The aim of this double-blind, randomized control trial was to compare the effectiveness of intra-articular ropivacaine alone or with morphine or ketoprofen for controlling pain after arthroscopic knee surgery. One hundred fifty-six patients scheduled for elective knee arthroscopy were recruited. All patients received general anesthesia and were randomly assigned to 4 groups to receive intra-articular ropivacaine 40 mg (group R), ropivacaine 24 mg plus morphine 8 mg (group R+M), ropivacaine 36 mg plus ketoprofen 100 mg (group R+K), or normal saline (group N/S). Pain, sedation, orientation, nausea, vomiting, and urine retention were recorded at 0, 1, 2, 4, 8, 12, and 24 hours postoperatively. Pain was evaluated by a 10-cm visual analog scale (VAS). When the pain was >2, a suppository of 400 mg paracetamol plus 10 mg codeine plus 50 mg caffeine was given. Results showed that at 4 hours postoperatively, pain differed significantly among the 4 groups (P<.001), with less pain recorded in the R+M group. Similarly, the number of suppositories administered postoperatively to the R+M group was significantly less (P<.001) vs the other groups. Patients who received ropivacaine and morphine or normal saline had a higher incidence of nausea and vomiting vs the other groups (P=.001 and P=.036, respectively).
The combination of intra-articular ropivacaine and morphine is associated with less pain after knee arthroscopy during early recovery but with a higher incidence of nausea and vomiting. However, the addition of ketoprofen to ropivacaine provides relatively satisfactory pain relief, but with fewer side effects compared to morphine.
Knee arthroscopy is one of the most common orthopedic surgical procedures. Although postoperative pain has been reported to be slight to moderate and have a short duration, intra-articular administration of various drugs has proven effective in the reduction of postoperative pain.1-3 The intra-articular administration of local anesthetics and opioids has been shown by many studies to provide early postoperative analgesia compared with placebo.4-7
The aim of this study was to compare the analgesic efficacy of intra-articular ropivacaine alone or combined with morphine or ketoprofen in postoperative knee arthroscopy pain at rest, to assess the need of supplemental analgesia and the possible side effects. We hypothesized that the intra-articular addition of morphine or ketoprofen will enhance the efficacy of ropivacaine given intra-articulary.
Materials and Methods
After obtaining approval from the Hospital Ethics Committee and each patients written consent, 156 patients with American Society of Anesthesiologists (ASA) physical status I or II, between ages 18 and 42 years, and undergoing elective knee arthroscopy were consecutively enrolled in this prospective, randomized, double-blind study. Exclusion criteria were: body weight >20% of the ideal; advanced knee osteoarthritis; use of analgesic, antidepressant, or antiepileptic drugs; neurological or neuromuscular disease; and known allergy and contraindications to local anesthetics, opioids, or nonsteroidal anti-inflammatory drugs (NSAIDs).
A 10-cm visual analog scale (VAS) for pain was used, with 0 cm as no pain and 10 cm as worst imaginable pain. No premedication was given. In the operating room, a catheter was inserted in a peripheral vein and Ringers lactate infusion was started at a rate of 4 mL/kg/h. Routine electrocardiography lead II, noninvasive blood pressure, capnography, and oxygen saturation monitoring was applied. General anesthesia was induced with intravenous propofol 2.5 mg/kg and fentanyl 2 µg/kg. Endotracheal intubation was facilitated by intravenous administration of cisatracurium 0.2 mg/kg. Anesthesia was maintained with 50% nitrous oxide in oxygen and 2% sevoflurane. After tracheal intubation, a tourniquet was applied to the thigh ipsilateral to the operative side and inflated up to 350 mm Hg. Paracetamol 1200 mg in 200 mL saline was administrated intravenously over 30 minutes.
All surgeries and intra-articular injections were performed by the same surgeon. In all patients, the standard anteromedial and anterolateral arthroscopic portals were used. All the internal structures of the knee were carefully inspected using a probe. Interventions were limited to arthroscopic partial or subtotal meniscectomy, removal of loose bodies, hypertrophic plicas removal, or a combination of these procedures. In the few cases in which articular cartilage wear was identified (more than grade II according to the Outerbridge classification8), the patients were excluded from the study.
When the surgical procedure was completed, patients were assigned to 1 of 4 groups (n=39 in each) in a double-blinded and randomized manner according to a table of random numbers to receive intra-articular 40 mg ropivacaine (R group), 24 mg ropivacaine plus 8 mg morphine (R+M group), 36 mg ropivacaine plus 100 mg ketoprofen (R+K group), or normal saline (N/S group). All groups intra-articularly received a total volume of 20 mL. The tourniquet was deflated 10 minutes after intra-articular injection. The analgesic solutions were prepared by an anesthesiologist and administered by the orthopedic surgeon. Except for the anesthesiologist who prepared the analgesics, other anesthesiologists, surgeons, nurses, and the patients were not aware of the intra-articular treatment.
Postoperative pain, sedation, orientation, nausea, vomiting, and urine retention were recorded immediately after extubation and 1, 2, 4, 8, 12, and 24 hours postoperatively. Pain was assessed only at rest. Pain was evaluated by a VAS. When pain was >2, a suppository of 400 mg paracetamol plus 10 mg codeine plus 50 mg caffeine was given. Nausea and vomiting were recorded as separate variables with yes or no.
Orientation was scored from 1 to 4 based in the following questions: where are you (1 point), what day is today (1 point), what is the date (1 point), and when is your birthday (1 point). Sedation was scored from 1 to 3 points as follows: 1 point when the patient was completely cooperative, 2 points when the patient responded to a light touch, and 3 points when the patient responded to a push. Nausea and vomiting were treated with 10 mg metoclopramide and 40 mg methylprednisolone given intravenously.
Power analysis revealed that to detect a minimum clinically significant difference of 25% in the variable analgesics among the 4 groups with a power of 0.8 (or 80%) at a 5% level of significance, 37 patients in each group were needed. This was based on the means and standard deviations of the first 7 patients from each group.
Response feature analysis was applied to all continuous variables with repeated measurements on the same individual. The mean or median postoperative score was tested among the 4 treatment groups, while the baseline levels were used as a covariate (analysis of covariance for normally distributed responses) or Kruskal-Wallis for non-normally distributed variables. When a significant difference was found, post hoc Bonferroni comparisons were performed to assess the differences among groups. As for categorical variables (vomiting, nausea, sedation, orientation, urine retention), chi-squared tests were performed to assess group differences.
Patient characteristics did not differ among the 4 groups (Table 1). The mean VAS pain scores were significant different among the 4 groups (P<.001) (Figure, Table 2). Individual intergroup comparisons of the VAS scores showed a significant difference among all groups (P<.0001, for all possible combinations) except for the R+K vs R+M groups, where no significant difference was found (P=.111). The R+M group had the lowest pain scores with less supplementary analgesia for the first 4 postoperative hours. In the R+K group, we found lower pain scores than in the R group and the N/S group. The R group had lower pain scores than the N/S group. The N/S group had higher VAS values and required more supplementary analgesia between 0 and 4 hours postoperatively.
|Figure: Mean visual analog (VAS) score. Abbreviations: N/S, normal saline; R, ropivacaine alone; R+K, ropivacaine plus ketoprofen; R+M, ropivacaine plus morphine. |
Supplemental analgesia (suppository) use differed significantly among the 4 groups during the first 4 postoperative hours (P<.001 for 0, 1, and 4 hours postoperatively, and P=.005 for the first 2 hours postoperatively) (Table 3).
Sedation and orientation did not differ among the groups at any time point. None of the patients reported urine retention.
The N/S and R+M groups presented significantly higher incidences of nausea (26% and 36%, respectively) vs the R+K and R groups (0% and 15%, respectively) immediately after extubation but not thereafter (Table 4). The postoperative incidence of vomiting in the N/S and R+M groups was 20% and 28%, respectively, vs 8% and 8% in the R+K and R groups, respectively (P=.036). A higher incidence of vomiting was also found 4 hours postoperatively (P=.031) (Table 5).
Our results show that intra-articular injection of analgesics during knee arthroscopy decreases pain and analgesic requirements during the first postoperative hours. Various parameters have been implicated in pain following arthroscopic surgery, including preoperative pain scores, duration of surgery, experience of the surgeon, type of surgery, anesthesia, and analgesia.1-3,7 Intra-articular analgesia used for arthroscopy aims to establish the smallest drug dose providing effective analgesia with minimum side effects.1,4,7,9-11
The literature on single-dose intra-articular analgesia is controversial because of the different concentrations and volumes of local anesthetics used in combination with different adjuvants. In our study, as a local anesthetic we used ropivacaine alone or in combination with morphine or ketoprofen. We found that the best combination was intra-articular ropivacaine with morphine, which decreased the analgesic requirement only during the first 4 postoperative hours.
In our study, patients receiving intra-articular ropivacaine 40 mg alone consumed more analgesics compared to ropivacaine plus ketoprofen or ropivacaine plus morphine. These results are in agreement with studies in which a single dose of intra-articular local anesthetic for pain relief after knee arthroscopy exhibited a small to moderate analgesic effect of short duration.12,13 In fact, several studies report no analgesic effect of low doses of ropivacaine when administrated alone.14-17 However, studies on higher doses of intra-articular ropivacaine, such as 75, 100, and 150 mg, have shown an analgesic effect lasting as long as 24 hours.11
The combination of ropivacaine and morphine results in better analgesia.7,18 In our study, the intra-articular administration of morphine and ropivacaine provided effective postoperative pain relief after knee arthroscopy, but only for the first 4 hours. The onset of the analgesic effect of this group was immediate. Early postoperative pain and analgesic requirements were less than in the other groups. However, this group had a high incidence of nausea and vomiting due to morphine, but no other side effects.
Systematic reviews suggest that morphine exerts postoperative analgesia via a peripheral effect, which is dose dependent. As a result, many investigators administer intra-articularly local anesthetic and morphine in an attempt to improve analgesia in the immediate postoperative period.19-21 In our study, we observed an immediate effect from this combination. The immediate analgesic effect cannot be attributed to the administration of local anesthetic, since in the group of patients that received ropivacaine alone we did not notice similar results. Therefore, we attribute the immediate analgesic effect to the morphine. Patients who received intra-articular ropivacaine plus morphine had better postoperative analgesia than patients who received ropivacaine alone. It is difficult to conclude whether this effect is due to the cumulative analgesic effect of the 2 drugs or to synergism.
The addition of ketoprofen to the intra-articular ropivacaine was associated with higher analgesic consumption compared to the morphine group, as these patients received supplementary analgesia immediately and at the first postoperative hour, which suggests a delayed pain relief. Several clinical studies have reported effective analgesia, reduction in postoperative analgesic requirements, and prolongation of analgesia provided by local anesthetics and NSAIDs.13 When the drugs are combined intra-articulary, many authors suggest a synergic action.4,9,22 Other investigators failed to demonstrate an analgesic effect after the use of intra-articular NSAIDs over placebo.23 Although concerns exist regarding the safety of intravenous NSAIDs, Elhakim et al24 used intra-articular tenoxicam routinely in patients for years with no adverse effects due to intra-articular administration. In our study, the addition of ketoprofen to ropivacaine was less efficacious regarding postoperative pain than morphine. So far, there is no clear explanation of the different results among the published studies.
In our study, the placebo group had higher pain scores than the other groups and a higher percentage of supplementary analgesia. Paracetamol, given intraoperatively, did not provide adequate postoperative analgesia, since >70% of patients in the ropivacaine group and the control group needed supplementary analgesia immediately after recovery.
Tourniquet usage may also affect the efficacy of intra-articular analgesics. In our study, tourniquet release was performed 10 minutes after intra-articular injection. Whitford et al25 observed that keeping the tourniquet inflated for 10 minutes provided superior analgesia and decreased the need for supplementary analgesics compared with releasing the tourniquet immediately after intra-articular injection of morphine. It is possible that by increasing the time interval between intra-articular injection and tourniquet release, the drugs have more time for local action.
Under the present experimental design, intra-articular ropivacaine plus morphine provides better postoperative pain relief after elective knee arthroscopy than ropivacaine plus ketoprofen or ropivacaine alone. However, this treatment is associated with a higher incidence of nausea and vomiting. Ketoprofen plus ropivacaine provide relatively satisfactory pain relief, but with fewer side effects compared to morphine.
- Gupta A, Bodin L, Holmström B, Berggren L. A systematic review of the peripheral analgesic effects of intraarticular morphine. Anesth Analg. 2001; 93(3):761-770.
- Rosseland LA, Stubhaug A, Sandberg L, Breivik H. Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline. Pain. 2003; 104(1-2):25-34.
- Strassels SA, McNicol E, Suleman R. Postoperative pain management: a practical review, part 2. Am J Health Syst Pharm. 2005; 62(19):2019-2025.
- Alagol A, Calpur OU, Usar PS, Turan N, Pamukcu Z. Intraarticular analgesia after arthroscopic knee surgery: comparison of neostigmine, clonidine, tenoxicam, morphine and bupivacaine [published online ahead of print May 24, 2005]. Knee Surg Sports Traumatol Arthrosc. 2005; 13(8):658-663.
- Convery PN, Milligan KR, Quinn P, Sjövall J, Gustafsson U. Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint. Br J Anaesth. 2001; 87(4):570-576.
- Liu SS, Wu CL. The effect of analgesic technique on postoperative patient-reported outcomes including analgesia: a systematic review. Anesth Analg. 2007; 105(3):789-808.
- Vintar N, Rawal N, Veselko M. Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine. Anesth Analg. 2005; 101(2):573-578.
- Outerbridge RE. The etiology of chondromalacia patellae. J Bone Joint Surg Br. 1961; (43):752-757.
- Axelsson K, Gupta A, Johanzon E, et al. Intraarticular administration of ketorolac, morphine, and ropivacaine combined with intraarticular patient-controlled regional analgesia for pain relief after shoulder surgery: a randomized, double-blind study. Anesth Analg. 2008;106(1):328-333.
- Sadjak A, Wintersteiger R, Zakel D, et al. Peripheral analgesic effect of intra-articularly applied clonidine [in German]. Schmerz. 2006; 20(4):293-299.
- Santanen U, Rautoma P, Luurila H, Erkola O. Intra-articular ropivacaine injection does not alleviate pain after day-case knee arthroscopy performed under spinal anaesthesia. Ann Chir Gynaecol. 2001; 90(1):47-50.
- Møiniche S, Mikkelsen S, Wetterslev J, Dahl JB. A systematic review of intra-articular local anesthesia for postoperative pain relief after arthroscopic knee surgery. Reg Anesth Pain Med. 1999; 24(5):430-437.
- Sawynok J. Topical and peripherally acting analgesics. Pharmacol Rev. 2003; 55(1):1-20.
- Rautoma P, Santanen U, Avela R, Luurila H, Perhoniemi V, Erkola O. Diclofenac premedication but not intra-articular ropivacaine alleviates pain following day-case knee arthroscopy. Can J Anaesth. 2000; 47(3):220-224.
- Klein SM, Nielsen KC, Martin A, et al. Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine. Anesth Analg. 2001; 93(3):601-605.
- Woods GW, OConnor DP, Calder CT. Continuous femoral nerve block versus intra-articular injection for pain control after anterior cruciate ligament reconstruction [published online ahead of print February 21, 2006]. Am J Sports Med. 2006; 34(8):1328-1333.
- Iskandar H, Benard A, Ruel-Raymond J, Cochard G, Manaud B. Femoral block provides superior analgesia compared with intra-articular ropivacaine after anterior cruciate ligament reconstruction. Reg Anesth Pain Med. 2003; 28(1):29-32.
- Ng HP, Nordström U, Axelsson K, et al. Efficacy of intra-articular bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac on postoperative pain relief after ambulatory arthroscopic knee surgery: a randomized double-blind study. Reg Anesth Pain Med. 2006; 31(1):26-33.
- Drosos GI, Vlachonikolis IG, Papoutsidakis AN, Gavalas NS, Anthopoulos G. Intra-articular morphine and postoperative analgesia after knee arthroscopy. Knee. 2002; 9(4):335-340.
- Rosseland LA, Stubhaug A, Grevbo F, Reikerås O, Breivik H. Effective pain relief from intra-articular saline with or without morphine 2 mg in patients with moderate-to-severe pain after knee arthroscopy: a randomized, double-blind controlled clinical study. Acta Anaesthesiol Scand. 2003; 47(6):732-738.
- Rosseland LA, Helgesen KG, Breivik H, Stubhaug A. Moderate-to-severe pain after knee arthroscopy is relieved by intraarticular saline: a randomized controlled trial. Anesth Analg. 2004; 98(6):1546-1551.
- Izdes S, Orhun S, Turanli S, Erkilic E, Kanbak O. The effects of preoperative inflammation on the analgesic efficacy of intraarticular piroxicam for outpatient knee arthroscopy. Anesth Analg. 2003; 97(4):1016-1019.
- Cook TM, Nolan JP, Tuckey JP. Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine. Anesth Analg. 1997; 84(2):466-467.
- Elhakim M, Fathy A, Elkott M, Said MM. Intra-articular tenoxicam relieves post-arthroscopy pain. Acta Anaesthesiol Scand. 1996; 40(10):1223-1226.
- Whitford A, Healy M, Joshi GP, McCarroll SM, OBrien TM. The effect of tourniquet release time on the analgesic efficacy of intraarticular morphine after arthroscopic knee surgery. Anesth Analg. 1997; 84(4):791-793.
Drs Lykoudi and Setaki are from the Department of Anesthesiology, Konstantopoulion, Agia Olga Hospital, Nea Ionia, Drs Kottis and Fassoulaki are from the Department of Anesthesiology, Aretaieion Hospital, Medical School, University of Athens, and Dr Efstathopoulos is from the 2nd Orthopedic Department, Medical School, Athens University, Athens, Greece; and Dr Nikolaou is from McGill University Health Centre, Montreal, Quebec, Canada.
Drs Lykoudi, Kottis, Nikolaou, Setaki, Fassoulaki, and Efstathopoulos have no relevant financial relationships to disclose.
The authors thank Mrs Katerina Dimitriou for her invaluable help in the statistical analysis of the results of this study.
Correspondence should be addressed to: Vassilios S. Nikolaou, MD, PhD, McGill University Health Centre, 2021 Atwater Ave, Montreal, QC, H3H2P2, Canada (email@example.com).