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Intra-synovial, compared to intra-articular morphine provides better pain relief following knee arthroscopy menisectomy

[L'administration intra-synoviale de morphine, comparée à l'administration intra-articulaire, fournit une meilleure analgésie à la suite d'une ménisectomie arthroscopique du genou]

From the Department of Orthopaedic Surgery, Carmel Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa Israel.

Dr. Mordechai Kligman, Department of Orthopaedic Surgery, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel. Phone: 04-8250276; Fax: 04-8250275; E-mail: kaligan{at}netvision.net.il

	Abstract

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Purpose: To evaluate the analgesic effect of morphine 1 mg administered into the synovial tissue and the outer third of the meniscus after knee arthroscopy.

Methods: In a prospective, double-blind, randomized study, 60 patients who required elective knee arthroscopy were assigned to two groups: Group A consisted of 30 patients who received a direct injection of morphine 1 mg into either the synovial tissue or the outer third of the meniscus following menisectomy. Group B consisted of 30 patients who received a direct injection of NaCl 0.9% 1 mL into the synovial tissue or the outer third of the meniscus following menisectomy. At the end of the operation Group A received an intra-articular injection of NaCl 0.9% 1 mL and bupivacaine 0.5% 10 mL and Group B received an intra-articular injection of morphine 1 mg and bupivacaine 0.5% 10 mL. Analgesic effect was evaluated by pain intensity (visual analogue scale; VAS) and analgesic requirements (paracetamol) during the first one, three, six, 12, 24, and 48 hr postoperatively.

Results: There was no significant difference between the two groups within the first six hours and after 24 hr following the operation regarding VAS score and analgesic requirements. At 12 and 24 hr following the operation, the VAS score and the analgesic requirements were significantly higher in Group B compared to Group A (P <0.01 and P <0.01, respectively). No patient developed side effects.

Conclusion: We conclude that direct morphine injection into the synovia or the outer third of the meniscus provided better pain relief than intra-articular morphine after knee arthroscopy.

	Introduction

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ARTHROSCOPIC partial menisectomy is a common procedure that is frequently associated with postoperative pain. Various studies have reported on pain reduction following intra-articular injection with analgesics or opioids.¹ The rationale for intra-articular morphine injection is the evidence of synovial opioid receptor activation in the presence of inflammation.² Yet, there is no evidence of an opioid meniscal receptor, since the meniscus is a fibrocartilage, which has blood and lymphatic vessels, and is innervated only in its outer third. Most studies have demonstrated a prolonged analgesic effect as late as eight to 12 hr following intra-articular administration of morphine.^3,4

However, many reports also showed increased pain scores after 12 hr.^5,6 Thus, it is reasonable to perform the nerve block as close as possible to the pain receptors, which enables local tissue-binding to opioid receptors, enhancing the analgesic effect. To the best of our knowledge, there is no report on the direct injection of analgesics or opioids within the synovia or outer third of the meniscus following knee arthroscopy in the English medical literature. The aim of this study was to evaluate the analgesic effect of the direct injection of morphine 1 mg into either the synovium or the meniscus after arthroscopy.

	Methods

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Sixty consecutive patients undergoing elective day-case knee arthroscopic partial, subtotal, or total menisectomy by the same surgeon (K.M.) were included in the study. Patients with chronic pain or with known hypersensitivity to morphine were excluded.

The study was a double-blind, parallel-group comparison of synovial and meniscal direct injection of either morphine 1 mg (1 mL) orNaCl 0.9% 1 mL.

Using a numbered list, patients were randomly assigned to one of two groups:

Group A comprised 30 patients who received an injection of morphine 1 mg (1 mL) either into the synovial tissue or the outer third of the meniscus following menisectomy; Group B comprised 30 patients who received an injection of 1 mL 0.9% NaCl into either the synovial tissue or the meniscus following menisectomy. This randomized study was approved by the Institutional Ethics Committee. All patients gave written informed consent before having the operation.

The anesthetic procedure in both groups included lidocaine 1% 15 mL (Xylocaine, Astra) followed by bupivacaine 0.5% 10 mL for local anesthesia. A tourniquet was not used. At the end of the surgical procedure, a lumbar puncture needle (size: 20G x 9 cm) was inserted endoscopically in the synovial tissue and the outer third of the meniscus, followed by fluid aspiration. Then the morphine 1 mg (1 mL) in Group A and saline 0.9% (1 mL) in Group B were injected into the menicus or synovial tissue. In both groups the lumbar needle was not flushed. Thus, the true morphine dose was 0.9 mg. The precise needle location was verified by mild resistance to the injection; if such resistance was absent, the needle was relocated endoscopically. Thereafter, patients in Group A received an intra-articular injection of NaCl 0.9% 1 mL and bupivacaine 0.5% 10 mL and patients in Group B received an intra-articular injection of morphine 1 mg and bupivacaine 0.5% 10 mL.

The patients were evaluated by two of the authors (K.M. and R.V.)postoperatively for pain intensity visual analogue scale (VAS) and analgesic requirements (paracetamol) during the first one, three, six, 12, 24, and 48 hr, at rest and during 20° knee flexion.

Patient evaluations
Patients were evaluated in the hospital at one, three, six, 24 and 48 hr after the operation. Patient evaluation at 12 hr after the operation was performed in the patient's home.

Pain intensity was recorded using a VAS (0=no pain 10=severe pain). Patients were allowed paracetamol 500–1000 mg for pain relief, as needed. There was no criteria for pain treatment and each patient decided by himself when and how much analgesic to use. However, the patient was limited to use no more than 1000 mg in three hours.

Data for pain intensity (VAS), and analgesic requirements were analyzed using Kruskall-Wallis test and Dunn's procedure for post-hoc evaluation. P values of less than 0.05 were considered statistically significant.

Power analysis was calculated using the mean and the SD in both groups. We decided that a reduction of 50% of pain would be a clinically acceptable difference between the two groups.

	Results

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There were no significant differences between the two groups in the demographic data with regard to sex, age, weight, duration of surgery, or surgical procedure (Table I).

There was a significant difference in rescue analgesic requirements between the two groups throughout the six to 24 hr following the operation (P <0.01). Sevenpatients in Group A required supplemental analgesia within the six to 12 hr period, while in Group B, 13 patients used analgesia in the same time period (Table III). However, in the first six hours and after 24 hr, there was no significant difference between the two groups. One patient in Group A and two in Group B were allowed to take another analgesic in order to provide more adequate pain relief.

Based on the results, it was calculated that the power to detect a 50% reduction in pain at 12 and 24 hr after the operation and consumption of rescue analgesics between six and 24 hr was above 80% (=0.05). However, based on pain scores up to six hours or at 48 hr, the power to detect a 50% reduction of pain or consumption of rescue analgesics was insufficient (less than 50%).

No patient developed significant postoperative side effects, nausea, or vomiting, which required medication.

	Discussion

TOP Abstract Introduction Methods Results Discussion References

 
Postoperative pain is considered the main cause of morbidity after knee arthroscopy. Various studies report reduction of both postoperative pain and analgesic drug consumption after systemic administration of non-steroidal anti-inflammatory drugs (NSAID), intra-articular steroids, NSAID, and opioids.¹ The latter, reportedly, have the longest analgesic effect, lasting as long as eight to 12 hr following the intra-articular administration of morphine.^3,4

It is known that opioid receptors are present on peripheral nerves.⁷ Two mechanisms are responsible for the analgesic effect of locally administrated opioids.^3,4 First, disruption of the perineurium at the end of the peripheral nerve, allows easier access of opioids to the neuronal receptors. Second, in the presence of inflammation, the inactive opioid receptors become active and local tissue binding to opioids increases. Direct injection into the inflamed tissue of either the meniscus or the synovia may increase the period of tissue-binding to opioids, creating a longer and stronger effect. Whitford et al. found that after keeping the tourniquet inflated for ten minutes, opioids had a superior analgesic effect, probably because of increased tissue-binding.⁸

In the current study, direct opioid injection into the inflamed tissue of both the synovium and the outer third of the meniscus was evaluated in terms of the duration of analgesic effect. In Group A, direct injection of morphine 1 mg into the synovia or the outer third of the meniscus significantly reduced pain scores at 12 hr and 24 hr postoperatively. Although the difference in pain scores between patients in Group A and Group B was statistically significant, absolute pain scores were quite low. The clinical benefit of intra-synovial injection was confirmed by reduced requirements for additional analgesia po.

Another variable that may affect the analgesic efficacy of intra-articular morphine is dosage.^2,9–12 High doses of morphine may be associated with central nervous system side effects. Intra-synovial injection of morphine may decrease dose requirements, providing pain relief and diminishing side effects. In the present study, the doseof morphine was 1 mg, rendering the incidence of side effects negligible.

We conclude that direct injection of morphine into the synovial tissue or the outer third of the meniscus provides better pain relief than intra-articular morphine. We hypothesize that the presence of meniscal opioid receptors at the outer part of the meniscus, in addition to the known opioid receptor in synovial tissue, may explain our findings.

	References

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2 Richardson MD, Bjorksten AR, Hart JAL, McCullough K. The efficacy of intra-articular morphine for postoperative knee arthroscopy analgesia. Arthroscopy 1997; 5: 584–9.

3 Stein C. Peripheral mechanisms of opioid analgesia. Anesth Analg 1993; 76: 182–91.[Abstract/Free Full Text]

4 Stein C, Yassouridis A. Peripheral morphine analgesia (Editorial). Pain 1997; 71: 119–21.[Medline]

5 Aasbø V, Raeder JC, Grøgaard B, Roise O. No additional analgesic effect of intra-articular morphine or bupivacaine compared with placebo after elective knee arthroscopy. Acta Anaesthesiol Scand 1996; 40: 585–8.[Medline]

6 Laurent SC, Nolan JP, Pozo JL, Jones CJ. Addition of morphine to intra-articular bupivacaine does not improve analgesia after day-case arthroscopy. Br J Anaesth 1994; 72: 170–3.[Abstract/Free Full Text]

7 Lawrence AJ, Joshi GP, Michalkiewicz A, Blunnie WP, Moriarty DC. Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue. Eur J Clin Pharmacol 1992; 43: 351–5.[Medline]

8 Whitford A, Healy M, Joshi GP, McCarroll SM, O'Brien TM. The effect of tourniquet release time on the analgesic efficacy of intraarticular morphine after arthoscopic knee surgery. Anesth Analg 1997; 84: 791–3.[Abstract]

9 Boden BP, Fassler S, Cooper S, Marchetto PA, Moyer RA. Analgesic effect of intaarticular morphine, bupivacaine, and morphine/bupivacaine after arthroscopic knee surgery. Arthroscopy 1994; 10: 104–7.[Medline]

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12 Reuben SS, Connelly NR. Postarthroscopic meniscus repair analgesia with intraa-rticular ketorolac or morphine. Anesth Analg 1996; 82: 1036–9.[Abstract]

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