Spinal anaesthesia with ropivacaine 5 mg ml1 in glucose 10 mg ml1 or 50 mg ml1
J. B. Whiteside*,
D. Burke and
J. A. W. Wildsmith
University Department of Anaesthesia, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK*Corresponding author
Accepted for publication: August 11, 2000
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Abstract
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Forty patients undergoing spinal anaesthesia for a variety of surgical procedures were randomly allocated to receive 3 ml of ropivacaine 5 mg ml1 in glucose 10 mg ml1 or 50 mg ml1. Onset of sensory block to T10 was significantly faster (P=0.03) with the glucose 50 mg ml1 solution (median 5 min, range 220 min) than with the 10 mg ml1 solution (median 10 min, range 225 min). Maximum extent of cephalad spread was virtually the same in both groups (10 mg ml1 median T6/7, range T3T10; 50 mg ml1 median T6, range T3T10) with similar times to regression beyond S2 (10 mg ml1 median 210 min, range 150330 min; 50 mg ml1 median 210 min, range 150330 min). Complete motor block was produced in the majority of patients (10 mg ml1 90%; 50 mg ml1 85%) and the time to complete regression was the same in both groups (median 120 min, range 90210 min). A block adequate for the projected surgery was achieved in all patients.
Br J Anaesth 2001; 86: 2414
Keywords: anaesthetic techniques, subarachnoid; anaesthetics local, ropivacaine; physics, baricity
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Introduction
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Ropivacaine, a recently introduced amino-amide local anaesthetic agent similar to bupivacaine in chemical structure, has been little studied for intrathecal use. Early evaluation of the drug included two studies of glucose-free solutions performed primarily to allay concern regarding the safety of ropivacaine should accidental intrathecal injection occur during epidural block.1 2 Sensory block of variable extent and intermediate duration was produced. Currently, ropivacaine is not licensed for intrathecal use, but one clinical study of the plain solution has compared ropivacaine unfavourably to bupivacaine,3 as did a small study of glucose containing solutions in volunteers.4 The present study was designed to evaluate the clinical efficacy of hyperbaric solutions containing glucose in two different concentrations.
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Methods
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Forty patients gave written informed consent for the study that was approved by the local research ethics committee. Patients of ASA grade III scheduled to undergo lower abdominal, perineal or lower limb surgery under spinal anaesthesia were recruited and randomized to receive 3 ml ropivacaine 5 mg ml1 with glucose 10 or 50 mg ml1. Premedication consisted of oral temazepam 1020 mg.
On arrival in the anaesthetic room, continuous monitoring with ECG, non-invasive arterial pressure and pulse oximetry was commenced and a suitable vein cannulated. No fluid was administered and the patient was placed in the left lateral position for lumbar puncture, which was performed using a midline approach at the 2nd or 3rd lumbar inter-space. A 25 swg Whitacre needle (Vygon, UK) was inserted with the distal port facing laterally and 3 ml of ropivacaine 5 mg ml1 in glucose 10 or 50 mg ml1 was injected over 1015 s. The study solutions were prepared aseptically immediately before injection by an anaesthetist, who was not one of the investigators, using appropriate volumes of ropivacaine 10 mg ml1, glucose 100 mg ml1 and sodium chloride 9 mg ml1 (Table 1). The patient was placed supine immediately after injection.
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Table 1 Constituents of 0.5% ropivacaine solutions (prepared to 10 ml, 3 ml administered). Densities of solutions at 37°C (mean (SD) n=3 for each solution) measured with DE50 density meter (Mettler-Toledo Laboratories, UK)
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A blinded investigator who did not know which solution had been injected observed the developing block. The extent of sensory block (analgesia to pinprick with a 27 swg short-bevel dental needle), degree of lower limb motor block (modified Bromage scale: 0=full movement; 1=inability to raise extended leg, can bend knee; 2=inability to bend knee, can flex ankle; 3=no movement), arterial pressure and heart rate were recorded at 2, 5, 10, 15, 20, 25 and 30 min, and at 30 min intervals thereafter until complete regression of the block. The caudad limit of sensory block assessment was restricted to S2 and, where there was a difference in height of block between left and right, the mean of the two was recorded. After 30 min, patients were transferred to theatre for surgery and intra-operative sedation was provided with a target controlled propofol infusion in the dose range 0.52.0 µg ml1 (titrated to maintain verbal contact). Hypotension, defined as a decrease of >30% from baseline systolic blood pressure, was treated with i.v. ephedrine 3 mg. Fluids were only administered to replace intra-operative losses and bladder catheterization was performed only if surgically indicated. Patients were visited at 24 h and telephoned at 37 days.
The sample size was chosen to show a difference in extent of sensory block of three dermatomes between the groups, based on an
risk of 0.05 and a ß risk of 0.20 using data from a previous study of intrathecal ropivacaine.1 Data are presented as median (range), mean (SD), or frequencies as appropriate. Patient characteristics and the duration of surgery were compared using the two-tailed two-sample t-test except for sex (chi-squared test). Block characteristics were compared using the two-tailed Mann-Whitney U-test or Fishers exact test (number of patients with complete motor block). No correction was applied for multiple two-way testing. Statistical advice was that there is no appropriate correction factor available for dealing with sets of data, which, like these, are not strictly independent. In all categories P<0.05 was considered statistically significant. Data were analysed using Arcus Quickstat version 1.0 (Research Solutions Ltd, UK).
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Results
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The groups were comparable with regard to age, sex, height, weight and ASA status (Table 2).
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Table 2 Patient characteristics and types of surgery in two groups of 20 patients undergoing spinal anaesthesia with ropivacaine 0.5% in glucose 10 mg ml1 or 50 mg ml1. Data are mean (SD) or frequencies
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The onset of pinprick analgesia at T10 was more rapid (P=0.03) with the greater concentration of glucose. Median block height was slightly higher throughout in that group (Fig. 1), but the difference was only statistically significant at 90 min (P=0.02).

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Fig 1 Profile of sensory block in two groups of 20 patients after intrathecal injection of 3 ml ropivacaine 5 mg ml1 with 10 mg ml1 or 50 mg ml1 glucose. *P<0.05 between the groups. (60 min: glucose 10 mg ml1 n=12, glucose 50 mg ml1 n=8; 90 min: glucose 10 mg ml1 n=16, glucose 50 mg ml1 n=16.)
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Degree of motor block was similar in both groups (10 mg ml1 glucose: grade 3 n=18, grade 2 n=2; 50 mg ml1 glucose: grade 3 n=17, grade 2 n=3), and its total duration was the same (Table 3). Complete regression of motor block had occurred at 4 h, and of sensory block at 6 h, in all patients. Cardiovascular changes were minimal and there were no statistical differences between the groups.
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Table 3 Characteristics of neural block and frequency of adverse events in two groups of 20 patients undergoing spinal anaesthesia with ropivacaine 0.5% in glucose 10 mg ml1 or 50 mg ml1. Data are median (range) or number (%); NS=not significant
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The block was suitable for surgery in all patients. Fifteen patients in the glucose 10 mg ml1 group and 12 in the glucose 50 mg ml1 group requested intra-operative sedation. Three patients in each group developed mild localized tenderness at the site of lumbar puncture at 24 h, but there were no neurological symptoms and no patient developed a post dural puncture headache. Hypotension, as defined above, required treatment with a single dose of ephedrine 3 mg in seven patients (10 mg ml1 group, n=4; 50 mg ml1 group, n=3), but repeated dosing was not necessary. All patients not requiring catheterization for surgical indications (10 mg ml1 group, n=14; 50 mg ml1group, n=10), passed urine normally within 8 h.
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Discussion
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This study has shown that glucose containing solutions of ropivacaine, hyperbaric relative to CSF,5 can produce predictable and reliable spinal anaesthesia for a wide range of surgical procedures. This is in contrast to the results of the two early clinical studies of intrathecal ropivacaine, which described blocks that varied widely in extent and were frequently inadequate for surgery.1 2 However, those studies used glucose-free solutions. Comparison of individual patient maximum block heights from the current study with those from a group that received the same dose of ropivacaine in one of those earlier studies (with an otherwise almost identical protocol) clearly shows the influence of adding glucose (Fig. 2). The major effect is to reduce the proportion of very limited blocks without producing significantly more extensive blocks, especially at the lower glucose concentration. Similar general findings on the effects of adding glucose have been noted in previous studies of both tetracaine6 and bupivacaine.710

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Fig 2 Upper levels of sensory block in individual patients. Horizontal bars represent the medians. Data for plain 0.5% ropivacaine reproduced from van Kleef and colleagues (with permission). All patients received 15 mg ropivacaine in 3 ml.
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The results of the current study are also in contrast with the general conclusions of the two more recent studies of intrathecal ropivacaine, both of which questioned its suitability for spinal anaesthesia in comparison with bupivacaine.3 4 Gautier and colleagues used plain glucose-free preparations, but in larger volumes of less concentrated solutions that are normally used in clinical practice.3 When equal doses of ropivacaine and bupivacaine were compared, the onset and extent of sensory block was similar, but the duration of that sensory block and the degree of motor block produced were both less with ropivacaine. These findings, particularly the shorter duration of action, led the authors to claim that ropivacaine is less potent than bupivacaine and that it offers no significant advantage, even though the patients who received ropivacaine passed urine and mobilized more rapidly than those who received bupivacaine.
McDonald and colleagues compared hyperbaric preparations of the two drugs in volunteer subjects not undergoing surgery.4 Their solutions were also less concentrated than are normally used clinically, as were the total doses injected. Equal doses of ropivacaine and bupivacaine produced sensory blocks of similar onset and extent, but there was less motor block, which regressed faster, with ropivacaine. Again, primarily on the basis of the shorter duration of action, and despite equivalence in the onset and extent of sensory block, the authors concluded that ropivacaine is less potent than bupivacaine. This study also found a higher incidence of backache after ropivacaine and concluded that the incidence of side effects was higher even though the difference was not statistically significant. Although it did not involve any comparison with bupivacaine, our study does not support the implication that ropivacaine is not suitable for spinal anaesthesia.
The features (rate of onset, total spread and rate of offset) of the block produced by the intrathecal injection of any solution are the result of an interaction between the individual patients characteristics and three completely separate components of the solution, for example: the pharmacological properties of the drug used; the amount (volume, concentration and their product, dose) injected and the physical properties (primarily density relative to CSF) of the solution in which it is administered.
This is because there are two processes involved in the onset of a spinal anaesthetic. First, the solution must spread physically through the CSF. This depends primarily on the properties of the solution, and is independent of the drugs properties. These, along with the dose, will influence the second process, diffusion into (and subsequently out of) the nerve roots.
The factors that influence intrathecal spread have been the subject of a great deal of clinical investigation and this work has been reviewed.11 12 It is essential that the effects of the different components listed above are identified and recognized because each will impact on the clinical features (rate of onset, total extent, quality/degree and duration) of a spinal block. Thus, when comparisons are made between drugs, the results cannot be assessed properly unless all of the information about the solutions is presented. In addition to drug concentration and the volume injected, data on solution density must be available, especially when non-standard preparations are used. Both Gautier and colleagues, and McDonald and colleagues, used unusually dilute solutions and failed to give details of physical characteristics.3 4 Even when such information is available, the impact of the various factors on clinical effect must be clearly analysed and understood.
In addition to being a preliminary examination of the features of spinal anaesthesia with ropivacaine, this study formed part of an ongoing programme of work evaluating the factors that influence intrathecal drug spread. This is the primary reason that two different concentrations of glucose were compared. Apart from a slightly slower rate of onset, ropivacaine in glucose 10 mg ml1 produced blocks that were much the same as glucose 50 mg ml1, replicating a previous finding with tetracaine.6 Slightly lower glucose concentrations than 10 mg ml1 are needed to produce intrathecal spread that is definitively less widespread.7 10 Of wider interest is that this study has confirmed the benefit of adding glucose to solutions for intrathecal injection, a finding that has been made repeatedly since the first description of spinal anaesthesia, particularly with the advent of each new drug for this indication.13
In conclusion, the addition of glucose to clinically relevant concentrations of ropivacaine can provide reliable spinal anaesthesia of intermediate duration. Further comparative work with bupivacaine is required using clinical effect as a measure of outcome, and not duration of action as a measure of potency, to define the role of this drug for spinal anaesthesia.
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Acknowledgements
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We thank Mr C. Magee (Mettler-Toledo Ltd, UK) for performing the density measurements. The study was supported by a grant from AstraZeneca.
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References
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