***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: & NA ; Tramadol hydrochloride is a synthetic & mgr;‐opioid agonist with additional monoaminergic activity . Tramadol 's analgesic effect has been equated with that of pethidine , with a more favourable side‐effect profile . Tramadol has been the most‐selling prescription analgesic in Germany for several years , and it is now available in many other European countries , but still there is a lack of adequately controlled clinical studies of its analgesic properties . The purpose of this study was to compare the analgesic efficacy of 50 and 100 mg oral tramadol with our st and ard analgesic for postoperative pain treatment , 1000 mg paracetamol + 60 mg codeine , and placebo . A single‐dose , parallel group , double‐blind design was used . One hundred forty‐four patients were enrolled the day after total hip replacement if they had a pain intensity of 60 mm or more on a 0–100 mm visual analogue scale . Treatments were compared on the basis of pain intensity and derived variables ( pain intensity difference , and summed pain intensity differences ) , the need of rescue medication , and a global evaluation . Serum concentrations confirmed rapid and good absorption comparable with the reported in healthy volunteers . The active drug control , paracetamol + codeine , was significantly superior to placebo for all efficacy variables ( P = 0.0002–0.004 ) , confirming good assay sensitivity .  Paracetamol + codeine  was also significantly superior to both 50 mg tramadol ( P = 0.002–0.03 ) and 100 mg tramadol ( P = 0.002–0.02 ) . There was no difference between placebo and 50 and 100 mg tramadol for any of the efficacy variables . Adverse events were more common with tramadol than with the active control ( P < 0.02 ) , with significantly more emetic episodes after 50 and 100 mg tramadol ( P < 0.05 ) . Thus , this double‐blind , placebo‐ and active drug‐controlled study after orthopaedic surgery shows that 50 and 100 mg oral tramadol is well absorbed but has no significant analgesic effect in doses that are tolerable as single doses by mouth . We emphasize the importance of proper study design with documented assay sensitivity and sufficiently high initial pain intensity for differentiation between analgesics of different potencies Reports on pain relief with intra-articular morphine  after arthroscopic knee operation are conflicting . To assess the long-term antinociceptive effect of intraarticular morphine , we studied pain at rest , pain on st and ing and ability to walk for 7 days after intraarticular injection of bupivacaine 100 mg  ( group 1 , n = 11 ) , bupivacaine 100 mg and morphine 1 mg ( group 2 , n = 10 ) and bupivacaine 100 mg and morphine 3 mg ( group 3 , n = 10 ) at the end of operation . Pain and walking were assessed by visual analogue and walking scales , respectively . Pain was treated with morphine i.v . in the recovery room and Tylenol No. 3 after discharge . Assessment s were made before operation , and 1 , 3 , 6 and 12 h after injection and on days 1 - 7 after operation . There were significant differences between the groups in pain scores ( pain at rest , P < 0.05 ; pain on st and ing , P < 0.01 ) . The pain scores in group 3 were lower than those in group 1 . The differences in pain scores at rest were significant at 12 h and on day 1 after operation and differences in pain scores on st and ing were significant at 12 h and on days 1 and 2 after operation . The scores in group 2 were intermediate between those in groups 1 and 3 . The walking scores in group 3 were significantly better than those in group 1 at 12 h. The amount of analgesics received in groups 2 and 3 was significantly less than that in group 1 until day 3 after operation . ( ABSTRACT TRUNCATED AT 250 WORDS We performed a r and omised double-blind controlled study in patients undergoing elective knee arthroscopy  to assess the effect of intra-articular morphine on postoperative pain relief . Patients in the study group ( n = 10 ) received 5 mg of morphine in a 25 ml dilution intra-articularly while those in the control group ( n = 10 ) received 25 ml of saline .  Postoperative pain was assessed at intervals by a visual analogue scale and the requirement for supplementary analgesia was recorded . Those in the study group had significantly lower pain scores and required less systemic analgesics than those in the control group . Plasma profiles for morphine and its metabolites were assayed and showed that they were too low to produce effective analgesia . Evidence suggests that analgesia was mediated by local action within the joint & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo .  Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained with placebo is one‐third of the maximum possible ( and does not vary ) , and that one‐third of patients respond to placebo . The results show that the amount of relief obtained with placebo varies considerably between patients , that 38 % of patients obtained more than 10 % of the maximum possible relief , and 16 % obtained greater than 50 % . In double‐blind , r and omised parallel‐group studies of high quality placebo scores should not vary . Despite these conditions being met the placebo scores did vary . The previous explanation , of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported This study sought to compare the effects of morphine , bupivacaine , and saline injected into the knee after ar throscopic surgery . In a double-blind , r and omized trial , 124 patients received either bupivacaine , morphine , bupivacaine and morphine , or saline at the completion of surgery .  Postoperative pain was assessed with a 100-mm visual analog pain scale . Analgesic require ments were calculated , and weightbearing status was recorded . We found that morphine alone injected in traarticularly at the completion of arthroscopic knee sur gery had no significant effect on postoperative pain , need for supplemental analgesia , or weightbearing sta tus . Patients receiving morphine in combination with bupivacaine did not demonstrate any statistically sig nificant improvement over those receiving bupivacaine alone . Therefore , our results failed to show any ben eficial effect of morphine used for postoperative anal gesia , either alone or in combination with bupivacaine . The overall pattern in all patients demonstrated de creased pain scores , decreased analgesic use , and in creased weightbearing status as the observation period progressed . Finally , preoperative pain was correlated with pain at discharge , indicating that the most signifi ca nt predictor of postoperative pain was preoperative level of discomfort The purpose of the study was to compare the duration of analgesia and the amount of supplemental postoperative analgesics required when morphine combined with bupivacaine was injected into the knee joint at the end of knee arthroscopy surgery .  Varying tourniquet times of 0 , 8 , or 16 minutes were used after the injection . The variables examined were the duration of analgesia , and the amount of supplemental postoperative analgesics required in each subgroup . A sample of 45 subjects was recruited and studied from an outpatient surgery center . The 45 subjects were r and omly assigned to one of three groups ( n = 15 ) . At the end of the procedure , morphine combined with bupivacaine was injected into the intraarticular space and the tourniquet was released or left on for an additional 8 or 16 minutes . The duration of analgesia and the amount of supplemental postoperative analgesics administered in a 24-hour period were measured . No statistical differences were found between groups . All patients received analgesia with no reported side effects . Increasing the tourniquet time had no effect on the duration of analgesia or the amount of supplemental narcotics required in the postoperative period & NA ; A r and omized , double‐blind , controlled study was conducted in patients undergoing elective knee arthroscopy to assess the analgesic effect of intraarticular morphine and bupivacaine , alone and in combination . Patients in group 1 ( n = 10 ) received 5 mg of morphine in 25 mL of saline ;  patients in group 2 ( n = 10 ) received 25 mL of 0.25 % bupivacaine ( 62.5 mg ) ; patients in group 3 ( n = 10 ) received a combination of 5 mg of morphine and 62.5 mg of bupivacaine in 25 mL dilution ; and patients in group 4 ( n = 10 ) received 25 mL of saline . All the drugs were injected intraarticularly . Postoperative pain was assessed using the visual analogue scale at 1 , 2 , 4 , 8 , and 24 h after the intraarticular injection . The need for supplemental analgesia was recorded . Results showed that there was no significant difference in the pain scores or analgesic requirements between groups 1 and 3 . Patients in groups 1 and 3 had significantly lower pain scores than those in groups 2 and 4 . These low pain scores were associated with lower requirements of supplementary analgesics . The patients in group 4 showed the highest pain scores and analgesic requirements . We conclude that intraarticular morphine significantly reduces postoperative pain following knee arthroscopy and that there is no advantage of combining bupivacaine with morphine . ( Anesth Analg 1993;76333‐6 Bupivacaine ( Marcaine ) pharmacokinetics were determined in 11 patients receiving the drug intraarticularly after arthroscopic procedures performed on the knee with patients under general anesthesia . Forty milliliters of 0.25 % bupivacaine ( 100 mg ) were given as a bolus into the intraarticular space of the knee of each patient . The thigh tourniquet was released 2 - 3 min after injection and blood sample s were obtained 5 , 10 , 15 , 20 , 30 , 60 , 120 , 180 , 250 , and 300 min after tourniquet release . Pharmacokinetic parameters obtained were ( mean + /- SD ) : Vd beta 206 + /- 88 L ; Cle 0.816 + /- 0.378 L/min ; t 1/2 beta 189 + /- 84 min ; ka 9.92 + /- 6.79 x 10/min ; Cpmax 0.48 + /- 0.20 micrograms/ml ; and tmax 43.4 + /- 23.1 min . Correlations between higher peak plasma concentrations and longer tourniquet times ( p = 0.02 ) and shorter intervals from injection to tourniquet deflation ( p = 0.03 ) were found using multiple linear regression . Our results indicate that injections of 100 mg of bupivacaine intraarticularly after knee arthroscopy will produce peak blood levels within the 1st h after surgery and that these levels will be well below those noted to produce toxic reactions . Peak levels can be minimized with shorter tourniquet inflation times and with longer injection to tourniquet release intervals .  Ninety healthy adult outpatient knee arthroscopy patients also were studied to evaluate the effectiveness of bupivacaine in relieving postoperative knee discomfort when injected immediately postoperatively . The subjects were r and omized into four groups : ( a ) intraarticular injection of saline , ( b ) intraarticular injection of bupivacaine , ( c ) subcutaneous injection of bupivacaine at the portal sites , and ( d ) both intraarticular and subcutaneous injection of bupivacaine . ( ABSTRACT TRUNCATED AT 250 WORDS Both ketorolac , a nonsteroidal antiinflammatory drug , and morphine , an opioid agonist , provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular route . This study was design ed to determine whether ketorolac or morphine results in better patient analgesia and whether their combination would provide superior analgesia to either drug alone . Patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation were evaluated . Each of the study groups evaluated received ketorolac ( either via the parenteral or intraarticular route ) and morphine ( via either the parenteral or intraarticular route ) . This study revealed a significant benefit from the individual intraarticular administration of both morphine and ketorolac . The combination of these drugs did not result in decreased postoperative pain or need for postoperative analgesics , and it did not result in an increased analgesic duration . We conclude that the use of either intraarticular 
    Output:
    
We conclude that intra-articular morphine may have some effect in reducing  postoperative pain intensity and consumption of analgesics .
Trials of better method ological quality are needed for a conclusive answer that intra-articular morphine is analgesic , and that any analgesia produced is clinical ly useful