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Anesth Analg 2001;92:205-208
© 2001 International Anesthesia Research Society

REGIONAL ANESTHESIA AND PAIN MEDICINE

Minimum Local Anesthetic Volume Blocking the Femoral Nerve in 50% of Cases: A Double-Blinded Comparison Between 0.5% Ropivacaine and 0.5% Bupivacaine

Andrea Casati, MD, Guido Fanelli, MD, Luca Magistris, MD, Paolo Beccaria, MD, Marco Berti, MD, and Giorgio Torri, MD

Department of Anesthesiology, University of Milan, Milan, Italy

Address correspondence and reprint requests to Andrea Casati, MD, Department of Anesthesiology, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Address e-mail to casati.andrea{at}hsr.it


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Recent studies demonstrated that ropivacaine was nearly 40% less potent than bupivacaine in the first stage of labor, but contrasting results have been reported. We, therefore, conducted a prospective, randomized, double-blinded study to determine the effects of the ropivacaine/bupivacaine potency ratio on the minimum volume of local anesthetic required to produce effective block of the femoral nerve in 50% of patients. Fifty adults premedicated with IV midazolam, 0.05 mg/kg, undergoing elective knee arthroscopy received femoral nerve blocks with a multiple-injection technique with a nerve stimulator (contractions of vastus medialis, vastus intermedius, and vastus lateralis were elicited with a 0.5-mA stimulating current). Patients randomly received either 0.5% ropivacaine (n = 25) or 0.5% bupivacaine (n = 25). The anesthetic volume was decided according to Dixon’s up-and-down method, starting from 12 mL and being equally divided among the three elicited twitches. Successful nerve block was loss of pinprick sensation in the femoral nerve distribution with concomitant block of the quadriceps muscle within 20 min after injection, as assessed by a blinded observer. Positive or negative responses determined a 3-mL decrease or increase for the next patient, respectively. According to the up-and-down sequences, the minimum local anesthetic volume providing successful nerve block in 50% of cases was 14 ± 2 mL in the ropivacaine group (95% CI: 12–16 mL) and 15 ± 2 mL (95% CI: 13–17 mL) in the bupivacaine group (P = 0.155). We conclude that the volume of 0.5% ropivacaine required to produce effective block of the femoral nerve in 50% of patients is similar to that required when using 0.5% bupivacaine.

Implications: Considering the risk for drug-related systemic toxicity, the equipotency ratio between ropivacaine and bupivacaine is crucial for daily practice. Despite the 40% reduction in the analgesic potency of ropivacaine reported during epidural analgesia for labor pain, results of this prospective, randomized, double-blinded study demonstrated that the same volume of 0.5% ropivacaine or 0.5% bupivacaine is required to produce an effective block of the femoral nerve in 50% of cases.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Recent studies evaluating the analgesic potency of ropivacaine and bupivacaine during epidural analgesia for labor pain demonstrated that ropivacaine was nearly 40% less potent than bupivacaine in the first stage of labor (1,2), whereas contrasting results have been reported in similar clinical settings (3).

When providing surgical anesthesia with peripheral nerve blocks, the total injected volume of local anesthetic solution is a crucial factor affecting the success rate and predictability (4,5). However, the relative potency of local anesthetic solutions we are injecting might further influence the doses and volumes required to obtain the same clinical effect. The aim of this prospective, randomized, double-blinded study was to compare the effect of ropivacaine and bupivacaine on the minimum volume of local anesthetic required to produce effective peripheral nerve block in 50% of patients.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
With Ethical Committee approval and written informed consent, 50 ASA physical status I and II inpatients, aged 18–65 yr and scheduled for elective knee arthroscopy under combined sciatic-femoral nerve block, were studied. Patients with contraindications to regional anesthesia; patients with respiratory or cardiac disease, diabetes, or peripheral neuropathy; and patients receiving chronic analgesic therapy were excluded.

After an 18-gauge IV cannula had been placed at the forearm, all patients received standard IV premedication with midazolam (0.05 mg/kg) 10 min before placing the block. First, we performed a sciatic nerve block with 10 mL of 2% mepivacaine by using the classic Labat’s approach and a multiple-injection technique (the volume of local anesthetic was equally divided between flexion and dorsiflexion of the foot) (6,7). Afterward, the patient was turned to the supine position, and a femoral nerve block was performed with the aid of a nerve stimulator ( Plexival TM; Medival, Padua, Italy) that used short, beveled, Teflon-coated stimulating needles (Locoplex, Vygon, France; needle length and diameter were 3.5 cm and 25-gauge, respectively). The stimulation frequency was set at 2 Hz, whereas the intensity of the stimulating current, initially set to deliver 1 mA, was gradually decreased to <0.5 mA after each elicited muscular twitch was observed. The stimulating needle was inserted lateral to the femoral artery at the intersection between the femoral artery and a line connecting the anterior superior iliac spine to the pubic tubercle. Paresthesias were never sought. In all patients, a multiple-injection technique was used. The stimulating needle was inserted and redirected to elicit contractions in each of the following muscles: the vastus medialis, vastus intermedius, and vastus lateralis (6–8). If the injection of 1 mL of the study solution immediately stopped the muscular twitch elicited at 0.5 mA, the needle location was considered adequate, and the remaining volume was injected (6–8). The determined volume of local anesthetic solution was equally divided among the three muscular twitches. All three muscular twitches had to be elicited; in case it was not possible to elicit one of the three muscular twitches, the patient was excluded from the study.

Patients were allocated to one of two groups in a prospective, randomized, double-blinded study design. The first group (n = 25) received 0.5% ropivacaine (Naropin; ASTRA, Sodertalije, Sweden), and the second group (n = 25) received 0.5% bupivacaine (Marcaine; ASTRA). The syringes containing the local anesthetic solutions were prepared in a double-blinded fashion by one of the authors, who was not involved in further patient evaluation. All femoral nerve blocks were placed by two anesthesiologists with substantial expertise in regional anesthesia and who were unaware of the local anesthetic solution injected. After completion of nerve block placement, sensory and motor blocks were evaluated every 2 min for the first 10 min after injection and then every 5 min until 20 min after injection, by a blinded observer who was not present during injection and was unaware of both the volume and type of local anesthetic injected. Sensory block was evaluated as loss of pinprick sensation (20-gauge hypodermic needle), whereas motor block was evaluated as ability or inability to extend the affected leg with the hip passively flexed. Successful nerve block was defined as complete loss of pinprick sensation in the femoral nerve distribution, with concomitant inability to extend the affected leg within 20 min after local anesthetic injection (7,8).

According to our previous clinical experience (6–8), the initial volume of local anesthetic solution was 12 mL, although the outcome of each patient’s response determined the dose for the next patient. When successful femoral nerve block, as defined above, was achieved within 20 min after injection, the volume of local anesthetic solution for the next patient was decreased by 3 mL (1 milliliter per twitch). Conversely, when successful femoral nerve block was not observed, the volume of local anesthetic solution for the next patient was increased by 3 mL (1 milliliter per twitch).

In patients showing incomplete block of the femoral nerve within 20 min after injection, IV fentanyl (0.1 mg) and intraarticular anesthesia (20 mL lidocaine 2% with 1:20,0000 adrenaline) were given, then surgery started. If patients complained of pain despite supplemental fentanyl analgesia, general anesthesia was induced with IV propofol (1 mg/kg bolus followed by a 3–5 mg · kg-1 · h-1 continuous infusion).

Statistical analysis was performed with the program Systat 7.0 (SPSS Inc, Chicago, IL). Continuous variables were analyzed with unpaired Student’s t-tests or Mann-Whitney U-tests as indicated. Ordinal data were analyzed by using the contingency table analysis with the Fisher’s exact test. Data are presented as mean (SD and 95% CI) and count as appropriate. The mean effective volume of ropivacaine and bupivacaine was estimated from the up-and-down sequences by using the methods of Dixon and Massey (9) and Dixon (10): this up-and-down method concentrated on testing the anesthetic volume, giving a 50% probability of successful nerve block (10). The mean (SD) and 95% confidence intervals of the volume of either ropivacaine or bupivacaine providing successful nerve block in 50% of patients were calculated from the midpoints of pairs of volumes from consecutive patients in whom a negative response was followed by a positive one (9,10).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
No differences in age (50 ± 12 yr in the ropivacaine group and 47 ± 13 yr in the bupivacaine group), weight (70 ± 19 kg in the ropivacaine group and 70 ± 9 kg in the bupivacaine group), height (167 ± 8 cm in the ropivacaine group and 168 ± 7 cm in the bupivacaine group), sex (13 men and 12 women in the ropivacaine group and 12 men and 13 women in the bupivacaine group), or ASA physical status (17 ASA status I and 8 ASA status II in the ropivacaine group and 18 ASA status I and 7 ASA status II in the bupivacaine group) were reported between the two groups.

In three patients (6%) it was not possible to elicit the contraction of vastus lateralis (two patients in the bupivacaine group and one patient in the ropivacaine group): these patients were excluded from the study, but patients after each excluded patient received the same volume and type of local anesthetic solution. Thirteen patients in the ropivacaine group (52%) and 12 patients in the bupivacaine group (48%) had successful nerve blocks within 20 min after injection. The surgical procedure was successfully completed in all patients: general anesthesia was never required to complete surgery in any patient, and none of those patients with effective nerve blocks within 20 min after injection required supplemental fentanyl administration during surgery.

Figure 1 shows the sequences of effective and ineffective blocks of the femoral nerve in the two studied groups. The minimum local anesthetic volume providing successful nerve block in 50% of cases, as calculated with the formula of Dixon and Massey, was 14 ± 2 mL in the ropivacaine group (95% CI: 12–16 mL) and 15 ± 2 mL (95% CI: 13–17 mL) in the bupivacaine group (P = 0.155).



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  		Figure 1. The volume of local anesthetic solution producing effective nerve block in 50% of patients as determined by the up-and-down sequential allocation technique with either 0.5% ropivacaine (n = 25) or 0.5% bupivacaine (n = 25). The minimum local anesthetic volume was 14 mL and 15 mL, with 0.5% ropivacaine and 0.5% bupivacaine, respectively. Error bars represent 95% confidence intervals; the testing interval was 3 mL. Filled and empty marks represent ineffective and effective nerve blocks, respectively.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Comparison of relative potencies of local anesthetics in intact subjects is always difficult and can be influenced by various factors, including the study design. Many clinical reports have demonstrated that ropivacaine and bupivacaine produce equally effective nerve blocks when used in equal concentrations and doses for epidural anesthesia (11,12) and analgesia (3), as well as for axillary (13) and interscalene (14,15) brachial plexus anesthesia or lower-limb peripheral nerve blocks (16). However, recent studies evaluating the minimum local anesthetic concentration (MLAC) of ropivacaine and bupivacaine providing effective epidural analgesia during labor pain demonstrated that ropivacaine was nearly 40% less potent than bupivacaine, requiring larger doses to produce the same clinical effect (1,2). Accordingly, larger volumes (and doses) should be required to produce effective femoral nerve block when using 0.5% ropivacaine rather than 0.5% bupivacaine. However, results of this prospective, randomized, double-blinded study failed to demonstrate a clinically or statistically significant increase in the volume of 0.5% ropivacaine required to produce effective block of the femoral nerve in 50% of patients, as compared with 0.5% bupivacaine.

A major shortcoming of this study could be the lack of objective measurements of neurologic function after local anesthetic injection, such as transcutaneous electrical stimulation or muscle strength dynamometry: successful nerve block was arbitrarily defined as the loss of pinprick sensation in the femoral nerve distribution, with the concomitant block of the quadriceps muscle within 20 min after injection. However, ineffectiveness of muscle contraction in elevating the limb against gravity and loss of pinprick sensation are clinically used methods to assess the efficacy of a nerve block before starting surgery (17,18). Frequent use of painful stimulations, such as transcutaneous electrical stimulation, before the onset of nerve block was judged unethical.

The volume of local anesthetic providing effective block in >=95% of patients could seem more clinically relevant because effective anesthesia must be provided in all patients receiving a peripheral nerve block. However, the use of an up-and-down sequential allocation, rather than a random allocation method, allowed us to minimize the number of potentially inadequate anesthetic blocks (19); for this reason, we determined only the volume effective in 50% of patients. Further, the application of such a particular statistical method has been previously applied to determine dose-effect relationships in different fields of anesthesia research, including inhaled and IV anesthetics and epidural analgesia (1,2,20,21).

In this investigation, the femoral nerve was blocked by using a multiple-injection technique, which shortens the onset time and improves the quality of nerve block as compared with a single injection (8). Therefore, the minimum effective local anesthetic volume for the more commonly used single-injection technique may be larger than those observed in this study. However, because the same technique of block placement was used in both groups, no systematic bias should have been introduced when comparing ropivacaine and bupivacaine.

A possible explanation for the lack in differences between ropivacaine and bupivacaine could be related to the different vasoactivity of the two drugs. Ropivacaine has intrinsic vasoconstrictive properties, whereas bupivacaine increases the skin blood flow after intradermal injection, producing vasodilatation (22). In agreement with this finding, Nolte et al. (23) failed to demonstrate any significant effect with addition of vasoconstrictors on either latency or duration of ropivacaine nerve block. The vasoactivity of ropivacaine might increase the speed with which local anesthetic molecules penetrate into peripheral nerves as compared with bupivacaine, explaining the lack of differences between the two drugs in the volume required to produce effective nerve block within 20 min after injection.

In conclusion, when choosing between ropivacaine and bupivacaine in routine daily practice, the equipotency ratio between the two drugs may be clinically relevant, especially when considering the maximum tolerated doses and the risk for central nervous system and cardiovascular toxicity (24,25). Although the 40% reduction in the analgesic potency of ropivacaine demonstrated by previous MLAC studies suggests reconsideration of its therapeutic ratio, several studies have reported that ropivacaine and bupivacaine produce equally effective nerve blocks in equal concentrations and doses. In agreement with these findings, results of this prospective, randomized, double-blinded study demonstrated that the volume of ropivacaine required to produce effective block of the femoral nerve in 50% of patients is similar to that required when using bupivacaine. The 50% effective concentration reported in MLAC studies is only one point on a dose-response curve and cannot be extrapolated to other doses. For the same reasons, the potency difference reported in MLAC studies cannot be extrapolated to recommendations for maximum tolerated doses.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication September 19, 2000.




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