8% of the piroxicam-treated patients (chi-square with Yates correction, P = 0.048).
Tolerability The tolerability of the two study drugs was evaluated in all 57 patients. Table II summarizes the data on adverse effects. Six patients (2 in the piroxicam group and 4 in the piritramide group) experienced adverse effects, all of which were mild and were thought to be related to therapy. Overall evaluation of treatment tolerance was rated excellent or good 6050.
40-
"5
30-
!
1
[ ] Piroxicam group (n = 25) / /
IWPiritramide group (n = 25) 1
~ 20Q.
10
o
|
Excellent
Good
Fair
Poor
Figure 3. Overall impression of efficacy. 1514
D. WELRAEDS
40 35 30
13.
"5
25 20 [ ] Piroxicam group (n = 25)
+.,
15 o_
[ ] Piritramide group (n = 25)
10 5 ODay 0
Day 1
Day 2
Day 3
Figure 4. Percentage of patients requiring supplemental analgesic medication at each assessment day.
in 96.6% of the patients in the piroxicam group and 85.7% of the patients in the piritramide group (Mann-Whitney test, P = 0.0029) (Figure 5). DISCUSSION AND CONCLUSION
Postoperative pain may be inhibited peripherally at the starting point by using NSAIDs, which inhibit prostaglandin synthesis, 7 or at the central level by centrally acting analgesic agents, such as the opiates. The efficacy of NSAIDs, especially the injectable form, in relieving perioperative pain has been investigated in a number of studies. 2'9'11 In the present study, the actions of two successive IM injections of either piroxicam or piritramide on postoperative pain over 3 days were compared. The study protocol provided for the administration of a mild, short-acting pain reliever as needed in addition to piroxicam and piritramide. The two study drugs proved comparable overall. The pain score on the Table II. Adverse effects of therapy.
Vomiting Nausea Headache Dizziness Lack of appetite No. (%) of patients with adverse reactions
1515
Piroxicam (n = 29)
Piritramide (n = 28)
--1 1 -2 (7)
3 2 --1 4 (14)
PIROXICAM IN PAIN MANAGEMENT AFTER ORTHOPEDIC/TRAUMATOLOGIC SURGERY
9080 'E 70-
#_ 60 "5 50-
1
(D
[ ] Piroxicam group (n = 25) L
40-
o~ Q_
|
i P i r i t r a m i d e group (n = 25)1
30 20 100Excellent
Good
Fair
Poor
Figure 5. Overall impression of drug tolerability.
night after surgery was higher for piroxicam than for piritramide (Figure 1). Thus piritramide appears to have a faster onset of action. However, this should be balanced against the longer-lasting action of piroxicam. On day 2, 8% of the piroxicam-treated patients versus 36% of the piritramidetreated patients requested supplemental analgesia. The extended action of piroxicam probably results from its long elimination half-life, which has been widely reported. 3'4 This potential benefit, although not systematically evaluated in the study, is an appreciable asset in a nursing-intensive institution such as ours. Global evaluation at the end of the study showed piroxicam to be significantly (P = 0.003) more effective and better tolerated than piritramide. However, since this was an open-label study, this finding probably only indicates a trend, while reflecting a high degree of overall satisfaction with piroxicam. Global tolerability was rated excellent or good by 96.6% of the piroxicam-treated patients compared with 85.7% of the piritramide group. Nausea and vomiting, commonly reported with opiate agents, were noted in 4 (14%) of the piritramide-treated patients and in none of the piroxicamtreated patients, whereas one patient in the piroxicam group experienced headache and another reported dizziness. Unavoidable ethical and methodologic constraints justified the concomitant use of supplemental analgesia. Only on one day did the statistical analysis show a difference in analgesic requirements between the two groups. However, interference of these analgesics, particularly with respect to the time of their administration, with our results cannot be ruled out. Throughout the 3 postoperative days, residual pain was present in the majority of patients. Our experience suggests, though, the beneficial effect 1516
D. WELRAEDS
of combining an opiate agent, which provides rapid onset of pain relief, and an NSAID, which ensures more durable relief. However, these empirical findings need confirmation by means of large controlled studies. In conclusion, the two agents studied here provided comparable and significant pain relief after orthopedic/traumatologic surgery.
Acknowledgments The author wishes to thank D.I.C.E. (rue Eugene Toussaint 56, B-1090 Brussels) for the statistical review and Dr. Ph. Vandeven (Pfizer S.A., Brussels, Belgium) for the logistics of the study. This study was supported in part by Pfizer S.A. References:
1. Devine A. Empowering the patient to control post-operative pain. B r J Theatre Nurs. 1993;3(3):11-22, 29-30. 2. Mather LE, Kehlet H, Haljamae H, et al. Do the pharmacodynamics of the nonsteroidal anti-inflammatory drugs suggest a role in the management of postoperative pain? Drugs. 1992;44(Suppl 5):1-13. 3. Hutchinson GL, Crofts SL, Gray IG. Preoperative piroxicam for postoperative analgesia in dental surgery. B r J Anaesth. 1990;65:500-503. 4. Desjardins PJ. Analgesic efficacy of piroxicam in postoperative dental pain. A m J Med. 1988;84(Suppl 5A):35-41. 5. Sunshine A, Marrero I, McCormick DH, et al. The analgesic efficacy of piroxicam, aspirin and placebo in postoperative oral surgery pain. Clin Pharmacol Ther. 1985;39:232. Abstract. 6. Olson N, Sunshine A, Marrero I, et al. Piroxicam, aspirin and placebo in dental pain. Clin Pharmacol Ther. 1987;41:162. Abstract. 7. Melzack R, Bentley KC, Jeans ME. Piroxicam versus acetaminophen and placebo for the relief of postoperative dental pain. Curr Ther Res. 1985;37:1134-1140. 8. Breivik H, Stenseth R, Apalseth K, et al. Piroxicam, acetylsalicylic acid and placebo for postoperative pain. Acta Anaesthesiol Scand. 1984;28:37-39. 9. Serpell MG, Thomson MF. Comparison of piroxicam with placebo in the management of pain after total hip replacement. B r J Anaesth. 1989;63:354-356. 10. Martens M. Piroxicam treatment for postoperative pain of orthopedic surgery: A doubleblind comparative study. Curr Ther Res. 1991;49:750-763. 11. Sunshine A, Roure C, Colon A, et al. Analgesic efficacy of piroxicam in the treatment of postoperative pain. A m J Med. 1988;84(Suppl 5A):16-22.
1517