Postoperative pain after total knee arthroplasty (TKA) is a major concern. It is severe in 60% of patients and moderate in 30% (1) and hinders early intensive physical therapy, the most influential factor for good postoperative knee rehabilitation (2). After TKA, postoperative pain relief can be achieved by a variety of techniques, such as IV patient-controlled analgesia (PCA) (3), epidural analgesia (4), and extended “3-in-1” block (5). Recently, it has been demonstrated that both regional techniques provide better pain relief and allow more complete and faster postoperative knee rehabilitation than IV PCA with morphine (6,7). Compared with epidural analgesia, extended “3-in-1” block is associated with fewer side effects, and is, therefore, the preferred technique. The continuous infusion of 0.125% bupivacaine at the rate of 0.14 mL · kg−1 · h−1 is effective to maintain extended “3-in-1” block (8). However, this technique leads to the administration of large volumes of local anesthetic with a potential risk of toxicity caused by accumulation of the drug after a prolonged period of infusion (9). Thus, a “dose-sparing” infusion technique is desirable. For example, after hand trauma surgery, a PCA technique via an axillary brachial plexus catheter provides good postoperative analgesia and reduces local anesthetic consumption by 70% (10). This technique has not yet been evaluated with a femoral nerve sheath catheter. The aim of our study was to assess its efficacy after unilateral TKA.
After informed consent and with institutional approval, 45 ASA physical status I–III patients scheduled for elective unilateral TKA under general anesthesia were included in this study. Patients were excluded for the following reasons: if they had coagulation abnormality, age <18 or >80 yr, weight <50 or >100 kg, preexisting neurological deficit, diabetes, or inability to understand pain scales or use a PCA device.
In all patients, a “3-in-1” block was performed before the induction of general anesthesia by using the landmarks of Winnie, et al. (11). The femoral artery was located below the inguinal ligament, and an 18-gauge short-beveled cannula (Alphaplex®; Braun, Melsungen, Germany) was inserted just lateral to the artery. The femoral nerve was accurately located with a peripheral nerve stimulator (Anaestim MK III; Meda, Antwerpen, Belgium). With a starting output of 100 nanocoulombs (2.5 mA), the needle was advanced at an angle of 30° to 45° to the skin until twitches of the quadriceps muscle (ascension of the patella) were elicited. Its position was then optimized and judged adequate when output lower than 40 nanocoulombs (<1 mA) still elicited contractions of the quadriceps. By using a Seldinger technique, a 20-gauge catheter was then threaded 10–15 cm into the femoral nerve sheath. After a negative aspiration test for blood, 40 mL 0.25% bupivacaine with epinephrine 1:200,000 was injected.
In all patients, general anesthesia was induced with 0.3 μg/kg sufentanil, 3–5 mg/kg thiopental, and 0.5 mg/kg atracurium. The trachea was intubated, and controlled ventilation was started. Anesthesia was maintained with a 0.0025 μg · kg−1 · min−1 sufentanil infusion (stopped approximately 45 min before the end of the procedure) and a mixture of nitrous oxide (66%) and isoflurane (0.5% to 1%) in oxygen. In all patients, 30 mg of IV ketorolac was administered at the induction of general anesthesia, and then, three times daily during the first 48 h postoperatively.
In the recovery room, the correct position of the femoral nerve sheath catheter was confirmed by a sensory block (loss of temperature sensation assessed by using an ether-soaked swab) involving the distribution of the femoral nerve (anterior aspect of the thigh). Patients were then divided into three groups of 15 in a randomized fashion by using a computer-generated list of random permutations. During the first 48 h postoperatively, Group 1 received a continuous infusion of 0.125% bupivacaine with 1 μg/mL clonidine at the rate of 10 mL/h; Group 2 received a continuous infusion of the same solution at the rate of 5 mL/h plus PCA boluses of 2.5 mL with a lockout time of 30 min; and Group 3 received PCA boluses only of 10 mL of the same solution with a lockout time of 60 min. To blind the study, patients in Group 1 also had access to a PCA button which did not trigger any bolus administration.
Immediately after surgery, all three groups started identical physical therapy regimens. During the first 48–72 postoperative h, a continuous passive motion machine was applied, with the range of motion set at levels well tolerated by the patient. From the day after surgery until discharge, active and assisted knee and hip flexion and extension exercises were set against gravity, twice-daily.
Pain at rest and on movement (visual analog scale [VAS] ranging from 0 = no pain to 100 = worst pain imaginable), and sensory block (loss of temperature sensation assessed by using an ether-soaked swab) in the distributions of the femoral (anterior aspect of the thigh) and the obturator (inner aspect of the knee) nerve were assessed 4, 24, and 48 h after the operation. A postoperative pain score (0 = no pain; 1 = moderate pain only when moving; 2 = moderate pain at rest, severe pain when moving; 3 = constant severe pain) was also recorded by the nurses every 2 h during the first 12 postoperative hours and every 4 h afterward. Supplemental postoperative analgesia was standardized. If the postoperative pain score was ≥1, patients received 2 g of IV propacetamol followed by 10–20 mg of IM piritramide, a synthetic μ-agonist opioid, if the postoperative pain score remained unchanged after 30 min. Supplemental analgesia, bupivacaine consumption, side effects, and satisfaction score (by using a VAS ranging from 0 = not satisfied to 100 = entirely satisfied) at the end of the study period, were recorded. All data were collected by an anesthesiologist not involved in the administration of anesthesia nor in patient care in the recovery room.
The patients were seen at the surgeon’s clinic 6 wk and 3 mo after the procedure. They were then asked about any adverse effects or complications.
Based on a previous study (12), we hypothesized that we could observe at least a 30% reduction in the consumption of bupivacaine between Groups 1 and 2. A power analysis (mean consumption of 500 mg bupivacaine [Group 1] and 350 mg bupivacaine, [Group 2] with a standard deviation of 80) estimated that 10 patients would be needed in each group to provide a 95% chance of detecting such reduction at the 0.01 level of significance. Statistical analysis was performed by using the GB-Stat version 6.5 computer package. Parametric data were compared by using one-way analysis of variance followed by a Bonferroni t-test. PCA demands were analyzed with a Kruskal-Wallis test. Discrete variables (sex ratio, sensory block) were compared by using χ2. P < 0.05 was considered significant. Results are expressed as mean ± sem.
Population data are presented in Table 1. No difference was noted among the groups. In the recovery room, complete loss of temperature sense in the distribution of the femoral nerve was observed in all patients.
The VAS scores at rest and on movement, postoperative pain scores, supplemental analgesia, bupivacaine consumption, and satisfaction scores are presented in Table 2. Pain scores and supplemental analgesia were not significantly different among the three groups. When compared with Group 1, bupivacaine consumption was significantly lower in Groups 2 and 3 (P < 0.01). Moreover, Group 3 consumed significantly less bupivacaine than Group 2 (P < 0.01). At 48 h, satisfaction scores were high (no lower than 80 on a 100-point scale) and comparable among the three groups.
The use of PCA was significantly less frequent (median, 25th–75th percentiles): 0 (0–30), 66 (20–97), and 44 (28–126) demands/48h in Groups 1, 2, and 3, respectively, (overall P = 0.004) in Group 1 than in two other groups (P < 0.05).
Sensory block in the distribution of the femoral and obturator nerves is presented in Table 3. No significant difference was noted among the groups. In the three groups, femoral nerve block was well maintained during the entire study period. At 24 and 48 h postoperatively, obturator nerve block was more evanescent. Except for nausea-vomiting (three, four, and four patients, respectively, in Groups 1, 2, and 3), no side effects or technical problems were noted in the three groups.
The knee is innervated by the lumbosacral plexus. The femoral and obturator nerves innervate the anterior aspect of the knee, and the sciatic nerve innervates the posterior aspect. Blockade of both the sciatic and femoral nerves may be required to consistently provide postoperative analgesia after TKA. However, equal analgesic efficacy with either femoral or sciatic-femoral nerve blocks has been demonstrated (13). This observation suggests that sciatic innervation of the posterior knee is a relatively minor contribution to postoperative pain after TKA, which is why we performed only a femoral nerve sheath block.
The continuous infusion of 0.125% bupivacaine at the rate of 0.14 mL · kg−1 · h−1 is considered the “gold standard” to maintain extended “3-in-1” block (8). Neither the extent of anesthesia nor the quality of analgesia are improved by increasing infusion rate (14). However, this technique leads to the administration of large volumes of local anesthetic with a potential risk of toxicity caused by accumulation of the drug after prolonged periods of infusion (9). In our study, a reduction of the background infusion by one-half (5 mL/h), associated with the use of small size (2.5 mL) PCA boluses, provided excellent pain relief and a 32% reduction in the local anesthetic consumption. Moreover, as expressed by the patients, this technique allowed rapid reinforcement of the block before a knee physiotherapy session. PCA boluses alone (10 mL with a lockout time of 60 min) achieved comparable results with a more significant reduction (58%) in the bupivacaine consumption.
In our study, the extent of anesthesia during extended “3-in-1” block, varied with time. Although the femoral nerve block was well maintained in the three groups, obturator nerve block was more evanescent, particularly at 48 h postoperatively. Similar results have been obtained by Barthelet et al. (15). Both studies confirmed that the most influential factor for efficient pain relief after knee surgery is the presence of a femoral nerve block (13). At 48 h postoperatively, we detected no anesthesia in the femoral and obturator nerve distribution in 23% of patients. However, effective pain relief (VAS scores, <25 at rest and <40 on movement) without any increase in supplemental analgesia was observed in all of these patients. This could be probably explained by a “differential” block, i.e., weak concentrations of local anesthetic inducing analgesia without completely inhibiting impulse conduction (16).
The choice of lockout intervals in our PCA groups was based on experience with patient-controlled epidural analgesia. During patient-controlled epidural analgesia, lockout intervals of at least 15 to 30 min are recommended to minimize the possibility of the patient self-administering a bolus dose before the previous dose has had time to exert its analgesic effect (17). Moreover, studies on labor pain relief have shown that the quality of analgesia is unaffected by the duration of the lockout interval, as long as effective hourly doses of local anesthetic are administered (18). We speculated that it would be the same when using a PCA technique for extended peripheral nerve block.
In accordance with the concept of “balanced analgesia” advocated by Kehlet (19), IV ketorolac was systematically administered to all patients, and clonidine was included in our continuous infusion. When added to the local anesthetic solution, clonidine prolongs duration of both anesthesia and analgesia after a single-shot brachial plexus block (20). Unpublished data support the same effects during extended peripheral nerve block. This observation must be confirmed by a large, randomized study.
The underlying mechanism of action of clonidine on peripheral nerves is not known. Three mechanisms of action may be proposed. First, clonidine may activate postsynaptic adrenergic receptors leading to local vasoconstriction (21), thus prolonging local anesthesia by decreasing the systemic absorption of the local anesthetic. However, at least two studies showed that clonidine does not evoke local vasoconstriction (22,23). Second, clonidine may have local anesthetic activity. Compared with procaine, clonidine is equipotent in inhibiting impulse propagation on the frog sciatic nerve (24). When applied on the rabbit cornea, it is approximately 140 times more potent as a surface anesthetic than procaine (24). This might indicate that C fibers or Aδ fibers, which exclusively innervate the rabbit cornea, are especially sensitive to clonidine. Butterworth and Strichartz (25) hypothesized that analgesia seen after neuraxial application of clonidine might result from direct inhibition of impulse conduction in primary afferent nerve fibers. From the results of their study on rat sciatic nerves, they speculate that part of the efficacy of α2-adrenergic agonists in producing analgesia may result from their “local anesthetic” actions on Aα and, especially, C fibers. Finally, clonidine may have a potentiating effect on local anesthetics. Gaumann et al. (23) showed that a small dose of clonidine enhanced lidocaine-evoked inhibition of C fiber action potentials, and concluded that this effect might explain the clinical observation that clonidine prolongs the action of local anesthetics in peripheral nerve blocks.
In this study, there were no complications attributable to the use of PCA techniques. However, the small number of patients does not permit us to make definitive conclusions about its relative safety.
In conclusion, this prospective, randomized, double-blinded study confirmed that extended “3-in-1” block with bupivacaine and clonidine provides efficient pain relief after TKA and that, compared with a continuous infusion, PCA techniques reduce the local anesthetic consumption, without compromise in patient satisfaction or VAS scores. Of the two PCA techniques tested, PCA boluses (10 mL with lockout time of 60 min.) of 0.125% bupivacaine with 1 μg/mL clonidine was associated with the smallest local anesthetic consumption and is, therefore, the recommended extended “3-in-1” block technique.
The authors are grateful to F. Veyckemans, MD, for his valuable criticism of the manuscript and his comments.
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