Borgeat, Alain MD*,; Kalberer, Fabian MD†,; Jacob, Hilaire PhD‡,; Ruetsch, Yvan A. MD*,; Gerber, Christian MD†,
Ropivacaine is an enantiomerically pure (S-enantiomer) amino-amide local anesthetic. Several in vitro studies have shown that ropivacaine produces a decreased degree of block in heavily myelinated (motor) fibers and a faster onset of block in lightly myelinated (sensory) fibers than bupivacaine. These properties of ropivacaine would support the prediction of a greater differential effect (1,2). Ropivacaine is also a potent producer of frequency-dependent block in less myelinated fibers, which offers the prospect of a better differential blocking effect than that provided by bupivacaine (3). These properties would be particularly well suited to orthopedics because a good sensorimotor dissociation may facilitate rehabilitation and improve patient well being. Bupivacaine and ropivacaine have been used successfully to provide analgesia during the first 48 h postoperatively through an interscalene catheter after major shoulder surgery (4,5). However, the effects of these two drugs on motor function using patient-controlled interscalene analgesia (PCIA) technique have not been investigated. In this study, we compared the effects of a continuous infusion of ropivacaine 0.2% and bupivacaine 0.15% through an interscalene catheter on hand strength after major open shoulder surgery.
Patients and Methods
After we obtained approval of our institutional ethics committee and written informed consent from patients, 60 adult patients of both sexes (classified as ASA physical status I or II, age 18–75 yr, weight 50–100 kg) scheduled for elective shoulder arthroplasty, rotator cuff repair, or Bankart operation were enrolled in this prospective, randomized and double-blinded study. Exclusion criteria were any contraindications to interscalene block (ISB), including severe bronchopulmonary disease, known allergy to the trial drugs, previous analgesic treatment with other than nonsteroidal inflammatory drugs, pain in the shoulder resulting from other conditions, and any previous neurologic damage to the brachial plexus.
Patients were assigned a number between 1 to 60 by choosing a sealed envelope containing a number. Each patient number was passed on to a pharmacist who prepared the anesthetic set (bolus and maintenance package) of either ropivacaine or bupivacaine according to a computerized randomization list. All patients had an ISB performed before the induction of general anesthesia. The brachial plexus was identified using a nerve stimulator ( Stimuplex, DIG™; B. Braun Melsungen AG, Melsungen, Germany) connected to the proximal end of the metal inner needle of a plastic cannula ( Contiplex™; B. Braun Melsungen AG). Placement of the needle was considered successful when a contraction of the triceps muscle was obtained with a current output of <0.5 mA. A catheter (Contiplex; 23F with stylet) was introduced distally between the anterior and middle scalene muscles for up to 3–4 cm. The catheter was subcutaneously tunneled over 3–4 cm through an 18-gauge IV cannula and fixed to the skin with adhesive tape. ISB was performed with either 40 mL ropivacaine 0.6% or 40 mL bupivacaine 0.5%. All patients received the drug by means of the catheter. Interscalene block was confirmed by a sensory (inability to recognize cold temperature) and motor block (inability to extend the arm, pins and needles type of paresthesia in the tip of the first and third finger) involving the radial and median nerve within 20 min after the administration of local anesthetic.
The general anesthetic technique used (when necessary—patient’s wish) was standard for all patients. They were premedicated with 0.1 mg/kg midazolam given orally 1 h before the ISB. After the block was complete, the induction was performed with 1.5–2 mg/kg of propofol and anesthesia was maintained with 8–10 mg · kg−1 · h−1 of propofol. Tracheal intubation was facilitated using 0.8 mg/kg rocuronium and 1–1.5 μg/kg of fentanyl was given within 3 min before tracheal intubation. Those who had no general anesthesia were allowed to receive propofol for sedation, if needed. All patients received an infusion of local anesthetics through the interscalene catheter in the recovery room, starting 6 h after the initial ISB. Both groups had a continuous infusion (0.2% ropivacaine vs 0.15% bupivacaine) at a rate of 5 mL/h plus a bolus dose of 4 mL with a lockout time of 20 min. The infusion was stopped 48 h after the ISB and the study was completed 54 h after the ISB. All patients received 2 g of propacetamol (the predrug of acetaminophen) IV four times a day on a regular basis. Rescue treatment consisted of morphine 0.1 mg/kg subcutaneously given on patient request.
Hand strength was measured by means of a soft rubber bulb, the “bulb grip device” (Fig. 1), connected to an electronic pressure transducer (Abbott Critical Care Systems, Abbott, Ireland). The bulb could be held in the hand and squeezed comfortably and was filled with water to offer resistance. The rubber bulb is oval-shaped, as in common use for inflating the pneumatic cuff of a conventional sphygmomanometer. The inlet to the bulb was sealed with a plug after being filled with water. The hydrostatic pressure, which increased on being squeezed, was measured with the pressure transducer connected to the bulb outlet. The transducer delivered an analog electrical signal, directly proportional to the pressure. The pressure transducer was of the electrical resistance type, using a Wheatstone bridge circuit. The bridge was supplied from a 5V stabilized DC source and its output amplified by means of a DC amplifier (×100) before being led to a chart recorder ( Watanabe® Type WX 441; Watanabe Instrument Corp., Tokyo, Japan) adjusted to 0.1 V/cm sensitivity and set to a sweep rate of 1 cm/s (Fig. 1). The system was calibrated by use of a Bourdon-type manometer with a range of 0 to 760 mm Hg that allowed pressure to be read from a scale, graduated in steps of 10 mm Hg, simultaneously. For the purpose of calibration, an external source of pressure that could be adjusted by means of a valve was also connected to the system. The pressure was adjusted in steps of approximately 50 mm Hg from 0 to 650 mm Hg, and the output voltage was recorded. The output signal exhibited a linear relationship of 729 mm Hg/V, or 72.9 mm Hg/cm on the chart recorder. Analysis of four calibration sequences showed a linear regression coefficient of 0.996 with a standard deviation of ±17.7 mm Hg. The sensitivity of the device was mainly determined by the chart recorder, which could easily be read to within ±1mm (corresponding to ±7mm Hg). Strength of the hand was assessed by one of the surgeons involved in the study. Because the grip strength is dependent on the position of the limbs, the control measurement (preoperative value) was taken in the postoperative position. All patients were able to use the device. The measurement was repeated 24 h, 48 h, and 54 h after the initial ISB. Each measurement was repeated three times and the one with the highest reading chosen.
A research nurse who was not involved in the study was responsible for asking the patient about the pain score at rest, the appearance of side effects, the presence/absence of paresthesia at the tip of the fingers, and his or her satisfaction. Pain was assessed with a visual analog scale (VAS) ranging from 0 (no pain) to 100 (most severe pain imaginable) at rest, at the beginning of the PCIA (6 h after the ISB) and 14, 24, 32, 48, and 54 h after the ISB. Pain was also assessed with motion during the measurement of hand strength at 24, 48, and 54 h after ISB. These time points were chosen to avoid bias attributable to the various physiotherapy protocols according to each surgical procedure. The time of the first PCIA bolus was noted. The occurrence of paresthesia in the tip of the fingers was recorded at 24 h, 48 h, and 54 h after the ISB. Patient satisfaction was assessed 6 h after the end of the interscalene infusion (54 h after the ISB) using a VAS ranging from 0 (not satisfied) to 10 (entirely satisfied). Nausea and vomiting were treated with 2 mg tropisetron IV.
The primary end point of the study was the strength of the hand on the operated side. From our previous experience (4,5), we estimated the variation of strength between the patients in this clinical setting to be 25%. Using type I (α) and type II (β) errors of 0.05 and 0.2 respectively, and considering a 20% difference in the strength between the groups as a minimal relevant difference, we calculated that a sample of 25 patients per group would be necessary. To increase the power, we added five more patients per group. Data are reported as mean ± sd unless otherwise stated. Demographic data, time of first bolus, and patient satisfaction and number of auto-administered boli were assessed using the Mann-Whitney U-test. The strength in the hand and the pain scores were compared between the two groups by using the Mann-Whitney U-test with Bonferroni’s correction for multiple comparisons. Side effects were analyzed using Fisher’s exact test. The incidence of paresthesia was evaluated by Fisher’s exact test with Bonferroni’s correction for multiple comparisons. For all determinations, a P value < 0.05 was considered significant.
The two groups were similar with regard to demographic and surgical data, except for the number of women, which was more in the Bupivacaine group (P < 0.05) (Table 1). Eight patients in the Ropivacaine group and seven in the Bupivacaine group underwent surgery with an ISB without general anesthesia. The quantitative preoperative strength of the hand was 755 ± 170 mm Hg versus 672 ± 197 mm Hg for the Ropivacaine and Bupivacaine groups, respectively (NS). These values represent the initial 100% for each group, respectively. The strength of the hand on the operated side decreased by 48% 24 h after the ISB in the Ropivacaine group versus 66% in the Bupivacaine group (P < 0.05). At 48 h after the ISB, the decrease in strength was 21% versus 54% in the Ropivacaine and Bupivacaine groups, respectively (P < 0.05). At 6 h after discontinuation of the infusion the strength was fully restored in the Ropivacaine group, whereas a decrease of 25% was still present in the Bupivacaine group (P < 0.05) (Fig. 2). The decrease of hand strength, excluding the females, was 49% versus 64%, 22% versus 48% and 2% versus 24% 24 h, 48 h and 54 h after the ISB for the Ropivacaine and Bupivacaine groups, respectively (P < 0.05). The incidence of paresthesia was more frequent in the Bupivacaine group in the first three fingers 6 h after the end of the infusion (P < 0.05) and in the second and third finger 48 h after the ISB (P < 0.05) (Table 2). Paresthesia disappeared in all patients within 5 days except in two patients of the Bupivacaine group. One patient reported paresthesia in the first three fingers for 2 wk, which then progressively vanished. The other patient was found by electromyographic investigation to have carpal tunnel syndrome, which was later successfully operated on. Pain scores at rest and with motion was similar in both groups during the whole study period (Table 3). No difference between the level of pain at rest or during motion was observed in either group. Four patients (two in each group) received one dose of morphine during the first postoperative night, between the 18th and 20th h after the initial ISB. The incidence of nausea was 10% and 20% in the Ropivacaine and Bupivacaine groups, respectively (NS). Vomiting occurred in 3% in each group. The time of first bolus was comparable between the groups: 956 ± 391 min versus 1095 ± 425 min in the Ropivacaine and Bupivacaine groups, respectively. Patient satisfaction was 9.6 ± 0.7 in the Ropivacaine group and 9.7 ± 0.6 in the Bupivacaine group (NS). The total number of auto-administered boli was 693 in the Bupivacaine group (23 boli per patient, range 0 to 36) and 732 (24 boli per patient, range 0 to 44) in the Ropivacaine group (NS). The mean dose–without the initial bolus–given per patient was 612 mg and 453 mg for the Ropivacaine and Bupivacaine groups, respectively, which represents a mean infusion dose of 10.8 mg/h in the Bupivacaine group and 14.6 mg/h in the Ropivacaine group. All blocks were successful and there were no catheter dislocations during the course of the trial.
We demonstrated that a continuous infusion of 0.2% ropivacaine through an interscalene catheter produced less motor impairment, assessed by hand strength, than 0.15% bupivacaine for a an equivalent analgesia, assessed by pain VAS, after major open shoulder surgery. The presence and the persistence of paresthesia in the tip of the finger was also more pronounced in patients receiving 0.15% bupivacaine.
The evaluation of motor block associated with the application of local anesthetics still has no “gold standard” for reference. The use of the Bromage scale (6) or its modified version have been extensively applied during labor (7,8), after abdominal surgery (9,10) and in orthopedics (11,12). However, such scales may not permit detection of subtle variations in motor block and cannot be applied in patients after major open shoulder surgery. The assessment of hand strength is a good means to evaluate and compare the effects of a brachial plexus block (interscalene, infraclavicular, or axillary) on motor function. Available devices such as the Jamar dynamometer (13) proved, in our experience, to be difficult for patients to handle in this clinical setting because of its weight and decreased compliance. To overcome the conditions imposed by this type of surgery on the positioning of the arm, we built the “bulb grip device,” which is only 90 g when filled with water, easy to grip and handle, reliable, and permits the detection of small strength differences.
We chose to administer a bolus of 40 mL of either ropivacaine 0.6% or bupivacaine 0.5%, in contrast to 30 mL in our previous studies (4,5), as some patients wished to have the surgical procedure without general anesthesia. The analgesic regimen of 0.2% ropivacaine and 0.15% bupivacaine was chosen because our previous studies (4,5) have shown these two concentrations to be associated with good and comparable pain control after this type of surgery. Our previous experience has shown that smaller concentration than the above of either ropivacaine or bupivacaine do not produce adequate postoperative pain control in this context. This concentration difference of 25% (0.2% ropivacaine versus 0.15% bupivacaine) that leads to similar pain control complies with the shown difference in pharmacodynamics (potency) as shown by Capogna et al. (14) for these two drugs, although a direct comparison may not be applicable because in the latter study epidurals were studied. This point is crucial, as similar pain control is the required condition to be unbiased with respect to the effects of the therapy on the motor function of the hand. We do not believe that some patients having general anesthesia might have influenced the results because these patients received only 100 μg fentanyl for endotracheal intubation and a small-dose continuous infusion of propofol for maintenance of anesthesia, the effects of which rapidly disappear.
The pain was assessed at rest and in motion during the effort to squeeze the rubber bulb. Interestingly, the maximum effort needed to squeeze the bulb does not increase pain intensity. This observation points out that with use of the interscalene catheter technique with local anesthetic, good control of pain at rest will allow easy passive/active early rehabilitation (observation confirmed by our physiotherapist team), which is not the case with the IV opioid technique. Indeed, all patients who have a very small level of pain with the continuous ISB are able to perform movement of the shoulder without any significant increase in level of pain.
During the course of the trial, we did not feel it necessary to assess the sensory and motor block other than with VAS and hand strength because the randomized, double-blinded design of the study, similar ISB procedure, placement of the catheter in the proximity of the radial nerve in all patients, and absence of block failure or catheter dislocation should prevent any significant difference in block extension in either group.
Chance randomization led to an increased number of women in the Bupivacaine group. To avoid a bias resulting from sex difference, we performed a second statistical analysis by excluding the women and found the results to be similar. This led us to conclude that sex did not have a statistical influence on the results in the present study.
Most studies that compared ropivacaine and bupivacaine in the postoperative period after various surgical procedures found either a similar motor block or a decrease in motor block in patients receiving ropivacaine (15,16). However, the clear-cut differences in motor block between ropivacaine and bupivacaine may have been obscured by a different sensory block shown by the need of more analgesics in one group or the other (14) or by the method of assessment, the Bromage scale or its modified version. Indeed, Zaric et al. (17) demonstrated that the Bromage scale does not correlate with more sophisticated means of measurement, such as electromyographic and mechanical assessment of isometric muscle force. In this investigation, we measured the dose response of sensory and motor block during continuous epidural infusion of 0.1, 0.2, or 0.3% ropivacaine in volunteers, as compared with bupivacaine 0.25% and isotonic saline. The different solutions were infused for 21 h. They found that motor block was minimal with 0.1% ropivacaine, moderate with 0.2 and 0.3% ropivacaine, and most intense with 0.25% bupivacaine. The regression phase was significantly shorter with all three concentrations of ropivacaine than with bupivacaine. However, the sensory block, as evaluated by the thermo test, did not show any difference between the groups. Despite the different concentration of local anesthetics used in our protocol, some of the observations made by Zaric et al. (17) correlated with our results. Indeed, for an equivalent analgesia, the motor block assessed by hand strength was more pronounced in the Bupivacaine group, as well as the prolongation of regression phase, shown not only by hand strength, but also by the persistence of paresthesia. The transient paresthesia may not be considered in the present context as a complication, but most likely as a prolonged more intense motor blockade in the Bupivacaine group.
The total number of auto-administered boli was similar in the two groups, confirming the results found in our previous investigations (4,5) using a similar protocol for bupivacaine 0.15% and ropivacaine 0.2% respectively. Interestingly, the patients needed only 20% of the total number of boli permitted (18.3% and 19.3% for the Bupivacaine and Ropivacaine groups, respectively). We may therefore wonder if it would be possible to use a smaller local anesthetic concentration; however, in a previous pilot study (unpublished results), we found that bupivacaine 0.1% and ropivacaine 0.15% provided insufficient analgesia in more than 50% of patients after major open shoulder surgery.
We believe a better sensorimotor dissociation of ropivacaine is probably the most likely way to explain our results, although a different extension of the block could have occurred, but seems unlikely, as the technique was exactly the same in both groups. Rosenberg and Heinonen (2), using isolated sheathed vagus and phrenic nerves of rats, showed that ropivacaine at a small concentration produced a rapid and profound block of Aδ and C fibers and was more potent than similarly small concentration of bupivacaine in blocking the same fibers. At larger concentrations, ropivacaine and bupivacaine had similar blocking activity. An animal experimental study conducted by Wildsmith et al. (3) demonstrated that ropivacaine blocked C fibers faster than A fibers and was a potent producer of frequency-dependent block. It is known that low pKa and high lipid solubility are associated with preferential blockade of A fibers; high pKa and low lipid solubility are associated with preferential blockade of C fibers (1). The lower lipid solubility of ropivacaine compared with bupivacaine is presumed to retard penetration of myelin sheaths. The combination of higher degree of sensorimotor dissociation with ropivacaine at small concentrations and the property of being a potent producer of frequency-dependent block may in part explain some of its advantages for postoperative analgesia.
The incidence of nausea and vomiting was infrequent and similar in both groups and within the range of our previous results (4,5). The degree of patient satisfaction was high in the two groups and comparable to the one found in the previous trials (4,5).
In conclusion, this study demonstrates that the administration of ropivacaine 0.2% and bupivacaine 0.15% through an interscalene catheter after major open shoulder surgery provides good and comparable control of postoperative pain with few side effects and a high degree of patient satisfaction. However, the application of ropivacaine 0.2% by the PCIA technique is associated with a decreased incidence of paresthesia in the fingers and offers a better preservation of motor function, assessed by hand strength. If these factors facilitate early rehabilitation and improve patient well being, this warrants further investigations.
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