To the Editor:
We read Drs. Reuben and Connelly's paper on the use of intraarticular ketorolac, morphine, and bupivacaine with interest . We wish to raise several points.
First, the use of combinations of drugs at novel sites should ideally follow definitive evidence that the single drugs involved have the desired effect. This is established by placebo-controlled studies with single drugs.
While many institutions use local anesthetics at the termination of arthroscopic surgery for analgesia, there are several placebo-controlled studies in which no benefit of this technique was shown [2,3] and others in which the benefit was short lived .1 The intraarticular use of morphine has also not always been found to be effective [6-8]. Combinations of local anesthesia and morphine are not universally found to be effective [8-10].
(1) White AP, Laurent S, Wilkinson DJ. Ann R Coll Surg Engl 1990;72:350-2.
In the case of ketorolac, we are aware of two previous studies in which intraarticular ketorolac was used [11,12]. Both showed efficacy similar to that of intraarticular bupivacaine. The latter study  suggested that combining the drugs improved analgesia. In one study, pain scores were recorded only for the first two hours (the approximate duration of bupivacaine action). In the other, they were recorded daily for five days. Neither study contained a placebo group. Neither, therefore, clearly demonstrated that intraarticular ketorolac is an effective analgesic in this setting.
Second, the dose of ketorolac used is six times the parenteral dose currently recommended in the United Kingdom. This dose was revised downward after the occurrence of cases of gastrointestinal hamorrhage and renal failure when larger doses were used . The use of intraarticular nonsteroidal antiinflammatory drugs (NSAIDs) exposes the synovium and cartilage to high concentrations of the drugs. There is concern in the rheumatological and orthopaedic literature about the effects on cartilage of these drugs even when given parenterally . Damage results from the disruption of chondrocyte metabolism and inhibition of proteoglycan synthesis. These effects may be more pronounced in patients with osteoarthritis . Different NSAIDs have different effects on cartilage metabolism, with some having marked catabolic effects . It would be prudent to select those NSAIDs least likely to damage cartilage in studies of intraarticular use.
We have recently completed a study on the use of intraarticular tenoxicam for postarthroscopy analgesia in patients receiving general anesthesia. Tenoxicam has no solubilizing or preservative agents and has a long half-life, and in vitro studies suggest that it should not have deleterious effects on cartilage [16,17]. Our study was placebo-controlled and compared placebo, bupivacaine 0.5%, and tenoxicam 20 mg. We found a small reduction in analgesic requirements in the first 24 hours after knee arthroscopy in those patients receiving intraarticular tenoxicam. There was no reduction in patients' perception of their postoperative pain. We considered tenoxicam to be of negligible benefit for the patient.
We would caution against the widespread use of intraarticular NSAIDs until their safety and efficacy can be established. In addition, the use of combination therapy for intraarticular analgesia should wait until the efficacy of single drugs is clearly substantiated.
T. M. Cook, FRCA
J. P. Nolan, FRCA
J. P. Tuckey, FRCA
Department of Anaesthesia; Royal United Hospital; Combe Park; Bath BA1 3NG, United Kingdom
1. Reuben S, Connelly NR. Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine. Anesth Analg 1996;82:1036-9.
2. Milligan KA, Mawbray MJ, Mulrooney L, Standen PJ. Intra-articular bupivacaine for pain relief after arthroscopic surgery of the knee joint in daycase patients. Anaesthesia 1988;43:563-4.
3. Henderson RC, Campion ER, DeMasi RA, Taft TN. Postarthroscopy analgesia with bupivacaine: a prospective, randomized, blinded evaluation. Am J Sports Med 1990;18:614-7.
5. Khoury GF, Chen ACN, Garland DE, Stein C. Intraarticular morphine, bupivacaine, and morphine/bupivacaine for pain control after knee videoarthroscopy. Anesthesiology 1992;77:263-6.
6. Heard SO, Edwards WT, Ferrari D, et al. Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study. Anesth Analg 1992;74:822-6.
7. Raja SN, Dickstein RE, Johnson CA. Comparison of postoperative analgesic effects of intraarticular bupivacaine and morphine following arthroscopic knee surgery. Anesthesiology 1992;77:1143-7.
8. 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.
9. Joshi JP, McCarroll SM, O'Brien TM, Lenane P. Intraarticular analgesia following knee arthroscopy. Anesth Analg 1993;76:333-6.
10. Haynes TK, Appadurai IR, Power I, et al. Intra-articular morphine and bupivacaine analgesia after arthroscopic knee surgery. Anaesthesia 1994;49:54-6.
11. Monahan SJ, Johnson CJ, Downing JE, et al. Postarthroscopy analgesia with intraarticular ketorolac. Anesthesiology 1992;77:A854.
12. Reuben S, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995;80:1154-7.
13. Ketorolac: new restrictions on dose and duration of treatment. Current Problems, Committee on Safety of Medicines. London: Medicine Control Agency.
14. Brandt KD, Slowman-Kovacs S. Nonsteroidal antiinflammatory drugs in treatment of osteoarthritis. Clin Orthopaed 1986;213:84-91.
15. Fujii K, Tajiri K, Kajiwara T, et al. Effects of NSAID on collagen and proteoglycan synthesis of cultured chondrocytes. J Rheumatol Suppl 1989;18:28-31.
16. David MJ, Vignon E, Peschard MJ, et al. Effect of non-steroidal anti-inflammatory drugs on glycosyltransferase activity from human osteoarthritic cartilage. Br J Rheumatol 1992;31(Suppl):13-7.
17. Vignon E, Mathieu P, Louisot P, Richard M. In vitro effect of non-steroidal antiinflammatory drugs on proteoglycanase and collagenase activity in human osteoarthritic cartilage. Arthritis Rheum 1991;34:1332-5.