Anesth Analg 2008; 107:1746-1750
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318185cd5e
ANALGESIA
A Randomized, Prospective, Double-Blind Trial Comparing 3% Chloroprocaine Followed by 0.5% Bupivacaine to 2% Lidocaine Followed by 0.5% Bupivacaine for Interscalene Brachial Plexus Block
Soheila Jafari, MD,
Allison I. Kalstein, DO,
Habib M. Nasrullah, MD,
Mehrdad Hedayatnia, MD,
Joel M. Yarmush, MD, and
Joseph SchianodiCola, MD
From the Department of Anesthesiology, New York Methodist Hospital, Brooklyn, New York.
Address correspondence and reprint requests to Soheila Jafari, Department of Anesthesiology, New York Methodist Hospital, 506 Sixth St., Brooklyn, NY 11215. Address e-mail to s1jafari{at}aol.com or s1jafari{at}aim.com.
Abstract
BACKGROUND: The combination of 2-chloroprocaine and bupivacaine (C/B) for regional anesthesia has been described, but its use was largely abandoned due to equivocal results in efficacy. In this prospective, double-blind, randomized study, we compared the onset of an interscalene block using C/B versus a combination of lidocaine and bupivacaine (L/B).
METHODS: Thirty patients scheduled for shoulder arthroscopy under interscalene block were divided into two groups of 15 each. One group (C/B) received 3% 2-chloroprocaine combined with bicarbonate and epinephrine, immediately followed by 0.5% bupivacaine and epinephrine, whereas the other group (L/B) received 2% lidocaine instead of 3% 2-chloroprocaine. Motor and sensory block were assessed every 15 s. The primary end-point was the time of onset to complete motor block. Time-to-event (survival) statistical analysis tests were applied.
RESULTS: One L/B patient had a failed block, and was excluded. The median time to motor block for C/B and L/B was 90 (15–575) and 180 (15–3720) s, respectively (P = 0.0325), and to sensory block for C/B and L/B was 90 (30–600) and 210 (30–3900) s, respectively (P = 0.0185). Survival analysis showed that in 5 min, 13 of 15 patients from the C/B group but only 7 of 14 from the L/B group had a successful motor block. In 10 min, 15 of 15 patients from the C/B group but only 10 of 14 from the L/B group had a successful motor block. It took as long as 60 min to assess block success/failure for blocks in the L/B group.
CONCLUSIONS: This study demonstrates that a successful block was more rapid using C/B than L/B for interscalene blocks.
The local anesthetic used during regional blockade should ideally have a rapid onset and long duration of action. To provide both of these properties, combinations of local anesthetics have been used.1–3
2-Chloroprocaine in various combinations was studied in the 1970s and early 1980s4–11 with equivocal results. A study by Cunningham and Kaplan6 showed a significant decrease in onset time of axillary block without reducing the duration of block, when 2-chloroprocaine was mixed with bupivacaine. The study by Cohen and Thurlow9 in 1979 reported that mixing the two local anesthetics for epidural anesthesia produced a block similar to that produced by 2-chloroprocaine alone. Galindo and Witcher,10 in 1980, demonstrated that the recovery of block from a mixture of bupivacaine and 2-chloroprocaine was significantly prolonged if the pH of the mixture was more alkaline.10 The study by Corke and Carlson11 in 1984 suggested that hydrolysis of 2-chloroprocaine by plasma esterases produces the metabolite 4-amino-2-chlorobenzoic acid, which interferes with the binding or access of bupivacaine to its site of action. Because of the unfavorable results in some studies, the use of a chloroprocaine and bupivacaine combination has been largely abandoned.
We anecdotally noted that sequential administration of bicarbonated 2-chloroprocaine and bupivacaine was successful in producing surgical anesthesia for upper extremity surgery. As a result we conducted this prospective, double-blind, randomized study comparing sequentially administered bicarbonated 2-chloroprocaine and bupivacaine, with bicarbonated L/B.
METHODS
After IRB approval, written informed consent was obtained from 30 ASA physical status I or II patients scheduled to undergo elective shoulder arthroscopy.
Patients were randomized using a computer-generated randomization table to either the 2-chloroprocaine/ bupivacaine (C/B) group or the lidocaine/bupivacaine (L/B) group. Exclusion criteria were the presence of any neurological deficits in the upper extremity, history of allergy to local anesthetics, the presence of infection at the site of block, and hemostatic disorders. None of the patients reported a history of pseudocholinesterase deficiency. Patients with failed block were excluded from data analysis.
The blocks were performed by only one skilled and experienced anesthesiologist (SJ), and were facilitated by sedation with IV midazolam with or without small amounts of propofol. Supplemental analgesics (fentanyl intraoperatively and percocet postoperatively) were given to any patient who experienced any discomfort not related to the surgical site (low back pain, leg pain, etc.). All patients received a standard single injection interscalene block using the Winnie approach. A 50 mm, 22-gauge insulated needle (B-Braun/McGaw Medical, Bethlehem, PA) attached to a nerve stimulator was used to identify the brachial plexus. Placement of the needle was considered adequate if the deltoid muscle motor response was still present at 0.3 milliamps. The study drug solutions were prepared by one anesthesiologist who was not directly involved with the administration of the anesthetics or evaluation of the blocks. Each solution was prepared in a separate syringe and they were not mixed before or during administration.
Patients received 20 mL of either the 2-chloroprocaine or the lidocaine solution according to their randomization, followed shortly by 20 mL of the bupivacaine solution as follows:
C/B group: 20 mL of the following:
- 3% 2-chloroprocaine 18 mL + epinephrine 50 µg + 8.4% sodium bicarbonate 2 mL.
L/B group: 20 mL of the following:
- 2% lidocaine 18 mL + epinephrine 50 µg + 8.4% sodium bicarbonate 2 mL.
Both groups: 20 mL of the following after the first medication:
- 0.5% bupivacaine 20 mL + epinephrine 50 µg.
The needle extension tubing was connected to the syringes of local anesthetic via a three-way stopcock. After localization of the brachial plexus and negative aspiration, the fast-acting local anesthetic (either 2-chloroprocaine or lidocaine) was injected in increments of 5 mL with aspiration after each incremental injection, this was followed by the bupivacaine injection after a short pause. The two injections were completed within approximately 90 s. Upper extremity motor and sensory blocks were assessed every 15 s after the block was administered. The primary end-point for the study was the occurrence of complete motor block of the upper extremity. We calculated the duration between the needle withdrawal and the time to establish complete motor block (Tmotor). The motor block was considered complete when the patient was unable to lift his/her arm from the table against gravity. A secondary end-point for evaluation was the time to establish sensory block (Tsensory). We calculated the duration between the needle withdrawal and the time to establish sensory block. The sensory block was assessed by a standard pinprick in C5/C6 dermatomes for uniformity of assessment by the researcher. The sensory block was considered complete when the patient was unable to feel the pinprick in the entire surgical territory establishing a complete surgical anesthesia.
Motor and sensory block were assessed until a successful block was demonstrated, again at the end of surgery, and once again immediately before discharge. Pain scores and analgesic usage, if applicable, were also assessed and documented during the operation and in the postanesthesia care unit (PACU). Immediately before discharge from the PACU, patients were asked to indicate their degree of satisfaction with the anesthetic technique using a scale from 1 to 3, in which 1 meant "Not satisfied," 2 "Satisfied," and 3 "Extremely satisfied." Patients were asked if they would have the block should they need the same operation again. Since patients were discharged home before recovery from the anesthetic, patients were asked to document the time of the first occurrence of discomfort after discharge. Patients were contacted a day after discharge to collect data about recovery from the block but, due to unreliability of the data and lack of exact time when recovery occured in the majority of cases, the results were not included in the current study. Patients were given prescriptions for ibuprofen and Vicodin as needed.
Statistical Analysis
This was a time-to-event study. The statistical analysis was performed using STATA, version 8.2. The primary end-point of the study was the development of motor block (Tmotor) and the secondary end-point was the development of sensory block (Tsensory) in C/B and L/B groups. The sample size was determined using the comparison between proportions of patients who had the event (motor block) occur at a prespecified time point (3 min in our study). An earlier pilot study at New York Methodist Hospital showed that by the end of 3 min, 80% of patients who received the C/B combination had a motor block. A review of historical data from New York Methodist Hospital showed that at 3 min, only 15% of patients who received the L/B combination had a motor block. Based on these data, 28 patients, 14 patients in each group, were required to test the null hypothesis that the time to motor block is equal in both groups with a significance level of 0.05 (2 sided test) and a power of 80%. However, the sample size was adjusted to 30 (15 in. each group) to allow for a one case of block failure in each group.
Numerical data (i.e., Tmotor, Tsensory, age, height, and weight) are expressed as mean (standard deviation) or median (range). Categorical data (gender) are addressed as frequencies.
Numerical data that are of the time-to-event or survival type (i.e., Tmotor, Tsensory) were analyzed using Kaplan-Meier estimates and Kaplan-Meier plots. Log-rank tests were conducted to compare between the two groups. P value <0.05 was considered statistically significant.
RESULTS
There were no significant demographic differences between the two groups (Table 1). Of the 30 patients, one patient in the L/B group had an inadequate sensory and motor block, and required conversion to general anesthesia. After the operation, the patient was rechecked and no motor or sensory block was present. This patient was dropped from the data analysis. All other patients in both groups had a complete sensory and motor block throughout the operation and continuing through discharge from the PACU. Any variation in the duration of block was not clinically significant, as all patients continued to have motor and sensory blocks until they were discharged home.
No patient reported pain at the site of surgery during the operation. Four patients received supplemental analgesics for nonsurgical site discomfort. One patient in the C/B group received 200 mcg fentanyl. Three patients in the L/B group received 100 150, and 200 mcg fentanyl, respectively. One patient in the C/B group received one Percocet tablet in the PACU for discomfort.
All patients were discharged home on the same day of surgery. Sixteen patients rated their anesthetic as "satisfied," and 13 as "extremely satisfied." There was no significant difference in satisfaction scores between the two groups. All the patients answered that they would have the block should they need the same operation again.
There were no short-term complications, such as intravascular injection, neuraxial block, or local anesthetic toxicity. Patients were not examined specifically for long-term neurologic complications, but no neurologic complications were subsequently reported by the surgeons. All patients were discharged home from the PACU in stable condition. Table 2 shows that there was a statically significant difference in median onset times between Tmotor and Tsensory with group C/B median onset times being at least half of group L/B. The log rank test results that compare the time to motor and sensory block in both groups are also given.
Using the Kaplan-Meier estimate, at 5 min, a successful motor block was present in 13 of 15 patients in the C/B group, but in only 8 of 14 from the L/B group (Fig. 1). Similarly, at 5 min, 13 of 15 patients in the C/B group had a successful sensory block, compared with 8 of 14 from the L/B group (Fig. 2). At 10 min, all patients (15 of 15) in the C/B group had both a successful motor block and a successful sensory block. At 10 min, only 10 of 14 patients in the L/B group had a successful motor block and a successful sensory block. It would take as much as 60 min for all patients in the L/B group to have a successful motor block and a successful sensory block.
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Figure 1. Time to motor block. Kaplan-Meier curves showing the time to event probability (Y-axis) versus the time to motor block (Tmotor) in seconds for 2-Chloroprocaine/Bupivacaine (C/B) and Lidocaine/Bupivacaine (L/B).
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Figure 2. Time to sensory block. Kaplan-Meier curves showing the time to event probability (Y-axis) versus the time to sensory block (Tsensory) in seconds for 2-Chloroprocaine/Bupivacaine (C/B) and Lidocaine/Bupivacaine (L/B).
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Based on the analysis of the study data, using Kaplan-Meier estimates with a 95% confidence interval, if interscalene block were performed on 1000 patients using the C/B medications, all of the patients would have a successful motor blocks by 10 min. On the other hand, if an interscalene block were performed on 1000 patients using the L/B medications, only 714 (476,912) and 929 (725,996) patients would have a successful motor block by 10 and 20 min, respectively. This difference is statistically significant with P < 0.05.
DISCUSSION
In the present study, we demonstrated that a C/B combination consistently resulted in faster onset times for interscalene block than L/B. C/B combination was abandoned by most clinicians by the early 1980s because it did not seem to work in the epidural space. However, we demonstrated that the C/B block was effective in the interscalene approach to the brachial plexus. The C/B block was equally effective as L/B in the brachial plexus block in terms of duration until discharge and requirements for intraoperative analgesic supplementation. The incongruity between our results and previous results may have a number of causes. The epidural space and the area near the brachial plexus may have different characteristics as to vascular absorption and esterase hydrolysis. This is consistent with the results of Cunningham and Kaplan,6 who had success with the C/B combination in an axillary block. Minimizing differences in pH by adding bicarbonate to both the lidocaine and 2-chloroprocaine solutions may also have played a role.
Both local anesthetic combinations, on average, provide rapid onset of surgical anesthesia. When the C/B combination was used, the demonstration of a successful block was more rapid than when the L/B combination was used. Based on survival analysis of the data, if the C/B combination is used and a block has not developed within 10 min, then it can be concluded that no block will develop later. On the other hand, survival analysis shows that 10 min is not enough time to exclude the success of a L/B block. Initially unsuccessful L/B blocks may become successful blocks for some time after placement. It takes up to 60 min to conclude that the L/B block is unsuccessful. The use of C/B in place of L/B permits a more rapid decision to abandon an unsuccessful block with a potential positive influence on operating room utilization and economic efficiency.
Study Limitations
We chose the time to onset of motor block rather than sensory block as the primary end-point despite the clinical importance of the sensory block in the practice of anesthesia. This was because of the objective nature of assessing motor block, as compared with the subjective quality of a sensory block. However, we also compared the time to sensory block as a secondary objective of the study and the results showed statistically significant difference between the two groups.
Finally, the duration of the block was not assessed in this study because of unreliability of the collected data. These data are critical to making a definitive recommendation regarding the superiority of one combination over the other.
CONCLUSION
This study showed that the C/B combination was characterized by a clinically and statistically significant faster onset than the L/B combination for interscalene blocks. Although both mixtures offered an adequate intraoperative anesthetic, faster onset of action of 2-chloroprocaine can facilitate the early recognition of an unsuccessful block. Further studies are required to confirm the role of this combination in enhancing operating room turnover time and postoperative analgesic requirements.
Footnotes
Accepted for publication June 18, 2008.
Supported by Department of Anesthesiology, New York Methodist Hospital, Brooklyn, New York. No other financial support was used.
Conflict of Interest: There is no conflict of interest.
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