Chung, Chan-Jong MD; Choi, So-Ron MD; Yeo, Kwang-Hwan MD; Park, Han-Suk MD; Lee, Soo-Il MD; Chin, Young-Jhoon MD
Ropivacaine is a long-acting amide local anesthetic with a structure closely related to bupivacaine and mepivacaine (1). It produces effective epidural anesthesia for cesarean delivery with a profile similar to bupivacaine (2–4). Epidural ropivacaine, however, provides a similar duration of sensory block, but shorter or similar duration of motor block than epidural bupivacaine for cesarean delivery (2–4). Ropivacaine has also been evaluated for use as a spinal anesthetic (5–8). Isobaric ropivacaine 12 mg produces a sensory and motor blockade similar to isobaric bupivacaine 8 mg for knee arthroscopy (7). Hyperbaric bupivacaine 4 mg is equivalent to hyperbaric ropivacaine 8 mg in volunteers (8).
The efficacy and dosage of spinal ropivacaine for cesarean delivery is unknown. Based on several previous studies (7,8) as well as data from a pilot study, we determined that 18 mg of 0.5% hyperbaric ropivacaine was comparable to 12 mg of 0.5% hyperbaric bupivacaine for spinal anesthesia in cesarean delivery.
The purpose of this study was to evaluate the efficacy and safety of spinal anesthesia with 0.5% hyperbaric ropivacaine, compared with 0.5% hyperbaric bupivacaine for elective cesarean delivery.
This study was approved by the ethics committee of our university hospital, and informed consent was obtained from 64 full-term women. All patients were ASA physical status I or II, were 156–165 cm in height, and were scheduled for elective cesarean delivery under spinal anesthesia. Parturients who had obstetric complications or evidence of fetal compromise were excluded. The patients were randomly assigned into two groups of 32 patients each to receive an intrathecal injection of either 12 mg of 0.5% hyperbaric bupivacaine in 8% glucose (Marcaine®, Astra, Sweden) or 18 mg of 0.5% hyperbaric ropivacaine. Hyperbaric ropivacaine solutions were made with 4 mL of 0.75% ropivacaine (Naropin®, Astra, Australia) and 2 mL of 20% dextrose. All solutions were prepared and injected by a resident. Patients, surgeons, and another resident, who was involved in the patient’s clinical assessment and treatment, were blinded to group assignment.
Per standard hospital protocol, all patients received premedication with glycopyrrolate 0.2 mg and ranitidine 10 mg IM 1 h before the spinal procedure. Lactated Ringer’s solution 15 mL/kg was infused for 10 min before the initiation of the spinal block. Spinal anesthesia was performed in the right lateral position with a 25-gauge Quincke needle by using a midline approach at the L2-3 or L3-4 interspace. Once free flow of clear cerebrospinal fluid was obtained, the study drug was injected at the rate of approximately 0.2 mL/s. With the spinal needle bevel facing cephalad, the anesthetic solution was injected without barbotage or aspiration. After the injection of the spinal medication, the patients were turned supine with left uterine displacement. Maternal heart rate and arterial blood pressure were measured with an automatic, noninvasive device. Baseline values were defined as blood pressure and heart rate values before the preanesthetic infusion. The values were recorded before the induction, every 2 min before delivery, and then every 5 min until discharge from the recovery room. Arterial oxygen saturation was continuously monitored by using pulse oximetry throughout surgery. Hypotension (defined as systolic blood pressure < 100 mm Hg) was treated with IV ephedrine 10 mg and additional lactated Ringer’s solution. Maternal bradycardia (defined as heart rate < 60 bpm) was treated with IV atropine 0.5 mg. Nausea or vomiting was treated with IV droperidol 0.5 mg. IV midazolam 2.5 mg was administered only after the delivery if the patients requested to sleep. If pain or discomfort occurred during surgery, IV fentanyl 50 μg was administered. Oxygen was routinely administered via a face mask at the rate of 5 L/min until the end of surgery. Surgery was started when a sensory block at or above the T6 dermatome was established. The condition of the neonate was evaluated by Apgar scores at 1 and 5 min after delivery and by umbilical venous or arterial pH.
The assessments of sensory block to pinprick were performed at 2, 4, 6, 8, 10, and 15 min after the intrathecal injection and then every 15 min until regression to L5. Results of the pinprick test were determined bilaterally at midclavicular level by using a short-beveled 27-gauge needle. Motor block in the lower limb was assessed by using a modified Bromage scale (0 = no paralysis, 1 = unable to raise extended leg, 2 = unable to flex knee, 3 = unable to flex ankle). These assessments were performed immediately after the assessments of sensory block until the return of normal motor function.
The quality of abdominal muscle relaxation was evaluated by the surgeon at the end of the surgery as excellent (no disturbing muscle strain), satisfactory (disturbing, but acceptable muscle strain), or unsatisfactory (unacceptable muscle strain). The overall quality of intraoperative analgesia was judged by the investigator at the end of surgery as excellent (no discomfort or pain), good (mild pain or discomfort, no need for additional analgesics), fair (pain that required additional analgesics), or poor (moderate or severe pain that needed more than fentanyl 100 μg or general anesthesia). Time to the first feeling of pain (complete analgesia) and time to first request of analgesics (effective analgesia) were measured. On postoperative Days 1 and 5, patients were evaluated regarding possible side effects including headache, back pain, and transient neurologic symptoms.
A power analysis was based on data from a pilot study of 15 patients in which the mean duration of motor blockade was measured with ropivacaine and compared with the previous data for bupivacaine (9,10). To detect a 30-min difference in mean duration of motor blockade between the groups for type 1 error of 0.01 and a power of 90%, a group size of 32 patients was necessary.
Data were expressed as mean ± sd, median (range), or frequencies (%), as appropriate. Continuous variables were analyzed by using unpaired t-test. Nominal or ordinal variables were analyzed by using χ2 test and Fisher’s exact test or Mann-Whitney U-test. P < 0.05 was considered statistically significant.
One patient in the Ropivacaine group refused spinal anesthesia in the operating room. More than three attempts of dural puncture were performed in one patient in each group. In one patient in the Bupivacaine group, surgical anesthesia was inadequate and general anesthesia was performed before delivery of the neonate. These four patients were excluded from this study. There were no significant differences in age, weight, height, gestational age, time from induction to skin incision, and duration of surgery between groups (Table 1).
Onset of sensory block to T10 or to the maximal level took longer in the Ropivacaine group (3.2 ± 1.2 min vs 10.6 ± 2.2 min) than in the Bupivacaine group (2.5 ± 1.0 min vs 8.1 ± 2.0 min) (P < 0.05). The median maximal level of sensory block was similar in both groups. Time for the block to recede to T10 did not differ between groups. Duration of sensory block was shorter in the Ropivacaine group than in the Bupivacaine group (P < 0.05) (Table 2).
The evolution of motor block with time, assessed by the modified Bromage scale, is shown in Figure 1. Complete motor block of the lower extremities (Bromage score 3) was obtained in all patients. Time to complete motor blockade was similar in both groups. Duration of complete motor block was shorter in the Ropivacaine group (90–135 min) than in the Bupivacaine group (105–225 min) (P < 0.000) (Table 2).
The qualities of intraoperative analgesia and abdominal muscle relaxation were similar in both groups (Table 3). No patient, regardless of group, complained of discomfort on skin incision. Three patients in the Bupivacaine group and two patients in the Ropivacaine experienced mild to moderate discomfort or pain at delivery. Two patients in the Bupivacaine group and three patients in the Ropivacaine group required supplementary analgesics (fentanyl 50 μg) during the last part of surgery. The time to first request of analgesics was earlier in the Ropivacaine group than in the Bupivacaine group (P < 0.05).
Apgar scores were similar in both groups. Two neonates in the Bupivacaine group and four neonates in the Ropivacaine group had an Apgar score < 8 at 1 min. All neonates had an Apgar score ≥ 9 at 5 min, and umbilical arterial or venous pH did not differ between groups (Bupivacaine = 7.24 ± 0.04, 7.31 ± 0.06; Ropivacaine = 7.25 ± 0.06, 7.33 ± 0.05).
Hypotension was the most common side effect in both groups. The incidence of hypotension (80% vs 66.9%), mean ephedrine use (11.3 ± 7.3 mg vs 7.7 ± 6.2 mg), and maximal percent decrease in systolic arterial pressure (-27.4 ± 11.1% vs -23.7 ± 11.0%) or heart rate (-21.3 ± 12.4% vs -18.7 ± 10.1%) did not differ between groups. The incidence of bradycardia, dyspnea, nausea or vomiting, and shivering during surgery did not differ between groups (Table 4). None of the patients developed postdural puncture headache or transient neurologic symptoms. Ten patients in the Bupivacaine and eight patients in the Ropivacaine group complained of mild or moderate backache. These backaches did not radiate to other areas, but were localized in the lumbosacral area.
The purpose of this study was to evaluate the clinical efficacy and safety of spinal anesthesia with 0.5% hyperbaric ropivacaine, compared with 0.5% hyperbaric bupivacaine for elective cesarean delivery. We found that 18 mg of 0.5% hyperbaric ropivacaine produced spinal anesthesia of similar and effective clinical quality with shorter duration of sensory and motor block, compared with 12 mg of 0.5% hyperbaric bupivacaine for elective cesarean delivery.
The analgesic spread with isobaric spinal ropivacaine is variable, extending from lumbosacral segments to upper thoracic segments (5–7). Actually, glucose-free ropivacaine and bupivacaine solutions are not isobaric at body temperature. Like glucose-free bupivacaine 0.5% solutions (baricity at 37°C: 0.9990), glucose-free ropivacaine solutions (baricity at 37°C: 0.9988) will behave as slightly hypobaric at body temperature. Consequently, the injection of glucose-free ropivacaine solutions may result in a higher spread when the patient is kept in the sitting position for at least 2 min after the injection, as has been demonstrated for bupivacaine. Plain spinal bupivacaine for cesarean delivery is unreliable and occasionally produces high spinal block (11,12). Therefore, a hyperbaric solution for spinal anesthesia, especially for cesarean delivery, is considered superior to an isobaric solution. The optimal dosage of spinal ropivacaine for cesarean delivery is unknown. The equipotent ratio between bupivacaine and ropivacaine has been 3:2 with isobaric solution for knee arthroscopy (7) or 2:1 with hyperbaric solution in volunteers (8). Based on previous studies (7,8) and our pilot studies, we determined that 18 mg of 0.5% hyperbaric ropivacaine was comparable to 12 mg of 0.5% hyperbaric bupivacaine for spinal anesthesia in cesarean delivery. Further studies, including a dose-response study, are required to determine the optimal dose, concentration, and baricity of spinal ropivacaine for cesarean delivery.
Ropivacaine is a relatively new local anesthetic that has not been marketed for intrathecal use. In this study, hyperbaric ropivacaine solutions were made with 4 mL of 0.75% ropivacaine (Naropin®) and 2 mL of 20% dextrose. The specific gravity of 0.5% ropivacaine in 6.7% glucose was 1.030 at 23°C. The specific gravity of 0.5% hyperbaric bupivacaine in 8% glucose (Marcaine®) was 1.030 at 23°C.
Epidural ropivacaine is associated with similar duration of sensory block, compared with epidural bupivacaine for cesarean delivery (2–4). When hyperbaric bupivacaine 8 mg was compared with hyperbaric ropivacaine 12 mg in volunteers, no difference in time to peak sensory level and duration of sensory block was found (8). Our data showed that the time to peak sensory block was later and the duration of sensory block was shorter in patients who received ropivacaine for cesarean delivery. The difference in the time to peak sensory block between groups, however, was not clinically significant.
These results confirm that spinal ropivacaine is less potent than bupivacaine. The lesser lipid solubility of ropivacaine may cause this drug to penetrate the large myelinated A fibers more slowly than the more lipid-soluble bupivacaine (13). A difference in the potency between ropivacaine and bupivacaine has been 20%–40% and 50% in epidural (14,15) and spinal (7,8) studies, respectively. Ropivacaine produces less motor blockade at the same dose as bupivacaine because it is less potent. Studies evaluating the use of intrathecal ropivacaine for ambulatory surgery (7,8) have reported that spinal ropivacaine offers no advantages over bupivacaine for use in outpatients. Spinal ropivacaine 12 mg has produced motor blockade equivalent to bupivacaine 8 mg (8). However, in this study, hyperbaric ropivacaine 18 mg produced a significantly shorter duration of motor blockade than hyperbaric bupivacaine 12 mg (P < 0.001). Although the patients’ satisfaction to recovery of motor block was not assessed clinically and objectively in this study, earlier recovery with spinal ropivacaine may be associated with more patient satisfaction.
In this study, intrathecal ropivacaine produced excellent intraoperative analgesia and abdominal muscle relaxation, indistinguishable from spinal bupivacaine. Small supplementary doses of IV analgesics (fentanyl 50 μg) were administered to three patients in the Ropivacaine group during the last part of the surgery. The duration of sensory block was shorter and the time to first request of analgesics was earlier with ropivacaine than with bupivacaine in this study. Cesarean delivery sometimes takes more than 1.5 hours. If that occurred, spinal ropivacaine might produce a block of inadequate duration. Adding an opioid to hyperbaric ropivacaine would improve the quality of anesthesia, similar to adding an opioid to hyperbaric bupivacaine (10).
The incidence of hypotension is frequent in both groups (80%–67%). Mean maximal reduction of maternal systolic pressure or heart rate, mean ephedrine use, and incidence of hypotension did not differ between groups. The hypotension was easily treated with ephedrine and did not cause maternal or fetal sequelae. In this study, the conditions of the neonates were good and similar in both groups. The number of neonates with unsatisfactory Apgar scores or umbilical blood pH values did not differ between groups. Backache is a common complaint during both pregnancy and the postpartum period. In this study, backache occurred in 30% of the patients with bupivacaine and 28% of the patients with ropivacaine. The relatively frequent incidence of backache in our patients was not likely to have been caused by neurotoxic effects of bupivacaine or ropivacaine. These backaches were mild or moderate and were localized only in the lumbosacral area. Kristensen et al. (16) reported that spinal ropivacaine does not affect spinal cord blood flow. As in other studies (5–8), spinal ropivacaine did not induce any neurologic symptoms in this study.
In conclusion, 18 mg of 0.5% hyperbaric ropivacaine provided similar and effective spinal anesthesia with shorter duration of sensory and motor block, compared with 12 mg of 0.5% hyperbaric bupivacaine for cesarean delivery.
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