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*Department of Anesthesiology, Pharmacology and Surgical Intensive Care, and Clinic of Orthopedic Surgery, University Hospitals, Geneva , Switzerland
Address correspondence and reprint requests to Anne Weber, Department of Anesthesiology, Pharmacology and Surgical Intensive Care, University Hospitals, 1211 Geneva 14, Switzerland. Address e-mail to Anne.Weber{at}hcuge.ch
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Abstract |
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IMPLICATIONS: We evaluated the effect of epinephrine on the duration of analgesia of 20 mL ropivacaine 0.5% or 0.2% injected in femoral three-in-one block for pain relief after total knee replacement. Our results show that epinephrine does not alter the duration of analgesia of the two solutions investigated.
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Introduction |
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One recent study concluded that the intermittent administration of bupivacaine, when compared with continuous infusion via a femoral catheter patient-controlled analgesia (PCA) device, allows decreases in the local anesthetic consumption without compromising pain scores (4). Although bupivacaine is the local anesthetic most frequently given, ropivacaine, being loss toxic than bupivacaine (5), seems more appropriate for prolonged administration via the femoral catheter.
Prolongation of ropivacaine action would be beneficial when this drug is given over days via an indwelling femoral catheter, because the total dose of ropivacaine administered, and thus the risk of toxic effects, could be further decreased. Epinephrine is added to local anesthetics to prolong the duration of spinal or epidural anesthesia. During epidural anesthesia, epinephrine has not altered the duration of ropivacaine 0.5% and 0.75% in humans (6) or of ropivacaine 1% in animals (7). In volunteers, the addition of epinephrine does not improve latency or duration of 2 mL ropivacaine 0.25%, 0.5%, 0.75%, or 1% in ulnar nerve block (8). In axillary blocks, epinephrine prolongs the anesthetic action of 40 mL lidocaine 1% (9), whereas the addition of epinephrine to 33 mL of ropivacaine 0.5% does not affect the characteristics of the subclavian perivascular brachial plexus block (10). However, the effects of epinephrine mixed with smaller doses or concentrations of ropivacaine for postoperative analgesia are not known. This study was designed to test the effects of adding epinephrine to 20 mL of ropivacaine 0.5% and ropivacaine 0.2% for postoperative analgesia via a femoral catheter after TKR, the main end point being the duration of action.
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Methods |
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For premedication, the patients received midazolam 7.5 mg orally 30–45 min before scheduled arrival in the operating room. Standard monitoring included continuous electrocardiogram, arterial oxygen saturation, and noninvasive blood pressure measurement. A peripheral venous catheter was inserted in all patients, whereas urinary, central venous, and arterial catheters were placed only when required by the patient’s clinical condition.
All patients received fentanyl 1.5 µg/kg IV before the insertion of a femoral catheter (ContiplexD Set®; B.Braun, Melsungen, Germany). According to the landmarks of Winnie et al. (11), the femoral nerve was located by using a nerve stimulator (Dual Stim; Life-Tech, Houston, TX). After observing a contraction of the quadriceps femoris (patella ascension) with impulses <0.4 mA, the catheter was introduced in the femoral sheath 15 cm from the skin.
By using sealed envelopes, the patients were randomly assigned to one of the two study groups and received in a double-blinded fashion one of the following solutions via the femoral catheter: Group ropivacaine-epinephrine (ROPI-EPI), 20 mL of ropivacaine 0.5% (Naropin®; Astra, Dietikon, Switzerland) mixed with 0.1 mg of epinephrine (1:200,000) in 1 mL normal saline; and Group ropivacaine alone (ROPI), 20 mL ropivacaine 0.5% mixed with 1 mL normal saline. These study solutions were prepared by one attending anesthesiologist not responsible for the patient.
After the injection of the study solution, a sciatic block with 30 mL bupivacaine 0.5% (Carbostesin®; Astra) with epinephrine 1:200,000 was performed in all patients by using the anterior approach (12). A 100-mm-long needle was linked to a nerve stimulator, and the anesthetic solution was injected after obtaining dorsal or plantar flexion of the foot with impulses <0.4 mA.
Fifteen minutes after each injection of local anesthetic solution, the sensory block was assessed by loss of temperature discrimination with ether drops at the anterior knee (femoral) and anterior foot (sciatic) areas. The block was considered present when no cold feeling was observed, doubtful when cold feeling was decreased, and absent when normal cold feeling was observed.
General anesthesia was then induced with sodium thiopental 4–6 mg/kg and rocuronium 0.6 mg/kg. After tracheal intubation, anesthesia was maintained with isoflurane (end-tidal concentration, 0.3%–1%) and nitrous oxide 60%–70% in oxygen. During surgery, fentanyl 1 µg/kg was given when, with 1% end-tidal isoflurane concentration, heart rate, mean arterial blood pressure, or both increased more than 30% above the preinduction levels.
After surgery, PCA via the femoral catheter was available, with 200 mL ropivacaine 0.2% mixed with 1 mg (1 mL) epinephrine (1:200,000) for Group ROPI-EPI and 200 mL ropivacaine 0.2% mixed with 1 mL normal saline for Group ROPI. These study solutions were prepared by nurses in the recovery room not participating in data collection. The PCA device was set to deliver 20-mL boluses with a lockout at 120 min. All the patients were instructed to quantify the postoperative knee pain intensity on a visual analog scale (VAS) ranging from 0 to 10 cm and to locate pain when possible in either the anterior or posterior knee area; they were further instructed to use ropivacaine via the femoral PCA device when the pain score in the anterior knee area was >3 cm or to ask for rescue morphine in the event of persistent pain in the posterior knee area. The interval between the initial ropivacaine injection and the first PCA injection determined the duration of 20 mL ropivacaine 0.5% with or without epinephrine, whereas the interval between the first and the second PCA injection determined the duration of 20 mL ropivacaine 0.2% with or without epinephrine.
Pain scores at rest every 4 h after the initial ropivacaine injection and over 48 h were recorded by the nurses in charge. Intervals between initial ropivacaine injection (Time 0) and the first PCA injection and between the first and second PCA injections, as well as the consumption of ropivacaine 0.2% over 24 and 48 h, were recorded by one investigator blinded to the ropivacaine solution used. Sciatic sensory block was assessed at 24 h by loss of temperature discrimination with ether drops by the same investigator.
Rescue morphine (0.1 mg/kg subcutaneously, maximum six doses in 24 h) was prescribed if the residual pain score at the anterior knee area was higher than 3 cm during the lockout interval of the PCA pump or for pain in the posterior knee area. Paracetamol 1 g (Dafalgan®; UPSA, Baar, Switzerland), ibuprofen 400 mg (Brufen®; Knoll, Liestal, Switzerland), or both were given orally for other pain (headache, back pain, or arthritic pain) as required. Analgesic requirements over 48 h were checked from nurses’ records.
There was an a priori decision that a difference in the duration of analgesia of at least 40% would be regarded as clinically relevant. We wished the SDs of the estimated means of duration not to exceed 40% of the means. Thus, for a two-tailed test with unpaired data, 
= 0.05, and ß = 0.20, a minimum of 16 patients were required per group. Data are presented as mean ± SD and were compared by using the unpaired Student’s t-test or 
2 test, as required; P < 0.05 was considered significant.
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Results |
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Among the remaining 41 patients, 21 had been allocated to the ROPI-EPI group and 20 to the ROPI group. Patient characteristics (Table 1) were comparable between the two groups.
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Anesthesia characteristics are presented in Table 2 and were comparable between the two groups. One patient in each group received fentanyl for hypertension during cuff inflation, and the remaining patient in the ROPI group received fentanyl by mistake for movements immediately after the start of surgery, with an isoflurane end-expiration concentration of 0.4%. Twenty-four hours after initial injection, sensory sciatic block was present in 13 patients in the ROPI-EPI group and in 15 patients in the ROPI group.
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The evolution of pain scores over 48 h after blockade is illustrated in Figure 1. The mean values remained <3 cm in both groups, and the differences were not significant.
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Discussion |
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We believe that the described analgesic management, including continuous femoral and long-lasting sciatic blocks, improved the accuracy of measurement of the duration of action of both ropivacaine solutions investigated. Because the knee joint receives nerve supplies from two different plexuses, it can sometimes be difficult for patients to distinguish pain sensations originating from the knee area that is dependent on either femoral or sciatic sensory fibers. The presence of a long-lasting sciatic block increases the probability that patients self-administer ropivacaine for pain arising from the anterior knee area; thus, the time of PCA administration allows precise determination of the duration of action of ropivacaine solutions. Indeed, sensory sciatic block was already present in 28 of 41 patients at 24 hours after blockade, which is much longer when compared with a maximum duration of 11–12 hours for ropivacaine injected in a femoral catheter. In one study that used continuous infusions of local anesthetic mixed with clonidine and morphine in the femoral sheath for postoperative analgesia after TKR, pain in the posterior knee area was clearly reported and recognized as disturbing for the patients (3).
Continuous femoral block associated with long-lasting single-shot sciatic block is a standard procedure in our institution in patients undergoing TKR under general anesthesia. Although the utility of an additional sciatic block for postoperative analgesia has been questioned (13), we have shown that this block, in addition to a continuous femoral block, improved postoperative pain relief in at least two thirds of the patients undergoing TKR under spinal anesthesia (14). Sciatic block performed before surgery probably contributed to the small perioperative analgesic requirements in our patients; these seem to be lower than when TKR is performed under general anesthesia with femoral block only (2,3). The mean VAS values lower than 1 cm during the first 16 postoperative hours (Fig. 1) in both groups further support the analgesic efficacy of sciatic block.
In this study, no effect of adding epinephrine to 20 mL ropivacaine 0.5% or 0.2%, in terms of improved analgesic duration, was detected. It is accepted that epinephrine prolongs the anesthetic action of 40 mL lidocaine 1% (short-acting local anesthetic) (9) but not of 33 mL ropivacaine 0.5% (considered long acting) (10). Using a smaller volume but mainly a smaller concentration (i.e., 0.5% vs 0.2%) of ropivacaine, we expected a prolongation of the duration of analgesia by adding epinephrine; this, however, was not the case. The mean duration of analgesia observed for both 20 mL ropivacaine 0.5% (12 h) and 20 mL ropivacaine 0.2% (7 h) is probably too long to be influenced by epinephrine. These findings are in agreement with previously published data studying the association of ropivacaine with epinephrine in peripheral blocks in both patients (10) and volunteers (8) or in epidural anesthesia in both patients (6) and animals (7).
Another possible explanation for the lack of effect of epinephrine could be the intrinsic vasoconstrictor property of ropivacaine (15). Thus, epinephrine added to ropivacaine in peripheral nerve blocks can be useful only for early detection of intravascular injection, which can be associated with serious complications (16,17).
Only intermittent injections of ropivacaine 0.2% by use of a PCA pump (20-mL bolus, 120-minute lockout) were prescribed in our patients. Recently, it has been shown that after TKR, boluses of 10 mL bupivacaine 0.125% with 1 µg/mL clonidine (lockout 60 minutes) were associated with a significantly smaller anesthetic consumption than when continuous infusions of 10 mL/h or continuous infusions of 5 mL/h plus boluses of 2.5 mL (lockout 30 minutes) of the same solution were used (4). Analgesic effects of these three study solutions and patient satisfaction were not different, confirming the advantage of intermittent administration of local anesthetics. In this study, we used larger boluses and longer lockout times. With or without epinephrine, approximately three boluses of 20 mL ropivacaine 0.2% were administered for the first 24 hours, and four or five were administered for the following 24 hours. The average consumption of ropivacaine 0.2% was 3–4 mL/h, which is consistent with previously described intermittent techniques (4) and much smaller than with continuous infusions (2,3,18).
Excellent pain control was obtained in all patients with the described analgesic management. Mean VAS scores never exceeded 2 cm during the first 24 hours and 3 cm in the following 24 hours in both study groups (Fig. 1). Morphine requirements during the first 24 hours were negligible; larger morphine consumption from 24 to 48 hours (Table 3) can be attributed to the resolution of sciatic block. Indeed, in the majority of patients, the morphine injections (10 of 14) were given for pain at the posterior or lateral knee area corresponding to sciatic innervation; the remaining four patients received morphine for diffuse knee pain. We did not test pain scores at mobilization, because in our institution postoperative knee mobilization starts 48 hours after surgery. Nevertheless, the femoral catheters were withdrawn only when the patients spontaneously stopped using the PCA pump, which generally occurred between the third and fifth postoperative day.
In conclusion, the results of this study show that epinephrine does not influence the duration of analgesia of either ropivacaine concentration investigated. Epinephrine added to ropivacaine can be useful only for early detection of intravascular injection. Nevertheless, the described peripheral analgesic technique provided excellent pain relief over 48 hours after TKR.
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Footnotes |
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This article has been cited by other articles:
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  A. Weber, R. Fournier, N. Riand, and Z. Gamulin Duration of analgesia is similar when 15, 20, 25 and 30 mL of ropivacaine 0.5% are administered via a femoral catheter: [La duree de l'analgesie est similaire quand 15, 20, 25 et 30 mL de ropivacaine a 0,5 % sont administres par un catheter femoral] Can J Anesth, April 1, 2005; 52(4): 390 - 396. [Abstract] [Full Text] [PDF]
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 S. S. Liu and F. V. Salinas Continuous Plexus and Peripheral Nerve Blocks for Postoperative Analgesia Anesth. Analg., January 1, 2003; 96(1): 263 - 272. [Full Text] [PDF]
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