|Year : 2015 | Volume
| Issue : 2 | Page : 173-177
Effects of isobaric ropivacaine with or without fentanyl in subarachnoid blockade: A prospective double-blind, randomized study
Kaushik Rao Seetharam1, Gayathri Bhat2
1 Department of Anaesthesia, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
2 Department of Anaesthesia, K S Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India
|Date of Web Publication||6-May-2015|
Kaushik Rao Seetharam
Department of Anaesthesia, Kasturba Medical College, Manipal University, Mangalore - 575 001, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The addition of fentanyl to ropivacaine has shown to improve the quality of analgesia without compromising its benefits such as early mobilization and early voiding.
Aim: The aim of the study was to evaluate the effects of the isobaric ropivacaine in combination with fentanyl and compare it with the isobaric ropivacaine alone in spinal anesthesia for lower abdominal and lower limb surgeries.
Settings and Design: Double-blinded randomized controlled trial.
Subjects and Methods: Hundred patients belonging to American Society of Anesthesiologists physical status I and II scheduled for either lower abdominal or lower limb surgery under spinal anesthesia were included. The study was a prospective double-blinded randomized controlled trial where patients were randomly allocated into two groups to receive either 2.5 ml of 0.75% (18.75 mg) isobaric ropivacaine with 25 μg fentanyl (Group RF) or 2.5 ml of 0.75% (18.75 mg) isobaric ropivacaine with 0.5 ml of 0.9% saline (Group R) intrathecally.
Statistical Analysis: Data analysis was done by Student's unpaired t-test. SPSS version 16 was used. P < 0.05 was considered as statistically significant.
Results: We found no significant difference in hemodynamics, onset of sensory and motor block, peak level of block, recovery from motor block, return of micturition and incidence of side effects with the addition of fentanyl to ropivacaine. First request for analgesia was required earlier in the control group. There was also a significant prolongation of the duration of sensory block (mean - 341.6 min) and postoperative analgesia in Group RF (mean - 442.2 min) (P < 0.001).
Conclusion: The addition of fentanyl to ropivacaine significantly prolongs the duration of postoperative analgesia with clinically insignificant influence on hemodynamics and motor blockade with minimal side effects.
Keywords: Fentanyl, intrathecal, postoperative analgesia, ropivacaine
|How to cite this article:|
Seetharam KR, Bhat G. Effects of isobaric ropivacaine with or without fentanyl in subarachnoid blockade: A prospective double-blind, randomized study. Anesth Essays Res 2015;9:173-7
|How to cite this URL:|
Seetharam KR, Bhat G. Effects of isobaric ropivacaine with or without fentanyl in subarachnoid blockade: A prospective double-blind, randomized study. Anesth Essays Res [serial online] 2015 [cited 2020 Jan 25];9:173-7. Available from: http://www.aeronline.org/text.asp?2015/9/2/173/152149
| Introduction|| |
Spinal anesthesia is a very old and popular anesthetic technique with a high success rate and a good safety profile. In order to improve further and understand safety issues as well as the clinical use of spinal anesthesia, new local anesthetics and analgesic additives are being investigated for different applications. As the practice of medicine focuses increasingly on out-patient care, spinal anesthetics should provide short acting and adequate anesthesia without compromising early ambulation and discharge from the day surgery unit. Ropivacaine is one local anesthetic that could have potential in this area. 
Ropivacaine is an amide local anesthetic with properties similar to bupivacaine producing similar sensory block at equipotent doses, but with a shorter duration of motor block.  It has consistently demonstrated an improved safety profile over bupivacaine, with a reduced neurotoxic and cardiotoxic potential and was approved in the European union in February 2004 for intrathecal administration. , Postoperative analgesia is a concern with ropivacaine that limits its usage. The addition of adjuvants to ropivacaine has shown to improve the quality of intra-operative and postoperative analgesia without compromising its benefits such as early mobilization and early voiding.  But each of them have their own side effects. The search for an ideal adjuvant that would provide hemodynamic stability as well as prolonged postoperative analgesia with minimal side effects continues.
Fentanyl is an opioid that has shown to enhance the analgesic potency of ropivacaine for spinal anesthesia. The addition of fentanyl to ropivacaine for spinal anesthesia has been shown to prolong the duration of analgesia in the early postoperative period. Thus it is improving the quality of anesthesia. However, there are limited studies on intrathecal ropivacaine-fentanyl combination for postoperative analgesia in lower abdominal and lower limb surgeries.
This study was undertaken to compare the safety, quality, efficacy and duration of analgesia of intrathecal fentanyl and isobaric ropivacaine combination as compared to the isobaric ropivacaine alone for lower abdominal and lower limb surgery.
| Subjects and methods|| |
This study was approved by the Ethics Committee. Written informed consent was obtained from 100 patients who fulfilled the following inclusion criteria: Elective lower abdominal and lower limb surgeries under spinal anesthesia, American Society of Anesthesiologists (ASA) physical status I-II, age 18-65 years, height ≥150 cm, and weight ≥50 kg. Patients who had contraindications to spinal anesthesia, allergy to amide local anesthetics were excluded. This study was conducted in the form of a prospective, randomized, double-blind, controlled fashion. The patients were randomized by closed envelope method into two groups: Group RF (n = 50, fentanyl group) received 2.5 ml (18.75 mg) of 0.75% isobaric ropivacaine + 25 μg fentanyl (0.5 ml) and Group R (n = 50, saline group) received 2.5 ml (18.75 mg) of 0.75% isobaric ropivacaine + 0.5 ml normal saline intrathecally.
Preanesthetic evaluation was carried out for all patients on the previous day of surgery. All patients were informed that he/she would receive analgesics in the postoperative period only after request for analgesia. Patients were kept nil per oral from midnight and were premedicated with tablet diazepam 10 mg PO and tablet ranitidine 150 mg PO at night and 2 h before surgery. In the operation theatre, standard monitors including noninvasive blood pressure (NIBP), electrocardiography and pulse oximeter were connected and the baseline values of heart rate (HR), NIBP, oxygen saturation were noted. Preloading was done with 20 ml/kg of Ringer lactate infusion over 20 min. Lumbar puncture was performed with a 25 gauge Quincke spinal needle at L3-L4 level and with the spinal needle bevel in cephalad orientation, 3.0 ml of the test drug was injected over 10 s intrathecally.
The anesthesiologist was blinded to the solution administered intrathecally. Following intrathecal injection, the following parameters were monitored in both the groups. HR, systolic blood pressure (SBP), diastolic blood pressure (DBP) every 1 min for the first 10 min, then every 5 min till 60 min, then every 20 min till completion of surgery. Level of sensory blockade was assessed every minute using 23 gauge hypodermic needle with loss of sensation to pin prick testing along mid-clavicular line bilaterally. Sensory block was assessed until sustained peak level of sensory block was reached (i.e., once the level had stabilized after four consecutive tests). Time taken for T10 level of blockade, peak level of blockade achieved and its time taken were noted. Degree of motor blockade was assessed with Bromage scale every minute till level of sensory block stabilized. Onset time for complete motor blockade (Grade IV) was noted.
The level of sensory blockade and degree of motor blockade were noted after the completion of surgery. Occurrence of side effects like hypotension, bradycardia, nausea, vomiting, shivering, pruritus, respiratory depression (respiratory rate <8/min) and urinary retention were attended and managed accordingly and mentioned in the study sheet. Ensuing hypotension and bradycardia were managed adequately. In the postoperative ward HR, SBP and DBP were recorded every 20 min till 180 min postintrathecal injection. In addition level of sensory block and intensity of motor blockade was assessed very 20 min. Analgesics were avoided until demanded by the patients. Injection tramadol 50 mg intravenous (IV) was given at patient's first request for analgesia. In addition, the duration of sensory block, time to the first request for analgesia, duration of analgesia and occurrence of side effects were noted. Monitoring was continued till complete recovery from motor blockade (Grade I in Bromage scale), regression of sensory block to S2 and return of the voluntary micturition. Duration of sensory block was defined as the period from the time of intrathecal injection of the drug to regression of blockade to S2 level. Duration of analgesia was defined as from the time of intrathecal injection of the drug to the time of the first request for analgesia.
Statistical analysis was performed using SPSS version 16.0 (SPSS Inc., Chicago, IL). All repeated measures tests were compared using repeated measures ANOVA comparing the mean and the standard deviations. Chi-square test was used for ASA grading, type of surgery and side effects. Individual time period and remaining all parameters were compared using Student's t-test. P < 0.05 was considered statistically significant.
| Results|| |
Patient characteristics were comparable, and there was no significant difference in the duration and type of surgery between the two groups [Table 1]. Hundred patients were randomized into two groups. There was no significant difference in the HR, SBP and DBP values between the two groups at baseline and postspinal at all intervals measured [Figure 1]. There was no significant difference in the meantime of onset of T10 level of sensory block and peak level of sensory block which was 4.76 min and 7.22 min (Group RF), 4.82 min and 7.30 min (Group R) respectively [Table 2]. Also there was no significant difference in the peak level of block attained between the two groups with the median (range) upper sensory level T6 (T4-T9) in Group RF and T8 (T6-T10) in Group R.
All patients in the both groups achieved Bromage score of 4 (complete motor block). The mean onset time of complete motor block was similar in both groups (Group RF vs. Group R, 5.28 min vs. 5.36 min, P = 0.698). Time for recovery from motor blockade was statistically significant between the two groups but clinically it was considered insignificant (Group RF vs. Group R, 206.4 min vs. 197.6 min, P < 0.006).
The time to S2 regression and time to micturition was significantly prolonged in Group RF (P < 0.001). However, we considered the difference in time to micturition as clinically insignificant. No patients required supplemental analgesia intra-operatively. The mean time of first analgesic request was significantly prolonged in the fentanyl group than the saline group (442.2 vs. 314.3 min, P < 0.001) [Figure 2].
|Figure 2: Comparison of time to S2 regression, micturition and first request for analgesia|
Click here to view
There was no significant difference in the incidence of side effects when comparing the two groups. Intra-operative hypotension requiring treatment was 8% in the fentanyl group and 6% in the saline group. Two patients in both groups had shivering and were treated with IV tramadol 50 mg. Only one patient in the fentanyl group had pruritus and was treated with IV ondansetron 8 mg.
| Discussion|| |
Spinal anesthesia is a widely used technique of anesthesia that offers many advantages, but problems like intra-operative hypotension, postoperative pain and residual motor blockade can make it an unpleasant experience for the patient. Hence hemodynamic stability, effective and prolonged analgesia along with early ambulation and recovery are essential for optimum care of the patient. Numerous drugs have been used for spinal anesthesia, among which bupivacaine is most popular. Bupivacaine, the first long-acting amino amide local anesthetic is widely used because of its prolonged duration of action, however certain features of bupivacaine like prolonged motor blockade, cardiotoxic and neurotoxic effects have made ropivacaine a safer choice. ,
Ropivacaine is a pure S enantiomer of bupivacaine with a similar structure, physiochemical properties, pharmacology and mechanism of action, but with a shorter duration of motor block and less cardiotoxic and neurotoxic effects. Because of its shorter duration of motor block, it enables early mobilization in the postoperative ward. But there is a need to intensify and prolong its duration of sensory block without increasing the intensity and duration of motor block, thus prolonging the duration of postoperative analgesia. ,
Many adjuvants have been studied with ropivacaine in order to improve its quality of analgesia. Opioids have shown to possess synergistic analgesic effect with local anesthetics when administered intrathecally and thus improve the quality of intra-operative analgesia and enhance benefits such as early mobilization. The addition of fentanyl to ropivacaine for spinal anesthesia has shown to enhance the analgesic potency of ropivacaine, prolonging the duration of analgesia in the early postoperative period. The present study was designed to study the effects of the isobaric ropivacaine with or without fentanyl in the subarachnoid blockade for lower abdominal and lower limb surgeries. In our study, both the groups were comparable with respect to age, sex, height, weight and ASA physical status, duration and type of surgery. No patients had to be excluded from the study. Hemodynamic changes that is, HR, SBP and DBP were compared between the two groups. Also, characteristics of sensory and motor block, incidence of side effects, return of voluntary micturition and duration of analgesia were noted in both the groups and compared.
In our study we found that following subarachnoid block; changes in HR, SBP and DBP were similar in both the groups. Mean HR, SBP and DBP at baseline were 70.92 ± 9.113 bpm, 123.66 ± 12.732 mmHg and 74.52 ± 5.926 mmHg in study group (Group RF) and 72.1 ± 8.239 bpm, 128.36 ± 11.897 mmHg and 75 ± 7.442 mmHg in control group (Group R) respectively, which were comparable. Following spinal anesthesia the differences in the HR, SBP and DBP between the two groups was found to be statistically insignificant at all intervals measured. Hypotension occurred only in four patients in Group RF (8%) as compared to three patients in Group R (6%) and was treated with injection ephedrine 6 mg IV boluses. This was found to be statistically insignificant. No episodes of bradycardia were seen in our study.
Koltka et al. compared the effects between 2.6 ml (19.5 mg) ropivacaine (7.5 mg/ml) with 20 μg of fentanyl (50 μg/ml) or 2.6 ml of bupivacaine (5 mg/ml) with 20 μg of fentanyl for spinal anesthesia in lower abdominal surgeries. Peak level of sensory block achieved in the ropivacaine group in this study was T7 (T4-T9) (median [range]) comparable to T6 (T4-T9) in Group RF of our study. Also, in this study, only 20% of patients who received ropivacaine with fentanyl had hypotension and 3% had bradycardia compared to our study where incidence of hypotension was 8% in Group RF and 3% in Group R, with no episodes of bradycardia in either group, showing that combination of ropivacaine with fentanyl provides good cardiovascular stability. About 68% of patients in the ropivacaine group achieved complete motor blockade, whereas in our study all patients achieved complete motor blockade. No patients in this study had nausea, vomiting, pruritus, shivering, respiratory depression. In our study, only four patients (2 in each group) had shivering, and one patient belonging to Group RF had pruritus. 
In a study conducted by Wahedi et al., failure rate with 15 mg (3 ml of 5 mg/ml solution) of the intrathecal plain ropivacaine for abdominal surgery was 20%.  Similar results (16%) were obtained in the study done by Malinovsky et al. with 15 mg of the plain ropivacaine for urological surgery.  Mcnamee et al. found 98% of patients had adequate block with 18.75 mg of plain ropivacaine for orthopedic surgery, whereas in the study by Koltka et al. with 19.5 mg of plain ropivacaine all patients achieved a block height of T10 or higher. , Hence, for our study, we choose a dose of 18.5 mg of the isobaric ropivacaine for lower abdominal and lower limb surgeries. All patients in our study achieved an adequate block height of T10 or higher.
Boztug et al. studied the effects of intrathecal ropivacaine and intrathecal ropivacaine with fentanyl for out-patient arthroscopic knee surgery. 10 mg (3 ml) of the isobaric ropivacaine (Group R) was compared with 8 mg isobaric ropivacaine combined with 25 μg fentanyl (Group RF). The onset for T10 level of blockade was faster in Group R compared to Group RF (3.60 ± 1.84 min vs. 5.25 ± 2.04 min), but the results were not statistically significant. In our study, there was no significant difference in the mean onset time for T10 level of blockade between the two groups (Group R vs. Group RF, 4.82 ± 0.748 min vs. 4.76 ± 0.797 min). There was no significant difference in time to first the micturition between the two groups in this study (Group R vs. Group RF, 281.00 ± 55.46 vs. 261.81 ± 86.31). Similarly, in our study, no significant difference was present between both groups with respect to voiding (Group R vs. Group RF, 343 ± 9.897 min vs. 353.6 ± 15.221 min). 
Sanli et al. evaluated the effects of addition of fentanyl to ropivacaine for caesarean section. Patients were randomly divided into two groups: Group S (saline group) received 2.5 ml (15 mg) hyperbaric ropivacaine + 0.5 ml saline; Group F (fentanyl group) received 2.5 ml (15 mg) hyperbaric ropivacaine + 10 μg fentany in 0.5 ml intrathecally. Time to reach the peak level of block did not differ significantly between both the groups (Group S vs. Group F, 9.3 ± 1.7 min vs. 8.4 ± 1.3 min). This was comparable to the result of our study (Group R vs. Group RF, 7.3 ± 0.886 min vs. 7.22 ± 0.815 min). There was no significant difference in onset times for complete motor blockade between both the groups (Group S vs. Group F, 6.2 ± 1.2 min vs. 6.4 ± 1.3 min). A similar result was obtained in our study when both groups were compared (Group R vs. Group RF, 5.36 ± 0.942 min vs. 5.28 ± 1.107 min). Complete recovery from motor blockade also did not significantly differ in this study (Group S vs. Group F, 118.8 ± 14.6 min vs. 122.8 ± 18.9 min) like in our study (Group R vs. Group RF, 197.6 ± 11.168 min vs. 206.4 ± 19.141 min). Time to regression to L5 was significantly prolonged in the fentanyl group in this study (Group S vs. Group F, 150.3 ± 13.4 min vs. 168.3 ± 17.3 min). In our study also the regression to S2 was significantly prolonged in ropivacaine + fentanyl group (Group R vs. Group RF, 240.4 ± 13.087 min vs. 341.6 ± 15.032 min). Also, in this study, the time to first request for analgesia was significantly longer with fentanyl group (Group S vs. Group F,161.2 ± 32.6 min vs. 213.0 ± 29.3 min), which was comparable with our study (Group R vs. Group RF, 314.3 ± 15.682 min vs. 442.2 ± 25.378 min). 
From the above studies and from our study, the addition of fentanyl to ropivacaine for spinal anesthesia seems to prolong the duration of sensory block and duration of analgesia postoperatively without significantly affecting hemodynamics, onset of sensory and motor block, peak level of sensory block and return of micturition. Thus, it improves the overall quality of anesthesia of ropivacaine, at the same time preserves its benefits like good hemodynamic stability, early mobilization and early voiding.
| Conclusion|| |
Hence, we conclude that the combination of 0.75% ropivacaine with fentanyl (25 μg) is better compared to 0.75% ropivacaine alone in providing analgesia, as the combination offers a convenient, simple, inexpensive, effective and safe means of good postoperative analgesia and is suitable for lower abdominal and lower limb surgery.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]