Synovial metabolism after different degrees of trauma. Effects of pharmacolgical and physiological intervention : A microdialysis study of the knee joint synovium

Background Knee arthroscopy is one of the most common orthopedic procedures. Postoperative pain and knee swelling is often a problem. Optimal pain management in knee arthroscopic procedures is important to permit same-day discharge and to contribute to early mobilisation, reduced cost and increased patient satisfaction. The process of nociception, inflammation and postoperative pain perception is not fully understood. Pre-, intra- and postoperative treatment may be improved by increasing the knowledge regarding local metabolic and inflammatory response in the knee synovium. Aim and Hypothesis The aim of these studies were to monitor local changes in classic metabolic compunds and PGE2 in relation to the magnitude of surgical trauma and pain subjectively experienced by the patient and to analyze the local effects of intervention with commonly used intra-articular medication and postoperative cryotherapy. Our hypothesis was that the degree of surgical trauma and postoperative pain as experienced by the patient would be reflected by disturbances in synovial metabolism and inflammatory reactions. We further hypothesised that intra-articular administration of morphine, ketorolac or postoperative application of cryotherapy would be reflected by decreased disturbances in expression of classic metabolic compounds and inflammatory reactions. Material and Methods In total 130 patients completed the studies. Inclusion criteria were indication for arthroscopy due to signs of meniscus injury (Study 1-4) or a symptomatic ACL injury requiring reconstruction (Study 2). In study 1 patients were divided in two groups; NO need of rescue medication (n=8) and need for rescue medication (n=6). In study 2; 20 patients undergoing knee arthroscopy were compared to 10 patients undergoing ACL reconstruction. In study 3; 60 patients were randomised into three equal subgroups; intra-articular administration of morphine, ketorolac and placebo. In study 4; 40 patients were randomised into two equal subgroups; application of cooling and compression and NO application of cooling and compression. Synovial metabolism and inflammatory reaction was monitored by microdialysis of glucose, lactate, glycerol, PGE2, (study 1-4) and glutamate (study 3-4). Local temperature; intra-articular, in the joint capsule and on skin were monitored in study 4. Results Study 1: Higher PGE2 levels that decreased over time and consumption of glucose were found in patients experiencing more postoperative pain. Study 2: In comparison with the knee arthroscopy group the ACL group showed lower levels of PGE2 and less lactate increase and glucose consumption. Study 3: There were no apparent effects of morphine but ketorolac significantly reduced PGE2 levels. Study 4: Less lactate increase was noted in the cooling and compression group. Expression of PGE2 was temperature sensitive. Discussion Pain after arthroscopy was reflected by increased glucose utilization and PGE2 production by the synovial membrane (study 1). This indicates that there is a state of hypermetabolism in patients experiencing pain and that PGE2 is a pain marker. ACL reconstruction did not influence the local synovial metabolism or induce an inflammatory response at the same degree as seen after knee arthroscopy (study 2). Intra-articular injection of morphine and/or the use of a combined cooling and compression device in the ACL group may have influenced the findings. Intra-articular injection of ketorolac significantly lowered PGE2 levels but no apparent effects for morphine were seen (study 3). This is in agreement with the known effects of prostaglandin synthesis inhibitors, NSAIDs, on prostaglandins and pain. Local cryotherapy after knee arthroscopy significantly lowered knee temperature postoperatively. A correlation with synovial PGE 2 and temperature was found. Hypothermia blunted the previously shown lactate increase (study 4). This implicates a positive anti-inflammatory effect induced by postoperative local cooling and compression. Hypothermia is proposed to have a tissue protective effect during reperfusion by means of a decreased metabolic rate