Factors Affecting the Spread and Duration of Epidural Anesthesia with Ropivacaine

The current study was conducted at the Self Defense Force Hanshin Hospital in Hyogo, Japan, and was approved by the hospital ethics committee. Twenty-seven patients with American Society of Anesthesiologists physical status I, who provided written informed consent, were enrolled in the study. Under epidural anesthesia with ropivacaine, they underwent orthopedic lower limb surgery with a thigh tourniquet. Apart from the usual contraindications for epidural anesthesia, patients with obvious spinal postural abnormalities (kyphosis) or neurologic disturbances were excluded from the study.

Low thoracic and lumbosacral axial MR images for the measurement of dural SA, EVPV, and other measurements were obtained using an MR imaging system (Excel Art; Toshiba, Tokyo, Japan) operating at 1.5 T. Posterior–anterior lumbar spine radiographs were used for the identification of the spinal level, marking the intersection of a line joining the iliac crests. MR images and radiographs were obtained a few days before anesthesia. Axial MR images were obtained at 8-mm increments with a fast-spin echo sequence using a method similar to that previously described.8One of the authors (Y. A.), who was not involved in the assessment of the patients receiving epidural anesthesia with ropivacaine, determined the dural sac and spinal cord areas for each image using the NIH Image 1.63 program for Macintosh (Research Services Branch of the National Institutes of Mental Health, Bethesda, MD). The level of the disk between the 11th and 12th thoracic vertebrae was determined, and the perimeter length of the sac and the area of the sac minus the area of the cord were measured caudal from this site. This perimeter length and area multiplied by 8 mm resulted in the dural SA and CSF volume, respectively. Similarly, posterior epidural fat volume was measured by multiplying the area of epidural fat by 8 mm (fig. 1A). Although the posterior epidural fat is not continuous with that of the lateral compartment in general,9caudal to the L3–L4 disk, the fat is sometimes interconnected. In such cases, the back of the superior articular process was defined as posterior. In addition, the area of the spinal canal was measured to compare with the area of the sac at the lamina of L3. Measurements of CSFV and EVPV at the L3–L4 disk levels were derived from phase-contrast MR imaging by scans oriented approximately perpendicular to the CSF direction of flow, using the method similar to that used previously except for the definition of the region of interest (ROIs).8Briefly, electrocardiography triggering was used for prospective gating of acquisition. Cardiac gating produced a series of phase-contrast images at different cardiac phases. Although fixed circular ROIs of 10 mm²were used in our previous study as reported by Greitz et al. ,16ROIs in the current study were defined by tracing the outlines of the CSF and EVP, which were observed adjacent to the CSF, as reported by Bhadelia et al. ,17because of the small size of the EVP (normal, 0.5–3 mm; fig. 1B). The CSFV profile at this site had both caudad systolic (CSFV^systolic) and cephalad diastolic (CSFV^diastolic) components. From these phase-contrast images, we measured peak CSFV^systolic, peak CSFV^diastolic, and average CSFV at the L3–L4 levels. In contrast to the caudad and cephalad CSF flow, the EVPV profile had a mostly cephalad flow (figs. 1B and C). Accordingly, we calculated only average EVPV.

Thirty minutes before transfer to the operating room, all patients received an intramuscular injection of atropine (0.5 mg). After placement of standard noninvasive monitoring devices, an epidural puncture was performed using a 20-gauge Tuohy needle (Perican®; B. Braun, Tokyo, Japan), at the L3–L4 level, using the loss-of-resistance technique with saline, taking care not to inject more than 1 ml saline. A medial approach with the patient in the lateral decubitus position with the operated side up was used. The L3–L4 level interspace was identified by counting the spines of the vertebrae and palpation of the iliac crest. After ensuring no aspiration of CSF or blood, a test dose of 3 ml ropivacaine, 1.0%, was administered with the bevel of an epidural needle positioned cephalad. Three minutes later, when there were no signs of inadvertent or subarachnoid injection, 7 ml ropivacaine, 1.0%, was administered at a rate of 0.5 ml/s. The patient was then turned in the supine position and remained horizontal until the end of surgery. The time of administration in all patients was approximately 1:00 pm. The spread of the sensory block was assessed by pinprick (23-gauge) on the skin on the midline from top to bottom of the body up to T12 and on the nondependent side thereafter. For practical reasons, motor block was only evaluated on the nonoperated side using the previously described modified Bromage scale (0 = able to move hip, knee, ankle, and toes; 1 = unable to move hip, able to move knee, ankle, and toes; 2 = unable to move hip and knee, able to move ankle and toes; 3 = unable to move hip, knee, and ankle, able to move toes; 4 = unable to move hip, knee, ankle, and toes).8Data sampling was performed every 5 min for the first 45 min after epidural injection and then every 15 min until the end of the observation period, which was defined as regression of the sensory block level to S3. After complete motor block was obtained, patients were encouraged to urinate every 15 min. Time to urinate was recorded. These data were recorded by the nurses of the operating room and orthopedic ward in charge of the patient, who were unaware of the purpose of the study, and who were instructed to accurately report the sensory block level and the degree of the motor block. Acetated Ringer’s solution was administered at 5 ml/kg 1 h before epidural anesthesia and at 1 ml · kg⁻¹· h⁻¹during and after anesthesia. Ephedrine (5 mg) was administered intravenously if mean arterial pressure decreased by more than 30% of the baseline value. A decrease in heart rate to less than 45 beats/min was treated with 0.5 mg intravenous atropine.

The patient sample size was determined by power analysis (α= 0.05, β= 0.10) to reveal a significant correlation coefficient. Power analysis indicated that 25 patients were required to obtain a significant correlation coefficient, assuming that the two variables were continuous data and the correlation coefficient between dural SA and onset time of the peak sensory block was 0.60, which was based on a preliminary study. Continuous data were expressed as mean ± sd, and discrete data were expressed as median and range. Statistical correlation coefficients (ρ) were assessed by Spearman rank correlation among patient demographics, measures of MR imaging such as dural SA, the peak sensory block level to pinprick, the time until the development of the peak sensory level to pinprick and maximum motor block, the degree of motor block, the time required for the peak sensory block level to regress across two segments, the time required for pinprick analgesia to regress to the L3, L4, L5, S1, S2, and S3 dermatomes, the time until complete motor recovery, and the time until spontaneous voiding. A P  value of less than 0.05 was considered statistically significant. In addition, multiple linear regression analysis (forward stepwise selection) was used to examine the relative importance of patient and MR imaging variables to the aforementioned measures of epidural anesthesia. Age, height, weight, body mass index, dural SA, CSF volume, fat volume, average EVPV, peak CSFV^systolic, peak CSFV^diastolic, and average CSFV were considered independent variables. For adding variables, the F ratio criterion was 4.0, which is the squared value obtained from a t  test for the hypothesis that the coefficient of the variable in question equals zero.8 

Twenty-six (25 men, 1 woman) of 27 patients, aged 18–45 y, who received epidural ropivacaine were analyzed. One patient was excluded from the analysis because a spinal tap occurred. Demographics and characteristics of variables measured by MR imaging are presented in table 1. The caudad systolic and cephalad diastolic components of CSF flow in the lumbar spine at the L3–L4 level are shown, whereas the direction of lumbar EVP flow was consistently cephalad. In general, the caudal direction increased when CSF flow became caudal, although the relation between EVP and CSF flow remained the same (figs. 1B and C).

Although one patient experienced tourniquet pain and two patients had mild discomfort at the site of surgery, they were treated with a single dose of fentanyl (50–100 μg), and none of the patients required general anesthesia. No patient required intravenous ephedrine because of a decrease in mean arterial pressure of more than 30% from the baseline or urinary catheterization for urinary retention. The main epidural anesthetic data are summarized in table 2.

Correlations between the values of patient characteristics and the measures of MR imaging, and the measures of epidural anesthesia, assessed by Spearman rank correlation, are presented in table 3. There was an inverse correlation between dural SA and peak sensory block level (ρ=−0.73, P = 0.0003; fig. 2). Dural SA positively correlated with the onset time of caudal block (ρ= 0.62, P = 0.002; fig. 3A) and inversely correlated with the onset time of cephalad block (ρ=−0.63, P = 0.002; fig. 3B). CSF volume also correlated with the peak sensory block level (ρ=−0.77, P = 0.0001), the onset time of the caudal block (ρ= 0.57, P = 0.004), and the onset time of the cephalad block (ρ=−0.72, P = 0.0003; table 3). Posterior fat volume correlated with the degree of motor block (ρ=−0.47, P = 0.018; fig. 4A) and with the onset time of maximum motor block (ρ=−0.53, P = 0.008; fig. 4B). There were significant correlations between posterior epidural fat volume and the regression to L5 (ρ=−0.47, P = 0.019), S1 (ρ=−0.44, P = 0.029), S2 (ρ=−0.54, P = 0.008; table 3), and S3 (ρ=−0.54, P = 0.0007; fig. 5). These correlations between fat volume and measures of epidural anesthesia were significant, even if the score from the patient with the highest fat volume (7.1 ml) was excluded. Average EVPV correlated with the onset of the peak caudal block level (ρ= 0.51, P = 0.011), and the regression to L3 (ρ=−0.42, P = 0.038; table 3) and L4 (ρ=−0.48, P = 0.017; fig. 6). Neither peak CSFV^systolicnor average CSFV correlated with the epidural anesthesia measures (table 3). There were significant inverse correlations between peak CSFV^diastolicand the degree of motor blockade (ρ=−0.49, P = 0.014) and between peak CSFV^diastolicand the onset of maximum motor blockade (ρ=−0.56, P = 0.005; table 3).

Among the variables considered to be independent in the multiple linear regression analysis, there were several significant correlations between patient characteristics and MR imaging measures (table 3). Besides these correlations, there were significant correlations between dural SA and EVPV (ρ= 0.53, P = 0.008), between fat volume and peak CSFV^diastolic(ρ= 0.56, P = 0.005), and between peak CSFV^diastolicand peak CSFV^systolic(ρ=−0.61, P = 0.002). There was also a highly significant correlation between dural SA and CSF volume (ρ= 0.88, P < 0.0001). CSF volume was significantly correlated with EVPV (ρ= 0.50, P = 0.012). The significant multiple linear regression coefficients are shown in table 4. Multiple regression analysis revealed that dural SA significantly contributed to the peak sensory block level (R  ²= 0.61, P < 0.0001; table 4), suggesting that dural SA is the primary determinant of sensory block of epidural anesthesia with ropivacaine. Dural SA was the only significant predictive variable for the onset of the peak caudal block level (R  ²= 0.38, P = 0.0005; table 4). On the other hand, CSF volume was the only significant predictive variable for the onset of the peak cephalad block level (R  ²= 0.46, P < 0.0001; table 4). In addition to being the only significant predictive variable for the regression to L5–S3, fat volume was also the only significant predictive variable for the onset of maximum motor block (R  ²= 0.24, P = 0.006; table 4). Peak CSFV^diastolicwas the only significant predictive variable for the degree of motor block (R  ²= 0.26, P = 0.005; table 4).

The most striking finding of the current study was the significant correlation between dural SA and the peak sensory block level achieved after epidural injection of 100 mg ropivacaine. Furthermore, multiple regression analysis indicated that the R  ²of the peak sensory block level was greater than 0.5, suggesting that dural SA is the primary determinant of the spread of epidural anesthesia with ropivacaine. To the best of our knowledge, this is the first study to demonstrate a critical intrinsic factor that influences the spread of epidural anesthesia. In addition, the results of the current study demonstrate that the posterior epidural fat volume might influence the intensity of the motor block and the duration of the sensory block after epidural anesthesia with ropivacaine. They also suggest that EVPV influences the duration of epidural anesthesia with ropivacaine.

A number of factors influence the spread of local anesthetic solutions in the epidural space.1,2In the current study, these extrinsic factors were standardized. We injected an identical dose of ropivacaine epidurally with the needle aperture directed cephalad at the same rate and site of injection. A single injection technique without catheter placement was selected to minimize technical variations, which are more likely to occur with catheter techniques. Although many studies report that age, height, pregnancy, and arteriosclerosis are intrinsic factors,1,2,4we limited our study to healthy patients within a narrow age range. In addition, our patients were injected epidurally at the same time (1:00 pm) to avoid chronobiologic variations in epidural anesthesia. Debon et al.  11reported a circadian variation of analgesia duration after epidural ropivacaine injection in laboring women.

The epidural space contents are discontinuous circumferentially and repeat metamerically. The anterior epidural space is isolated from the rest of the epidural space and is nearly filled with veins except caudal to the L4–L5 disk, where a fat-filled anterior epidural space develops.9The lateral epidural compartments contain nerves and fat, which is lobulated by septae. The posterior fat-filled epidural compartment is enclosed and not continuous with the lateral compartment. This fat is homogeneous and without any apparent fibrous septation.9In the current study, we measured only the posterior epidural fat volume because the posterior epidural space contains mostly fat and this triangular posterior fat is easily discriminated in T2-weighted MR images (fig. 1A).18Further, it is assumed that local anesthetic solutions are likely injected into or near the posterior epidural fat, not into the lateral or anterior space, when a single injection with a medial approach is used.

The spread of local anesthetic solutions in the epidural space and their principal sites of action are complicated and subject to debate. It was demonstrated in the study by Hogan,5,6using epidurography with computerized tomographic imaging and cryomicrotome imaging, that the passage of solution injected into the epidural space is almost completely circumferential, encircling anterior to the dura, as well as posterior. However, patterns of distribution exhibit great variability, including outlining of posterior fat, at least on one side, or preferential accumulation in the anterior or posterolateral areas, as well as variable amounts passing through the foramina.5,6Suggested sites of action of local anesthetic solutions after epidural injection are the spinal nerves intradurally, the mixed nerves in the paravertebral spaces, and the spinal cord.1,2By diffusing thorough the dural sleeves, local anesthetics block the spinal nerves intradurally. In the current study, dural SA was inversely correlated with the peak sensory block level and the onset of peak caudad spread, whereas it was positively correlated with the onset of peak cephalad spread (figs. 1, 2A, and 2B). These results indicate that dural SA variability among patients accounts for the interindividual variability in the spread of epidural anesthesia, supporting the hypothesis of the cylindrical reservoir as proposed by Bromage.1,2Although the exact mechanism for this relation remains to be elucidated, the results of the current study suggest that the dural SA is the primary determinant of epidural longitudinal distribution of local anesthetics. Also, this mechanism might explain the more extensive epidural anesthesia in patients with increased abdominal pressure, which occurs with obesity or pregnancy, because of compression of the dural sac, resulting in a decrease in the dural SA.1,2,19However, it is also possible that the opposite is true. The greater block extent that results from a thoracic epidural local anesthetic dose as compared with lumbar administration might be due, at least in part, to a reduced posterior epidural space.2In analogy, therefore, it is possible that a greater dural SA results in greater block extent because a large thecal sac should result in less epidural space if the size of the spinal canal is the same. However, it is unlikely that greater dural SA results in less epidural space, because the area of the sac significantly correlated with that of the spinal canal at the lamina of L3 (r = 0.76 by linear regression analysis, P < 0.001), i.e. , a larger thecal sac was associated with a larger spinal canal.

Diffusion of local anesthetics through the dura also results in the appearance of local anesthetics in the CSF, with peak concentrations occurring 5–45 min after epidural injection in human.1,2,20As mentioned earlier, the lumbosacral CSF volume is the main/primary determinant of sensory block spread of spinal anesthesia.7,8Analogous to spinal anesthesia, therefore, one might argue that CSF volume is the main determinant of sensory block spread of epidural anesthesia because local anesthetics in the CSF through the dura are diluted by CSF. CSF volume is significantly correlated with the peak sensory block level and the onset of peak caudad and cephalad spread, similar to dural SA. In addition, multiple regression analysis revealed that CSF volume was the only significant predictive variable for the onset of cephalad spread. Considering the calculation methods, however, these correlations were inevitable: CSF volume was calculated by multiplying the dural sac area by length, whereas SA was calculated by multiplying the perimeter of dural sac by length. Although the exact contribution of the subarachnoid site of action of local anesthetics to establish initial neural blockade after an epidural loading dose is unclear, it is generally assumed that this process has a minor role.1,2One of the reasons for its minor role is the dissociation of epidural anesthesia and concentration of local anesthetics in CSF.1 

Rosenberg et al.  10investigated the absorption of amide local anesthetics in vitro  and speculated that interindividual variability in the amount of extraneural fatty tissue might be a reason for the varying spread and intensity of regional anesthesia. In the current study, fat volume correlated with the degree of motor block and onset time of maximum motor block, supporting the suggestion of Rosenberg et al.  10On the other hand, we did not demonstrate a significant correlation between the posterior fat volume and the peak sensory block level and between the posterior fat volume and the onset time of peak caudal block level. One possible explanation for the lack of a statistical correlation might be related to the molecular size and the lipid solubility of ropivacaine, both of which are intermediate to bupivacaine and lidocaine.10The smaller molecular size with less lipid solubility of local anesthetics favors penetration into the nerve sodium channels.10Consequently, the absorption of ropivacaine into the epidural fat might be slower than epidural longitudinal distribution. Another explanation might be that we did not investigate the intensity of sensory block because we measured sensory block only by pinprick, whereas the degree of the motor block was evaluated by the modified Bromage scale. Investigating the intensity of sensory block combining it with a different measurement of sensory block, such as transcutaneous electric stimulation, might account for the differential effect in sensory and motor block in the current study. In addition, the number of patients included in the current study might be insufficient to identify a correlation between fat volume and the peak sensory block level (ρ=−0.38, P = 0.058).

Emanuelsson et al.  3reported that the duration of the sensory block after epidural injection of ropivacaine correlated with the slow systemic absorption half-life and that the differences in the rate of absorption of ropivacaine from the epidural space might be one factor responsible for the variability in duration. In the current study, there was a significant correlation between posterior epidural fat volume and regression to L5–S3 (table 3and fig. 3), supporting our hypothesis. This correlation is consistent with the findings obtained by Emanuelsson et al.  3in that slow absorption from the epidural space reflects the duration of epidural block using ropivacaine. Although it is unclear whether the posterior epidural fat volume correlates with the slow systemic absorption half-life, which is measured by pharmacokinetic calculation, the longer disposition with the greater amount of epidural fat might influence the larger absorption half-life. Further, the correlation between the posterior epidural fat volume and the duration of epidural anesthesia with ropivacaine might also be consistent with the fact that the bioavailability of opioids in the epidural space is determined by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.21In addition, the correlation is consistent with a case reported by Lang et al. ,22in which a patient experienced repeated failed epidural analgesia (quick fade of analgesia) associated with an unusually large amount of posterior epidural fat.

To our knowledge, there is no published study in which the lumbar EVP flow was quantitatively measured, although there are a few studies that investigated cervical EVP flow, which had conflicting results.14,15Levy and Di Chiro14reported that cervical EVP flow is closely coupled to CSF flow. In systole, CSF flow became caudal and EVP flow sometimes became cephalad.14In contrast, Enzmann and Pelc15reported that the flow characteristics of cervical EVP did not have a consistent phase relation with CSF flow. In the current study, the direction of lumbar EVP flow was consistently cephalad, whereas the CSF flow in the lumbar spine at the L3–L4 level was cephalad and caudal. In general, the cephalad direction increased when CSF flow became caudal, consistent with the findings obtained by Levy and Di Chiro.14In the current study, the average EVPV and EVP flow rates, which were calculated for each image by multiplying the average signal intensity of an ROI with its area,17were 0.8 cm/s and 3.8 ml/min, respectively. The validity of these values is unclear because there is no information regarding EVPV at the L3–L4 level. In this regard, EBF measured by a local ¹³³Xe clearance technique was 5.0–6.0 ml · min⁻¹· 100 g tissue⁻¹.13,23 

Mogensen et al.  13reported that changes in EBF during continuous epidural infusion of bupivacaine might be an important factor contributing to differences in the rates of regression of sensory block. Two of seven patients whose EBF remained constant after the initial increase maintained the initial sensory block level, whereas the sensory block level in the other five patients whose EBF significantly increased after epidural bupivacaine decreased five to seven segments.13In the current study, there were significant correlations between the regression to L3 and to L4 and EVPV, i.e. , increased EVPV was associated with a shorter time for the block to regress to L3 and L4 (fig. 6). In addition, EVPV correlated with the onset of the peak caudal block level. These findings suggest that EVPV influences the spread and duration of epidural anesthesia with ropivacaine. However, the EVPV findings in the current study must be interpreted cautiously. First, EVPV after epidural ropivacaine is unclear. EBF decreases after epidural ropivacaine because ropivacaine has a vasoconstrictor effect.24Accordingly, EVPV might be expected to decrease with great variability in the extent of decrease after epidural ropivacaine. Further, there are several disadvantages to the cardiac gating phase-contrast technique, which was discussed in our previous report.8Further study is required before making conclusions regarding the influence of EVPV, EBF, or both on the extent and duration of epidural anesthesia with ropivacaine.

Other potential study limitations include the following: Although the mean values of peak CSFV^systolic, peak CSFV^diastolic, and average CSFV in this study were in accord with those obtained in our previous study,8peak CSFV^diastoliccorrelated with weight and body mass index in the current study, contrary to the previous study. The reason for this discrepancy is unclear, because it is unlikely that the difference in the definition of ROI between the previous and current studies explains this discrepancy. Similarly, it is also difficult to explain the significant correlations between peak CSFV^diastolicand measures of motor block. The correlations between peak CSFV^diastolicand measures of motor block might be statistically significant because of the significant correlation between fat volume and peak CSFV^diastolic. Therefore, as mentioned above, there are several methodologic inaccuracies in the measurement of CSF flow using phase-contrast MR imaging. In addition, we did not measure the anterior or lateral fat volume because they were not as easy to measure as compared with the posterior fat volume. However, solution injected into the epidural space usually spreads circumferentially.5,6Improved resolution with new MR imaging technology will reveal the role of epidural fat in the spread, intensity, and duration of epidural anesthesia. Further, we must comment on the multiple regression analysis. Although all selected predictive values must ideally be uncorrelated,25there were significant correlations among the selected variables in the current study. In our previous study, we used forward and backward stepwise selection because we believed that it was important to select parameters that make R  ²close to 1.0, being careful to detect multicollinearity.8However, almost all the variables would have been selected if backward stepwise selection was used in the current study. This means that there was multicollinearity.25As a consequence, we used forward stepwise selection to identify the most useful variables for predicting the extent and duration of epidural anesthesia with ropivacaine. In addition, this study was performed in a limited situation. Ropivacaine was injected epidurally with a single injection technique in small Japanese patients aged younger than 46 yr. It is therefore possible that there would be different results in different populations using the catheter technique. Finally, we must consider the possible influence of the injection site. This issue has been discussed previously.26,27 

Our findings provide valuable insight into the mechanism and a better explanation of the unpredictability of spread and duration of epidural anesthesia with ropivacaine. However, the findings will not be helpful for guiding clinical practice. Although the dural SA is reliably predictive of the peak sensory block level, our results cannot be expected to improve the ability to predict the spread of epidural anesthesia with ropivacaine in clinical practice, because MR imaging is not always obtained before anesthesia.

In summary, the current study indicates that the dural SA is the primary determinant for the peak sensory block of epidural anesthesia with ropivacaine and the main factor that influences the onset time of the peak block level. The current study also indicates that posterior epidural fat volume is associated with the degree of the motor block and with the duration of the sensory block. The results of the current study also suggest that EVPV at the L3–L4 level influences the onset time of the peak caudal block level and the regression to L3 and L4.

The authors thank the surgeons and nurses in the operating room and orthopedic wards and the workers in the Department of Radiology of Self Defense Force Hanshin Hospital (Kawanishi, Hyogo, Japan) for their cooperation.