Intra-articular morphine and postoperative analgesia after knee arthroscopy

The Knee 9 (2002) 335–340

Intra-articular morphine and postoperative analgesia after knee arthroscopy G.I. Drososa,*, I.G. Vlachonikolisb, A.N. Papoutsidakisa, N.S. Gavalasa, G. Anthopoulosa a Crete Naval Hospital, Souda, Crete, Greece Department of Social Medicine, University of Crete, Heraklion, Crete, Greece

b

Received 21 September 2001; received in revised form 18 April 2002; accepted 18 June 2002

Abstract The aim of this study was to evaluate the postoperative analgesic effect of intra-articular administration of a low- and a highdose morphine solution after knee arthroscopy. Thirty patients who underwent diagnostic arthroscopy or arthroscopic meniscectomy were allocated in three groups. At the end of the arthroscopic procedure patients in Group A received intra-articularly 20 ml normal saline (NyS), Group B received 5 mg morphine in 20 ml NyS and Group C received 15 mg morphine in 20 ml NyS. The postoperative pain was assessed using a visual analogue scale for 24 h, while all the patients stayed at hospital. Side effects from the central action of opioids were not detected. Although the pain scores in the group of low-dose morphine were lower than in the control group, we failed to detect any significant differences in pain scores among the three groups. There was evidence that a high-dose can cause hyperalgesia. 䊚 2002 Elsevier Science B.V. All rights reserved. Keywords: Knee arthroscopy; Morphine; Pain; Intra-articular analgesia

1. Introduction Many different methods have been used in an effort to provide adequate analgesia after knee surgery w1–7x. Knee arthroscopy is a very common procedure. The degree of postoperative pain varies and in an effort to find the ideal regime for sufficient postoperative analgesia of long duration and no side effects; many clinical studies have been published on intra-articular administration of different drugs in various doses, volumes and combinations w1,2,4,5,8–13x. The presence of peripheral opioid receptors and the possibility of locally mediated analgesia after intraarticular administration of morphine have been raised w1,14,15x. Since then many clinical studies have shown effective postoperative pain relief after intra-articular administration of a low-dose of morphine w8,9,16–23x, while others have found no significant effect of such analgesia w11–13,24–32x. Thus, data from clinical studies of intra-articular administration of a low dose and *Corresponding author. Ag. Sofias 29, 15451 N. Psihiko, Athens, Greece. Tel.: q30-10-6727197y944-380694; fax: q30-10-6727197. E-mail address: [email protected] (G.I. Drosos).

concentration of morphine and post-arthroscopy analgesia are still inconclusive. In one study, a higher dose of 10 mg in 20 ml normal saline (NyS) was used and found to provide better and long-lasting postoperative pain relief than the control group w22x. The aim of this study was to evaluate the influence of the dose of morphine on the postoperative pain. We studied the postoperative analgesic effect after intraarticular administration of a low-dose (5 mg) and a high-dose morphine (15 mg) in 20 ml of NyS, in a prospective, placebo-controlled, double blind trial. 2. Patients and methods Patients scheduled for elective knee arthroscopy, ASA I–II, participated in this study. An informed patient consent was obtained. Thirty patients who underwent diagnostic arthroscopy or arthroscopic meniscectomy were included. The exclusion criteria were chronic knee pain, daily intake of steroids, nonsteroidal anti-inflammatory drugs or opioids.

0968-0160/02/$ - see front matter 䊚 (2002) Elsevier Science B.V. All rights reserved. PII: S 0 9 6 8 - 0 1 6 0 Ž 0 2 . 0 0 0 7 4 - 1

G.I. Drosos et al. / The Knee 9 (2002) 335–340

336 Table 1 Demographic and clinical data

Sex (M:F) Agea Knee (R:L) Type of arthroscopy (diagnosticymeniscectomy) Tourniquet time (min)a a

Group A

Group B

Group C

P

8:2 21.5"4.8 5:5 6:4 38.0"19.6

8:2 28.2"11.5 5:5 3:7 54.5"17.7

9:1 28.4"8.4 6:4 2:8 48.5"8.8

0.787 0.148 0.875 0.155 0.086

Mean"S.D.

All patients were instructed preoperatively in the use of the 10-cm visual analogue scale (VAS) for pain, 0s no pain to 10sthe worst pain w33x. All operations were performed under general anaesthesia. The night before and in the morning before the surgery the patients received 3 mg bromazepam and 150 mg ranitidine orally. General anaesthesia was induced with fentanyl 1–1.5 gykg and propofol 2.0 mgykg intravenously. After 10 min the dose of propofol was 10 mgykgyh then 8 mgykgyh for 10 min, reduced to 6 mgykgyh for the rest of the procedure or Isofluran, as far as it was required. The patient breathed N2O 70% and O2 30% through laryngeal mask or endotracheal tube. A femoral tourniquet was applied during surgery and until 10 min after the intra-articular injection of the tested drug into the knee joint at the end of the procedure. The patients were randomly assigned to three groups for double-blind administration of the tested drug: Group A (n: 10) received 20 ml isotonic saline, Group B (n: 10) received 5 mg morphine in solution in 20 ml isotonic saline, Group C (n: 10) received 15 mg morphine in solution in 20 ml isotonic saline. The test drug was given to the surgeon who administered the injection at the end of the procedure without knowing the contents, through the arthroscope in order to ensure that the tested drug will be delivered into the joint. The patients were evaluated by VAS at 1, 8, 16, 24 h after surgery. In the recovery room patients received morphine 2.5 mg intravenously if the pain was strong (e.g. VAS)8 cm) and the time was registered. Supplementary analgesia—pethidine 0.5 mgykg intramuscularly—were given at patients request and the time of administration was registered. The occurrence of side effects such as nausea, vomiting, strong sedation or itching were noted. Postoperatively the patients commenced isometric quadriceps exercises as soon as they returned to the ward and mobilized on crutches when felt comfortable, under the supervision of a physiotherapist. All the patients stayed in the hospital for at least 24 h before discharge.

2.1. Statistical analysis The association between categorical variables was assessed by means of the x2-test for contingency tables w34,35x. Pain scores for consecutive time-points postoperatively (1, 8, 16 and 24 h) and for other grouping variables (such as procedure, dose of morphine administrated and supplementary anaesthesia) were assessed by analysis of variance for repeated measures w34,35x. Non-significant ‘group by time’ interactions were removed from final model w34x. A P-value of less than 0.05 was considered significant. 3. Results Thirty patients were included in this study. There were no significant differences between the three groups with respect to the demographic data, or the tourniquet time (Table 1). Signs of central opioid effects were not detected in any patient from any the three groups. There were more diagnostic arthroscopies in Group A than in Groups B and C (diagnosticymeniscectomy: 6y4, 3y7, 2y8, respectively). The difference however, is not significant (x2s3.73; d.f.s2; Ps0.16) (Table 1). There was no significant difference in postoperative pain between the two types of procedure—diagnostic or meniscectomy—(Fs0.02; d.f.s1.28; Ps0.89). The differences between the two types were all non-significant (Table 2). With respect to time, it appears that pain is reduced after 8 h post-operatively. The difference between times (1, 8, 16 and 24 h post-operatively) was marked, just failing to be significant at the 5% level (Fs2.67; d.f.s3.84; Ps0.052). The ‘procedure by time’ interaction was not significant (Fs1.45; d.f.s 3.84; Ps0.235) and by removing it from the model, the difference between times became significant (Fs 2.72; d.f.s3.87; Ps0.049). The latter effect was characterized by a significant linear trend (Fs6.50; d.f.s 1.29; Ps0.016), similar in both procedures, indicating a linear reduction of pain as time progresses from 1 to 24 h post-operatively (Table 2). There was no significant difference in postoperative pain between Groups A, B and C (Fs1.13; d.f.s2.27;

G.I. Drosos et al. / The Knee 9 (2002) 335–340

337

Table 2 Postoperative pain (mean values and S.D.) by type of procedure at 1, 8, 16 and 24 h

Table 3 Postoperative pain by groups (control, 5 mg morphine, 15 mg morphine) at 1, 8, 16 and 24 h

Time (h)

Time (h)

Procedure

Mean 1

8

16

24

N

VAS

95% CI

Group

S.D.

Diagnostic Meniscectomy Difference Total

2.36 2.11 0.25 2.20

2.50 2.21 0.88 2.28

11 19

Diagnostic Meniscectomy Difference Total

2.45 2.11 0.34 2.23

1.63 1.73 0.64 1.68

11 19

Diagnostic Meniscectomy Difference Total

1.45 1.79 y0.34 1.67

1.51 1.32 0.53 1.37

11 19

Diagnostic Meniscectomy Difference Total

1.18 1.74 y0.56 1.53

1.54 1.59 0.60 1.57

11 19

S.D.

Control 5 mg Morphine 15 mg Morphine Total

2.50 1.30 2.80 2.20

2.76 1.57 2.30 2.28

10 10 10 30

8

Control 5 mg Morphine 15 mg Morphine Total

2.30 2.20 2.20 2.23

1.57 1.93 1.69 1.68

10 10 10 30

16

Control 5 mg Morphine 15 mg Morphine Total

1.50 1.40 2.10 1.67

1.58 1.17 1.37 1.37

10 10 10 30

24

Control 5 mg Morphine 15 mg Morphine Total

2.30 2.00 2.00 1.53

2.06 1.76 1.33 1.57

10 10 10 30

y1.55y2.05

y0.98y1.66 30

y1.42y0.74 30

y1.78y0.66

Mean 1

30

30

N

VAS

95% Confidence intervals (CI) for differences between groups.

Ps0.34). The difference between times (1, 8, 16 and 24 h post-operatively) was also not significant (Fs 2.11; d.f.s3.81; Ps0.11). This result remained unchanged (Ps0.10) after removing the non-significant ‘group by time’ interaction (Fs0.75; d.f.s6.81; Ps0.61). Although, a reduction of pain by time, similar to the one before (reduction after the 8 h), was also evident here, the case for Group C (15 mg morphine) was not so obvious. It does seem that pain in this group remained almost flat throughout the 24-h postoperative period, but a further analysis to test the difference in time-trend between Group C and the other two, yielded a nonsignificant result (Ps0.52) (Table 3 Fig. 1).

Supplementary analgesia requested by 2 patients in Group A and C and one patient in Group B. There was no significant difference in postoperative pain between patients who requested supplementary analgesia or not (Fs1.13; d.f.s1.28; Ps0.28). The differences between these two groups were all non-significant (Table 4). The difference between times (1, 8, 16 and 24 h postoperatively) was also not significant (Fs1.78; d.f.s 3.84; Ps0.16) and remained so (Ps0.14) after removing the non-significant ‘analgesia by time’ interaction (Fs0.45; d.f.s3.84; Ps0.72). There was, however, a marked linearly decreasing time trend (Fs2.98; d.f.s1.29; Ps0.09), thus indicating a marked linear

Fig. 1. Graphic that shows the mean rate of VAS between Groups A, B and C, each time of measuring.

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338

Table 4 Postoperative pain (mean values and S.D.) by groups according to requested supplementary analgesia at 1, 8, 16 and 24 h Time (h)

1

8

16

24

Supplementary analgesia

N

VAS Mean

S.D.

No Yes Difference Total

2.04 3.00 y0.96 2.20

2.05 3.39 1.12 2.28

No Yes Difference Total

2.08 3.00 y0.92 2.23

1.61 2.00 0.82 1.68

No Yes Difference Total

1.64 1.80 y0.16 1.67

1.41 1.30 0.68 1.37

No Yes Difference Total

1.40 2.20 y0.80 1.53

1.61 1.30 0.77 1.57

95% CI

25 5 y3.26y1.34 30 25 5 y2.60y0.78 30 25 5 y1.56y1.24 30 25 5 y2.37y0.77 30

95% Confidence intervals (CI) for differences between groups.

reduction of pain as before, consistent in both groups (Table 4). 4. Discussion Peripheral opioid receptors may be activated only in the presence of tissue inflammation and opioid binding sites have been identified in synovial tissue indicating that analgesia is locally mediated w15,1,2,36,37x. Nevertheless the results from clinical studies as far as the post-arthroscopy analgesic effect of intra-articular morphine are controversial. In a recently published metaanalysis Gupta et al. w38x found a variability not only between studies but also within studies (patients variability) as well as lack of consistency between studies (early beneficial effect in some studies, and only late effect in other studies). In this study neither the low- or the high-dose of morphine solution administered intra-articularly, provided significantly better analgesia compared to the control group. The pain scores in the group of low-dose of morphine were lower than in the control group but the difference did not reach statistical significance. Although the number of patients in this study is small, the study protocol we used and the number of patients in each group are the same or similar to other studies that showed the beneficial effect of intra-articular administration of a low-dose of morphine w8,23x. The analgesic effects of the intra-articular morphine may be related to the dose w13,22,27,39,40x and the volume of the intra-articular injection w11x, to the application of tourniquet and the time of its removal w8,41,42x, and to the systemic effects.

Some studies suggest a dose-dependent effect of intraarticular morphine while others do not w13,22,27,39,40x. Further more in some studies it was found that patients received higher doses of morphine had more pain than those received lower doses w13,27,40x. It has been suggested that the mechanism for short-lasting hyperalgesia seen in these studies, is the release of histamine caused by morphine w38x. In our study there was an evidence of such a hyperalgesia. Although there was no statistical significant difference in the pain scores between the three groups, it is interesting that the pain score in Group C (15 mg morphine) was higher than the pain score in Group A and Group B the first postoperative hour. Further more the reduction of pain by time, in the case for Group C (15 mg morphine) was not so obvious and it did seem that pain in this group remained almost flat throughout the 24-h postoperative period. Our protocol as far as the volume injected into the joint and the use of tourniquet was the same or similar to previous studies where a low-doses of intra-articular morphine was found to be effective w8,23x. Although we did not measure plasma concentration of morphine we found no central opioid side effects in either group. If a systemic effect takes place one would expect that the plasma concentration and thus the analgesic effect of the 15 mg morphine to be more pronounced in this Group C of our study. Other factors that may be related to the level of postarthroscopy pain, as suggested by previous studies, is the preoperative level of discomfort, the amount of surgical trauma, the residual effects of peri-operative analgesia, and the sensitivity of methods for postoperative pain registration w11,29,32,41x. The preoperative level of discomfort was not accessed in our study. The amount of surgical trauma may be related to the postoperative pain level w11,41x. We found no statistical significant difference in pain scores between diagnostic arthroscopy and arthroscopic meniscectomy as Joshi et al. w8x suggested. By using the same anaesthetic technique any residual analgesia provide by the peri-operative opioids—used only during the induction to the anaesthesia—should be similar to all our patients. The fact that the patients stayed in the hospital during the entire period of the study may have the benefit of more accurate registration of the pain scores and the required supplementary analgesia, as well as similar postoperative levels of patient’s activity. The postoperative pain levels in this study were relatively low. Rosseland et al. w32x found postoperative analgesic affects of intra-articular morphine only in a subgroup of patients with higher pain intensity in the immediate post-anaesthetic period. The authors suggested that lower pain intensity might be responsible for

G.I. Drosos et al. / The Knee 9 (2002) 335–340

low study sensitivity due to weak pain stimulus. If this is true and if the intra-articular administration of a lowdose morphine does have a beneficial analgesic effect, this could explain the lack of our results to show this effect. 5. Conclusions Using a similar protocol with previous studies we failed to show that a low-dose intra-articular morphine produced significant postoperative analgesia in patients who underwent knee arthroscopy. In our opinion, this study failed to show the beneficial analgesic effect of the intra-articular administration of a low-dose morphine after knee arthroscopy (if this does exist) because of the low postoperative pain intensity of the patients. Whether this low postoperative pain intensity of our patients related or not to low preoperative level of discomfort we are unable to say, as we did not assessed this parameter. A high-dose intra-articular morphine did not produced any significant postoperative analgesia. There was an evidence that this dose can cause hyperalgesia. References w1x Stein C, Comisfl K, Haimerl E, et al. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. The New Eng. J. Medicine 1991;325(16):1123 –1126. w2x Khoury GF, Chen ACN, Garland DE, Stein CS. Intraarticular morphine, bupivacaine, and morphineybupivacaine for pain control after knee videoarthroscopy. Anesthesiology 1992;77:263 –266. w3x McDermott ID, Crowhurst EC, Crawfurd EJP, Tordoff SG. Does the addition of morphine to intra-articular bupivacaine injection improve pain relief after knee arthroscopy? The Knee 1999;6:17 –19. w4x Reuben SS, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth. Analg. 1995;80:1154 –1157. w5x Reuben SS, Connelly NR. Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine. Anesth. Analg. 1996;82:1036 –1039. w6x Joshi GP, McCarroll SM, Brady OH, Hurson BJ, Walsh G. Intra-articular morphine for pain relief after anterior cruciate repair. Br. J. Anaesth. 1993;70:87 –88. w7x Dodds RDA, McMeniman PJ, Krippner R, Myers PT. Comparison of intravenous pethidine infusion with ‘3 in 1’ lumbar plexus block after anterior cruciate ligament reconstruction. The Knee 1995;2:43 –46. w8x Joshi GP, McCarroll SM, Cooney CM, Blunnie WP, O’ Brien TM, Lawrence AJ. Intra-articular morphine for pain relief after knee arthroscopy. J. Bone Joint Surg. wBrx 1992;74-B:749 – 751. w9x Joshi GP, McCarroll SM, O’Brien TM, Lenane P. Intraarticular analgesia following knee arthroscopy. Anesth. Analg. 1993;76:333 –336. w10x McSwiney MM, Joshi GP, Kenny P, McCarroll SM. Analgesia following arthroscopic knee surgery. A controlled study of intra-articular morphine, bupivacaine or both combined. Anaest. Intens. Care 1993;21:201 –203.

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