Comparison of efficacy and safety of ropivacaine with bupivacaine for intrathecal anesthesia for lower abdominal and lower limb surgeries.

BACKGROUND: A prospective randomized clinical study was conducted to study the efficacy and safety of ropivacaine with bupivacaine intrathecally for lower abdominal and lower limb surgeries.
MATERIAL AND METHODS: 70 patients aged between 18 to 65 years were randomized into two groups, n = 35 in each group. Group A received 3 ml of (0.5%) isobaric bupivacaine (15 mg) and Group B 3 ml of (0.75%) isobaric ropivacaine (22.5 mg). Spinal anesthesia procedure was standardized. Haemodynamic parameters, onset and duration of sensory and motor blockade, level achieved, regression and side effects were compared between the two groups.
RESULTS: Onset and regression of sensory blockade in ropivacaine group was faster with a P < 0.001 which was statistically significant. Onset of motor blockade was rapid in both the groups but duration of motor blockade was significantly shorter in ropivacaine group. Excellent analgesia, with no side effects and stable haemodynamics was noted in ropivacaine group.
CONCLUSION: Hence ropivacaine was safe and equally effective as bupivacaine for lower abdominal and lower limb surgeries with early motor recovery, providing early ambulation.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

In this highly evolving and fast paced world, need for early ambulation, faster and complete recovery with minimal side-effects has risen and regional anesthesia has emerged with wide-spread acceptability among anesthesiologists world-wide with a lot of advantages.[12]

Traditionally, bupivacaine has emerged as the most commonly used drug for spinal anesthesia. However, since it has undesirable effects such as hypotension, bradycardia, prolonged duration of motor paralysis, cardiotoxicity and central nervous system toxicity,[3456] there led to the identification of long acting pure S-enantiomer of ropivacaine.[7]

Ropivacaine is nearly identical to bupivacaine in onset, quality and duration of sensory block, but it produces lesser duration of motor blockade, has a better safety profile.[1] This was very helpful for short duration surgeries as well as for early ambulation. Hence, there was a need for this study to compare its safety and efficacy with bupivacaine for lower abdominal and lower limb surgeries.

MATERIALS AND METHODS

After obtaining approval from hospital ethics committee and written informed consent from patients, the study was conducted at the tertiary care teaching hospitals.

A sample size of 70 patients of American Society of Anesthesiologists Grade I and II, aged between 18 and 85 years and height more than 160 cm scheduled for elective lower abdominal and lower limb surgeries under spinal anesthesia was decided upon.

This prospective randomized study was designed to compare 3 ml of 0.75% isobaric ropivacaine with 3 ml of 0.5% isobaric bupivacaine for subarachnoid block with respect to level, duration, sensory blockade along with hemodynamic stability and side effects.

Patients who are unwilling, posted for emergency surgeries, contraindicated for spinal anesthesia, allergic to amide local anesthetic, with a history of drug or alcohol abuse, obesity (body mass index >29 kg/m2) were excluded from the study.

Patients were randomized into two groups using sealed envelope method. Two groups (n = 35) with power of 80% and an μ value of 0.05 was assumed. Group A received 3 ml of 0.5% isobaric bupivacaine (15 mg) and Group B received 3 ml of 0.75% isobaric ropivacaine (22 mg).

Before the commencement of anesthesia, patients were instructed on the methods of sensory or motor assessments. Intravenous line secured, Ringer's lactate solution (10 ml/kg) was infused for 15 min before the initiation of the procedure. Non-invasive monitors connected and baseline values of heart rate, blood pressure and oxygen saturation were noted before the procedure.

Spinal anesthesia was performed in left lateral position with 25 G Quincke babcock spinal needle with a midline approach at the L3-4 interspace. Once free flow of clear cerebrospinal fluid was obtained, study drug was injected at the rate of 0.2 ml/s. After the procedure, patients were turned supine, heart rate, blood pressure and oxygen saturation were recorded every 5 min after intrathecal drug administration and thereafter every 10 min until the end of the procedure and 1 h after the end of the operation. Side-effects were noted, i.e., hypotension, bradycardia, nausea and vomiting were noted and treated.

Surgery was started when a sensory block at or above T6 dermatome was established.

Sensory blockade was tested every 5 min until loss of sensation to pinprick and then every 10 min until its full recovery by using a hypodermic needle. Motor Blockade was tested by modified Bromage scale.

Onset time of sensory or motor blockade was defined as the interval between intrathecal administration and maximum pinprick score (time for maximum level of sensory block or a Bromage score of 3) respectively. Duration of sensory or motor blockade was defined as interval from intrathecal administration to the point of complete resolution of the sensory block or to the point in which Bromage score was back to zero respectively. Thus, the maximum level of sensory block, onset time, duration of sensory and motor blockade as well as the interval from intrathecal administration to the point of a two segment regression of sensory blockade was recorded.

Quality of intraoperative analgesia was graded as excellent (no discomfort or pain), good (mild pain or discomfort, no need for analgesics), fair (pain that required additional analgesics), poor (moderate or severe pain requiring 100 mg fentanyl or G.A).

On post-operative days 1 and 5, patients were evaluated for side effects such as headache, back pain and transient neurological symptoms.

Statistical analysis

Demographic data was analyzed using two-tailed Student's t-test assuming equal variance for both the study groups. Maximum sensory level was analyzed using Chi-square test, Regression time, Bromage score, onset and duration of sensory and motor blockade was compared using two-tailed Student's t-test. Incidence of hypotension, bradycardia and oxygen desaturation was compared using two tailed Fisher's exact test. All statistical analysis where carried out using MedCalc statistical software version 11.0 (MedCalc, software, Buba, Belgium). P <0.05 was considered to be statistically significant.

RESULTS

There was no significant difference between the two groups with respect to age, height, weight, sex and duration of surgery [Table 1]. Heart rates in both groups were comparable with no significant statistical differences [Table 2]. The statistical analysis shows that differences are significant from the 5 min interval onward. P < 0.05 between the two study groups with steadier blood pressure in Group B [Graph 1]. Diastolic blood pressures in both groups were comparable with no significant statistical difference [Graph 2]. Oxygen saturation values in both the groups were comparable with no significant statistical difference [Graph 3]. T4 was achieved in 7 patients in Group A and 11 patients in Group B. T6 level was achieved in 20 patients in group A and 24 patients in Group B, whereas T8 level was achieved as a maximum sensory level in 8 patients in Group A only.

Table 1

Demographic information

Table 2

Heart rate changes

Graph 1

Systolic blood pressure changes (ROP-Ropivacaine, BUP-Bupivacaine)

Graph 2

Distolic blood pressure changes (ROP-Ropivacaine, BUP-Bupivacaine)

Graph 3

Oxygen saturation (ROP-Ropivacaine, BUP-Bupivacaine)

Most of the patients in Group A (57.1%) had a maximum sensory level of T6, which was comparable with Group B where the maximum number of patients (68.6%) achieved a level of T6 (P < 0.05) [Graph 4].

Graph 4

Maximum sensory level (ROP-Ropivacaine, BUP-Bupivacaine)

The mean time duration for 2 segment regression in Group A was 61.57 ± 10.05 min and Group B was 81.14 ± 8.40 min, which was statistically significant. The time required for regression to T10 segment in Group A was 81.25 ± 19.78 min and in Group B was 113.57 ± 8.27 min, which was also statistically significant. The two segment regression and regression to T10 was faster in Group A with statistical significance of P < 0.001. We found no statistically significant difference between both groups in achieving the Bromage score of 1, 2 and 3 i.e., all the patients in both groups achieved complete motor blockade (Bromage 3) [Graph 5].

Graph 5

Sensory regression

The mean onset of sensory blockade (maximum sensory level in min) in Group A was 15.4 ± 4 min and Group B 15.57 ± 5.25 min. The mean onset of motor blockade (Bromage score 3) in Group A was 15.42 ± 3.5 min and in Group B 15.71 ± 4.56 min. The statistical analysis shows no significant differences in the onset of both sensory and motor blockade [Table 3]. The mean duration of sensory blockade (full sensory blockade recovery at T10) in Group A was 121 ± 11.93 min and Group B was 180 ± 9.62 min. The mean duration of motor blockade (Bromage score back to zero) in Group A was 153.57 ± 15.65 min and in Group B 211 ± 11.29 min. The statistical analysis shows the differences are significant in both the duration of sensory and motor blockade with P < 0.001 between the two study groups suggesting shorter duration of sensory and motor blockade in Group A [Graph 6].

Table 3

Comparison of mean onset of sensory and motor block

Graph 6

Duration of sensory and motor blockade (BUP-Bupivacaine, ROP-Ropivacaine)

Nearly 91.4% of the patients in Group A had an excellent pain relief (Score 1), whereas all the patients in Group B had excellent pain relief of 2.9% of the patients had a good pain relief, 2.9% had fair pain relief which required additional analgesics, whereas 2.9% of the patients had severe pain requiring general anesthesia [Table 4].

Table 4

Comparison of analgesic score

Nearly 85.7% of patients in Group A and 91.4% in Group B had no complications. 2.9% of patients in Group A had back pain and 5.7% of the patients in Group B had hypotension. Around 8.6% of patients in Group B had hypotension, bradycardia and dyspnea with a P value of 0.15, which was not statistically significant.

DISCUSSION

Subarachnoid block is a very well accepted and an excellent anesthetic technique in this modern era with a high success rate and a good safety profile. Hence, the search is always on for a drug which is safer, efficacious and less toxic with an early recovery profile, which provides an early ambulation. In order to further improve and understand the safety issues, new local anesthetics are being investigated and as the focus is mainly on improving the outpatient care, drugs should provide short acting and adequate anesthesia without compromising the early ambulation and discharge. Hence, we conducted this study in order to determine the potential of ropivacaine in this area by comparing it with most commonly used and well established drug bupivacaine.

Baseline hemodynamic parameters did not show any difference between the groups. 57.1% of patients in Group A had a maximum sensory level of T6 in comparison with Group B in which 68.6% achieved a level of T6. The level T4 was achieved in 20% of the patients in Group A and 31.4% of the patients in Group B. A maximum sensory level of only up to T8 was achieved in 22.9% of patients in Group A. The upper extent of the sensory block was higher in Group A, when compared with Group B, which was statistically significant. The level of block was sufficient for all the surgeries in both groups, before the surgical incision.

Malinovsky et al.[8] in a study comparing intrathecal isobaric ropivacaine 15 mg versus bupivacaine 10 mg in transurethral resection of the prostate surgeries, found that cephalad spread of sensory blocks was higher with bupivacaine than with ropivacaine, which is similar to the findings in our study group as well. It may be argued that the volume of diluted anesthetic solutions may alter the cephalad extent of anesthesia. However, there are large inter individual variations in the total volume of cerebrospinal fluid.[9] and dilution does not significantly affect the spread of intrathecal anesthesia.[10] Finally, the major determinant for the spread of intrathecal anesthesia is the dose of local anesthetic injected Greene NM.[11] Our findings regarding the level of sensory block correlates well with another study conducted by McNamee et al.[12] which revealed that there was a trend for the patients in bupivacaine group to achieve a higher upper dermatomal level of sensory block. Kallio et al.[13] proved in their study that, time of onset of sensory block was comparable between both the drugs. In our study, the two segment regression time and the time required for regression to T10 segment in ropivacaine group were both statistically significant with a P < 0.001.

The onset of motor blockade was rapid in both groups with mean onset of 15.42 ± 3.5 min in Group A and 15.71 ± 4.56 min in Group B and these observations are in accordance with the similar studies conducted by McNamee et al.[12] and Kallio et al.[13] The time required to achieve individual Bromage score was also similar in both groups with no statistically significant difference, which is supported by a study conducted by Gudul et al.[14]

In our study, the duration of sensory blockade was assessed at the level of T10. The mean duration of sensory blockade (i.e., full sensory blockade recovery at T10) in Group A was significantly shorter. The similar finding was stated by Mantouvalou et al.[15] who conducted a study comparing plain ropivacaine and plain bupivacaine for lower abdominal surgeries in which he concluded faster resolution of sensory blockade in ropivacaine group.

Our study findings where the mean duration of motor blockade in Group A was 153.57 ± 15.65 min and in Group B 211 ± 11.29 min indicating significantly lower duration of motor blockade in ropivacaine group, is well supported by an earlier study by Gudul et al. Similar conclusion regarding the duration of motor blockade was derived by Eryilmaz and Gunaydin.[16] in their study of spinal anesthesia in parturients. Both groups provided excellent analgesia with only one patient having mild discomfort and another patient requiring additional analgesics due to inadequate pain relief in ropivacaine group. Only one patient in ropivacaine group required general anesthesia due to inadequate duration of blockade. The abdominal muscle relaxation was excellent with no disturbing muscle strain in patients of both the groups who underwent lower abdominal surgeries.

We did not note any significant differences between the two groups regarding hemodynamic variables, heart rate and oxygen saturation. However, the fall in systolic and the diastolic blood pressure from the 5 min interval was noticed more in the ropivacaine group, which was almost comparable with bupivacaine group by the end of the surgery. Danelli et al.[17] noticed no difference in clinical hypotension requiring ephedrine administration in 60 women undergoing elective cesarean delivery under spinal anesthesia with either ropivacaine or bupivacaine, which further supports our study findings.

One patient in Group A complained of back pain and another patient in the same group was administered general anesthesia due to inadequate duration of block. During the follow-up, none of the patients experienced any neurological symptoms.

CONCLUSION

Hence based on the above study, we conclude that use of ropivacaine for intrathecal anesthesia in the lower abdominal and lower limb surgeries provided an adequate level of block for the surgery with faster onset of sensory and motor blockade, lesser duration of motor blockade with good analgesia and stable hemodynamics.