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Anesth Analg 2004;98:1779-1782 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000117147.56528.33
David J. Birnbach Section Editor |
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Abstract |
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This study established the median effective dose (ED50) for motor block of intrathecal 1% and 0.1% ropivacaine and determined the effects of the concentration of the solution injected on the motor block obtained. We enrolled into this prospective, randomized, double-blind, sequential allocation study 54 parturients undergoing elective Cesarean delivery under combined spinal-epidural technique. Parturients were randomized to receive intrathecal ropivacaine either 1% or 0.1%. The initial dose was chosen to be 4 mg, with subsequent doses being determined by the response of the previous patient (testing interval, 1 mg). The occurrence of any motor block in either lower limb within 5 min from the intrathecal injection of the study solution was considered effective. The motor block at 5 min was 6.1 mg for 1% ropivacaine (95% confidence interval [CI], 5.1–7.1) and was 9.1 mg (95% CI, 7.8–10.3) for 0.1% ropivacaine (P = 0.0013; 95% CI difference, 1.3–4.7). The relative efficacy ratio of the 2 concentrations was 1.5 (95% CI difference, 1.2–1.9) in favor of the larger concentration. The ED50 of spinal ropivacaine to produce motor block in pregnant patients was significantly influenced by the concentration of the local anesthetic, with dose requirements being increased by 50% for the smaller concentration.
IMPLICATIONS: The minimum local anesthetic dose for motor block with 0.1% ropivacaine is 50% larger than the 1% concentration with a relative efficacy ratio of 1.5. Our findings suggest that more diluted local anesthetic solutions determine less motor block, and this may be considered in ambulant laboring parturients.
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The relationship between dose, volume, and concentration of local anesthetic solutions on the profile of spinal block is controversial (1–4). Previous studies conducted with full anesthetic doses reported that varying the volume of hypobaric or isobaric solutions, with or without keeping the dose constant, has little effect on the spinal block (5–9).
Whether variation in volume and concentration of local anesthetic may affect the characteristics of the spinal block with smaller doses remains to be substantiated.
The minimum local analgesic concentration has been established as a research tool to be used to determine the median effective concentrations (EC50) of local anesthetics and the respective potency ratios (10). This method has also been used to determine the ED50 for motor block with intrathecal bupivacaine (11) as well as for epidural bupivacaine, ropivacaine, and levobupivacaine (12,13).
The aim of this study was to estimate the ED50 for motor block with 2 concentrations (1% and 0.1%) of intrathecal ropivacaine and then determine the effects of concentration on dose requirements for motor block.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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After institutional ethical approval and written informed consent, 54 parturients, ASA physical status I or II, at more than 37 wk gestation, undergoing elective Cesarean delivery with a combined spinal-epidural technique (CSE) were enrolled into this prospective randomized, double-blind, sequential allocation study.
All parturients received 700 mL IV of Ringer’s lactate solution before the institution of the block. The epidural space was located using a Tuohy needle and loss of resistance to saline technique at the L3-4 interspace, with the woman in the left lateral position. After the sighting of cerebrospinal fluid (CSF) in the hub of a 27-gauge pencil-point needle passed through the Tuohy needle, the study drug was injected into the intrathecal space. The spinal needle was then withdrawn, and an epidural catheter was threaded through the epidural needle. Parturients were then immediately turned supine with a wedge under the right hip.
Parturients were assigned, according to a computer-generated list, to 1 of 2 equal groups of 27 parturients each to receive either 1% or 0.1% intrathecal ropivacaine.
The dose of ropivacaine received by a particular parturient was determined by the response of the previous parturient in that group to the larger or smaller dose, according to the technique of up-down sequential allocation. The exception to this was the first parturient in each group, for whom the starting dose was chosen to be 4 mg for both concentrations of ropivacaine. The study solutions were freshly prepared using the commercial preparation of 1% ropivacaine (Naropin, AstraZeneca, Wilmington, DE) and adding saline 0.9% as the diluent to achieve the 0.1% concentration.
We determined the specific gravity of the solutions by using the pyknometric method (DR45 Combined Meter, Mettler Toledo Inc, Toledo, OH) with a resolution of five places. A baseline measurement of muscle strength was made in all patients before the institution of the block. Efficacy was considered to be the occurrence of any motor block, in either lower limb, within 5 min from the subarachnoid injection of the study solution. Time 0 was considered to be the end of the injection of the spinal local anesthetic.
Motor block was assessed in both legs every minute for 5 min using a modified Bromage scale (14) to evaluate motor function of knees and feet and an additional scale to evaluate hip flexion (Hip Motor Function Scale [HMFS]) (15) (Table 1).
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Two outcomes were considered (16). Effective required a Bromage or a HMFS score >0 in either leg within 5 min from the subarachnoid injection and directed a decrement of 1 mg of the study solution for the next parturient assigned to that group. Ineffective required a Bromage or a HMFS score = 0 within 5 min and directed an increment of 1 mg of the study solution for the next parturient assigned to that group.
An anesthesiologist who was unaware of the given study solution performed all the assessments. We also evaluated the occurrence of any motor block at 10 min. In addition, we assessed the loss to pinprick sensation at the S2 level in all the parturients to ascertain that the local anesthetic was administered correctly into the subarachnoid space.
After the completion of the study, all parturients received incremental epidural boluses of 2% pH-adjusted lidocaine with epinephrine 1:200.000 to achieve a satisfactory anesthetic level for Cesarean delivery.
Demographic and obstetric data are presented as mean (SD) and analyzed using Student’s t-test. The ED50 with 95% confidence intervals (CI) were estimated from the up-down sequences using the method of Dixon and Massey (16). The sequences were also subjected to Wilcoxon and Litchfield probit regression analysis as a backup or sensitivity test. The study had a 89% power to detect at least a 30% reduction in dose requirement for ropivacaine.
Analyses were performed using the following software: Excel 2000 (Microsoft Corp, Redmond, VA), Number Crunching Statistical System 2000 (NCSS Inc, Kaysville, UT), and GraphPad Instat 3.01 (GraphPad Software Inc, San Diego, CA). Statistical significance was defined for an overall 
error at the 0.05 level. All P values were two sided.
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Results |
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Demographic and obstetric data were similar in the groups (Table 2). There were no differences in specific gravity between the 2 study solutions being 1.00655 and 1.00665 for 1% and 0.1% ropivacaine, respectively. All the parturients had a sensory block at the S2 level, indicating the correct injection of the study drug into the subarachnoid space.
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The sequences of effective and ineffective outcomes are shown in the Figure 1. Using the method of Dixon and Massey (16), the ED50 for motor block with 1% ropivacaine was 6.1 mg (95% CI, 5.1–7.1) and with 0.1% ropivacaine was 9.1 mg (95% CI, 7.8–10.3). Probit regression results used as a sensitivity or backup test are reported in Table 3.
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The ED50 for motor block was significantly more with the smaller 0.1% concentration (P = 0.0013; 95% CI difference, 1.30–4.71 mg), with a relative efficacy ratio of 1.5 (95% CI, 1.2–1.9) in favor of the larger 1% concentration. No parturient with an ineffective outcome (absence of any motor block) at 5 min developed any degree of motor block at the 10-min evaluation.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This is the first study to specifically assess the motor block potencies of two different concentrations of intrathecal local anesthetic. We have shown that the minimum local anesthetic dose for motor block with 0.1% ropivacaine is 50% larger than the 1% concentration.
Earlier studies reported that the anesthetic block is influenced by the dose and not by the concentration administered in pregnant patients. Van Zundert et al. (17) reported that the anesthetic effect as well as the degree of motor block produced by 70 mg of spinal lidocaine was similar with solutions ranging from 0.5% to 10%. Nielsen et al. (18) were not able to detect any difference in the onset and duration of sensory or motor block after 15 mg of isobaric 0.25% or 0.5% bupivacaine. Vucevic and Russell (19) have shown that 15 mg of spinal 0.125% isobaric bupivacaine produced similar final levels of block as compared to the same dose of 0.5% solution for Cesarean delivery. However, the above-mentioned studies involved large, full anesthetic doses that are more than the ED95 at the top of the dose-response curve where differences will be missed or apparently similar effects misinterpreted.
In our study, we used the up-down sequential allocation design, which is a very powerful tool for estimating the ED50 rather than traditional dose-response studies design because it focuses all the sampling doses in the immediate vicinity of the ED50. It allows the estimation of the ED50, which produces a defined outcome, whereas requiring fewer patients to be enrolled. By using such a sensitive method and using small doses of local anesthetic, we were able to demonstrate that the concentration of the spinal solution plays a significant role in determining the anesthetic effect.
To be more sensitive, we used two scales to evaluate the occurrence of any motor block. In addition to the Bromage scale, we graduated the ability to raise the extended leg on a three-point ordinal scale because this has been reported to be a more sensitive means of testing for motor block rather than the sole use of the Bromage scale (15,20).
Our results are consistent with those of Peng and Chan and Chan et al. (21,22) who found that when a relatively small hyperbaric spinal anesthetic dose is administered, a larger concentration is required to achieve the same degree of motor and sensory block. Another study showed that for hyperbaric bupivacaine, the less concentrated, larger volume injected yielded a less intense motor block compared with a small volume of more concentrated solutions (4). Our findings are unlikely to be a result of the drug itself, because the density of the two solutions were comparable.
Anatomic studies demonstrated that the dorsal nerve roots have relatively larger size as compared with ventral roots with packaging into easily separable strands (23). Although a larger dorsal nerve root would seem more impenetrable to local anesthetics, the separation of the dorsal root into component bundles creates a much larger surface area for local anesthetic penetration than the single smaller ventral nerve root. This anatomic finding may help to explain the relative ease of sensory versus motor block. Moreover, microscopic and endoscopic examination of the subarachnoid space revealed the presence of membranes surrounding nerve roots and ligaments within the arachnoid that potentially compartmentalize spinal CSF (24). These partitions could impede communication of CSF between dorsal and ventral nerve roots, thus again explaining the relative difficulty of achieving motor block. We speculate that as the concentration of the injected solution decreases, the concentration of ropivacaine penetrating the ventral roots is smaller, thus reducing the likelihood of motor block.
We determined that the minimum local anesthetic dose for the motor block of 0.1% ropivacaine is 50% larger than 1% ropivacaine, with a relative efficacy ratio of 1.5. Our results encourage further studies to investigate the appropriate concentration of local anesthetic for ambulant CSE analgesia in labor and suggest that more diluted local anesthetic solutions cause less motor block.
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References |
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