Khaw, Kim S. FRCA; Ngan Kee, Warwick D. MD, FANZCA; Wong, Mabel BHS; Ng, Floria BSc; Lee, Anna PhD
Use of ropivacaine for spinal anesthesia has been described for obstetric (1,2) and nonobstetric patients (3–7). Many investigators have reported ropivacaine to be less potent than bupivacaine (2,3,6,7), and in a previous dose-response study with plain ropivacaine for cesarean delivery we estimated the 95% effective dose (ED95) to be 26.8 mg (95% confidence interval [CI], 23.6–34.1 mg) (2). However, few data are available on the effect of injectate baricity on anesthesia with intrathecal ropivacaine. Previous studies with other local anesthetics have shown that the addition of glucose improved the cephalic spread and reliability of anesthesia (8,9) and also shortened the duration of sensory and motor block (10–12). Thus, the aim of this prospective, randomized, double-blinded study was to test the hypothesis that increasing the baricity of ropivacaine by the addition of glucose would change the clinical characteristics of subarachnoid block after intrathecal injection.
This study received approval from the Clinical Research Ethics Committee of the Chinese University of Hong Kong and all patients gave informed written consent. We enrolled 40 ASA physical status I or II patients scheduled for elective cesarean delivery at term using spinal anesthesia. Patients with multiple pregnancies, suspected fetal abnormality, or complicated pregnancies were excluded. All patients received premedication of 150 mg ranitidine orally the night before and on the morning of surgery. Sodium citrate 30 mL orally was given upon arrival to the operating room. Patients had standard monitoring, including continuous electrocardiogram, pulse oximetry, and noninvasive measurement of arterial blood pressure, cycled at 1-min intervals. IV access was secured in the nondominant forearm under local anesthesia, and IV preload of 20 mL/kg of lactated Ringer’s solution was given over approximately 15 min.
Before the commencement of anesthesia, patients were instructed on the methods of sensory and motor assessments, and baseline measurements were made. Sensory changes were recorded bilaterally along the midclavicular line by assessing changes in pinprick sensation by use of a safety pin protruding 2 mm though a guard (13); changes in temperature sensation were assessed with frozen plastic ampules of water. Motor block in the lower limbs was graded according to the modified Bromage scale (0 = able to lift extended leg at the hip, 1 = able to flex the knee but not lift extended leg, 2 = able to move the foot only, 3 = unable to move even the foot).
Using separate spaces, a combined spinal and epidural technique was used with the patient in the right lateral position. After skin disinfection and infiltration with ropivacaine 1%, the epidural space was located at the L2-3 lumbar vertebral interspace by using a 16-gauge Tuohy needle, and an epidural catheter was inserted 2–3 cm and secured aseptically. The catheter was gently aspirated and checked for the presence of blood or cerebrospinal fluid, but no test dose was given. Midline lumbar puncture was then performed at the L3-4 interspace by using a 25-gauge Whitacre needle oriented with the orifice facing cephalad. Patients were randomly allocated, by drawing coded, shuffled, sealed opaque envelopes, to receive either ropivacaine 25 mg (Plain group, n = 20) or ropivacaine 25 mg with 8.3% glucose (Hyperbaric group, n = 20). The dose of ropivacaine was chosen on the basis of data from our previous dose-response study of ropivacaine in obstetric patients (2). The anesthetic solutions were prepared by mixing 2.5 mL of 1% ropivacaine with 0.5 mL of either normal saline or glucose 50%. This gave a total volume of 3.0 mL and resulted in a final glucose concentration of 8.3% in the Hyperbaric group. Preliminary analysis in our laboratory showed that the specific gravity at 37°C of the plain and hyperbaric solutions was 1.0092 and 1.0345, respectively (14). To facilitate blinding, all doses were prepared by an investigator not involved with subsequent patient assessments.
After confirming free flow of cerebrospinal fluid, spinal solutions were injected over approximately 60 s. Immediately after spinal injection, patients were turned supine with left lateral tilt. Sensory and motor assessments were performed at 1 and 2.5 min and subsequently at 2.5-min intervals for the first 30 min. Thereafter, the blocks were assessed at 15-min intervals until complete recovery of motor function and sensation at the S1 dermatome.
After 30 min, surgery was allowed to commence if the upper dermatomal level of loss of discrimination to pinprick was at or above T7 (15–17). Otherwise, the epidural catheter was topped up by using alkalinized lidocaine 2% with epinephrine 1:200,000 and fentanyl 75–100 μg, given in incremental doses until adequate dermatomal anesthesia was obtained. Patients who complained of intraoperative pain with moderate to severe discomfort were treated with an IV bolus dose of ketamine 10 mg, which was repeated if pain was unrelieved after 5 min. If pain remained intolerable, with a score of 7 or more on an 11-point numerical scale (0 = no pain and 10 = most severe pain) after the second dose of ketamine, the epidural was topped up. For patients requiring epidural top-up, the spinal anesthesia was classified as a “failure,” but data for the onset of spinal anesthesia before epidural top-up were included for analysis.
Hypotension, defined by a decrease in systolic arterial blood pressure to <100 mm Hg or <80% from baseline (18), was treated with IV boluses of ephedrine 9 mg as required. Nausea and vomiting were treated with 10 mg of metoclopramide IV once hypotension had been excluded.
Times of skin incision, uterine incision, delivery, and completion of surgery were recorded. After delivery, Apgar scores were assessed at 1 and 5 min by the attending pediatrician, and arterial and venous blood samples were taken from a double-clamped segment of umbilical cord for immediate blood gas analysis with a 278 Blood Gas System (Ciba-Corning, Medfield, MA) blood gas analyzer.
Postoperative analgesia was provided by patient-controlled analgesia (PCA) with a Graseby 9300 (Graseby Medical Ltd., Watford, Herts, UK). The PCA device was set to deliver a morphine bolus of 1.5 mg with a lockout time of 5 min and maximum 4-h limit of 30 mg. The time of first PCA demand was subsequently recorded from the electronic memory of the PCA device. All patients had routine follow-up by an anesthesiologist on the day after surgery and an assessment by a research nurse 24 h postoperatively, with instructions to report the occurrence of complications such as residual neurologic symptoms or back pain.
For assessment of the onset of anesthesia, the time for sensory block to develop to T7, T4, and maximum block height and the time to achieve each increment of Bromage score were compared. To assess the duration of the sensory block, the two-segment regression time from the maximum block height and time for regression to T7 and L1 were compared. Duration of motor block was assessed by comparison of time to each decrement of Bromage score.
Using data from our previous study (2), we calculated that a sample size of 20 patients in each group would have >90% power to detect a 25% difference in the duration of sensory anesthesia at L1 or duration of complete motor blockade, with a type I error probability of 0.05. Data were initially tested for equality of variances by using Levene’s test, and subsequently, the normal probability plot was used to test the normality assumption. Results are presented as mean and sd or median and range, as appropriate. Measurements from the right and left sides were averaged, and statistical comparisons were performed with the χ2 test, Student’s t-test, Fisher’s exact test, and the Mann-Whitney U-test, as appropriate. Analyses were performed with SPSS version 10.0 (SPSS Inc., Chicago, IL) and PASS version 6.0 (NCSS, Kaysville, UT). P < 0.05 was considered significant.
All patients completed the study. Demographic data were similar between the two groups for age, weight, and height (Table 1). Apgar scores and umbilical blood gas variables were similar, and all babies had 1- and 5-min Apgar scores ≥9 and umbilical arterial pH ≥7.25. Characteristics of anesthesia are shown in Figures 1–3 and are summarized in Tables 1 and 2. In the Hyperbaric group, all patients completed surgery successfully under spinal anesthesia, whereas in the Plain group, five (25%) patients (95% CI for differences, 3.8%–47%;P = 0.047) did not achieve adequate block height at 30 min and required conversion to epidural anesthesia. These five patients had a median (range) block height of T9 (T11 to T8) for pinprick and T7 (T11 to T4) for ice. Two patients in the Hyperbaric group experienced intraoperative pain and required IV ketamine, compared with four patients in the Plain group.
The onset of sensory anesthesia was faster in the Hyperbaric group compared with the Plain group (Table 2). The maximum height of block was greater in the Hyperbaric group compared with the Plain group (Fig. 1, Table 2) and showed less variability (coefficient of variation, 17.7% vs 21.9%). All patients developed full motor block (Bromage score 3), but the rate of onset for each grade of motor block was faster in the Hyperbaric group compared with the Plain group (Table 2).
Early recovery of sensory block, as evidenced by the time for regression of two dermatomal levels and regression of analgesia to T4 and T7, was similar between groups. However, regression to L1 was faster in the Hyperbaric group compared with the Plain group. The time taken for each grade of motor block to recover was faster in the Hyperbaric group (Table 2). The time from the spinal injection to the time for the first analgesic request was similar between groups.
The incidence of hypotension was more frequent in the Hyperbaric group compared with the Plain group. All patients in the Hyperbaric group had one or more episodes of hypotension, compared with 14 (70%) patients in the Plain group (P = 0.02). Patients in the Hyperbaric group required a mean (sd) total ephedrine dose of 23.4 (10.3) mg, compared with 12.2 (11.3) mg in the Plain group (P = 0.003). Ten (50%) patients in the Hyperbaric group had nausea or vomiting, compared with three (15%) patients in the Plain group (P = 0.02). One patient in the Plain group complained of postdural puncture headache for 3 days after surgery which resolved with conservative management. No patient in either group had residual neurologic symptoms at follow-up.
In this study we have shown that the addition of glucose to intrathecal ropivacaine produced spinal anesthesia with a more frequent success rate and a less frequent incidence of intraoperative pain compared with plain solution. In the Hyperbaric group, the maximum block height was greater and more consistent and had a faster onset and recovery compared with the Plain group. Episodes of hypotension and nausea and vomiting, however, were also more frequent as a consequence of the hyperbaric block characteristics. Despite the more rapid recovery from anesthesia, surprisingly, the times to first postoperative analgesic request were similar.
A number of studies have previously reported the use of plain (3–5,7) and hyperbaric (1,6,19) ropivacaine for spinal anesthesia. In a dose-response study of plain ropivacaine for cesarean delivery, we found that a dose of 25 mg was associated with some failures because of insufficient block height, and by extrapolation we determined the ED95 to be 26.8 mg (95% CI, 23.6–34.1 mg) (2). Other clinical studies using plain ropivacaine have also described wide variability of block height and a frequent incidence of insufficient cephalic spread requiring supplementary anesthesia or conversion to general anesthesia (4,7). However, evidence from studies of other local anesthetics suggests that the addition of glucose would improve reliability and might enable a smaller dose to be used. The addition of glucose to intrathecal ropivacaine was investigated by Whiteside et al. (19), who reported that solutions of ropivacaine 15 mg in glucose 1% and 5% had greater cephalic spread and less block variability compared with plain solutions. However, the plain solutions they compared were historical controls published from other centers. We are not aware of any other studies that have directly compared the clinical effects of plain and hyperbaric ropivacaine. However, similar findings have been reported for other local anesthetics, such as bupivacaine (8–10) and tetracaine (11).
We found that the rates of onset and recovery of sensory and motor block were faster in the Hyperbaric group than in the Plain group. Previous studies in nonpregnant subjects have also reported that increasing the baricity of ropivacaine (19) and other local anesthetics (11,20–22) resulted in faster onset and shorter duration of anesthesia compared with plain solutions. However, Russell and Holmqvist (23) found no differences in the onset and recovery of spinal anesthesia using either plain or hyperbaric bupivacaine in women having spinal anesthesia for cesarean delivery. In the context of spinal anesthesia for elective cesarean delivery, a small increase in the speed of onset of anesthesia may not necessarily be considered clinically important, although it may be more relevant in emergency cases, in which there may be some urgency to deliver the fetus. Conversely, the faster onset and the higher block height probably resulted in the increased incidences of hypotension and nausea and vomiting in the Hyperbaric group compared with the Plain group. However, this did not cause any adverse fetal outcomes, because all hypotensive episodes were promptly corrected and of short duration. In our study, IV prehydration was not effective, and better control of blood pressure may have been achieved if we had used a different vasopressor regimen (24,25).
A more rapid recovery from anesthesia can have advantages and disadvantages. For ambulatory anesthesia, this may be a highly desirable characteristic. However, for cesarean delivery, inadequate duration of anesthesia might increase the risk of needing to convert to general anesthesia. In our study, the duration of anesthesia with both solutions was adequate for surgery to be completed in all patients.
The characteristics of the block during spinal anesthesia are influenced by the interaction among baricity, gravity, and patient position. It was observed previously that when intrathecal injection was performed with patients in the lateral position, hyperbaric solutions tended to give a higher cephalic spread, whereas plain solutions frequently resulted in insufficient cephalic spread of anesthesia (8,9,21). This is probably the result of a gravity-dependent influence on a hyperbaric solution.
In women, the width of the hips is usually larger than the shoulders, thus resulting in a head-down tilt when lying in the lateral position (26). This difference may be exaggerated in pregnancy, and when a hyperbaric solution is injected in the lateral position, the tendency would be for it to spread by gravity in the cephalic direction. When the patient is turned supine, gravity would also spread the solution cephalad down the lumbar curvature. In contrast, a plain solution injected in the lateral position would not have such gravity-assisted spread and thus would concentrate in the lower lumbar segments. This would explain the lesser cephalic spread and also the longer time for recovery of sensory and motor block of the lower segments of the spinal cord in the Plain group.
The plain solution in our study had a specific gravity of 1.0092 at 37°C. Although compared with the mean (sd) specific gravity of cerebrospinal fluid in the pregnant state of 1.0070 (0.0004) at 37°C the plain solution was technically slightly hyperbaric (27), the results of our study demonstrated that this solution had the characteristics of an isobaric solution.
Because anesthesia was successful for all cases in the Hyperbaric group, a dose-finding study to determine the ED95 of hyperbaric ropivacaine would be of interest for comparison to plain ropivacaine. Adding an opioid may also confer a local anesthetic-sparing effect and reduce the incidence of intraoperative pain (16).
The effects of spinal anesthesia with ropivacaine, a relatively new local anesthetic, are still being studied, and the clinical benefits may not be immediately clear. Available data so far suggest that intrathecal ropivacaine is not associated with an increased risk of neurologic symptoms, and thus the use of ropivacaine as an alternative to local anesthetics currently available for spinal anesthesia is appropriate. The small propensity for motor blockade with ropivacaine may be of benefit given the respiratory disturbance that has been described with spinal anesthesia (28).
In conclusion, we have compared the effects of spinal anesthesia for elective cesarean delivery with plain and hyperbaric ropivacaine injected in the lateral position. Under the conditions of this study, hyperbaric ropivacaine produced spinal anesthesia with faster onset and recovery, more extensive spread, and a greater success rate, compared with plain ropivacaine. However, this was also associated with an increased incidence of hypotension.
We thank the staff of the Labor Ward, Prince of Wales Hospital, Shatin, Hong Kong SAR, China, for their cooperation, and Bryan Ng, Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong, for technical help.
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