|Year : 2016 | Volume
| Issue : 3 | Page : 158-163
Recovery profile of intrathecal ropivacaine with or without fentanyl: A randomized double-blind controlled trial in equivalent doses
Nishat Akhtar, Abdul Quadir, Manazir Athar, Navnidhi Singh
Department of Anaesthesiology and Critical Care, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
|Date of Web Publication||5-Aug-2016|
Dr. Manazir Athar
Department of Anaesthesiology and Critical Care, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Since its inception, the subarachnoid block has remained the technique of choice for lower limb surgeries. However, nowadays, day surgery units are becoming popular which require anesthesia to be rapid, selective, and reversible with minimal hemodynamic alterations. Ropivacaine with its profile ideal for these types of surgeries is hereby compared with and without fentanyl as an adjuvant in patients undergoing spinal anesthesia for lower limb orthopedic surgery. Materials and Methods: A total of 60 American Society of Anesthesiologists Grade I/II patients posted for elective lower limb orthopedic surgeries were randomly given either 3 ml of 0.75% plain ropivacaine (22.5 mg) + 0.5 ml normal saline or 3 ml of 0.75% plain ropivacaine (22.5 mg) + 0.5 ml fentanyl (25 μg). The sensory and motor block characteristics, hemodynamic changes as well as any adverse effects were recorded. Results: Demographic data were similar between both groups. Onset to T 10 was faster (5.76 ± 1.4) in Group RF compared to R (7.47 ± 2.14; P < 0.001). The median (range) maximum height in Group RF was T 2 (C 7 -T 4 ) while in Group R was T 4 (T 1 -T 6 ). Time to reach maximum height was shorter in Group RF. The onset of motor block was faster (8.43 ± 1.80 min) in Group RF compared to Group R (12.27 ± 1.78; P < 0.001). Time to regression of sensory block to L 1 was longer in the Group RF than Group R (245.66 ± 22.35 min vs. 187.16 ± 17.053 min; P < 0.001). Group RF (289.33 ± 23.11) produced significantly longer duration of motor block compared to Group R (232.33 ± 18.65; P < 0.001). Duration of analgesia was significantly longer in Group RF than Group R (P < 0.001). Conclusion: Both groups achieved adequate anesthesia and analgesia, however, ropivacaine with fentanyl produced a more rapid and prolonged sensory and motor blockade with minimal hemodynamic changes.
Keywords: Day surgery, fentanyl, isobaric, ropivacaine, subarachnoid block
|How to cite this article:|
Akhtar N, Quadir A, Athar M, Singh N. Recovery profile of intrathecal ropivacaine with or without fentanyl: A randomized double-blind controlled trial in equivalent doses. Int J Health Allied Sci 2016;5:158-63
|How to cite this URL:|
Akhtar N, Quadir A, Athar M, Singh N. Recovery profile of intrathecal ropivacaine with or without fentanyl: A randomized double-blind controlled trial in equivalent doses. Int J Health Allied Sci [serial online] 2016 [cited 2021 Mar 7];5:158-63. Available from: https://www.ijhas.in/text.asp?2016/5/3/158/187806
| Introduction|| |
"Cocainization of the spinal cord" was first described by Augustus Bier in 1899.  The technique has been refined since then and has evolved into the modern concept of subarachnoid block or spinal anesthesia. While growing in popularity, it has largely been reserved for inpatient surgery. However, nowadays, it is increasingly becoming popular among anesthetists worldwide as a technique to provide anesthesia for patients undergoing ambulatory surgery in day surgery units (DSUs). It blunts the "stress response" to surgery, decreases intraoperative blood loss, lowers the incidence of postoperative thromboembolic events, and decreases the morbidity in high-risk surgical patients. It serves as a useful method to extend analgesia into the postoperative period, where its use has been shown to provide better analgesia than parenteral opioids. 
Bupivacaine, available in both hyperbaric and isobaric formulations as 0.75% and 0.5% is the most commonly used local anesthetic agent for spinal anesthesia. It has been developed as an alternative to lidocaine for spinal anesthesia and is frequently used with very little incidence of transient neurological symptoms.  The anesthesia with bupivacaine is rapid and significantly longer than with any other commonly used local anesthetic. However, this long duration of action delays recovery of motor function and prolongs Postanaesthesia Care Unit stay after surgery. In addition, there have been reports of fatal cardiovascular toxicity following use of bupivacaine in regional anesthesia.  Several studies have shown that bupivacaine has more central nervous system and cardiac toxicity compared to other local anesthetics. ,
Ropivacaine the first pure S(-) enantiomer local anesthetic with structural and pharmacodynamic properties similar to bupivacaine is less toxic than the racemic bupivacaine.  Ropivacaine blocks nerve fibers involved in pain transmission (Ad and C fibers) to a greater degree than those controlling motor function (Aβ fibers).  Therefore, ropivacaine has been found to induce less intense motor blockade than bupivacaine.  Hence, its shorter duration, faster recovery of motor function, lower toxicity profile, and minimal hemodynamic alterations have been identified as a potential benefit for surgery of intermediate duration as well as for ambulatory surgery in DSUs.
A variety of medications, for example, morphine, fentanyl, adrenaline, phenylephrine, clonidine, and dexmedetomidine have been developed as an adjuvant and are frequently added to the local anesthetic to modify its effect while reducing the amount required to produce anesthesia. Fentanyl, a short-acting, lipophilic, synthetic opioid, is known to improve the quality of spinal anesthesia and has been widely and successfully used. The effect of adding a small dose of fentanyl to the local anesthetic solution is profound. It improves the quality of analgesia and reduces the incidence of block failure. The synergistic action of this combination significantly decreases the amount of local anesthetic required for subarachnoid block and hence decreases the associated adverse effects. Studies have shown that addition of intrathecal fentanyl to isobaric or hyperbaric ropivacaine can increase the quality of intraoperative analgesia, as well as the duration of analgesia. ,,, In addition, it has been demonstrated that adding up to 25 μg intrathecal fentanyl does not impair respiratory function or drive even in elderly patients with significant respiratory disease.  The subtherapeutic use of local anesthetic in these situations may lead to early mobilization, reduced risk of thromboembolism along with reduced hospital stay.
Therefore, the current study is designed to compare block characteristics, hemodynamic alterations along with any side effects of isobaric ropivacaine with or without fentanyl in patients receiving spinal anesthesia for lower limb orthopedic surgery.
| Materials and Methods|| |
Following approval by the Ethical Committee, this prospective, randomized, double-blinded study was conducted on sixty American Society of Anesthesiologists (ASA) Grade I/II patients of either sex, aged between 18 and 60 years undergoing spinal anesthesia for lower limb orthopedic elective surgery [Figure 1]. Patients with contraindication for spinal anesthesia, known allergy to local anesthetic drugs and patients having h/o diabetes, neurological or musculoskeletal diseases that could make our technique difficult were excluded from this study. The patients were randomly divided into two groups of thirty each (Group R and Group RF) by computer-generated randomization. Patients in Group R received intrathecal injection of 3 ml 0.75% plain ropivacaine (22.5 mg) and 0.5 ml normal saline while patients in Group RF received intrathecal injection of 3 ml 0.75% of plain ropivacaine (22.5 mg) and 0.5 ml fentanyl (25 μg). To ensure blinding, the drugs were prepared and coded by an independent anesthetist who has no role in data collection and analysis. Patients had standard monitoring including electrocardiography, pulse oximetry, and noninvasive blood pressure (BP) monitoring. All patients received oxygen via Hudson mask at the rate of 6 L/min until the surgery ends. Intravenous (IV) access was secured, and patients were premedicated with IV ondansetron 0.1 mg/kg body weight and preloaded with lactated Ringer's solution 15 ml/kg body weight. Under strict aseptic precautions, the skin was infiltrated with lidocaine 2% and lumbar puncture was performed in the sitting position with a 25-gauge Quincke spinal needle (Becton Dickinson, Madrid, Spain), using a midline approach at the L 3-4 intervertebral space. Identification of the intended intervertebral space was done by noting the location of the L 4 spinous process on Tuffier's line (line connecting the superior aspects of the iliac crests). Correct needle placement was identified by the free flow of cerebrospinal fluid (CSF) and confirmed by aspiration and reinjection of CSF before and after the administration of the study drug solution. The study drug was injected over 15-20 s. After the injection of the spinal medication, the patients were placed supine immediately at the end of injection, the time of which was recorded as "zero." The level of sensory block was evaluated by loss of pinprick sensation. The test was performed every 5 min till loss of discrimination to pinprick. After confirming the loss of pinprick sensation at T 10 in comparison to C 5-6 dermatome, all patients was given IV midazolam 0.03 mg/kg body weight and surgeons were allowed to go ahead with the incision. Inability to achieve T 10 sensory level within 30 min was considered as "Failure." These patients were administered general anesthesia. They were not included for analysis but only reported as the total number of failures according to per protocol analysis. Motor block in the lower limbs was graded according to the modified Bromage (MB) scale (Grade 0 = no motor block, Grade 1 = inability to raise extended leg, able to move knees and feet, Grade 2 = inability to raise extended leg and move knee, able to move feet, Grade 3 = complete motor block of the lower limbs). Thereafter, blocks were assessed at 30 min interval till complete sensory and motor recovery. Pulse Rate (PR), BP, and SpO 2 were recorded every 5 min for first 30 min and thereafter every 15 min till complain of pain by the patients. Hypotension was defined as systolic BP <90 mmHg and was treated with mephentermine of 6 mg IV bolus and fluids. Bradycardia was defined as heart rate <50 beats/min and treated with IV atropine of 0.5 mg, if symptomatic. For assessment of the onset of anesthesia, the time for sensory block to develop to T 10 , maximum block height and time to achieve maximum height were noted. To assess the duration of the sensory block, time for regression to L 1 and duration of analgesia (interval from intrathecal injection to the point where patients demanded rescue analgesics for pain relief) were compared. Time to achieve motor block Grade 3, duration of the motor block along with any side effects were also noted.
Power analysis estimated that a sample size of 27 patients per group would yield 95% power for testing the hypothesis at equivalence margin of 30 min difference in mean time to first analgesic requirement (PS Power and Sample Size Calculator, Version 3.0.43, Dupont WD, Plummer WD). The Type I error probability associated with this test, for the null hypothesis that ropivacaine with or without fentanyl is similar in terms of duration of analgesia was α = 0.05. Statistical analysis was performed using SPSS software (Version 17, SPSS Inc., USA). Data are presented as mean (±standard deviation), median (range), or frequencies (%) as appropriate. Group demographic data and adverse events were compared using unpaired t-test or Chi-square (χ2 ) test, whichever applicable. Comparison of block characteristics, duration of analgesia and hemodynamics were made using unpaired t-test. A P < 0.05 was considered statistically significant.
| Results|| |
There were no significant differences between the two groups with respect to age, sex, ASA grade, or duration of surgery [Table 1]. The onset of analgesia to pinprick at T 10 was more rapid in Group RF than Group R (5.76 ± 1.4 min in Group RF and 7.47 ± 2.14 min in Group R; P < 0.001). The median (range) maximum height achieved was T 2 (C 7 -T 4 ) in Group RF while T 4 (T 1 -T 6 ) in Group R. The time to reach maximum height was shorter in Group RF (13.47 ± 1.8 min) as compared to Group R (18.57 ± 1.85 min) with a P < 0.001 [Table 2]. The onset of motor block to MB-3 grade was 8.43 ± 1.80 min in Group RF and 12.27 ± 1.78 min in Group R with P < 0.001. The time to complete recovery of motor block was 289.33 ± 23.11 min in Group RF while 232.33 ± 18.65 min in Group R with a P < 0.001. Time to regression of sensory block to L 1 dermatome was longer in the Group RF than Group R (245.66 ± 22.35 min vs. 187.16 ± 17.053 min; P < 0.001). Duration of analgesia was also significantly longer in Group RF than Group R (313.67 ± 23.45 min. in Group RF compared to 243.83 ± 21.03 min. in Group R with P < 0.001). Baseline hemodynamic parameters were comparable in both groups. The mean PR and mean arterial pressure (MAP) decreased significantly in both groups compared to baseline (P < 0.05), however, there was no significant intergroup variation [Figure 2].
|Figure 2: Significant intragroup variation in mean arterial pressure from baseline with no intergroup variation|
Click here to view
No serious side effects were noted in either group during the study. The incidence of nausea was found to be 10% in Group R and 13.34% in Group RF [Table 3]. The incidence of shivering was 10% in Group R while no patient in Group RF complained of shivering. Pruritus complained by 10% patients from Group RF, but none from Group R. Intraoperative bradycardia occurred in only 3% patient in Group R while hypotension was reported in 27% patients in Group R and 10% patients in Group RF. However, there was no significant difference between the two groups with regard to the total amount of mephentermine used (P > 0.05). No incidence of postdural puncture headache or respiratory depression was observed in either group.
| Discussion|| |
In this study, isobaric ropivacaine alone or in combination with fentanyl (25 μg) produced adequate analgesia and anesthesia for lower limb surgery, with no incidence of failure of spinal anesthesia. However, ropivacaine with fentanyl produced a more rapid onset of sensory as well as motor blockade along with delayed regression of sensory block and delayed motor recovery compared to ropivacaine alone.
Intrathecal opioids with local anesthetics have become a well-accepted practice in spinal anesthesia for surgical procedures. Several combinations of local anesthetics such as lidocaine, bupivacaine, or ropivacaine, and opioids such as fentanyl have been reported for a variety of surgical procedures. The addition of small-dose fentanyl (10-25 μg) intrathecally to local anesthetics during spinal anesthesia has been shown to enhance the potency and duration of sensory analgesia. ,,,,, It increases the mean spread of local anesthetic drugs in the CSF.  This is because all opioids except meperidine are hypobaric, and the addition of these reduces the density of the mixture, making the solution slightly more hypobaric. ,, In addition, there is a pharmacological enhancement of subclinical block at the limits of the local anesthetic's spread through the CSF, thereby increasing the spread.  Several investigators attempted to use fentanyl in combination with hyperbaric ropivacaine in their study. They observed that the quality of intraoperative as well as postoperative analgesia was significantly improved by adding fentanyl to hyperbaric ropivacaine.
In this study, ropivacaine with fentanyl produced a more extensive spread of sensory block than ropivacaine alone. The median (range) maximum height achieved in terms of dermatomes was T 4 (T 2 -T 6 ) which was comparable to the findings obtained by Gunaydin and Tan.  Isobaric ropivacaine alone resulted in a highly variable spread of analgesia, with a median cephalic spread of T 6 (T 5 -T 8 ). However, the maximum height achieved was adequate for the surgery. With respect to block characteristics, ropivacaine with fentanyl produced a more rapid onset of sensory as well as motor blockade compared to ropivacaine alone in this study. The time to reach maximum height was also shorter in Group RF in comparison to Group R. These findings are in agreement with previous studies with slight differences which can be attributed to different amounts of drug used. ,,
The time to regression of sensory block to L 1 dermatome in this study was significantly prolonged in the ropivacaine-fentanyl group than ropivacaine group. Gunaydin and Tan  investigated the efficacy of 15 mg plain ropivacaine with 20 μg fentanyl for the elective cesarian section and found time to L 1 regression as 220 min. Our results are also consistent with the findings obtained by Khaw et al.  and Wong et al.  Moreover, ropivacaine with fentanyl produced significantly longer duration of motor block compared to the ropivacaine alone and it is comparable to the findings obtained by previous studies. ,
The slight variation in the sensory and motor block characteristics of different studies can be attributed to the mechanism of intrathecal drug spread which depends on characteristics of CSF (density) and solution injected (baricity, concentration, volume), clinical techniques and patient's characteristics. As glucose-free ropivacaine is slightly hypobaric, injection of glucose-free ropivacaine may result in a higher spread of analgesia when the patient is kept in the sitting position for at least 2 min after the injection, as has been demonstrated for bupivacaine in various studies. ,
Intrathecal fentanyl significantly prolongs the duration of complete analgesia, and the time to the first dose of analgesic administration was significantly longer in the fentanyl group. These effects of intrathecal fentanyl have been reported in previous studies in which fentanyl was used in combination with hyperbaric ropivacaine or bupivacaine. ,,,, Chung et al.  have shown that the addition of 10 μg fentanyl improved the quality of intraoperative analgesia and prolonged its duration by approximately 40 min and that of effective analgesia by approximately 70 min. Similarly, Sanli et al.  showed that addition of 10 μg fentanyl to 15 mg hyperbaric ropivacaine prolongs the duration of complete analgesia by approximately 24 min and the time to the first dose of analgesic administration by approximately 52 min in the fentanyl group.
In this study, mean PR and mean MAP decreased significantly in both groups compared to their baseline/preoperative values; however, there was no significant intergroup variation (P > 0.05). There were eight patients in ropivacaine group and three patients in the ropivacaine-fentanyl group who developed hypotension during the intraoperative period and required vasopressor in the form of 6 mg IV boluses of mephentermine, these episodes were of short duration and promptly treated without any serious consequences. However, there was no significant difference between the two groups with regard to the total amount of mephentermine used (P > 0.05). One patient developed bradycardia which was successfully treated with IV atropine 0.5 mg while the incidence of nausea and vomiting was similar in both groups.
| Conclusion|| |
Ropivacaine alone as well as ropivacaine-fentanyl combination achieved adequate anesthesia and analgesia, however, ropivacaine with fentanyl produced a more rapid and prolonged sensory blockade with minimal hemodynamic changes.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]