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Comparison of ropivacaine 0.2% and 0.25% with lidocaine 0.5% for intravenous regional anesthesia
Journal of Clinical Anesthesia (2009) 21, 401–407
Original contribution
Comparison of ropivacaine 0.2% and 0.25% with lidocaine 0.5% for intravenous regional anesthesia Ibrahim Asik MD (Associate Professor)a , Aysu Inan Kocum MD (Specialist)b , Asutay Goktug MD (Specialist)c , K. Sanem Cakar Turhan MD (Specialist)a,⁎, Neslihan Alkis MD (Professor) a a
Department of Anesthesiology and Reanimation, Ankara University Medical School, Ankara, Turkey Department of Anesthesiology and Reanimation, Baskent University Medical School, Ankara, Turkey c Department of Anesthesiology, Ankara Education and Research Hospital, Ankara, Turkey b
Received 15 September 2007; revised 9 October 2008; accepted 11 October 2008
Keywords: Intravenous regional anesthesia; Forearm surgery; Hand surgery; Lidocaine; Ropivacaine
Abstract Study Objective: To compare the anesthetic effects of two different concentrations and doses of ropivacaine (0.2% and 0.25%) with those of a conventional dose of lidocaine 0.5%. Design: Prospective, randomized, double-blinded, clinical investigation. Setting: Large metropolitan university hospital. Patients: 66 adult ASA physical status I and II patients undergoing forearm and hand surgery. Interventions: Patients were randomly allocated to three groups to receive intravenous regional anesthesia (IVRA). Study groups were: ropivacaine 0.2% (Group I, n = 22), ropivacaine 0.25% (Group II, n = 22), and lidocaine 0.5% (Group III, n = 22). Measurements: Tourniquet tolerance times and regression of sensory analgesia were noted. Verbal numerical pain scores (VNS), cumulative analgesic consumption, and side effects were recorded during surgery and postanesthesia care unit (PACU). Time to first pain medication intake and number of patients receiving analgesics in the PACU were recorded. Main Results: Additional tolerance times for the distal tourniquet were significantly higher in the ropivacaine 0.25% group than the other two groups. Regression of sensory anesthesia was fastest in the lidocaine group. During the PACU stay, VNSs were significantly lower in the first 20 minutes in the ropivacaine groups than the lidocaine group. Time to first intake of pain medication in the PACU was soonest in the lidocaine group. The number of patients given analgesics in the PACU was highest in the lidocaine group. The number of patients taking N two tablets of tramadol was significantly lowest in the ropivacaine 0.25% group. No serious side effects were observed in any study group. Conclusion: Longer tolerance times for the distal tourniquet, prolonged analgesia after tourniquet release, and lower analgesic requirements postoperatively make ropivacaine 0.2% and 0.25% an alternative to lidocaine for IVRA. © 2009 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Samur sok. 38/5 06600, Kurtuluş/Ankara, Turkey. Tel.: +90 312 508 23 93; fax: +90 312 311 50 57. E-mail address: [email protected] (K.S.C. Turhan). 0952-8180/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2008.10.011
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1. Introduction Ropivacaine was introduced as a new amide local anesthetic that was structurally related to bupivacaine with a duration of action almost as long as for bupivacaine; however, it has lower central nervous system (CNS) and cardiovascular toxicity compared with bupivacaine, presumably because it is a pure s-enantiomer [1]. In several volunteer studies, intravenous (IV) ropivacaine 0.2% for IV regional anesthesia (IVRA) was as effective as lidocaine 0.5% [1,2]. Clinical use of ropivacaine 0.2% was established for IVRA in one study. Despite the low number of patients, it was reported that ropivacaine yielded satisfactory surgical anesthetic conditions intraoperatively and long-lasting analgesia in the immediate postoperative period [3]. Ropivacaine 0.375% also provided effective anesthesia and superior postoperative analgesia compared with lidocaine 0.5% when forearm IVRA was used [4]. Therefore, there may be clinical demand for a longer duration of surgical analgesia after tourniquet cuff release for hand and forearm surgery. To determine whether ropivacaine is beneficial for IVRA, a clinical study that compared the anesthetic effects of two different concentrations of ropivacaine (80 and 100 mg) with those of a conventional dose of lidocaine (200 mg) was conducted. We hypothesized that ropivacaine produces sensory and motor block comparable in onset and efficacy to that of lidocaine but longer post-block analgesia after tourniquet deflation. We also hypothesized that ropivacaine 0.25% might provide superior postinflation analgesia compared with ropivacaine 0.20%.
2. Materials and methods After Ankara Education and Research Hospital institutional ethics committee approval and informed consent, 66 adult, ASA physical status I and II patients who were scheduled to undergo forearm and hand surgery lasting less than one hour, were enrolled in the study. Exclusion criteria were liver disease, renal dysfunction, sickle cell disease, cardiac conduction abnormalities, neurological and vascular abnormalities in the operative limb, uncontrolled hypertension, diabetic neuropathy, pregnancy, history of seizure or allergy to local anesthetic agents, and a body mass index (BMI) b 20 or N 27 kg/mg2. Patients were randomly assigned, via sealed envelope technique, to undergo IVRA with ropivacaine 0.2% (80 mg), 0.25% (100 mg), or lidocaine 0.5% (200 mg) in a double-blinded manner. An investigator who did not participate in data collection provided syringes containing the local anesthetic solutions. All of the agents were administered using standard techniques. The anesthesiologist responsible for the case, the patient, surgeon, and the research assistant were blinded to the randomization. All of the patients fasted overnight and received no premedication. On the morning of the operation, a 20-gauge
I. Asik et al. IV cannula was inserted into a distal vein on the dorsum of the hand of the operative extremity to permit delivery of local anesthetic for IVRA. A second IV cannula was placed in the antecubital vein of the contralateral upper extremity to provide a route for fluid therapy and emergency drug administration. Throughout the operation, patients were monitored continuously with noninvasive blood pressure (BP) measurement, electrocardiogram, and pulse oximetry. Patients were randomized to one of three treatments: ropivacaine 0.2% (Group I, n = 22), ropivacaine 0.25% (Group II, n = 22), or lidocaine 0.5% (Group III, n = 22). Immediately after exsanguination with an Esmarch bandage, circulation of the arm undergoing surgery was occluded by the proximal cuff of a double-cuffed pneumatic tourniquet applied to the upper arm and inflated to a pressure of at least 100 mmHg above baseline systolic blood pressure. Limb occlusion pressure was verified by the loss of pulse oximetry tracing of the ipsilateral index finger. Minimal tourniquet time was set at 30 minutes. Local anesthetic was then injected as a 40 mL bolus over one minute by an anesthesiologist who was blinded to the injected drug. The end of injection was taken as time zero. After injection of the study agent, onset of anesthesia in the sensory distribution of the median, ulnar, radial, and musculocutaneous nerve dermatomes was evaluated with a 0-2 scale (0 = no sensation, 1 = dull sensation, and 2 = sharp [normal] sensation) by pinching the skin with a pair of Allis forceps at one, three, and 5 minutes and until providing adequate sensorial anesthesia before the initation of surgery. Onset of anesthesia was defined as the time when the patient developed diminished or absent sensation to pinch in the surgical area. Pain in response to surgical incision was evaluated on a verbal numerical scale (VNS). AVNS b 2 was chosen as representing acceptable surgical conditions. Motor function was evaluated by asking the patient to squeeze a BP cuff that was preinflated to 40 mmHg at 5-minute intervals. Three subsequent measurements were taken for each testing. When the proximal tourniquet pressure became unbearably painful (rated as 10 on a VNS, where 0 = no pain and 10 = the worst pain imaginable), the distal cuff was inflated followed by release of the proximal tourniquet. Additional tolerance times when the distal tourniquet pressure became unbearably painful were also recorded. The distal tourniquet remained inflated until the surgery was completed or at least 30 minutes after injection of the study agent. Intraoperatively, patients remained awake or were sedated. Fentanyl 0.5 μg/kg and midazolam one to 4 mg were administered in case of tourniquet pain (VNS ≥ 4). If the tourniquet pain persisted, patients were allowed to have additional doses of fentanyl. Hemodynamic and oxygen saturation data were recorded before anesthesia induction (baseline) and every 5 minutes throughout the surgery. After the surgery was completed or at least 30 minutes after inflation, whichever occurred sooner, the tourniquet was deflated in a biphasic manner; that is, an initial 30second deflation was followed by a 60-second inflation and
Ropivacaine vs. lidocaine in IVRA
403
then final deflation. After tourniquet deflation, patients were continuously monitored for cardiac arrhythmias and asked for the presence of any CNS side effects such as dizziness, tinnitus, lightheadedness, or a metallic taste. A study-blinded observer made assessments at 10-minute intervals while each patient was in the postanesthetic care unit (PACU) and until discharge from the hospital. During these same time points, pain scores were recorded on a VNS of 0-10 (0 = no pain; 10 = worst imaginable pain). Regression of sensory anesthesia was evaluated by pin prick test (VNS) graded as 0 = no sensation to 10 = normal sensation in sensory distribution of the median, ulnar, radial, and musculocutaneous nerve dermatomes. A VNS ≥ 5 was chosen to represent regression of sensory anesthesia. While in the PACU, pain was rated by verbal rating scale (VRS) graded as 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain, and 4 = excruciating pain. When VRS ≥ 2 for analgesia, 25 mg of IV pethidine was given to patients in the PACU for a maximum dose of 100 mg at two hours. Patients were also instructed to take the oral nonsteroidal antiinflammatory drugs, nimesulide 100 mg and tramadol 50 mg, for pain medication, when needed. The dosing interval of nimesulide was at least 4 hours. During this 4-hour period, patients were allowed to take tramadol for a maximum dose of 100 mg. If pain was not controlled, a subsequent dose of nimesulide 100 mg and tramadol 50 mg was ordered. The maximum daily doses of nimesulide and tramadol were 400 mg each. Time to first analgesic requirement and cumulative analgesic consumption during the subsequent 24 hours after surgery were recorded. We contacted patients by telephone after their discharge to home. Patients were instructed about how to complete a diary at home to record postoperative analgesic requirements, pain scores, and any side effects experienced during the subsequent 24 hours after discharge from the PACU. Patient information was completed when their written diaries were received. All patients who completed the study also submitted a written diary. To calculate the required sample size, we took into account results of a previous study by Atanassoff et al [3] with ropivacaine 0.2% and lidocaine 0.5% for IVRA. We wanted to detect a 35% difference in sensory block
Table 1
regression times between groups, accepting a type I error of 0.05 and a type II error of 0.20. Based on these calculations, the required study size was 20 patients per group. Data are expressed as means ± standard deviation, medians, quartiles, and numbers of patients. Patients' characteristics were compared using one-way analysis of variance (ANOVA) with posthoc analysis (t-test) and chi square test. Other study parameters such as onset of analgesia, duration of surgery, tourniquet times, time to first analgesic intake, and total analgesic consumption, were compared among groups using ANOVA with posthoc analysis (t-test) and expressed as means and standard deviations. As the regression of sensory and motor block and VNS data did not fulfill the criteria for normal distribution, they were compared among groups with the Kruskall Wallis one-way ANOVA (Mann-Whitney U test as posthoc analysis) and expressed as medians and quartiles. All statistical analyses were done with an IBM-compatible personal computer using SPSS 11.0 software (Statistical Program for Social Sciences [SPSS], Chicago, IL). A P-value less than 0.05 was considered statistically significant.
3. Results A total of 61 patients completed the investigation successfully. Five patients (two in the lidocaine group, two in the ropivacaine 0.2% group, and one in the ropivacaine 0.25% group) were excluded because of inadequate anesthesia requiring suppplemental infiltration. There were 21 patients in the lidocaine group and 20 patients in each ropivacaine group. No differences with respect to age, gender, weight, height, and the types of surgery among the three patient groups were noted (Table 1). Duration of surgery, tourniquet times, onset of anesthesia, onset of motor block, and the times from injection of local anesthetic to surgical incision also were similar among groups. Tolerance times for the proximal tourniquet were the same; additional tolerance times for the distal tourniquet were higher in the ropivacaine 0.25% group
Demographic data, patient characteristics, and types of surgeries
Age (yrs) Gender (F/M) (n) Weight (kg) Height (cm) Type of surgery carpal tunnel release tenolysis ganglionectomy hardware removal Data are means ± SD.
Ropivacaine 0.2% (n = 20)
Ropivacaine 0.25% (n = 20)
Lidocaine 0.5% (n = 21)
P
40 ± 7 11/9 75 ± 5 168 ± 8
39 ± 9 10/10 73 ± 8 170 ± 9
37 ± 10 11/10 76 ± 6 166 ± 12
NS NS NS NS
6 7 5 2
7 7 4 2
7 6 5 3
NS NS NS NS
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I. Asik et al.
Table 2 Surgical times, interval between local anesthetic injection and surgical incision, number of patients needing switching of the tourniquet cuff, onset of sensory block, total tourniquet and proximal and distal tourniquet tolerance times, total midazolam dose, total fentanyl dose, postanesthesia care unit (PACU) stay, regression of sensory block, time to first intake of pain medication in PACU, number of patients administered analgesics in PACU, total pethidine dose in PACU, and cumulative analgesic consumption
Surgical times (min) Interval between local anesthetic injection and surgical incision (min) Patients needing switching of the tourniquet cuff (n) Onset of anesthesia (min) Total tourniquet times (min) Proximal tourniquet tolerance time (min) Distal tourniquet tolerance time (min) Total midazolam dose (mg) Total fentanyl dose (μg) PACU stay (min) Regression of sensory block (min) Time to first intake of pain medication in PACU (min) Patients given analgesics in PACU (n) Total pethidine dose in PACU (mg)
Ropivacaine 0.2% (n = 20)
Ropivacaine 0.25% (n = 20)
Lidocaine 0.5% (n = 21)
29.1 ± 2.8 12.7 ± 2.4
31.2 ± 3.4 12.2 ± 3.1
28.4 ± 3.2 11.8 ± 1.3
17
16
18
7.1 ± 3.3 44.8 ± 5.2 20.2 ± 4.1 9.1 ± 2.6 2.5 ± 0.8 50 ± 15 57.8 ± 8.2 20.5 ± 4.6 27.5 ± 7.3
7.7 ± 4.1 47.4 ± 6.5 21.6 ± 5.2 15.3 ± 2.3 ⁎ 2.0 ± 0.75 35 ± 12 56.4 ± 9.5 23.5 ± 4.8 29.8 ± 4.9
6.5 ± 2.8 46.2 ± 4.5 19.3 ± 4.3 9.0 ± 2.1 3 ± 0.6 45 ± 15 59.2 ± 11.2 3.5 ± 1.1 † 11.3 ± 3.9 ‡
11 75 ± 20
10 50 ± 25
18‡ 80 ± 15
Data are means ± SD. ⁎ P b 0.05, ropivacaine 0.25% group vs. the other two groups. † P b 0.01, lidocaine group vs. the other two groups. ‡ P b 0.05, lidocaine group vs. the other two groups.
than the ropivacaine 0.2% or lidocaine 0.5% groups (15.3 ± 2.3 sec vs. 9.1 ± 2.6 sec and 9.0 ± 2.1 sec, respectively; P b 0.05). Intraoperatively, no medication other than midazolam for sedation was given to patients. No difference was noted among the three groups in total midazolam and fentanyl doses given. After release of the tourniquet, the first evidence of sensation to pinprick test in the corresponding area of the forearm and hand supplied by the median, ulnar, radial, and musculocutaneous nerves occurred at a median of 3.5 ± 1.1 min in the lidocaine group, and at 20.5 ± 4.6 min and
23.5 ± 4.8 min in the ropivacaine 0.2% and 0.25% groups, respectively; P b 0.05) (Table 2). PACU stays were similar in all groups. At the time of admission to the PACU, VNSs were significantly lower in patients who received ropivacaine 0.2% and 0.25% for IVRA when compared with those who were given lidocaine (P b 0.05; Fig. 1). During the interval between 30 minutes after admission to the PACU and discharge from the PACU, the difference in pain scores among the three groups became less prominent (P = NS). Residual analgesia times and time until first intake of pain medication after local anesthetic injection were longer in the ropivacaine groups than the lidocaine group (P b 0.01 and P b 0.05, respectively). The number of patients to whom analgesics were given in the PACU was lower in the ropivacaine 0.2% and 0.25% groups than the lidocaine group (11 and 10 pts vs. 18 pts, respectively). At the time when the patients took their first analgesic medication in the PACU, pain scores were similiar among groups. The total amount of pethidine administered in
Table 3
Tramadol consumption after 24 hours postoperatively Ropivacaine Ropivacaine Lidocaine 0.2% (n = 20) 0.25% (n = 20) 0.5% (n = 21)
Fig. 1 Verbal numerical pain scores (VNS) during postanesthesia care unit (PACU) stay. Admission = admission to the PACU; Discharge = release from the PACU to home. *P b 0.05, lidocaine 0.5% group vs. ropivacaine groups, with higher VNSs at admission to the PACU and 10 and 20 minutes after admission.
0 - two tablets 2 N two tablets 18
17 ⁎ 3⁎
5 16
⁎ P b 0.01, ropivacaine 0.25% vs. lidocaine 0.5% and ropivacaine 0.2 % groups.
Ropivacaine vs. lidocaine in IVRA Table 4
405
Nimesulide consumption after 24 hours postoperatively Ropivacaine Ropivacaine Lidocaine 0.2% (n = 20) 0.25% (n = 20) 0.5% (n = 21)
0 - two tablets 17 N two tablets 3
20 0
21 0
No significant differences among the three groups in nimesulide consumption was noted.
the PACU was similar in all groups. At home, the number of patients taking N two tablets of tramadol in the ropivacaine 0.25% group was significantly lower than the ropivacaine 0.2% and lidocaine 0.5% groups (3 vs. 18 and 16 pts, respectively) (Table 3). The frequency of nimesulide intake was similar in all groups (Table 4). Eight patients in the lidocaine 0.5% group reported one of these symptoms at the time of cuff deflation: light-headedness, tinnitus, and metallic taste. Similar symptoms were observed in two patients in the ropivacaine 0.2% group and three patients in the ropivacaine 0.25% group. Muscle twitching, dysarthria, and seizure were not observed throughout the study. Cardiotoxic events such as arrhythmias or hypotension were not observed with either local anesthetic.
4. Discussion Data from this study show that ropivacaine 0.2% and 0.25% produce similar quality of surgical anesthesia to that achieved with a conventional dose of lidocaine during IVRA but more long-lasting residual analgesia, particularly at the higher dose. A dose of 80 mg of ropivacaine 0.2% was considered appropriate for comparison with 200 mg of lidocaine 0.5% [1]. However, the optimal concentration of ropivacaine for IVRA has not yet been determined. In a recent study, Chan et al [2] gave the mean concentration of 0.22% and 0.36% ropivacaine to volunteers for IVRA, limiting the maximum dose to 180 mg. They found that the analgesic effectiveness of ropivacaine 0.22% was inferior to that of the higher concentration. Their findings also suggest that the use of ropivacaine, especially at the higher dose for IVRA, can provide long-lasting residual analgesia. Even though our findings are similar to that of Chan et al, we chose to administer much lower doses of ropivacaine 0.2% (80 mg) and 0.25% (100 mg) to evaluate the clinical effects of two different concentrations for IVRA. We also standardized the volume of administration (40 mL) for IVRA. Our results suggest that both ropivacaine 0.2% and 0.25% are effective for use in IVRA. In the present study, after completion of the surgical procedure and subsequent to tourniquet release, ropivacaine provided a prolonged analgesic effect, and VNSs recorded were comparably lower at admission to the PACU and during the first 30 minutes of PACU stay in the ropivacaine groups. Patients in the ropivacaine groups took their first analgesic
medication significantly later than those patients in the lidocaine group. However, in clinical practice, the pain scores do not reflect the full advantage of prolonged analgesia as the patients would take analgesic agents to minimize the pain scores. Prolonged analgesia is better reflected by the reduction in analgesic consumption in the first 24 hours. In the current study, the amount of pain medication in the ropivacaine 0.25% group at the end of 24 hours (cumulative analgesic dosage) was less than in the ropivacaine 0.2% or lidocaine 0.5% groups. Similar to this finding, while ropivacaine 0.2% resulted in prolonged sensory block but not in analgesic consumption in the first 24 hours [3,5], the higher concentration of ropivacaine (0.375%) resulted in prolonged analgesia [4]. Although Niemi et al [5] found no clinically relevant difference between ropivacaine two mg/mL and prilocaine 5 mg/mL, they did suggest that an increase in the ropivacaine dose might provide additional prolongation of post-deflation sensory analgesia. In our study, residual analgesia lasted until 20 minutes after tourniquet deflation in the ropivacaine groups. Although the difference did not reach significance, patients in the ropivacaine 0.25% group had slightly lower VNS scores. We compared two different doses of ropivacaine with lidocaine 0.5% instead of prilocaine 0.5%. However, definitive dose-response curve studies have yet to be established for lidocaine and prilocaine in IVRA. Intraoperative fentanyl administration also might have contributed to this finding in our study, while Niemi et al [5] did not use an intraoperative analgesic regimen in their study. The discrepancy between the results of our study and those of Niemi et al in duration of sensory analgesia of the various innervation areas of the arm after tourniquet cuff deflation, may be due to the use of fentanyl during surgery, the method of sensory block testing, or the mode of tourniquet cuff release. The latest additions to the group of amide local anesthetics are the pure S-enantiomers, ropivacaine and levobupivacaine. They are devoid of the potential toxic dextrorotatory version of racemic local anesthetic mixtures, though sufficiently high doses may still induce CNS and cardiac toxicity. While ropivacaine is structurally related to bupivacaine, levobupivacaine is a single enantiomer of the racemic mixture. Both levobupivacaine and ropivacaine cause less depression of cardiac conduction and milder CNS side effects in preclinical and clinical trials or when accidentally injected intravascularly [6]. Scott et al [7] showed that with a slow IV infusion of 10 mg/min, volunteers could tolerate 124 ± 38 mg ropivacaine before the onset of CNS effects when the plasma venous ropivacaine concentration was between one and two μg/ mL. However, the safety of ropivacaine for IVRA has not been established and cannot be determined from the current study. Our study provides the anesthetic and residual analgesic effects of two doses of ropivacaine for IVRA. The longer duration of posttourniquet sensory block after IVRA with ropivacaine 0.2% and 0.25% may be attributable
406 to more complete and more persistent binding and lipid solubility and, hence, slower release of ropivacaine into the systemic circulation. The potential for superior postoperative analgesia in the immediate postoperative period needs to be determined. The margin of safety with ropivacaine may be greater than that with bupivacaine. Reports of cardiac arrest after intravascular absorption of larger volumes of bupivacaine have resulted in reconsideration and the eventual discontinuation of bupivacaine for IVRA [8]. Intravenous infusions of ropivacaine caused fewer severe CNS symptoms than equivalent infusions of bupivacaine [9,10]. This finding may be attributable to the fact that the lipid solubility of ropivacaine is less than 50% of that of bupivacaine [11]. The lipid solubility of ropivacaine is between that of lidocaine and bupivacaine. The fact that ropivacaine is only one-half to one-third as lipid-soluble as bupivacaine explains the higher threshold for CNS with ropivacaine. Mild CNS effects (lightheadedness, tinnitus, and metallic taste) were noted in 8 lidocaine group patients, two patients in the ropivacaine 0.2% group, and three patients in the ropivacaine 0.25% group. No seizures or cardiotoxic effects occurred in the ropivacaine groups. Similar results were obtained in a recent investigation in which lidocaine was compared with levobupivacaine [6]. This finding may be due to the peak plasma concentration of lidocaine in the plasma approximately three minutes after tourniquet release. It is consistent with the report that, within three minutes of tourniquet release, 58% of a compound similar to lidocaine was eliminated from the arm [12]. Systemic effects with this local anesthetic are not uncommon and actually may be underreported because of concomitant sedative medication [13-17]. The development of fewer systemic effects after ropivacaine administration is consistent with the delayed peak of ropivacaine plasma levels after tourniquet release, which results from the high tissue protein binding of this agent [9,10]. The mild CNS effects noted in the ropivacaine groups also presumably resulted from faster absorbtion of the drug from the extremity after tourniquet release. In all study subjects, tourniquets remained inflated at least 30 minutes. In the case of surgical procedures of shorter duration, the tourniquets were not deflated until 30 minutes. No tourniquet failure was observed during the study. Therefore, potential adverse effects were not seen due to possible inadvertent intravascular injection of ropivacaine in the current study. In addition, the doses used in the current study (80 and 100 mg) were much lower than the doses in the reported two patients who had convulsions after inadvertent intravascular injection of 150 mg and 200 mg of ropivacaine [18,19]. Atanassoff et al [10] reported a lower incidence of CNS side effects in volunteers who received IVRA with 40 mL of ropivacaine 0.2% versus lidocaine. Similarly, no seizures or cardiotoxic effects were observed in any group with the doses used in the current study. Based on these findings, the ropivacaine doses used in the present
I. Asik et al. investigation seem to be lower than the toxicity threshold in the case of accidental IV injection. However, the dose/ concentrations chosen should be optimal for both effectiveness and safety as the use of higher concentration may increase the incidence of side effects related to ropivacaine despite its safety and reliability. The main limitation of the present study was the potency ratio of ropivacaine versus lidocaine. Currently, there is no recommended dose for ropivacaine in IVRA. The use of an equipotent dose of ropivacaine has been suggested [1,3]. The potency ratio used in the current study was assumed as 2:0.8 and 2:1 for ropivacaine 0.2% and 0.25%, respectively, versus lidocaine 0.5%. Although definitive dose-response curve studies have not been established for lidocaine or ropivacaine, we chose these concentrations and doses as ropivacaine 0.2% for IVRA was effective in producing similar surgical anesthetic conditions compared with lidocaine 0.5% in other studies [1,2]. In addition, the clinical use of ropivacaine 0.2% is established for IVRA, and ropivacaine yielded satisfactory surgical anesthetic conditions intraoperatively in one study [3]. However, comparison trials should be completed with full knowledge of the relative potencies or the respective dose-response curves for any two drugs. In conclusion, longer tolerance times for the distal tourniquet, prolonged analgesia after tourniquet release, and lower analgesic requirement postoperatively make ropivacaine 0.2% and 0.25% a potential alternative to lidocaine for IVRA. By providing equally effective anesthesia and requiring less pain medication at home, ropivacaine 0.25% seems to be a preferable concentration for patients undergoing upper extremity surgery.
References [1] Hartmannsgruber MW, Silverman DG, Halaszynski TM, et al. Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesth Analg 1999;89:727-31. [2] Chan VW, Weisbrod MJ, Kaszas Z, Dragomir C. Comparison of ropivacaine and lidocaine for intravenous regional anesthesia in volunteers: a preliminary study on anesthetic efficacy and blood level. Anesthesiology 1999;90:1602-8. [3] Atanassoff PG, Ocampo CA, Bande MC, Hartmannsgruber MW, Halaszynski TM. Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in outpatient surgery. Anesthesiology 2001;95:627-31. [4] Peng PW, Coleman MM, McCartney CJ, et al. Comparison of anesthetic effect between 0.375 % ropivacaine versus 0.5% lidocaine in forearm intravenous regional anesthesia. Reg Anesth Pain Med 2002;27:595-9. [5] Niemi TT, Neuvonen PJ, Rosenberg PH. Comparison of ropivacaine 2 mg/ml and prilocaine 5 mg/ml for i.v. regional anesthesia in outpatient surgery. Br J Anaesth 2006;96:640-4. [6] Atanassoff PG, Aouad R, Hartmannsgruber MW, Halaszynski T. Levobupivacaine 0.125% and lidocaine 0.5% for intravenous anesthesia in volunteers. Anesthesiology 2002;97:325-8. [7] Scott BD, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989;69:563-9.
Ropivacaine vs. lidocaine in IVRA [8] Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979;51:285-7. [9] Knudsen K, Beckman SM. Blomberg, et al. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine, and placebo in volunteers. Br J Anaesth 1997;78:507-14. [10] Atanassoff PG, Hartmannsgruber MW. Central nervous system side effects are less important after intravenous regional anesthesia with ropivacaine 0.2% compared to lidocaine 0.5% in volunteers. Can J Anaesth 2002;49:169-72. [11] Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthestic. Anesthesiology 1990;72:322-9. [12] Hoffmann AC, Gessel EV, Gamulin Z, et al. Quantitative evaluation of tourniquet leak during intravenous regional anesthesia of the upper and lower limbs in human volunteers. Br J Anaesth 1995;75: 269-73.
407 [13] Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional Anesthesia: results of a prospective survey in France. Anesthesiology 1997;87:479-86. [14] Davies JA, Gill S, Weber JC. Intravenous regional analgesia using bupivacaine. Anaesthesia 1981;36:331. [15] Heath ML. Bupivacaine toxicity and Bier block. Anesthesiology 1983;59:481. [16] Henderson CL, Warriner CB, McEwen JA, Merrick PM. A North American survey of intravenous regional anesthesia. Anesth Analg 1997;85:858-63. [17] Moore JM, Liu SS, Neal JM. Premedication with fentanyl and midazolam decreases the reliability of intravenous lidocaine test dose. Anesth Analg 1998;86:1015-7. [18] Korman B, Riley RH. Convulsions induced by ropivacaine during interscalene brachial plexus block. Anesth Analg 1997;85:1128-9. [19] McClure JH. Ropivacaine. Br J Anaesth 1996;76:300-7.
Original contribution
Comparison of ropivacaine 0.2% and 0.25% with lidocaine 0.5% for intravenous regional anesthesia Ibrahim Asik MD (Associate Professor)a , Aysu Inan Kocum MD (Specialist)b , Asutay Goktug MD (Specialist)c , K. Sanem Cakar Turhan MD (Specialist)a,⁎, Neslihan Alkis MD (Professor) a a
Department of Anesthesiology and Reanimation, Ankara University Medical School, Ankara, Turkey Department of Anesthesiology and Reanimation, Baskent University Medical School, Ankara, Turkey c Department of Anesthesiology, Ankara Education and Research Hospital, Ankara, Turkey b
Received 15 September 2007; revised 9 October 2008; accepted 11 October 2008
Keywords: Intravenous regional anesthesia; Forearm surgery; Hand surgery; Lidocaine; Ropivacaine
Abstract Study Objective: To compare the anesthetic effects of two different concentrations and doses of ropivacaine (0.2% and 0.25%) with those of a conventional dose of lidocaine 0.5%. Design: Prospective, randomized, double-blinded, clinical investigation. Setting: Large metropolitan university hospital. Patients: 66 adult ASA physical status I and II patients undergoing forearm and hand surgery. Interventions: Patients were randomly allocated to three groups to receive intravenous regional anesthesia (IVRA). Study groups were: ropivacaine 0.2% (Group I, n = 22), ropivacaine 0.25% (Group II, n = 22), and lidocaine 0.5% (Group III, n = 22). Measurements: Tourniquet tolerance times and regression of sensory analgesia were noted. Verbal numerical pain scores (VNS), cumulative analgesic consumption, and side effects were recorded during surgery and postanesthesia care unit (PACU). Time to first pain medication intake and number of patients receiving analgesics in the PACU were recorded. Main Results: Additional tolerance times for the distal tourniquet were significantly higher in the ropivacaine 0.25% group than the other two groups. Regression of sensory anesthesia was fastest in the lidocaine group. During the PACU stay, VNSs were significantly lower in the first 20 minutes in the ropivacaine groups than the lidocaine group. Time to first intake of pain medication in the PACU was soonest in the lidocaine group. The number of patients given analgesics in the PACU was highest in the lidocaine group. The number of patients taking N two tablets of tramadol was significantly lowest in the ropivacaine 0.25% group. No serious side effects were observed in any study group. Conclusion: Longer tolerance times for the distal tourniquet, prolonged analgesia after tourniquet release, and lower analgesic requirements postoperatively make ropivacaine 0.2% and 0.25% an alternative to lidocaine for IVRA. © 2009 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Samur sok. 38/5 06600, Kurtuluş/Ankara, Turkey. Tel.: +90 312 508 23 93; fax: +90 312 311 50 57. E-mail address: [email protected] (K.S.C. Turhan). 0952-8180/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2008.10.011
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1. Introduction Ropivacaine was introduced as a new amide local anesthetic that was structurally related to bupivacaine with a duration of action almost as long as for bupivacaine; however, it has lower central nervous system (CNS) and cardiovascular toxicity compared with bupivacaine, presumably because it is a pure s-enantiomer [1]. In several volunteer studies, intravenous (IV) ropivacaine 0.2% for IV regional anesthesia (IVRA) was as effective as lidocaine 0.5% [1,2]. Clinical use of ropivacaine 0.2% was established for IVRA in one study. Despite the low number of patients, it was reported that ropivacaine yielded satisfactory surgical anesthetic conditions intraoperatively and long-lasting analgesia in the immediate postoperative period [3]. Ropivacaine 0.375% also provided effective anesthesia and superior postoperative analgesia compared with lidocaine 0.5% when forearm IVRA was used [4]. Therefore, there may be clinical demand for a longer duration of surgical analgesia after tourniquet cuff release for hand and forearm surgery. To determine whether ropivacaine is beneficial for IVRA, a clinical study that compared the anesthetic effects of two different concentrations of ropivacaine (80 and 100 mg) with those of a conventional dose of lidocaine (200 mg) was conducted. We hypothesized that ropivacaine produces sensory and motor block comparable in onset and efficacy to that of lidocaine but longer post-block analgesia after tourniquet deflation. We also hypothesized that ropivacaine 0.25% might provide superior postinflation analgesia compared with ropivacaine 0.20%.
2. Materials and methods After Ankara Education and Research Hospital institutional ethics committee approval and informed consent, 66 adult, ASA physical status I and II patients who were scheduled to undergo forearm and hand surgery lasting less than one hour, were enrolled in the study. Exclusion criteria were liver disease, renal dysfunction, sickle cell disease, cardiac conduction abnormalities, neurological and vascular abnormalities in the operative limb, uncontrolled hypertension, diabetic neuropathy, pregnancy, history of seizure or allergy to local anesthetic agents, and a body mass index (BMI) b 20 or N 27 kg/mg2. Patients were randomly assigned, via sealed envelope technique, to undergo IVRA with ropivacaine 0.2% (80 mg), 0.25% (100 mg), or lidocaine 0.5% (200 mg) in a double-blinded manner. An investigator who did not participate in data collection provided syringes containing the local anesthetic solutions. All of the agents were administered using standard techniques. The anesthesiologist responsible for the case, the patient, surgeon, and the research assistant were blinded to the randomization. All of the patients fasted overnight and received no premedication. On the morning of the operation, a 20-gauge
I. Asik et al. IV cannula was inserted into a distal vein on the dorsum of the hand of the operative extremity to permit delivery of local anesthetic for IVRA. A second IV cannula was placed in the antecubital vein of the contralateral upper extremity to provide a route for fluid therapy and emergency drug administration. Throughout the operation, patients were monitored continuously with noninvasive blood pressure (BP) measurement, electrocardiogram, and pulse oximetry. Patients were randomized to one of three treatments: ropivacaine 0.2% (Group I, n = 22), ropivacaine 0.25% (Group II, n = 22), or lidocaine 0.5% (Group III, n = 22). Immediately after exsanguination with an Esmarch bandage, circulation of the arm undergoing surgery was occluded by the proximal cuff of a double-cuffed pneumatic tourniquet applied to the upper arm and inflated to a pressure of at least 100 mmHg above baseline systolic blood pressure. Limb occlusion pressure was verified by the loss of pulse oximetry tracing of the ipsilateral index finger. Minimal tourniquet time was set at 30 minutes. Local anesthetic was then injected as a 40 mL bolus over one minute by an anesthesiologist who was blinded to the injected drug. The end of injection was taken as time zero. After injection of the study agent, onset of anesthesia in the sensory distribution of the median, ulnar, radial, and musculocutaneous nerve dermatomes was evaluated with a 0-2 scale (0 = no sensation, 1 = dull sensation, and 2 = sharp [normal] sensation) by pinching the skin with a pair of Allis forceps at one, three, and 5 minutes and until providing adequate sensorial anesthesia before the initation of surgery. Onset of anesthesia was defined as the time when the patient developed diminished or absent sensation to pinch in the surgical area. Pain in response to surgical incision was evaluated on a verbal numerical scale (VNS). AVNS b 2 was chosen as representing acceptable surgical conditions. Motor function was evaluated by asking the patient to squeeze a BP cuff that was preinflated to 40 mmHg at 5-minute intervals. Three subsequent measurements were taken for each testing. When the proximal tourniquet pressure became unbearably painful (rated as 10 on a VNS, where 0 = no pain and 10 = the worst pain imaginable), the distal cuff was inflated followed by release of the proximal tourniquet. Additional tolerance times when the distal tourniquet pressure became unbearably painful were also recorded. The distal tourniquet remained inflated until the surgery was completed or at least 30 minutes after injection of the study agent. Intraoperatively, patients remained awake or were sedated. Fentanyl 0.5 μg/kg and midazolam one to 4 mg were administered in case of tourniquet pain (VNS ≥ 4). If the tourniquet pain persisted, patients were allowed to have additional doses of fentanyl. Hemodynamic and oxygen saturation data were recorded before anesthesia induction (baseline) and every 5 minutes throughout the surgery. After the surgery was completed or at least 30 minutes after inflation, whichever occurred sooner, the tourniquet was deflated in a biphasic manner; that is, an initial 30second deflation was followed by a 60-second inflation and
Ropivacaine vs. lidocaine in IVRA
403
then final deflation. After tourniquet deflation, patients were continuously monitored for cardiac arrhythmias and asked for the presence of any CNS side effects such as dizziness, tinnitus, lightheadedness, or a metallic taste. A study-blinded observer made assessments at 10-minute intervals while each patient was in the postanesthetic care unit (PACU) and until discharge from the hospital. During these same time points, pain scores were recorded on a VNS of 0-10 (0 = no pain; 10 = worst imaginable pain). Regression of sensory anesthesia was evaluated by pin prick test (VNS) graded as 0 = no sensation to 10 = normal sensation in sensory distribution of the median, ulnar, radial, and musculocutaneous nerve dermatomes. A VNS ≥ 5 was chosen to represent regression of sensory anesthesia. While in the PACU, pain was rated by verbal rating scale (VRS) graded as 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain, and 4 = excruciating pain. When VRS ≥ 2 for analgesia, 25 mg of IV pethidine was given to patients in the PACU for a maximum dose of 100 mg at two hours. Patients were also instructed to take the oral nonsteroidal antiinflammatory drugs, nimesulide 100 mg and tramadol 50 mg, for pain medication, when needed. The dosing interval of nimesulide was at least 4 hours. During this 4-hour period, patients were allowed to take tramadol for a maximum dose of 100 mg. If pain was not controlled, a subsequent dose of nimesulide 100 mg and tramadol 50 mg was ordered. The maximum daily doses of nimesulide and tramadol were 400 mg each. Time to first analgesic requirement and cumulative analgesic consumption during the subsequent 24 hours after surgery were recorded. We contacted patients by telephone after their discharge to home. Patients were instructed about how to complete a diary at home to record postoperative analgesic requirements, pain scores, and any side effects experienced during the subsequent 24 hours after discharge from the PACU. Patient information was completed when their written diaries were received. All patients who completed the study also submitted a written diary. To calculate the required sample size, we took into account results of a previous study by Atanassoff et al [3] with ropivacaine 0.2% and lidocaine 0.5% for IVRA. We wanted to detect a 35% difference in sensory block
Table 1
regression times between groups, accepting a type I error of 0.05 and a type II error of 0.20. Based on these calculations, the required study size was 20 patients per group. Data are expressed as means ± standard deviation, medians, quartiles, and numbers of patients. Patients' characteristics were compared using one-way analysis of variance (ANOVA) with posthoc analysis (t-test) and chi square test. Other study parameters such as onset of analgesia, duration of surgery, tourniquet times, time to first analgesic intake, and total analgesic consumption, were compared among groups using ANOVA with posthoc analysis (t-test) and expressed as means and standard deviations. As the regression of sensory and motor block and VNS data did not fulfill the criteria for normal distribution, they were compared among groups with the Kruskall Wallis one-way ANOVA (Mann-Whitney U test as posthoc analysis) and expressed as medians and quartiles. All statistical analyses were done with an IBM-compatible personal computer using SPSS 11.0 software (Statistical Program for Social Sciences [SPSS], Chicago, IL). A P-value less than 0.05 was considered statistically significant.
3. Results A total of 61 patients completed the investigation successfully. Five patients (two in the lidocaine group, two in the ropivacaine 0.2% group, and one in the ropivacaine 0.25% group) were excluded because of inadequate anesthesia requiring suppplemental infiltration. There were 21 patients in the lidocaine group and 20 patients in each ropivacaine group. No differences with respect to age, gender, weight, height, and the types of surgery among the three patient groups were noted (Table 1). Duration of surgery, tourniquet times, onset of anesthesia, onset of motor block, and the times from injection of local anesthetic to surgical incision also were similar among groups. Tolerance times for the proximal tourniquet were the same; additional tolerance times for the distal tourniquet were higher in the ropivacaine 0.25% group
Demographic data, patient characteristics, and types of surgeries
Age (yrs) Gender (F/M) (n) Weight (kg) Height (cm) Type of surgery carpal tunnel release tenolysis ganglionectomy hardware removal Data are means ± SD.
Ropivacaine 0.2% (n = 20)
Ropivacaine 0.25% (n = 20)
Lidocaine 0.5% (n = 21)
P
40 ± 7 11/9 75 ± 5 168 ± 8
39 ± 9 10/10 73 ± 8 170 ± 9
37 ± 10 11/10 76 ± 6 166 ± 12
NS NS NS NS
6 7 5 2
7 7 4 2
7 6 5 3
NS NS NS NS
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I. Asik et al.
Table 2 Surgical times, interval between local anesthetic injection and surgical incision, number of patients needing switching of the tourniquet cuff, onset of sensory block, total tourniquet and proximal and distal tourniquet tolerance times, total midazolam dose, total fentanyl dose, postanesthesia care unit (PACU) stay, regression of sensory block, time to first intake of pain medication in PACU, number of patients administered analgesics in PACU, total pethidine dose in PACU, and cumulative analgesic consumption
Surgical times (min) Interval between local anesthetic injection and surgical incision (min) Patients needing switching of the tourniquet cuff (n) Onset of anesthesia (min) Total tourniquet times (min) Proximal tourniquet tolerance time (min) Distal tourniquet tolerance time (min) Total midazolam dose (mg) Total fentanyl dose (μg) PACU stay (min) Regression of sensory block (min) Time to first intake of pain medication in PACU (min) Patients given analgesics in PACU (n) Total pethidine dose in PACU (mg)
Ropivacaine 0.2% (n = 20)
Ropivacaine 0.25% (n = 20)
Lidocaine 0.5% (n = 21)
29.1 ± 2.8 12.7 ± 2.4
31.2 ± 3.4 12.2 ± 3.1
28.4 ± 3.2 11.8 ± 1.3
17
16
18
7.1 ± 3.3 44.8 ± 5.2 20.2 ± 4.1 9.1 ± 2.6 2.5 ± 0.8 50 ± 15 57.8 ± 8.2 20.5 ± 4.6 27.5 ± 7.3
7.7 ± 4.1 47.4 ± 6.5 21.6 ± 5.2 15.3 ± 2.3 ⁎ 2.0 ± 0.75 35 ± 12 56.4 ± 9.5 23.5 ± 4.8 29.8 ± 4.9
6.5 ± 2.8 46.2 ± 4.5 19.3 ± 4.3 9.0 ± 2.1 3 ± 0.6 45 ± 15 59.2 ± 11.2 3.5 ± 1.1 † 11.3 ± 3.9 ‡
11 75 ± 20
10 50 ± 25
18‡ 80 ± 15
Data are means ± SD. ⁎ P b 0.05, ropivacaine 0.25% group vs. the other two groups. † P b 0.01, lidocaine group vs. the other two groups. ‡ P b 0.05, lidocaine group vs. the other two groups.
than the ropivacaine 0.2% or lidocaine 0.5% groups (15.3 ± 2.3 sec vs. 9.1 ± 2.6 sec and 9.0 ± 2.1 sec, respectively; P b 0.05). Intraoperatively, no medication other than midazolam for sedation was given to patients. No difference was noted among the three groups in total midazolam and fentanyl doses given. After release of the tourniquet, the first evidence of sensation to pinprick test in the corresponding area of the forearm and hand supplied by the median, ulnar, radial, and musculocutaneous nerves occurred at a median of 3.5 ± 1.1 min in the lidocaine group, and at 20.5 ± 4.6 min and
23.5 ± 4.8 min in the ropivacaine 0.2% and 0.25% groups, respectively; P b 0.05) (Table 2). PACU stays were similar in all groups. At the time of admission to the PACU, VNSs were significantly lower in patients who received ropivacaine 0.2% and 0.25% for IVRA when compared with those who were given lidocaine (P b 0.05; Fig. 1). During the interval between 30 minutes after admission to the PACU and discharge from the PACU, the difference in pain scores among the three groups became less prominent (P = NS). Residual analgesia times and time until first intake of pain medication after local anesthetic injection were longer in the ropivacaine groups than the lidocaine group (P b 0.01 and P b 0.05, respectively). The number of patients to whom analgesics were given in the PACU was lower in the ropivacaine 0.2% and 0.25% groups than the lidocaine group (11 and 10 pts vs. 18 pts, respectively). At the time when the patients took their first analgesic medication in the PACU, pain scores were similiar among groups. The total amount of pethidine administered in
Table 3
Tramadol consumption after 24 hours postoperatively Ropivacaine Ropivacaine Lidocaine 0.2% (n = 20) 0.25% (n = 20) 0.5% (n = 21)
Fig. 1 Verbal numerical pain scores (VNS) during postanesthesia care unit (PACU) stay. Admission = admission to the PACU; Discharge = release from the PACU to home. *P b 0.05, lidocaine 0.5% group vs. ropivacaine groups, with higher VNSs at admission to the PACU and 10 and 20 minutes after admission.
0 - two tablets 2 N two tablets 18
17 ⁎ 3⁎
5 16
⁎ P b 0.01, ropivacaine 0.25% vs. lidocaine 0.5% and ropivacaine 0.2 % groups.
Ropivacaine vs. lidocaine in IVRA Table 4
405
Nimesulide consumption after 24 hours postoperatively Ropivacaine Ropivacaine Lidocaine 0.2% (n = 20) 0.25% (n = 20) 0.5% (n = 21)
0 - two tablets 17 N two tablets 3
20 0
21 0
No significant differences among the three groups in nimesulide consumption was noted.
the PACU was similar in all groups. At home, the number of patients taking N two tablets of tramadol in the ropivacaine 0.25% group was significantly lower than the ropivacaine 0.2% and lidocaine 0.5% groups (3 vs. 18 and 16 pts, respectively) (Table 3). The frequency of nimesulide intake was similar in all groups (Table 4). Eight patients in the lidocaine 0.5% group reported one of these symptoms at the time of cuff deflation: light-headedness, tinnitus, and metallic taste. Similar symptoms were observed in two patients in the ropivacaine 0.2% group and three patients in the ropivacaine 0.25% group. Muscle twitching, dysarthria, and seizure were not observed throughout the study. Cardiotoxic events such as arrhythmias or hypotension were not observed with either local anesthetic.
4. Discussion Data from this study show that ropivacaine 0.2% and 0.25% produce similar quality of surgical anesthesia to that achieved with a conventional dose of lidocaine during IVRA but more long-lasting residual analgesia, particularly at the higher dose. A dose of 80 mg of ropivacaine 0.2% was considered appropriate for comparison with 200 mg of lidocaine 0.5% [1]. However, the optimal concentration of ropivacaine for IVRA has not yet been determined. In a recent study, Chan et al [2] gave the mean concentration of 0.22% and 0.36% ropivacaine to volunteers for IVRA, limiting the maximum dose to 180 mg. They found that the analgesic effectiveness of ropivacaine 0.22% was inferior to that of the higher concentration. Their findings also suggest that the use of ropivacaine, especially at the higher dose for IVRA, can provide long-lasting residual analgesia. Even though our findings are similar to that of Chan et al, we chose to administer much lower doses of ropivacaine 0.2% (80 mg) and 0.25% (100 mg) to evaluate the clinical effects of two different concentrations for IVRA. We also standardized the volume of administration (40 mL) for IVRA. Our results suggest that both ropivacaine 0.2% and 0.25% are effective for use in IVRA. In the present study, after completion of the surgical procedure and subsequent to tourniquet release, ropivacaine provided a prolonged analgesic effect, and VNSs recorded were comparably lower at admission to the PACU and during the first 30 minutes of PACU stay in the ropivacaine groups. Patients in the ropivacaine groups took their first analgesic
medication significantly later than those patients in the lidocaine group. However, in clinical practice, the pain scores do not reflect the full advantage of prolonged analgesia as the patients would take analgesic agents to minimize the pain scores. Prolonged analgesia is better reflected by the reduction in analgesic consumption in the first 24 hours. In the current study, the amount of pain medication in the ropivacaine 0.25% group at the end of 24 hours (cumulative analgesic dosage) was less than in the ropivacaine 0.2% or lidocaine 0.5% groups. Similar to this finding, while ropivacaine 0.2% resulted in prolonged sensory block but not in analgesic consumption in the first 24 hours [3,5], the higher concentration of ropivacaine (0.375%) resulted in prolonged analgesia [4]. Although Niemi et al [5] found no clinically relevant difference between ropivacaine two mg/mL and prilocaine 5 mg/mL, they did suggest that an increase in the ropivacaine dose might provide additional prolongation of post-deflation sensory analgesia. In our study, residual analgesia lasted until 20 minutes after tourniquet deflation in the ropivacaine groups. Although the difference did not reach significance, patients in the ropivacaine 0.25% group had slightly lower VNS scores. We compared two different doses of ropivacaine with lidocaine 0.5% instead of prilocaine 0.5%. However, definitive dose-response curve studies have yet to be established for lidocaine and prilocaine in IVRA. Intraoperative fentanyl administration also might have contributed to this finding in our study, while Niemi et al [5] did not use an intraoperative analgesic regimen in their study. The discrepancy between the results of our study and those of Niemi et al in duration of sensory analgesia of the various innervation areas of the arm after tourniquet cuff deflation, may be due to the use of fentanyl during surgery, the method of sensory block testing, or the mode of tourniquet cuff release. The latest additions to the group of amide local anesthetics are the pure S-enantiomers, ropivacaine and levobupivacaine. They are devoid of the potential toxic dextrorotatory version of racemic local anesthetic mixtures, though sufficiently high doses may still induce CNS and cardiac toxicity. While ropivacaine is structurally related to bupivacaine, levobupivacaine is a single enantiomer of the racemic mixture. Both levobupivacaine and ropivacaine cause less depression of cardiac conduction and milder CNS side effects in preclinical and clinical trials or when accidentally injected intravascularly [6]. Scott et al [7] showed that with a slow IV infusion of 10 mg/min, volunteers could tolerate 124 ± 38 mg ropivacaine before the onset of CNS effects when the plasma venous ropivacaine concentration was between one and two μg/ mL. However, the safety of ropivacaine for IVRA has not been established and cannot be determined from the current study. Our study provides the anesthetic and residual analgesic effects of two doses of ropivacaine for IVRA. The longer duration of posttourniquet sensory block after IVRA with ropivacaine 0.2% and 0.25% may be attributable
406 to more complete and more persistent binding and lipid solubility and, hence, slower release of ropivacaine into the systemic circulation. The potential for superior postoperative analgesia in the immediate postoperative period needs to be determined. The margin of safety with ropivacaine may be greater than that with bupivacaine. Reports of cardiac arrest after intravascular absorption of larger volumes of bupivacaine have resulted in reconsideration and the eventual discontinuation of bupivacaine for IVRA [8]. Intravenous infusions of ropivacaine caused fewer severe CNS symptoms than equivalent infusions of bupivacaine [9,10]. This finding may be attributable to the fact that the lipid solubility of ropivacaine is less than 50% of that of bupivacaine [11]. The lipid solubility of ropivacaine is between that of lidocaine and bupivacaine. The fact that ropivacaine is only one-half to one-third as lipid-soluble as bupivacaine explains the higher threshold for CNS with ropivacaine. Mild CNS effects (lightheadedness, tinnitus, and metallic taste) were noted in 8 lidocaine group patients, two patients in the ropivacaine 0.2% group, and three patients in the ropivacaine 0.25% group. No seizures or cardiotoxic effects occurred in the ropivacaine groups. Similar results were obtained in a recent investigation in which lidocaine was compared with levobupivacaine [6]. This finding may be due to the peak plasma concentration of lidocaine in the plasma approximately three minutes after tourniquet release. It is consistent with the report that, within three minutes of tourniquet release, 58% of a compound similar to lidocaine was eliminated from the arm [12]. Systemic effects with this local anesthetic are not uncommon and actually may be underreported because of concomitant sedative medication [13-17]. The development of fewer systemic effects after ropivacaine administration is consistent with the delayed peak of ropivacaine plasma levels after tourniquet release, which results from the high tissue protein binding of this agent [9,10]. The mild CNS effects noted in the ropivacaine groups also presumably resulted from faster absorbtion of the drug from the extremity after tourniquet release. In all study subjects, tourniquets remained inflated at least 30 minutes. In the case of surgical procedures of shorter duration, the tourniquets were not deflated until 30 minutes. No tourniquet failure was observed during the study. Therefore, potential adverse effects were not seen due to possible inadvertent intravascular injection of ropivacaine in the current study. In addition, the doses used in the current study (80 and 100 mg) were much lower than the doses in the reported two patients who had convulsions after inadvertent intravascular injection of 150 mg and 200 mg of ropivacaine [18,19]. Atanassoff et al [10] reported a lower incidence of CNS side effects in volunteers who received IVRA with 40 mL of ropivacaine 0.2% versus lidocaine. Similarly, no seizures or cardiotoxic effects were observed in any group with the doses used in the current study. Based on these findings, the ropivacaine doses used in the present
I. Asik et al. investigation seem to be lower than the toxicity threshold in the case of accidental IV injection. However, the dose/ concentrations chosen should be optimal for both effectiveness and safety as the use of higher concentration may increase the incidence of side effects related to ropivacaine despite its safety and reliability. The main limitation of the present study was the potency ratio of ropivacaine versus lidocaine. Currently, there is no recommended dose for ropivacaine in IVRA. The use of an equipotent dose of ropivacaine has been suggested [1,3]. The potency ratio used in the current study was assumed as 2:0.8 and 2:1 for ropivacaine 0.2% and 0.25%, respectively, versus lidocaine 0.5%. Although definitive dose-response curve studies have not been established for lidocaine or ropivacaine, we chose these concentrations and doses as ropivacaine 0.2% for IVRA was effective in producing similar surgical anesthetic conditions compared with lidocaine 0.5% in other studies [1,2]. In addition, the clinical use of ropivacaine 0.2% is established for IVRA, and ropivacaine yielded satisfactory surgical anesthetic conditions intraoperatively in one study [3]. However, comparison trials should be completed with full knowledge of the relative potencies or the respective dose-response curves for any two drugs. In conclusion, longer tolerance times for the distal tourniquet, prolonged analgesia after tourniquet release, and lower analgesic requirement postoperatively make ropivacaine 0.2% and 0.25% a potential alternative to lidocaine for IVRA. By providing equally effective anesthesia and requiring less pain medication at home, ropivacaine 0.25% seems to be a preferable concentration for patients undergoing upper extremity surgery.
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