A Comparative Study of 0.25% Ropivacaine and 0.25% Bupivacaine for Brachial Plexus Block Rosemary Hickey, MD, Cheryl L. Rowley, MD, Kenneth D. Candido, MD, Joan Hoffman, RN, MSN, Somayaji Ramamurthy, MD, and Alon P. Winnie,
MD
Departments of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, and University of Illinois College of Medicine at Chicago, Chicago, Illinois
The present study compares the effectiveness of 0.25% ropivacaine and 0.25% bupivacaine in 44 patients receiving a subclavian perivascular brachial plexus block for upper extremity surgery. The patients were assigned to two equal groups in this randomized, double-blind study; one group received ropivacaine 0.25% (112.5 mg) and the other, bupivacaine 0.25% (112.5 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C-5 through T-1 brachial plexus dermatomes did not differ significantly between the two groups. The mean onset time for analgesia ranged from 11.2 to 20.2 min, and the mean onset time for anesthesia ranged from 23.3 to 48.2 min. The onset of motor block differed only with respect to paresis in the hand, with bupivacaine demonstrating a shorter on-
R
opivacaine is a new long-acting local anesthetic that is a chemical congener of bupivacaine and mepivacaine. In the initial studies in humans, 0.5% ropivacaine, both with and without epinephrine, provided effective sensory and motor blockade when used to provide brachial plexus anesthesia (1). More recently, a double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine demonstrated the two drugs to be similar in terms of both onset and duration of sensory and motor block and in terms of the incidence of analgesia, anesthesia, paresis, and paralysis (2). Both bupivacaine and mepivacaine contain a chiral center and thus can exist as a pair of stereoisomers or enantiomers, currently designated as either R- or S-configurations ( 3 ) .Nonetheless, both of these local anesthetics are prepared and used clinically as the racemate despite differences in the pharmacodynamThis study was supported by a grant from Astra Pain Control AB, Sodertalje, Sweden. Accepted for publication May 20, 1992. Address correspondence to Dr. Hickey, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7838.
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Anesth Analg 1992;75:6024
set time than ropivacaine. The duration of sensory and motor block also was not significantly different between the two groups. The mean duration of analgesia ranged from 9.2 to 13.0 h, and the mean duration of anesthesia ranged from 5.0 to 10.2 h. Both groups required supplementation with peripheral nerve blocks or general anesthesia in a large number of cases, with 9 of the 22 patients in the bupivacaine group and 8 of the 22 patients in the ropivacaine group requiring supplementation to allow surgery to begin. In view of the frequent need for supplementation noted with both 0.25% ropivacaine and 0.25% bupivacaine, we do not recommend using the 0.25% concentrations of these local anesthetics to provide brachial plexus block. (Anesth Analg 1992;75:6024)
ics and pharmacokinetics of such enantiomers. The S-enantiomer is the principal agonist (the eutomer), because it possesses true local anesthetic activity, whereas the R-enantiomer (the distomer) not only possesses less local anesthetic activity, but greater toxicity (4-7). When ropivacaine, a congener of mepivacaine and bupivacaine, was considered as a replacement for bupivacaine in regional anesthesia, it was made available as the pure S-enantiomer, the assumption being that the use of the S-enantiomer would provide greater local anesthetic potency and less local anesthetic toxicity than the racemic mixture. Subsequently, animal data have indicated that ropivacaine does possess anesthetic properties that are very similar to those of its racemic relative, bupivacaine, but with considerably less anesthetic toxicity, particularly in terms of the cardiovascular system (6,7). Because ropivacaine is the pure S-enantiomer, and bupivacaine is the racemic mixture of the R- and S-enantiomers, ropivacaine should have greater anesthetic potency (i.e., a lower concentration of ropivacaine might have the anesthetic potency of a higher concentration of bupivacaine). A small, open, pilot study undertaken by two of the authors in a small el992 by the International Anesthesia Research Society 0003-2999192$5.00
ANESTH ANALG 1992;75:6024
REGIONAL ANESTHESIA AND PAIN MANAGEMENT HICKEY ET AL. 0.25% ROPIVACAINE AND 0.25% BUPIVACAINE
group of five patients undergoing upper extremity surgery indicated that 0.25% ropivacaine provided excellent surgical anesthesia in all five patients. The purpose of the present study is to expand on that pilot study and to compare the anesthetic characteristics of this concentration of ropivacaine with those of 0.25% bupivacaine when used for brachial plexus block using the subclavian perivascular approach.
Methods This study was designed as a randomized, doubleblind, parallel-group clinical trial. The institutional review boards at both institutions provided approval before initiation of the study, and all patients gave informed consent before being included. The 44 patients selected for inclusion were ASA physical status I and 11 and were scheduled to undergo elective surgery on the upper extremity under brachial plexus block anesthesia. Excluded from the study were patients with a history of allergy to amide local anesthetics and women who were-pregnant. The patients were randomly assigned to two equal groups on the basis of the local anesthetic to be utilized, so that 22 patients received 0.25% ropivacaine without epinephrine and 22 patients received 0.25% bupivacaine, also without epinephrine. The same protocol was followed at each institution. All of the patients were unpremedicated until they arrived in the operating room, at which time midazolam was titrated intravenously to a maximum of 3.0 mg to relieve anxiety before administration of the block. Each patient then received a subclavian perivascular block according to the technique previously described by Winnie (8). After a paresthesia radiating to a point below the shoulder had been elicited and aspiration for blood was negative, 3 mL of the study drug was injected rapidly to produce a ”pressure paresthesia” to confirm proper placement of the needle. The remaining 37 mL was then injected over a period of approximately 1 min, with aspiration repeated every 5 mL. The intercostobrachial and medial brachial cutaneous nerves were then blocked separately by a subcutaneous injection of 5 mL of the study drug superficial to the axillary artery. In any given case, if after the injection of the study drug there was inadequate analgesia for the surgical procedure, appropriate supplemental nerve blocks were performed or general anesthesia was induced. Whenever supplementary nerve blocks were required, data were included only from those dermatomes that exhibited blockade before the supplemental blocks. Evaluation of sensory and motor function was performed before the administration of the block and then at 2, 5, 10, 15, 20, 25, and 30 min after the block.
hn? ---
Table 1. Clinical Characteristics of 44 Patients Undergoing Upper Extremity Surgery Study group Ropivacaine 0.25% Bupivacaine 0.25%
Age
Height
(Yr)
(cm)
43 44
? ?
15 14
173 2 11 174 2 9
Weight (kg) 78
? 20 79 2 17
Gender (M/F) 1913 19/3
M, male; F, female Mean k SD.
For the next 5 h, sensory and motor function were evaluated every 15 min, for the subsequent 7 h every 30 min, and then every 60 min until recovery was complete. Sensory function was assessed in the C-2 through T-2 dermatomes and graded such that no loss of sensation to pinprick was scored as 0, analgesia (patient feels touch but not pinprick) was scored as 1, and anesthesia (patient does not even feel touch) was scored as 2. Motor block was assessed at the shoulder by asking the patient to elevate the arm while keeping the elbow straight to evaluate the degree of blockade of the superior trunk and at the hand by determining the strength of handgrip to evaluate the degree of blockade of the middle and inferior trunks. Motor function was graded such that no weakness was scored as 0, paresis was scored as 1, and paralysis was scored as 2. In addition to sensory and motor function, heart rate and arterial blood pressure were monitored and recorded before premedication; before administration of the block; 2, 5, 10, 15, 20, 25, 30, 45, and 60 min after the block; and then every 30 min for an additional 2 h. Any signs or symptoms of central nervous system toxicity or any other adverse experiences were also recorded. For statistical analysis of the data, continuous variables such as onset and duration of analgesia, anesthesia, paresis, and paralysis were tested using a Wilcoxon rank sum test. Binary variables, such as the presence or absence of sensory or motor block, were analyzed with the ,$ test or Fisher’s exact test. A P value of 50.05 was considered to represent statistical significance.
Results There was no significant difference between the two groups of patients in terms of age, height, weight, or male/female ratio (Table 1).The frequency of analgesia in the C-2 through T-2 dermatomes did not significantly differ between the 0.25% ropivacaine and 0.25% bupivacaine groups: 76% or more of the patients in both groups developed analgesia in the C-5 through T-1 dermatomes of the brachial plexus, whereas few patients developed analgesia in the C-2
604
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ANESTH ANALG W 2 ; 7 5 :602-6
Paresis
1007
c2
c3
c4
C5
C6
C?
Dermatome Figure 1. The frequency of analgesia was 76% or greater in the C-ST-1 brachial plexus dermatomes and did not differ significantly between the 0.25% ropivacaine (=) and 0.25% bupivacaine ( I3) groups. Few patients developed cervical plexus (C-2-C-4) analgesia.
c u) .
Paralysis
loo]
Dermatome Figure 2. The frequency of anesthesia in the C-5-T-I brachial plexus dermatomes ranged from 57% to 82% and did not differ significantly between the 0.25% ropivacaine (m)and 0.25% bupivacaine ( U) groups. Anesthesia developed infrequently in the cervical plexus (C-2-C-4).
through C-4 dermatomes of the cervical plexus (Figure 1). There was no significant difference between the two groups with respect to the frequency of anesthesia in the C2 through T-2 dermatomes: 57%82% of the patients in both groups developed anesthesia in the C-5 through T-1 dermatomes of the brachial plexus, and again, only a small percent of patients developed anesthesia in the C-2 through C-4 dermatomes of the cervical plexus (Figure 2). The onset times for analgesia and anesthesia also did not differ significantly between the ropivacaine and bupivacaine groups (Table 2). The mean onset time for analgesia ranged from 12.0 to 19.7 min for ropivacaine and 11.2 to 20.2 min for bupivacaine, whereas the mean onset time for anesthesia ranged from 23.7 to 48.2 min for ropivacaine and 23.3 to 47.1 min for bupivacaine. The duration of analgesia and anesthesia also did not differ significantly between the two groups, with a mean duration of analgesia ranging from 9.2 to 13.0 h and a mean
Shoulder
Hand
Shoulder
Hand
Figure 3. There was no significant difference between the 0.25% ropivacaine (=) and 0.25% bupivacaine ( U) groups in the frequency of motor block of any degree (paresis/paralysis of the hand and shoulder). Although motor paresis of the shoulder and hand was frequent (>80% of patients), paralysis of the hand was less common (52%-59% of patients).
duration of anesthesia ranging from 5.0 to 10.2 h (Table 3). Paresis of the shoulder and hand muscles developed in >80% of patients in both groups, whereas complete paralysis was less frequent (Figure 3). There was no significant difference between groups in the frequency of paresis or paralysis of either the shoulder or hand (Figure 3). Similarly, the onset and duration of motor block did not differ between groups (Table 4) except for the onset of paresis in the hand, which was significantly faster in the bupivacaine group. Nine patients in the bupivacaine group and eight patients in the ropivacaine group required supplemental blocks or general anesthesia. The specific types of supplemental blocks used are listed in Table 5. One patient in the bupivacaine group was excluded from the analysis of efficacy because of a deviation from the protocol. Three patients in each group had Horner's syndrome, and one patient in each group experienced tourniquet pain. There were no significant differences between the two groups with respect to changes in systolic or diastolic blood pressure, heart rate, mean arterial pressure, or ratepressure product at any time during the study.
Discussion The efficacy of 0.25% ropivacaine for brachial plexus anesthesia was virtually identical to that of 0.25% bupivacaine in terms of onset and duration of sensory block as well as the need for supplementation. However, the 0.25% concentration of both agents appears to be unsuitable for brachial plexus block because of a high failure rate. The supplementation rate of 36%for the ropivacaine group and 43% for the bupivacaine group is in sharp contrast to the supplementation rate
REGIONAL ANESTHESIA AND PAIN MANAGEMENT HICKEY ET AL. 0.25% ROPIVACAINE AND 0.25% BUPIVACAINE
ANESTH ANALG 1992;75:602-6
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Table 2. Onset of Sensory Block Onset of analgesia (rnin)
Onset of anesthesia (min)
Level
Ropivacaine 0.25%
Bupivacaine 0.25%
c-5 C-6 c-7 C-8 T-1
19.2 t 22.2 12.0 5 10.7 18.6 t 22.9 15.1 ? 24.0 19.7 ? 32.2
11.5 t 14.0 20.2 t 28.7 14.3 2 18.7 11.2 2 16.4 11.6 5 17.4
Mean
Ropivacaine 0.25%
48.1 47.8 48.2 43.8 23.7
t 43.4 t 51.4 t 42.7
t 44.6 t 21.3
Bupivacaine 0.25%
37.8 t 40.7 47.1 t 60.4 40.7 t 35.7 23.3 5 21.9 26.5 t 34.5
5 SD.
Table 3. Duration of Sensory Block Duration of analgesia (h)
Duration of anesthesia (h)
Level
Ropivacaine 0.25%
Bupivacaine 0.25%
c-5 C-6 c-7 C-8 T-1
10.7 2 2.6 10.2 2 3.5 9.2 t 4.2 9.4 t 3.5 9.8 2 2.5
13.0 t 4.9 11.6 t 3.2 11.0 2 4.4 12.1 t 5.2 12.2 2 4.4
Mean
Ropivacaine 0.25%
5.0 5 6.0 5 6.7 2 7.3 5 7.7 2
2.8 3.4 2.7 3.2 2.2
Bupivacaine 0.25%
8.2 t 4.7 8.0 2 3.0 8.1 t 4.1 10.2 t 3.8 9.2 t 3.9
2 SD.
Table 4. Onset and Duration of Motor Block (min) Duration of motor block (h)
Onset of motor block (rnin)
Hand Paresis Paralysis Shoulder Paresis Paralysis
Ropivacaine 0.25%
Bupivacaine 0.25%
Ropivacaine 0.25%
Bupivacaine 0.25%
29.0 t 41.0" 41.7 2 45.8
7.1 t 6.4" 27.0 t 35.2
9.4 t 3.6 8.0 t 3.0
12.1 t 4.2 9.8 t 4.9
9.1 t 16.5 12.2 t 8.3
5.3 t 5.3 14.8 t 13.4
10.8 2 2.7 8.6 t 1.8
13.6 t 5.4 11.4 t 5.6
Mean ? SD "P < 0.05.
of 8% for both local anesthetics when used in a 0.5% concentration (2) observed in a previous study. The high rate of supplementation noted for the 0.25% concentrations appears to be due to the fact that this concentration is borderline with respect to the threshold necessary to develop anesthesia; for, although the incidence of analgesia in the C-5 through T-1 dermatomes ranged from 76% to 9670, the incidence of anesthesia in these dermatomes was much less. Likewise, although motor paresis at the shoulder and hand frequently developed (in >80% of all patients), complete motor paralysis was frequently not seen (in the hand 59% and 52%, respectively, for ropivacaine and bupivacaine). The main advantage of ropivacaine over bupivacaine is its lesser potential for cardiac toxicity. In isolated rabbit Purkinje fiber ventricular muscle preparations, Moller and Covino (9) demonstrated that the effect of ropivacaine on altering various electrophysiologic variables was greater than lidocaine but
less than bupivacaine. Feldman et al. (7) demonstrated in a dog model that although the convulsive doses of ropivacaine and bupivacaine were similar, ropivacaine was less arrhythmogenic than bupivacaine. Other animal studies have confirmed the lower cardiac toxicity of ropivacaine compared with bupivacaine (6,10,11). The one human study that has examined the acute toxicity of ropivacaine was reported by Scott et al. (12) in a group of 12 volunteers who received intravenous infusions of ropivacaine and bupivacaine up to a maximal dose of 150 mg. It was noted that ropivacaine caused less central nervous system symptoms and could be tolerated at a larger total dosage than bupivacaine (12). In addition, electrocardiogram and echocardiogram evidence of depression of conductivity and contractility appeared at smaller dosage and lower plasma concentrations with bupivacaine than with ropivacaine (12). In our study, we noted no overt signs of cardiac or central nervous system toxicity with either bupivacaine
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0.25% ROPIVACAINE AND 0.2570 BUPIVACAINE
Table 5. Number of Patients Requiring Supplementation of Anesthesia and Analgesia Ropivacaine Bupivacaine 0.25% 0.2570 Total no. of patients requiring supplementation General anesthesia Nerve blocks Axillary block Radial nerve Median nerve Ulnar nerve Medial antebrachial cutaneous nerve Local infiltration
8
9
4
4
1 1 3 4
1 2 4 1
1
(0.89-2.0 mg/kg) or ropivacaine (0.81-2.3 mgikg). In the two previous brachial plexus studies reported with slightly higher doses (up to 3.2 mg/kg of bupivacaine and 3.1 mgikg of ropivacaine), there was also no evidence of toxicity. It should be noted, however, that in each of these studies, the vatients were premedicated with midazolam, which could increase the at least for system toxicity. In addition, unlike the volunteers studied by Scott et al. (12), our patients did not undergo formal Or echocardiographic studies to determine more subtle signs of cardiac toxicity. In conclusion, we have demonstrated that for subclavian perivascular brachial plexus block, despite theoretical potency Of rOpiVaCaine because Of exclusion of the less potent d-isomer, 0.25% ropivacaine is in quality to 0’25% bupivacaine in most aspects. Both local anesthetics, however, are frequently associated with inadequate sensory or motor block, 1
or both. In view of the high rate of supplementation necessary with both 0.25% ropivacaine and 0.25% bupivacaine, we recommend using the 0.5% concentration of these local anesthetics to provide brachial plexus anesthesia.
References 1. Hickey R, Candido KD, Ramamurthy S, et al. Brachial plexus block with a new local anesthetic: 0.5% ropivacaine. Can J Anaesth 1990;37:732-8. 2. Hickey R, Hoffman J, Ramamurthy S. A comparison of ropivacaine 0.5% and bupivacaine 0.5% for brachial plexus block. Anesthesiology 1991;74:639-42. 3. Cahn RS, Ingold CK, Prelog V. The specification of asymmetric configuration in organic chemistry. Experientia 1956;12:81-124. 4. Aberg G. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds. Acta Pharmacol Toxicol 1972;31:273-86. 5. Luduena FP, Bogado EF, Tullar BF. Optical isomers of rnepivacaine and bupivacaine. Arch Int Pharmacodyn Ther 1972;200: 359-69. 6. Reiz S, Haggmark G, Johansson G, Nath S. Cardiotoxicity of ropivacaine-a new amide local anaesthetic agent. Acta Anaesthesiol Scand 1989;33:93-8. 7. Feldrnan HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 1989;69:794-801. 8. Winnie AP. The subclavian perivascular technique of brachial plexus anesthesia. Anesthesiology 1964;25:35=3. 9. Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology 1990;72: 322-9. 10. Nancarrow C, Rutten AJ, Runcirnan WB, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 1989;69:27&83. 11. Akerman B, Hellberg IB, Trossvik C. Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 1988;32:5714. 12, Scott DB, Lee A, Fagan D, Bowler GMR, Bloomfield p, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989;69:56>9.
MD
Departments of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, and University of Illinois College of Medicine at Chicago, Chicago, Illinois
The present study compares the effectiveness of 0.25% ropivacaine and 0.25% bupivacaine in 44 patients receiving a subclavian perivascular brachial plexus block for upper extremity surgery. The patients were assigned to two equal groups in this randomized, double-blind study; one group received ropivacaine 0.25% (112.5 mg) and the other, bupivacaine 0.25% (112.5 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C-5 through T-1 brachial plexus dermatomes did not differ significantly between the two groups. The mean onset time for analgesia ranged from 11.2 to 20.2 min, and the mean onset time for anesthesia ranged from 23.3 to 48.2 min. The onset of motor block differed only with respect to paresis in the hand, with bupivacaine demonstrating a shorter on-
R
opivacaine is a new long-acting local anesthetic that is a chemical congener of bupivacaine and mepivacaine. In the initial studies in humans, 0.5% ropivacaine, both with and without epinephrine, provided effective sensory and motor blockade when used to provide brachial plexus anesthesia (1). More recently, a double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine demonstrated the two drugs to be similar in terms of both onset and duration of sensory and motor block and in terms of the incidence of analgesia, anesthesia, paresis, and paralysis (2). Both bupivacaine and mepivacaine contain a chiral center and thus can exist as a pair of stereoisomers or enantiomers, currently designated as either R- or S-configurations ( 3 ) .Nonetheless, both of these local anesthetics are prepared and used clinically as the racemate despite differences in the pharmacodynamThis study was supported by a grant from Astra Pain Control AB, Sodertalje, Sweden. Accepted for publication May 20, 1992. Address correspondence to Dr. Hickey, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7838.
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Anesth Analg 1992;75:6024
set time than ropivacaine. The duration of sensory and motor block also was not significantly different between the two groups. The mean duration of analgesia ranged from 9.2 to 13.0 h, and the mean duration of anesthesia ranged from 5.0 to 10.2 h. Both groups required supplementation with peripheral nerve blocks or general anesthesia in a large number of cases, with 9 of the 22 patients in the bupivacaine group and 8 of the 22 patients in the ropivacaine group requiring supplementation to allow surgery to begin. In view of the frequent need for supplementation noted with both 0.25% ropivacaine and 0.25% bupivacaine, we do not recommend using the 0.25% concentrations of these local anesthetics to provide brachial plexus block. (Anesth Analg 1992;75:6024)
ics and pharmacokinetics of such enantiomers. The S-enantiomer is the principal agonist (the eutomer), because it possesses true local anesthetic activity, whereas the R-enantiomer (the distomer) not only possesses less local anesthetic activity, but greater toxicity (4-7). When ropivacaine, a congener of mepivacaine and bupivacaine, was considered as a replacement for bupivacaine in regional anesthesia, it was made available as the pure S-enantiomer, the assumption being that the use of the S-enantiomer would provide greater local anesthetic potency and less local anesthetic toxicity than the racemic mixture. Subsequently, animal data have indicated that ropivacaine does possess anesthetic properties that are very similar to those of its racemic relative, bupivacaine, but with considerably less anesthetic toxicity, particularly in terms of the cardiovascular system (6,7). Because ropivacaine is the pure S-enantiomer, and bupivacaine is the racemic mixture of the R- and S-enantiomers, ropivacaine should have greater anesthetic potency (i.e., a lower concentration of ropivacaine might have the anesthetic potency of a higher concentration of bupivacaine). A small, open, pilot study undertaken by two of the authors in a small el992 by the International Anesthesia Research Society 0003-2999192$5.00
ANESTH ANALG 1992;75:6024
REGIONAL ANESTHESIA AND PAIN MANAGEMENT HICKEY ET AL. 0.25% ROPIVACAINE AND 0.25% BUPIVACAINE
group of five patients undergoing upper extremity surgery indicated that 0.25% ropivacaine provided excellent surgical anesthesia in all five patients. The purpose of the present study is to expand on that pilot study and to compare the anesthetic characteristics of this concentration of ropivacaine with those of 0.25% bupivacaine when used for brachial plexus block using the subclavian perivascular approach.
Methods This study was designed as a randomized, doubleblind, parallel-group clinical trial. The institutional review boards at both institutions provided approval before initiation of the study, and all patients gave informed consent before being included. The 44 patients selected for inclusion were ASA physical status I and 11 and were scheduled to undergo elective surgery on the upper extremity under brachial plexus block anesthesia. Excluded from the study were patients with a history of allergy to amide local anesthetics and women who were-pregnant. The patients were randomly assigned to two equal groups on the basis of the local anesthetic to be utilized, so that 22 patients received 0.25% ropivacaine without epinephrine and 22 patients received 0.25% bupivacaine, also without epinephrine. The same protocol was followed at each institution. All of the patients were unpremedicated until they arrived in the operating room, at which time midazolam was titrated intravenously to a maximum of 3.0 mg to relieve anxiety before administration of the block. Each patient then received a subclavian perivascular block according to the technique previously described by Winnie (8). After a paresthesia radiating to a point below the shoulder had been elicited and aspiration for blood was negative, 3 mL of the study drug was injected rapidly to produce a ”pressure paresthesia” to confirm proper placement of the needle. The remaining 37 mL was then injected over a period of approximately 1 min, with aspiration repeated every 5 mL. The intercostobrachial and medial brachial cutaneous nerves were then blocked separately by a subcutaneous injection of 5 mL of the study drug superficial to the axillary artery. In any given case, if after the injection of the study drug there was inadequate analgesia for the surgical procedure, appropriate supplemental nerve blocks were performed or general anesthesia was induced. Whenever supplementary nerve blocks were required, data were included only from those dermatomes that exhibited blockade before the supplemental blocks. Evaluation of sensory and motor function was performed before the administration of the block and then at 2, 5, 10, 15, 20, 25, and 30 min after the block.
hn? ---
Table 1. Clinical Characteristics of 44 Patients Undergoing Upper Extremity Surgery Study group Ropivacaine 0.25% Bupivacaine 0.25%
Age
Height
(Yr)
(cm)
43 44
? ?
15 14
173 2 11 174 2 9
Weight (kg) 78
? 20 79 2 17
Gender (M/F) 1913 19/3
M, male; F, female Mean k SD.
For the next 5 h, sensory and motor function were evaluated every 15 min, for the subsequent 7 h every 30 min, and then every 60 min until recovery was complete. Sensory function was assessed in the C-2 through T-2 dermatomes and graded such that no loss of sensation to pinprick was scored as 0, analgesia (patient feels touch but not pinprick) was scored as 1, and anesthesia (patient does not even feel touch) was scored as 2. Motor block was assessed at the shoulder by asking the patient to elevate the arm while keeping the elbow straight to evaluate the degree of blockade of the superior trunk and at the hand by determining the strength of handgrip to evaluate the degree of blockade of the middle and inferior trunks. Motor function was graded such that no weakness was scored as 0, paresis was scored as 1, and paralysis was scored as 2. In addition to sensory and motor function, heart rate and arterial blood pressure were monitored and recorded before premedication; before administration of the block; 2, 5, 10, 15, 20, 25, 30, 45, and 60 min after the block; and then every 30 min for an additional 2 h. Any signs or symptoms of central nervous system toxicity or any other adverse experiences were also recorded. For statistical analysis of the data, continuous variables such as onset and duration of analgesia, anesthesia, paresis, and paralysis were tested using a Wilcoxon rank sum test. Binary variables, such as the presence or absence of sensory or motor block, were analyzed with the ,$ test or Fisher’s exact test. A P value of 50.05 was considered to represent statistical significance.
Results There was no significant difference between the two groups of patients in terms of age, height, weight, or male/female ratio (Table 1).The frequency of analgesia in the C-2 through T-2 dermatomes did not significantly differ between the 0.25% ropivacaine and 0.25% bupivacaine groups: 76% or more of the patients in both groups developed analgesia in the C-5 through T-1 dermatomes of the brachial plexus, whereas few patients developed analgesia in the C-2
604
REGIONAL ANESTHESIA AND PAIN MANAGEMENT 0.25% ROPIVACAINE AND 0.25% BUPIVACAINE
HICKEY ET AL.
ANESTH ANALG W 2 ; 7 5 :602-6
Paresis
1007
c2
c3
c4
C5
C6
C?
Dermatome Figure 1. The frequency of analgesia was 76% or greater in the C-ST-1 brachial plexus dermatomes and did not differ significantly between the 0.25% ropivacaine (=) and 0.25% bupivacaine ( I3) groups. Few patients developed cervical plexus (C-2-C-4) analgesia.
c u) .
Paralysis
loo]
Dermatome Figure 2. The frequency of anesthesia in the C-5-T-I brachial plexus dermatomes ranged from 57% to 82% and did not differ significantly between the 0.25% ropivacaine (m)and 0.25% bupivacaine ( U) groups. Anesthesia developed infrequently in the cervical plexus (C-2-C-4).
through C-4 dermatomes of the cervical plexus (Figure 1). There was no significant difference between the two groups with respect to the frequency of anesthesia in the C2 through T-2 dermatomes: 57%82% of the patients in both groups developed anesthesia in the C-5 through T-1 dermatomes of the brachial plexus, and again, only a small percent of patients developed anesthesia in the C-2 through C-4 dermatomes of the cervical plexus (Figure 2). The onset times for analgesia and anesthesia also did not differ significantly between the ropivacaine and bupivacaine groups (Table 2). The mean onset time for analgesia ranged from 12.0 to 19.7 min for ropivacaine and 11.2 to 20.2 min for bupivacaine, whereas the mean onset time for anesthesia ranged from 23.7 to 48.2 min for ropivacaine and 23.3 to 47.1 min for bupivacaine. The duration of analgesia and anesthesia also did not differ significantly between the two groups, with a mean duration of analgesia ranging from 9.2 to 13.0 h and a mean
Shoulder
Hand
Shoulder
Hand
Figure 3. There was no significant difference between the 0.25% ropivacaine (=) and 0.25% bupivacaine ( U) groups in the frequency of motor block of any degree (paresis/paralysis of the hand and shoulder). Although motor paresis of the shoulder and hand was frequent (>80% of patients), paralysis of the hand was less common (52%-59% of patients).
duration of anesthesia ranging from 5.0 to 10.2 h (Table 3). Paresis of the shoulder and hand muscles developed in >80% of patients in both groups, whereas complete paralysis was less frequent (Figure 3). There was no significant difference between groups in the frequency of paresis or paralysis of either the shoulder or hand (Figure 3). Similarly, the onset and duration of motor block did not differ between groups (Table 4) except for the onset of paresis in the hand, which was significantly faster in the bupivacaine group. Nine patients in the bupivacaine group and eight patients in the ropivacaine group required supplemental blocks or general anesthesia. The specific types of supplemental blocks used are listed in Table 5. One patient in the bupivacaine group was excluded from the analysis of efficacy because of a deviation from the protocol. Three patients in each group had Horner's syndrome, and one patient in each group experienced tourniquet pain. There were no significant differences between the two groups with respect to changes in systolic or diastolic blood pressure, heart rate, mean arterial pressure, or ratepressure product at any time during the study.
Discussion The efficacy of 0.25% ropivacaine for brachial plexus anesthesia was virtually identical to that of 0.25% bupivacaine in terms of onset and duration of sensory block as well as the need for supplementation. However, the 0.25% concentration of both agents appears to be unsuitable for brachial plexus block because of a high failure rate. The supplementation rate of 36%for the ropivacaine group and 43% for the bupivacaine group is in sharp contrast to the supplementation rate
REGIONAL ANESTHESIA AND PAIN MANAGEMENT HICKEY ET AL. 0.25% ROPIVACAINE AND 0.25% BUPIVACAINE
ANESTH ANALG 1992;75:602-6
605
Table 2. Onset of Sensory Block Onset of analgesia (rnin)
Onset of anesthesia (min)
Level
Ropivacaine 0.25%
Bupivacaine 0.25%
c-5 C-6 c-7 C-8 T-1
19.2 t 22.2 12.0 5 10.7 18.6 t 22.9 15.1 ? 24.0 19.7 ? 32.2
11.5 t 14.0 20.2 t 28.7 14.3 2 18.7 11.2 2 16.4 11.6 5 17.4
Mean
Ropivacaine 0.25%
48.1 47.8 48.2 43.8 23.7
t 43.4 t 51.4 t 42.7
t 44.6 t 21.3
Bupivacaine 0.25%
37.8 t 40.7 47.1 t 60.4 40.7 t 35.7 23.3 5 21.9 26.5 t 34.5
5 SD.
Table 3. Duration of Sensory Block Duration of analgesia (h)
Duration of anesthesia (h)
Level
Ropivacaine 0.25%
Bupivacaine 0.25%
c-5 C-6 c-7 C-8 T-1
10.7 2 2.6 10.2 2 3.5 9.2 t 4.2 9.4 t 3.5 9.8 2 2.5
13.0 t 4.9 11.6 t 3.2 11.0 2 4.4 12.1 t 5.2 12.2 2 4.4
Mean
Ropivacaine 0.25%
5.0 5 6.0 5 6.7 2 7.3 5 7.7 2
2.8 3.4 2.7 3.2 2.2
Bupivacaine 0.25%
8.2 t 4.7 8.0 2 3.0 8.1 t 4.1 10.2 t 3.8 9.2 t 3.9
2 SD.
Table 4. Onset and Duration of Motor Block (min) Duration of motor block (h)
Onset of motor block (rnin)
Hand Paresis Paralysis Shoulder Paresis Paralysis
Ropivacaine 0.25%
Bupivacaine 0.25%
Ropivacaine 0.25%
Bupivacaine 0.25%
29.0 t 41.0" 41.7 2 45.8
7.1 t 6.4" 27.0 t 35.2
9.4 t 3.6 8.0 t 3.0
12.1 t 4.2 9.8 t 4.9
9.1 t 16.5 12.2 t 8.3
5.3 t 5.3 14.8 t 13.4
10.8 2 2.7 8.6 t 1.8
13.6 t 5.4 11.4 t 5.6
Mean ? SD "P < 0.05.
of 8% for both local anesthetics when used in a 0.5% concentration (2) observed in a previous study. The high rate of supplementation noted for the 0.25% concentrations appears to be due to the fact that this concentration is borderline with respect to the threshold necessary to develop anesthesia; for, although the incidence of analgesia in the C-5 through T-1 dermatomes ranged from 76% to 9670, the incidence of anesthesia in these dermatomes was much less. Likewise, although motor paresis at the shoulder and hand frequently developed (in >80% of all patients), complete motor paralysis was frequently not seen (in the hand 59% and 52%, respectively, for ropivacaine and bupivacaine). The main advantage of ropivacaine over bupivacaine is its lesser potential for cardiac toxicity. In isolated rabbit Purkinje fiber ventricular muscle preparations, Moller and Covino (9) demonstrated that the effect of ropivacaine on altering various electrophysiologic variables was greater than lidocaine but
less than bupivacaine. Feldman et al. (7) demonstrated in a dog model that although the convulsive doses of ropivacaine and bupivacaine were similar, ropivacaine was less arrhythmogenic than bupivacaine. Other animal studies have confirmed the lower cardiac toxicity of ropivacaine compared with bupivacaine (6,10,11). The one human study that has examined the acute toxicity of ropivacaine was reported by Scott et al. (12) in a group of 12 volunteers who received intravenous infusions of ropivacaine and bupivacaine up to a maximal dose of 150 mg. It was noted that ropivacaine caused less central nervous system symptoms and could be tolerated at a larger total dosage than bupivacaine (12). In addition, electrocardiogram and echocardiogram evidence of depression of conductivity and contractility appeared at smaller dosage and lower plasma concentrations with bupivacaine than with ropivacaine (12). In our study, we noted no overt signs of cardiac or central nervous system toxicity with either bupivacaine
606
REGIONAL ANESTHESIA AND PAIN MANAGEMENT
HICKEY ET AL.
0.25% ROPIVACAINE AND 0.2570 BUPIVACAINE
Table 5. Number of Patients Requiring Supplementation of Anesthesia and Analgesia Ropivacaine Bupivacaine 0.25% 0.2570 Total no. of patients requiring supplementation General anesthesia Nerve blocks Axillary block Radial nerve Median nerve Ulnar nerve Medial antebrachial cutaneous nerve Local infiltration
8
9
4
4
1 1 3 4
1 2 4 1
1
(0.89-2.0 mg/kg) or ropivacaine (0.81-2.3 mgikg). In the two previous brachial plexus studies reported with slightly higher doses (up to 3.2 mg/kg of bupivacaine and 3.1 mgikg of ropivacaine), there was also no evidence of toxicity. It should be noted, however, that in each of these studies, the vatients were premedicated with midazolam, which could increase the at least for system toxicity. In addition, unlike the volunteers studied by Scott et al. (12), our patients did not undergo formal Or echocardiographic studies to determine more subtle signs of cardiac toxicity. In conclusion, we have demonstrated that for subclavian perivascular brachial plexus block, despite theoretical potency Of rOpiVaCaine because Of exclusion of the less potent d-isomer, 0.25% ropivacaine is in quality to 0’25% bupivacaine in most aspects. Both local anesthetics, however, are frequently associated with inadequate sensory or motor block, 1
or both. In view of the high rate of supplementation necessary with both 0.25% ropivacaine and 0.25% bupivacaine, we recommend using the 0.5% concentration of these local anesthetics to provide brachial plexus anesthesia.
References 1. Hickey R, Candido KD, Ramamurthy S, et al. Brachial plexus block with a new local anesthetic: 0.5% ropivacaine. Can J Anaesth 1990;37:732-8. 2. Hickey R, Hoffman J, Ramamurthy S. A comparison of ropivacaine 0.5% and bupivacaine 0.5% for brachial plexus block. Anesthesiology 1991;74:639-42. 3. Cahn RS, Ingold CK, Prelog V. The specification of asymmetric configuration in organic chemistry. Experientia 1956;12:81-124. 4. Aberg G. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds. Acta Pharmacol Toxicol 1972;31:273-86. 5. Luduena FP, Bogado EF, Tullar BF. Optical isomers of rnepivacaine and bupivacaine. Arch Int Pharmacodyn Ther 1972;200: 359-69. 6. Reiz S, Haggmark G, Johansson G, Nath S. Cardiotoxicity of ropivacaine-a new amide local anaesthetic agent. Acta Anaesthesiol Scand 1989;33:93-8. 7. Feldrnan HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 1989;69:794-801. 8. Winnie AP. The subclavian perivascular technique of brachial plexus anesthesia. Anesthesiology 1964;25:35=3. 9. Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology 1990;72: 322-9. 10. Nancarrow C, Rutten AJ, Runcirnan WB, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 1989;69:27&83. 11. Akerman B, Hellberg IB, Trossvik C. Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 1988;32:5714. 12, Scott DB, Lee A, Fagan D, Bowler GMR, Bloomfield p, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989;69:56>9.
