Double-blind comparison of ropivacaine 7.5 mg ml–1 with bupivacaine 5 mg ml–1 for sciatic nerve block

C. Connolly, D. M. Coventry and J. A. W. Wildsmith

Department of Anaesthesia, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK*Corresponding author

Accepted for publication: January 3, 2001


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Two groups of 12 patients had a sciatic nerve block performed with 20 ml of either ropivacaine 7.5 mg ml–1 or bupivacaine 5 mg ml–1. There was no statistically significant difference in the mean time to onset of complete anaesthesia of the foot or to first request for post-operative analgesia. The quality of the block was the same in each group. Although there was no statistically significant difference in the mean time to peak plasma concentrations the mean peak concentration of ropivacaine was significantly higher than that of bupivacaine. There were no signs of systemic local anaesthetic toxicity in any patient in either group.

Br J Anaesth 2001; 86: 674–7

Keywords: anaesthetic techniques, regional, sciatic; anaesthetics local, ropivacaine; anaesthetics local, bupivacaine; pharmacokinetics, bupivacaine


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Sciatic nerve block is a useful anaesthetic technique for unilateral lower limb surgery, particularly in patients thought unsuitable for a central block. A long acting local anaesthetic agent will provide prolonged post-operative analgesia, and bupivacaine has been considered the drug of choice for this reason. However, concerns have been raised over its potential cardiotoxicity after inadvertant i.v. administration. Ropivacaine, a newer amide agent, appears to have similar clinical characteristics, but less potential for systemic toxicity.14 Although a significant mass of local anaesthetic is required for sciatic nerve block, there have been few reports of systemic drug disposition. This study was designed to compare both the clinical efficacy and pharmacokinetics of sciatic nerve block with either ropivacaine 7.5 mg ml–1 or bupivacaine 5 mg ml–1.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Twenty-four ASA 1–3 patients presenting for elective unilateral metatarsal osteotomy under sciatic nerve block gave informed consent for the study, which was approved by the local ethics committee. Each patient received temazepam 10–20 mg orally, 1–2 h before surgery. Before the sciatic nerve block, each patient was allocated randomly to one of two groups: group A received 20 ml ropivacaine 7.5 mg ml–1, and group B 20 ml bupivacaine 5 mg ml–1.

On arrival in the anaesthetic room, a 20 g cannula was placed in a peripheral vein for the administration of sedative and other drugs, and a 14 g cannula was inserted in a vein of the antecubital fossa of the other arm for blood sampling. In addition to routine clinical monitoring devices, a separate temperature probe (Hewlett Packard – M1029A) was applied to the dorsum of each foot, over the space between the first and second metatarsal bones. These were covered and insulated with gauze swabs and the skin temperature of both feet was measured continuously, and recorded every minute.

Midazolam 1–2 mg was administered i.v. before the block procedure, which was performed aseptically. After infiltration of the skin and subcutaneous tissues with 1% lidocaine, the sciatic nerve injection was performed using the posterior approach of Labat. All blocks were performed by the same investigator, and neither patient or block administrator knew which solution was used. The nerve was located using a 120 mm, 21 swg, short-bevelled insulated needle attached to a ‘Stimuplex’ peripheral nerve stimulator (B. Braun medical). Needle placement was considered optimal when maximal gastrocnemius contraction and plantar flexion of the foot was obtained at a current of 0.5 mA. After careful aspiration, the test solution was injected over a 2-min period. The end of the injection was defined as time zero.

Development of nerve block was assessed in three ways. The sensory response to pin-prick on the dorsal and plantar aspects of the foot was assessed using a short-bevelled 27 swg dental needle before, and 5, 10, 15, 20, 25, and 30 min after injection. Sensation was categorized as ‘sharp’ (same as the contra-lateral foot), ‘dull’ (pin-prick perceived as pressure), or ‘absent’ (complete loss of awareness of pinprick). Onset of block was defined as the time taken to achieve complete loss of sensation on both dorsal and plantar aspects of the foot.

Motor block was assessed using a simple 3 point score:

0=normal muscle power;

1=reduced power (plantar or dorsiflexion); and

2=complete motor block (plantar and dorsiflexion).

The time of onset of a progressive increase in the temperature of the ‘blocked’ foot was used to indicate the onset of sympathetic nerve block.

Once the sensory block was complete, an arterial tourniquet was applied to the calf, one hand’s breadth below the tibial tuberosity to avoid proximal compression of the peroneal nerve. The patient was then taken into the operating theatre and positioned for surgery. The foot was exanguinated using an Esmarch bandage, and the arterial tourniquet inflated. During the surgical procedure the patient listened to music by themselves through headphones and was able to communicate with an investigator at all times.

The clinical efficacy of the block was assessed in two ways. Patients were asked to provide a verbal rating of the quality (excellent, good, fair, poor) of anaesthesia 10 min after the start of surgery, and again immediately after its end. The time that elapsed until the patient first requested post-operative analgesia was recorded as an indicator of the duration of sensory block.

Peripheral venous blood samples were taken before, and 10, 20, 30, 45, 60, and 120 min after the end of the injection. The blood was centrifuged immediately and the supernatant plasma frozen at –20°C for subsequent batch analysis using a gas chromatographic technique with a coefficient of variation of 6%.

Data are presented as median (range) and statistical comparisons were performed using the Mann–Whitney U test for the characteristics of the nerve block. Peak concentrations (Cmax) of the two drugs were compared by t-test after log transformation, and times to peak concentration (Tmax) by Wilcoxon signed rank test.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
More females than males were recruited to the study, but there were no differences in patient characteristics between the two groups (Table 1). All patients underwent a first metatarsal osteotomy, with a silastic implant or joint fusion. No patient required supplementation of the sciatic nerve block to allow the surgery to commence, but one needed a saphenous nerve block (10 ml prilocaine 10 mg ml–1) 5 min before the end of the operation to allow medial proximal extension of the wound.


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Table 1 Patient characteristics expressed as mean (SD)
 
All patients received i.v. midazolam. The dose was titrated to individual patient requirements, but all patients were awake and responsive. The median and range for total dose of midazolam throughout the whole procedure was 2 (range 0–6) mg.

There was some variability in the time to the onset of both a sustained increase in skin temperature and complete anaesthesia of the foot, but there were no differences between the two groups (Table 2). Eight patients in the ropivacaine, and seven in the bupivacaine group, developed complete motor block of the foot. The remaining patients developed only some degree of motor weakness, but this did not interfere with surgery. Ten min after surgery began, 10 patients in the ropivacaine group rated anaesthesia as ‘excellent’ and two as ‘good’. In the bupivacaine group, 10 rated anaesthesia as ‘excellent’ and two as ‘fair’.


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Table 2 Clinical characteristics of blocks expressed as median (range)
 
At the end of surgery, 11 patients in each group rated anaesthesia as ‘excellent’ and one in each group as ‘good’. Both drugs produced prolonged analgesia, with the time to first request for analgesia being slightly longer with bupivacaine. This difference was not statistically significant (Table 2).

Mean peak plasma concentration of ropivacaine was significantly higher than that of bupivacaine, but in no patient did the maximum figure exceed the accepted threshold for systemic effects (Table 3). The time taken to reach the peak plasma concentration was the same in both groups.


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Table 3 Pharmacokinetic data expressed as mean (SD)
 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
This study has shown that 20 ml of either ropivacaine 7.5 mg ml–1 or bupivacaine 5.0 mg ml–1 produces effective sciatic nerve block after nerve stimulator guided injection, although it is arguable that it might have been more logical to compare equal concentrations of the two drugs. However, these are the concentrations of these two drugs that are licensed in the UK for major peripheral nerve block and it was thought useful to compare the two preparations. A reduction in the volume of ropivacaine 7.5 mg ml–1 would have allowed comparison of equal doses of the two drugs, but with differing volumes. Because 20 ml of each solution was used, the dose discrepancy produced in comparing the two licensed preparations is acknowledged, although equal dose comparisons of these two drugs using other major peripheral nerve injection techniques (brachial plexus block) have shown little difference between them.58 Supplementation of the sciatic nerve block with saphenous block was required in only one patient, when the surgical wound required proximal extension. This correlates well with a previous study,16 in which 5% of patients required supplementation of sciatic block with saphenous nerve block.

Although similar doses of local anaesthetic are required, there has been far less study of systemic drug disposition after sciatic than epidural block. The peak plasma concentrations reported here for bupivacaine are of the same order as seen previously. Coventry and Todd compared standard and alkalinized formulations of bupivacaine with epinephrine in a slightly greater dose (2 mg kg–1) than used here.10 Peak plasma concentrations, 0.4 and 0.6 mg litre–1, respectively, were somewhat lower than reported here, but epinephrine was not added in the present study. Others have studied combinations of lower limb nerve blocks with bupivacaine. Moore and colleagues observed a peak plasma concentration of 1.6 mg litre–1 after 400 mg bupivacaine with epinephrine for combined sciatic, femoral, and lateral cutaneous nerve of thigh block.11 Misra and colleagues compared plasma concentrations after bupivacaine 3 mg kg–1, plain or with epinephrine, after combined sciatic and femoral 3-in-1 block, and noted peak concentrations of 0.75 and 0.7 mg litre–1, respectively.12

The peak concentrations of ropivacaine were somewhat higher than those for bupivacaine (Table 3). Primarily this would reflect the greater dose administered, although slightly higher concentrations of ropivacaine have been reported than after injection of equal doses of bupivacaine epidurally.13 Lee and colleagues did report that the threshold for early signs of systemic toxicity with ropivacaine was in the range 1–2 mg litre–1, but that study involved direct i.v. infusion of the drug in volunteers.14 Many subsequent clinical studies have found plasma concentrations of ropivacaine to be in that range, but, as here, this has been without any indication of systemic toxicity.13 Much higher concentrations have been reported after accidental i.v. administration of ropivacaine, but again without any real concern for patient safety.15

This study was designed to assess also the clinical efficacy of sciatic nerve block as the primary anaesthetic for foot surgery and to compare the effects of the two commercially available long acting agents, both of which performed well. Sciatic block is a useful technique for unilateral lower limb surgery, having several advantages over central nerve block in elderly patients in whom a regional technique is preferred. This is especially so in terms of avoidance of the complications to which the elderly are particularly disposed such as hypotension and urinary retention. It may also be used more readily in the presence of a minor degree of coagulopathy or after head injury when central block is relatively contraindicated. The more selective block distribution may improve post-operative mobility, and longer acting agents provide prolonged post-operative analgesia.

Adverse effects of sciatic block are rare, but would include intravascular injection.9 Because a significant total dose of local anaesthetic is deposited at a very specific site to achieve accurate block, it is possible that a significant proportion of the total dose could be injected i.v. The length of needle used may also conceal intravascular placement particularly if over-vigorous aspiration is applied. The total dose should, therefore, be given slowly in increments and the reduction in cardiotoxicity afforded by ropivacaine should be seen as a significant advantage in these circumstances. The addition of epinephrine to either of the study agents does not appear to offer any clinical advantage in terms of duration of block, but may be useful in determining early intravascular placement.


    Acknowledgements
 
We would like to thank Astra Pain Control, Sweden, for financial and statistical support, and Professor G. T. Tucker, University of Sheffield, for performing the plasma analyses.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
1 Feldman HS, ArthurGR, 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[Abstract]

2 Nancarrow C, Rutten AJ, Runciman WG, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine and ropivacaine in sheep. Anesth Analg 1989; 69: 276–83[Abstract]

3 Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563–9[Abstract]

4 McClure JH. Ropivacaine. Br J Anaesth 1996; 76: 300–7[Free Full Text]

5 Hickey R, Blanchard J, Hoffman J, Sjovall J, Ramamurthy S. Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block. Can J Anaesth 1990; 37: 878–82[Abstract]

6 Hickey R, Candido KD, Ramamurthy S, et al. Brachial plexus block with a new local anaesthetic: 0.5% ropivacaine. Can J Anaesth 1990; 37: 732–8[Abstract]

7 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[ISI][Medline]

8 Hickey R, Rowley CL, Candido KD, Hoffman J, Ramamurthy S, Winnie AP. A comparitive study of 0.25% ropivacaine and 0.25% bupivacaine for brachial plexus block. Anesth Analg 1992; 75: 602–6[Abstract]

9 Coventry DM. Plasma bupivacaine concentration after inadvertant intravenous injection. Anaesthesia 1989; 44: 162

10 Coventry DM, Todd JG. Alkalinisation of bupivacaine for sciatic nerve blockade. Anaesthesia 1989; 44: 467–70[Abstract]

11 Moore D, Mather L, Bridenbaugh L, Balfour R, Lysons D, Horton W. Arterial and venous plasma levels of bupivacaine following peripheral nerve block. Anesth Analg 1976; 55: 763–8[Abstract]

12 Misra U, Pridie A, McClymont C, Bower S. Plasma concentration of bupivacaine following combined sciatic and femoral 3-in-1 nerve blocks in open knee surgery. Br J Anaesth 1991; 66: 310–3[Abstract]

13 Tucker GT. Ropivacaine: human pharmacokinetics. Am J Anesthesiology 1996; 24: 8–13

14 Lee A, Fagan D, Lamont M, et al. Disposition kinetics of ropivacaine in humans. Anaesth Analg 1989; 69: 736–8

15 Brockway MS, Bannister J, McClure JH, McKeown D, Wildsmith JAW. Comparison of extradural ropivacaine and bupivacaine. Br J Anaesth 1991; 66: 31–7[Abstract]

16 Kilpatrick AWA, Coventry DM, Todd JG. A comparison of two approaches to sciatic nerve block. Anaesthesia 1992; 47: 155–7[Abstract/Free Full Text]





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