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Veselko, MD
*Department of Anesthesiology and Intensive Care, Department of Traumatology, University Medical Center Ljubljana, Slovenia, Department of Anesthesiology, University Hospital 
rebro, Sweden
Address correspondence and reprint requests to Neli Vintar, MD, Department of Anesthesiology and Intensive Care, University Medical Center, Zaloska 7, 1000 Ljubljana, Slovenia. Address e-mail to nvintar{at}hotmail.com.
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Abstract |
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Introduction |
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The aim of this study was to evaluate whether IA administration of ropivacaine and morphine via a catheter in the knee joint provides effective analgesia in patients undergoing ACLR under spinal anesthesia. The aim was also to compare the IA analgesic effects of the ropivacaine/morphine/ketorolac (RMK) mixture with ropivacaine/morphine (RM) on pain at rest and during movement and the need for supplemental IV morphine consumption.
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Methods |
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Preoperatively, all patients were instructed in the use of the 10-cm visual analog scale (VAS) with 0 and 10 labeled as "no pain" and "worst pain imaginable," respectively, and in the use of a patient-controlled analgesia (PCA) pump. As premedication, midazolam was administered IV (0.03 mg/kg) before the start of anesthesia.
Intraoperatively, a subarachnoid blockade was performed with the patient in the lateral position, with a 25-gauge Sprotte standard needle through an introducer-cannula (Pajunk) inserted at the L3-4 interspace using a median approach. Fifteen mg of plain 0.5% bupivacaine were injected (Marcaine spinal 0.5%, Astra Laboratories, Sweden).
The same surgeon performed all operations. The arthroscopic ACLR was performed using an autologous quadriceps tendon graft with adjacent bone block from the patella of the same knee. Before closing the wounds, a multiorifice epidural catheter (Portex clear 18-gauge epidural catheter with 3 lateral eyes) was placed IA through a Tuohy needle. Its position was confirmed arthroscopically. The catheter was secured to the skin by a sterile transparent dressing, flushed with 5 mL of saline, and connected to a Microject® PCA pump (Sorenson Medical, West Jordan, UT), using a Microject® cassette with incorporated 1.2-µm antimicrobial filter. The patients were instructed on how to self-administer the analgesic mixture in the knee (the pump was programed to administer a bolus of 10 mL with a 60-min lockout interval). Analgesic mixtures were prepared in 100-mL plastic bags and coded. In the 3 groups, patients received the following bolus of IA drugs on demand (per 10 mL): RM Group 0.25% ropivacaine and 2 mg morphine, RMK Group 0.25% ropivacaine combined with 2 mg morphine and 10 mg ketorolac, P group saline. Each patient also received 1 g of paracetamol orally every 6 h.
If the patient still experienced pain (VAS >3) 15 min after IA bolus administration, the protocol included rescue analgesia using IV morphine self-administered by a PCA pump. If needed, the patient could self-administer a bolus of 2 mg of morphine in 10-min lockout intervals.
To avoid confusing the patients, the IA PCA pump was marked with a green tape and the IV PCA pump was marked with a red tape. The numbers of IA and IV PCA boluses were recorded from the patient logbooks. The IV morphine consumption was calculated.
Each patient was given a logbook and asked to self-evaluate and record pain (according to the 10-cm VAS) before and 15 min after an IA bolus and before and after IV morphine dose was administered. The patient was asked to evaluate and record pain at rest and during movement and to mark the time of self-administration. To compare the groups, the following pain scores were included in the analysis: at rest after regression of spinal block (approximately 4 h after surgery), at 8 am the next morning (approximately 16 h after the procedure), 24 h after surgery, and during movement while performing the first physiotherapy (approximately 18 h after surgery). The presence of side effects (dizziness, nausea, vomiting, pruritus, urinary retention) and the degrees of the first knee flexion were collected by a blinded observer who was not otherwise involved in the study at 6 h and 24 h after surgery. Patients were asked to rate their satisfaction with pain treatment on a 3-point scale: 1) pain relief worse than expected, 2) as expected, 3) better than expected.
The IA catheter was removed 48 h after surgery and the tip was sent for microbiological analysis. Wound healing was assessed by the surgeon.
Data are expressed as mean ± sd. Demographic data were analyzed by analysis of variance for numerical data and 
2 test for categorical data. The VAS scores were analyzed by the analysis of variance; then pairs of groups were evaluated with the Student’s t-test. Side effects and other categorical variables were presented in contingency tables and then analyzed with the 2 test. A P value of <0.05 was considered statistically significant.
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Results |
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The VAS pain scores were similar at the time of the spinal block regression (4 h after surgery) and at 16 h and 24 h postoperatively (Fig. 1). During physiotherapy 18 h after the procedure, no statistically significant difference could be proven among the groups in VAS scores or in the achieved degrees of knee flexion.
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The number of PCA boluses self-administered IA during the first 24 h after surgery did not differ significantly among the groups. Figure 2 demonstrates IA boluses, administered over time.
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The 24-h rescue IV morphine total dose was 23 ± 20 mg in the RM group, 8 ± 8 mg in the RMK group, and 46 ± 21 mg in the placebo group and was significantly smaller in the RMK group (RMK versus RM and placebo group, P < 0.001; RMK versus the RM group, P = 0.002). Morphine consumption over time is shown in Figure 3.
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The incidence of individual morphine-related side effects such as dizziness, vertigo, nausea, vomiting, pruritus, and urinary retention was not statistically significantly different among groups (Table 2). There was no difference in patient satisfaction among the groups (Table 3).
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Microbiological analysis isolated Staphylococcus epidermidis on the tips of 3 catheters, all from the RM group, whereas the remaining 35 were sterile. No signs of local inflammation were noted in any of the patients, although in one patient with a positive tip result an increased body temperature and a higher level of C-reactive protein level were measured; this responded well to antibiotic treatment and did not delay the rehabilitation program. Wound healing assessed by the surgeon was considered normal in all patients.
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Discussion |
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The literature on single-dose IA analgesia is controversial because of different concentrations and volumes of local anesthetics and also as a result of the use of several drugs and drug combinations (1,2,4–6,9–20). A systematic review of single-dose IA local anesthesia for postoperative pain relief after arthroscopic knee surgery reported a small to moderate effectiveness of short duration (4,10). A similar review of the peripheral analgesic effects of IA morphine (21) demonstrated a definite but mild analgesic effect that may have been dose dependent (21,22). Although some studies reported no difference in pain relief with an IA mixture of morphine-bupivacaine compared with bupivacaine or morphine alone (10,13), many investigators noted that the combination resulted in significantly better analgesia (5,14,15,20). IA application of nonsteroidal drugs (NSAIDs) may also be beneficial (17,19). In our study, ketorolac was used in combination with ropivacaine and morphine. Ketorolac has a very high degree of protein and tissue binding, the most important factor slowing drug transport across the synovium and out of the joint (23), and may also have a protective effect by preventing the release of proinflammatory cytokines, notably interleukin-1, which has been implicated in triggering excessive cartilage degradation under inflammatory conditions (6). The principal therapeutic effect of NSAIDs is the inhibition of prostaglandin synthesis. The NSAIDs were IA combined either with bupivacaine or with morphine and the authors suggest the synergistic action of the drugs (12,16). They all agree that the IA application of NSAIDs compared with IV administration is more effective, but the doses in those studies were large (60 mg and 30 mg of ketorolac). A reduced dose of locally applied ketorolac (5 mg of ketorolac in a 5-mL volume and 0.25% bupivacaine 20 mL) provided comparable analgesia to a systemic dose (10 mg ketorolac IV) after arthroscopy of the knee, which has the potential of minimizing the systemic side effects of ketorolac while conferring the analgesic benefit of the drug (6). There are some concerns about the effects of ketorolac on wound healing. Long-term (21 to 35 days) parenteral treatment of postoperative pain with ketorolac compromised the healing of gastrointestinal anastomoses but not the corneal healing and bone remodeling (24). In the studies regarding IA administration, ketorolac was given as a single shot and no such effects were reported.
In the literature we found some reports about PCIA, but because of different study designs it is difficult to compare these results with those of our study. In the study of Dauri et al. (8) the IA analgesia with ropivacaine plus sufentanil was found insufficient for pain relief after ACLR. The IA infusion rate was slower compared with our bolus rate, as was the dose of IA opioid. In addition we used IA ketorolac, which has been shown to have analgesic effects (6,12,17).
Alford and Fadale (7) showed only mild analgesic effects of IA bupivacaine infusion after ACLR. In our study, better effects of IA analgesia in the RM and RMK groups can be attributed to a combination of drugs (5,11,15).
In a non-randomnized and unblinded trial Rasmussen et al. (25) studied continuous IA injection of morphine and ropivacaine after total knee replacement. The IA infusion led to a clinically relevant early improvement in motion and to a shortened hospital stay.
The advantage of our study is that it was randomized and double-blinded. In our study RMK was used, and PCIA with this combination of drugs offered effective postoperative pain relief after ACLR. The efficacy of our pain treatment was confirmed by significantly less IV morphine consumption in patients receiving IA analgesia compared with those receiving placebo. Patients receiving IA ketorolac needed significantly less IV morphine.
Regarding postoperative pain, our study was designed to be as comfortable for patients as possible. All patients had access to IV morphine PCA that also provided satisfactory analgesia in the placebo group at rest and during physical rehabilitation. This explains why there are no statistically significant differences in pain scores among the three groups.
The cost of analgesic modalities must be considered as well. The reusable Microject® PCA pumps are free if we buy 100 sets of casettes including tubing system, filter, and connection to catheters; the cost of each delivery system is $15. As all the patients in our study could use IA and/or IV PCA pumps, the difference in costs between IA and IV PCA analgesia is attributed to IA analgesic catheter ($13), 100 mL of ropivacaine ($10), and 100 mg of ketorolac ($6). The cost of a disposable pump would be $15, but it was not considered in our study because these have historically not been utilized to provide postoperative analgesia in our country.
Drains are regarded as an independent risk factor for wound infection and are associated with an increased incidence from 5% to 12% (25). Therefore, concerns related to the risk of infection caused by PCIA are reasonable. In our study, microbiological analysis of catheter tips showed that 35 of 38 tips were sterile; Staphylococcus epidermidis was isolated on the remaining 3 tips. It is possible that the inoculation happened during the removal of the catheter because no signs of local inflammation were noted in any of the patients and wound healing assessed by the surgeon was considered normal in all of them. However, in one patient with a positive tip, a higher body temperature and a higher C-reactive protein level were measured; this responded well to the antibiotic treatment. The catheters were removed after 48 h in our study, after 4 days in the report of Alford and Fadale (7), and after 72 h in the study of Rasmussen et al. (25). In both reports they found no increased risk of infection related to IA catheters. As there are few reports available regarding continuous IA analgesia, further studies are needed.
In many countries ACLR is not done as a day-case procedure because of moderate to severe pain despite oral analgesics. Our results may encourage more day-case surgery for ACLR. However, further studies are necessary to confirm this.
In conclusion, this is the first randomized, double-blind study to show the feasibility and efficacy of the IA regional PCA technique for pain relief after ACLR. The combination of IA RMK was superior to saline and to RM.
The authors wish to thank Maja Pohar for statistical analysis and her contribution to the graphic presentation of the results. We would also like to thank our resident Richard Knafelj for his assistance and dedication in working with patients and in our ward. The study could never have been performed without the kind cooperation of nurse-anesthetist Cvetka Kav
evi Gor
ak and the ward nursing staff.
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Footnotes |
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This article has been cited by other articles:
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  K. Axelsson, A. Gupta, E. Johanzon, E. Berg, G. Ekback, N. Rawal, P. Enstrom, and U. Nordensson 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., January 1, 2008; 106(1): 328 - 333. [Abstract] [Full Text] [PDF]
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 P. Pelissier and L. Svartz Continuous Local Anaesthetic Infusion after Trapeziectomy for Pain Relief J Hand Surg Eur Vol., December 1, 2006; 31(6): 692 - 693. [Full Text] [PDF]
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