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REGIONAL ANESTHESIA AND PAIN MEDICINE

A Comparison of Ropivacaine with Fentanyl to Bupivacaine with Fentanyl for Postoperative Patient-Controlled Epidural Analgesia

Peter S. Hodgson, MD^*, and Spencer S. Liu, MD^*

Departments of Anesthesiology, *Virginia Mason Medical Center; and University of Washington, Seattle, Washington

Address correspondence to Dr. Spencer S. Liu, Department of Anesthesiology, Virginia Mason Medical Center, 1100 Ninth Ave., P.O. Box 900, Mail Stop B2-AN, Seattle, WA 98111. Address e mail to anessl{at}vmmc.org

	Abstract

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Ropivacaine for patient-controlled epidural analgesia (PCEA) may facilitate postoperative patient mobilization because it causes less motor block than bupivacaine. Forty patients undergoing abdominal surgery were randomized in a double-blinded manner to the following: 0.05% bupivacaine/4 µg fentanyl, 0.1% bupivacaine/fentanyl, 0.05% ropivacaine/fentanyl, or 0.1% ropivacaine/fentanyl for standardized PCEA. We measured pain scores, side effects, and PCEA consumption for 42 h. Lower-extremity motor function was assessed with electromyography and isometric force dynamometry. Analgesia was equivalent among groups. Local anesthetic use was more in the 0.1% Ropivacaine and 0.1% Bupivacaine groups (77% increase, P = 0.001). Motor function decreased during PCEA (10%–35% decrease from preoperative, P < 0.001) and was equivalent among groups. Eight patients were transiently unable to ambulate. These patients used more local anesthetic (45 vs 33 mg mean, P < 0.05) with additional decrease in motor function (32%, P < 0.004) compared with ambulating patients. Other side effects were mild and equivalent among solutions. PCEA with bupivacaine/fentanyl and ropivacaine/fentanyl as 0.05% or 0.1% solutions appears clinically equipotent. Lower-extremity motor function decreases, but is unlikely to result in prolonged inability to ambulate. Use of a 0.05% solution may be advantageous to decrease local anesthetic use and prevent transient motor block.

Implications: Patient-controlled epidural analgesia with bupivacaine/fentanyl and ropivacaine/fentanyl as either 0.05% or 0.1% solutions are clinically similar. Lower-extremity motor function will decrease with the use of any of these combinations, but is unlikely to result in the inability to walk.

	Introduction

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Current fast-track postoperative rehabilitation regimens after abdominal surgery emphasize rapid patient mobilization in conjunction with satisfactory dynamic analgesia (1–3). Epidural analgesia provides optimal postoperative analgesia after abdominal surgery, and patient-controlled epidural analgesia (PCEA) has gained popularity (4–6). The use of combinations of bupivacaine and opioid for postoperative epidural analgesia results in an incidence of motor block of 4%–12%, which may delay postoperative recovery (4).

Ropivacaine is a new local anesthetic that may be superior to bupivacaine for epidural analgesia because of decreased potency for motor block (7). Ropivacaine as a sole epidural analgesic requires relatively concentrated solutions (0.2%–0.3%) and is often unsatisfactory because of inadequate analgesia or excessive motor block (8,9). The addition of epidural fentanyl (10) improves analgesia and allows the use of 0.1% and 0.05% solutions of epidural ropivacaine with decreased risk of motor block (11). There are no comparisons between PCEA regimens of 0.05%–0.1% ropivacaine/fentanyl versus bupivacaine/fentanyl to detect potential advantages, particularly with lower-extremity motor function. Thus, we performed this prospective, randomized, double-blinded trial to compare ropivacaine/fentanyl PCEA versus bupivacaine/fentanyl PCEA for analgesia, side effects, and motor block.

	Methods

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After IRB approval and informed consent were obtained, 43 patients were enrolled in our prospective, randomized, double-blinded protocol. Inclusion criteria included age 18–80 yr, ASA classification I–III, planned midline lower-abdominal surgical incision for colon, radical prostate, or gynecologic surgery, and epidural analgesia planned for at least two postoperative days. Exclusion criteria included a history of reactions to amide local anesthetics or fentanyl, current prescription opioid use, history of substance abuse within 5 yr, alcohol use more than two drinks per day, disorders of either knee, and inability to comprehend or perform verbal or physical assessments.

A baseline assessment of vital signs, pain, nausea, pruritus, and sedation scores, and lower-extremity motor strength was performed on all patients in a preoperative holding area (see below for details of measurements). All patients subsequently received a standard premedication of midazolam (0.04 mg/kg) and fentanyl (1 µg/kg) IV before placement of an epidural catheter 4–6 cm into the epidural in the T12-L2 vertebral interspaces. After a 3-mL 1.5% lidocaine test dose containing 15 µg epinephrine, a further 8–16 mL of 2% lidocaine with 1:200,000 epinephrine was dosed. After sensory blockade was substantiated, patients were randomized in a double-blinded manner by our investigational pharmacy to receive one of four epidural infusions: bupivacaine 0.05% with fen-tanyl 4 µg/mL, bupivacaine 0.1% with fentanyl 4 µg/mL, ropivacaine 0.05% with fentanyl 4 µg/mL, ropivacaine 0.1% with fentanyl 4 µg/mL. General anesthesia was induced with thiopental (3–6 mg/kg), fentanyl (2 µg/kg) and muscle relaxation at the discretion of the primary anesthesia team. General anesthesia was maintained with isoflurane in 100% oxygen. Additional muscle relaxation was administered per the primary anesthesia team. Approximately 60 min after the initial epidural injection, a 10-mL bolus of the study drug was administered and an infusion of study drug continued at 6 mL/h for the remainder of the anesthetic. No additional IV or epidural fentanyl was administered.

On admission to the postanesthesia care unit, patients received standard teaching in the use of the PCEA device. The standard settings included a fixed bolus of 2 mL of study solution, 10-min lockout, and a background infusion of 6 mL/h. Patients with inadequate analgesia (visual analogue scores [VAS] for pain at rest 50/100) received a 5-mL bolus of study drug and a 2-mL/h increase in the rate of infusion and were reassessed in 20 min. The same intervention was repeated until patients reported a VAS at rest <50/100. Patients were transferred to standard nursing care on the hospital ward when standard postanesthesia care unit discharge criteria were met. Inadequate analgesia on the hospital ward was treated as described above. The nursing team was instructed to call an anesthesiologist to assess the patient if more than two increases in the infusion rate for inadequate analgesia were required, if motor block developed, if patients developed hypotension (systolic pressure 90 mm Hg and 20% below baseline systolic blood pressure) or postural hypotension impairing ambulation. Hypotension on the ward was treated with a 500-mL bolus of normal saline. In addition, for hypotension or for motor-block impairing ambulation, the infusion was held for 1 h then restarted at half the previous hourly rate. If inadequate pain relief because of unilateral block was suspected, or if unilateral motor block was assessed, the epidural catheter was withdrawn 1 cm from the epidural space or the catheter was replaced. For interim treatment of inadequate analgesia, morphine sulfate 1–5 mg IV was administered.

All patients were assessed by a blinded investigator 1–4 h after completion of surgery to assure adequate analgesia, proper equipment function, and stable vital signs. In addition to the preoperative baseline assessment, patients underwent three subsequent assessments, occurring the morning (0700–0900) and afternoon (1500–1700) of the first postoperative day and the morning (0700–0900) of the second postoperative day. Study measurements included the following: supine and sitting blood pressure and heart rate; pain scores at rest, with ambulation, and with lower-extremity motor function assessments (VAS 0–100 scale); pruritus and nausea scores (VAS 0–100 scale); observer-rated sedation score 0–4 (0 = no sedation, 1 = mildly sedated, 2 = sleeping but easily aroused, 3 = sleeping but difficult to arouse, 4 = not arousable); and ability to ambulate (yes/no). For occurrence measurements, pruritus and nausea were considered to be present if VAS >50. Side effects were considered clinically significant if they persisted for two consecutive measurement periods despite adjustments to the analgesic regimen as described above.

Quantitative measurements of lower-extremity motor strength were performed at every assessment as described previously (11). For skin-surface electromyographic (EMG) measurements, electrodes were placed on both thighs anteriorly along the axis of the vastus intermedius muscle 6 cm above the upper border of the patella and at 6-cm intervals proximally (positive, ground, negative). In addition, a single three-electrode montage was placed in a uniform orientation at the upper border of the left rectus abdominus muscle. The position of the electrodes was indicated with indelible skin ink and was used for all measurements. Patients were trained to perform a straight-leg maximal isometric contraction of the quadriceps femoris in the supine position for 5 s without the use of the abdominal musculature as assessed by EMG. A time-averaged EMG value was performed over the middle 2-s interval during maximal contraction. This was repeated three times on each leg. The lower portion of the bed was subsequently positioned so that the legs were flexed at the hip (45°) and knee (90°), and a firm roll was placed beneath the knees as a fulcrum. Patients were instructed to extend the leg against resistance without using the abdominal musculature. A force dynamometer was positioned over the same location on the distal end of the tibia to measure the maximal isometric force during leg extension three times for each leg. Lack of abdominal muscle activity was assessed with surface EMG as described above.

Power analysis based on a previous study indicated that 10 subjects per group would allow detection of a 15% difference in lower-extremity motor block measured by EMG (P = 0.05, power = 0.8) (11). Patient characteristics were compared with analysis of variance (ANOVA) and contingency table. VAS pain scores were compared with repeated measures ANOVA. Presence of nausea, pruritus, hypotension, sedation, and motor block were compared with contingency tables. Epidural analgesic consumption was compared with ANOVA. Quantitative motor function was averaged for both lower extremities and normalized to the preoperative baseline measurements (current measurement/preoperative measurement x 100). Differences over time and among groups was compared with repeated measures or factorial ANOVA. Post hoc testing was performed with the Scheffé F test. A P < 0.05 was considered significant.

	Results

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Forty-three patients were enrolled and 40 completed the protocol with 10 patients per group. One subject was excluded because of a change in the surgical plan, and two were excluded because of protocol violations. Patient characteristics were similar ( Table 1). Pain scores were similar at rest, cough, during lower-extremity motor function assessment, and with ambulation (Fig. 1, A and B). Consumption of local anesthetic was significantly more in the 0.1% Bupivacaine and Ropivacaine groups (Table 1). Quantitative motor strength measurements of the lower extremities significantly decreased from the preoperative measurement and were not different among groups ( Fig. 2 and 3). Eight patients were transiently unable to ambulate (Table 1). These patients used more epidural local anesthetic (33 ± 13 vs 45 ± 17 mg, mean ± SD, P < 0.05) and had an additional decrease in lower-extremity motor function (32% further decrease on average, P < 0.004) when compared with patients without clinical motor block. All patients were able to ambulate by the next measurement period after appropriate clinical interventions to the PCEA regimen (Table 1) as described in Methods. The presence and severity of nausea, pruritus, and sedation were infrequent and similar among groups (Table 1).

View larger version (27K): [in this window] [in a new window]   Figure 1. Visual analog scores (VAS) for pain at rest (A) and during ambulation (B). There were no differences among groups. Mean and standard deviations are displayed.

View larger version (21K): [in this window] [in a new window]   Figure 2. Percent of baseline (preoperative) quadriceps strength as assessed by surface electromyography (EMG). *Different from baseline over time (P < 0.001). There were no differences among groups. Mean and standard deviations are displayed. POD = postoperative day.

View larger version (22K): [in this window] [in a new window]   Figure 3. Percent of baseline (preoperative) quadriceps strength as assessed by isometric force dynamometry. *Different from baseline over time (P < 0.001). There were no differences among groups. Mean and standard deviations are displayed. POD = postoperative day.

	Discussion

Top Abstract Introduction Methods Results Discussion References

Ropivacaine is a relatively new local anesthetic that may have decreased potency for motor block when compared on a mg/mg basis to bupivacaine for epidural use (13,14). Rapid patient mobilization is an integral component of rapid recovery clinical pathways after abdominal surgery, and these clinical pathways decrease duration of hospitalization by one to two days after abdominal surgery (1–3). Decreased motor block with epidural ropivacaine may confer an advantage over bupivacaine provided that sensory block potency is approximately equivalent.

There have been several previous studies examining relative potencies of sensory and motor block of epidural ropivacaine versus bupivacaine. In initial studies in volunteers comparing dilute concentrations of epidural ropivacaine (0.1%–0.3%) and bupivacaine (0.25%) suitable for postoperative analgesia, similar sensory block potency with decreased motor-block potency with ropivacaine were observed (14). This suggested a potential superiority of ropivacaine over bupivacaine for rapid patient mobilization. However, studies in postoperative patients and parturients using epidural analgesia infusions (0.125%–0.2%) of ropivacaine versus bupivacaine have been conflicting. Some studies reported equipotency (15,16), others reported equal analgesic potency but decreased motor-block potency with ropivacaine (17), whereas some have reported decreased analgesic potency with ropivacaine (18,19). Thus, relative potencies of epidural ropivacaine versus bupivacaine as sole drugs for postoperative epidural analgesia are unclear.

Previous comparisons of epidural analgesia with ropivacaine versus bupivacaine are further clouded by the addition of epidural opioids. Both epidural ropivacaine and bupivacaine are improved by the addition of small doses of fentanyl for postoperative analgesia (10,12). Although spinal selectivity of epidural fentanyl is modest compared with morphine, its clinical profile of relatively rapid onset, modest duration, and minimal risk of delayed respiratory depression is better suited to PCEA (4). Preliminary comparisons of epidural infusions of ropivacaine/opioid versus bupivacaine/opioid in postoperative patients and parturients tend to demonstrate equal analgesic potency with decreased motor block with epidural ropivacaine/opioid (20,21), although other investigators have observed decreased potency for both analgesia and motor block with ropivacaine/sufentanil compared with bupivacaine/sufentanil (22). Thus, relative potencies and potential advantages of ropivacaine versus bupivacaine with and without opioid for postoperative epidural analgesia have been unclear.

In the context of our optimized clinical comparison, 0.05% and 0.1% ropivacaine appear clinically equipotent to bupivacaine for analgesia and motor block when combined with fentanyl for PCEA. All epidural solutions produced satisfactory analgesia with significant decreases in lower-extremity motor function. Nonetheless, the use of appropriately dilute analgesic solutions and patient-controlled delivery resulted in minimal clinical side effects, including the inability to ambulate. We noted that the use of the 0.05% solutions of bupivacaine and ropivacaine resulted in decreased local anesthetic use without compromising analgesia. Because transient inability to ambulate was associated with increased use of local anesthetic, these solutions may be preferable to the 0.1% solutions to decrease local anesthetic use and risk of transient clinical motor block. However, appropriate titration of PCEA will still allow patient ambulation even with the 0.1% solutions. Overall, it appears unlikely that ropivacaine offers significant clinical advantage over bupivacaine as the local anesthetic component for postoperative PCEA with a dilute local anesthetic/fentanyl analgesic solution.

	Acknowledgments

 
Funded by the Daniel C. Moore/L. Donald Bridenbaugh Fellowship in Regional Anesthesia and an unrestricted grant from Astra USA Inc.

The authors thank Susan B. McDonald, MD, and Julie D. Deszo, RN, MSN, AOCN.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999